Clinical trial NCT02161718
Conditions: Schizophrenia Alcohol Use Disorder
Keywords: Alkermes Schizophrenia Alcohol Use Disorder ALKS 3831
Sponsor: Alkermes, Inc.
Start date: 2014-05-01; Completion date: 2017-02-01
Enrollment: 300 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This double-blind, randomized study will evaluate the efficacy, safety and tolerability of ALKS 3831 in subjects with schizophrenia and alcohol use disorder (AUD).

Detailed description:

Arms: arm 1: Active study drug arm 2: None
Interventions: intervention 1: Samidorphan + olanzapine (ALKS 3831) intervention 2: Placebo + olanzapine
Intervention descriptions: intervention 1: Oral tablet, taken once daily intervention 2: Oral tablet, taken once daily

Protocol documents:
Prot_000.pdf: 
A Phase 2, Efficacy, Safety, and Tolerability Study of ALKS 
3831 in Schizophrenia with Alcohol Use Disorder 
 
 
Unique Protocol ID: 
ALK3831-401 
NCT Number: 
NCT02161718 
Date of Protocol:  
01 Mar 2016 
 


Page 1 
1. 
TITLE PAGE 
 
CLINICAL STUDY PROTOCOL 
ALK3831-401 
EudraCT Number: 2014-001211-39 
Study Title 
A Phase 2, Efficacy, Safety, and Tolerability Study of 
ALKS 3831 in Schizophrenia with Alcohol Use Disorder 
Document Status 
Final 
Document Date 
Amendment #6: 01 Mar 2016 
Amendment #5: 28 July 2015 
Amendment #4: 20 May 2015 
Amendment #3-Bulgarian Sites Only: 15 December 2014 
Amendment #3: 07 August 2014 
Amendment #2 – EU: 13 June 2014 
Amendment #2: 22 May 2014 
Amendment #1: 02 May 2014 
Original Protocol: 04 February 2014 
Sponsor 
Alkermes, Inc. 
852 Winter Street 
Waltham, MA 02451 
USA 
Telephone: 
 
CONFIDENTIAL 
Information and data in this protocol contain trade secrets and privileged or confidential information, 
which is the property of Alkermes, Inc. No person is authorized to make it public without the written 
permission of Alkermes, Inc. These restrictions or disclosures will apply equally to all future 
information supplied to you that is indicated as privileged or confidential. 
PPD


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CONTACT INFORMATION 
Role in Study 
Name 
Address and Telephone 
Alkermes Medical Monitor  
 
Alkermes, Inc. 
Connaught House 
1 Burlington Road 
Dublin 4, Ireland 
Telephone: 
 
Alkermes Drug Safety 
Specialist 
 
Alkermes, Inc. 
852 Winter Street 
Waltham, MA 02451 
Telephone: 
 
 
Medical Monitor and 24-hour 
Emergency Contact 
 
 
 
 
C.P. 03900 
México D.F. 
Telephone: 
 
24-Hour Contact: 
 
(global reachable, chargeable number 
or 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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2. 
SYNOPSIS 
Name of Sponsor/Company: Alkermes, Inc. 
Name of Investigational Product: ALKS 3831 
Name of Active Ingredient: olanzapine and samidorphan 
Title of study: A Phase 2 Efficacy, Safety, and Tolerability Study of ALKS 3831 in Schizophrenia with 
Alcohol Use Disorder 
Investigator(s): Multicenter, multinational study 
Study Period: 
Estimated date of first subject’s consent: May 2014 
Estimated date of last subject’s completion: CY 2017 
Phase of Development: 2 
Objectives: 
Primary: 
• 
To evaluate the efficacy of olanzapine coadministered with samidorphan (ALKS 3831) 
compared with olanzapine coadministered with placebo in schizophrenia with alcohol use 
disorder (AUD) 
Secondary: 
• 
To evaluate the safety and tolerability of ALKS 3831 in schizophrenia with AUD 
Methodology: 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate 
the efficacy, safety, and tolerability of ALKS 3831 in schizophrenia with AUD. Subjects must have 
recently (within the last 6 months) experienced an exacerbation of disease symptoms (as defined in the 
protocol). ALKS 3831 is a combination of olanzapine, an approved antipsychotic treatment for 
schizophrenia, and samidorphan, a new chemical entity. 
The clinical presentation of schizophrenia often includes AUD, as it occurs in this population more 
frequently than in the general population and most other psychiatric disorders. Despite the prevalence of 
schizophrenia with AUD and the psychosocial consequences of this disease, there is no approved 
treatment that has been clinically tested for treating schizophrenia in this group. 
Potential subjects for this trial are adults with a diagnosis of schizophrenia (based on the Diagnostic and 
Statistical Manual of Mental Disorders 4th edition, text revision [DSM-IV-TR]) and AUD (based on 
DSM 5th edition [DSM-5]). Subjects must also have recently experienced an exacerbation of disease 
symptoms (eg, hospitalization) but cannot exceed a pre-defined level of symptom severity at the time of 
screening (as measured by assessments like the Positive and Negative Syndrome Scale [PANSS] and 
Clinical Global Impression-Severity [CGI-S]). 
All study visits will be outpatient. After informed consent and screening, subjects will begin a 4-week 
open-label olanzapine dosing period followed by a 2-week open-label ALKS 3831 period (see study 
schematic below). Once-daily, open-label olanzapine dosing will begin at Visit 2 with the dose level 
determined by the principal investigator (PI). Olanzapine dose adjustments may be made during the first 
3 weeks of treatment but should be fixed beginning with Visit 5. Once daily open-label ALKS 3831 
dosing (olanzapine coadministered with 10 mg samidorphan using separate tablets) will begin at Visit 6 
and last until Visit 8 (randomization). ALKS 3831 treatment will consist of a once-daily dose of 


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olanzapine (with dose level determined by the PI) plus samidorphan 10 mg to be taken at the same time 
(ie, coadministered) using separate tablets. 
At Visit 8, subjects will be randomized in a 1:1 fashion to 1 of 2 treatment groups and will begin a 
double-blind treatment period. The two treatment groups are as follows: 
• 
ALKS 3831: (ie, olanzapine [dose determined by the PI] plus samidorphan [10 mg]) 
• 
Olanzapine (dose determined by the PI) plus placebo 
Subjects randomized to double-blind treatment will be followed for a minimum of 9 months and a 
maximum of 15 months. Visits during the double-blind period will be every 2 weeks. Each visit will 
consist of clinical assessments plus drug dispensing or drug dispensing only. After the end of the double-
blind treatment period, subjects will complete a 3-week safety follow-up period. 
 
Abbreviation: V = Study Visit; ALKS 3831=olanzapine + samidorphan 
Number of Subjects Planned: 
Approximately 450 subjects will enter the open-label olanzapine period at Visit 2. Of those, 
approximately 270 are expected to be randomized at Visit 8. 
Main Criteria for Inclusion: 
Men and women 18 through 65 years of age (inclusive) with a DSM-IV-TR diagnosis of schizophrenia 
and a DSM-5 diagnosis of AUD who meet pre-specified symptom severity criteria may be eligible for this 
study. At a minimum, subjects must also meet sponsor criteria for a recent (within 6 months) exacerbation 
of schizophrenia symptoms and have experienced at least 10 drinking days in the 30 days prior to 
screening (as measured by the Timeline Follow-Back [TLFB] method), with at least 2 of these drinking 
days meeting criteria for a heavy drinking day (4 drinks in a day for women and 5 drinks in a day for 
men), to be eligible for this study. 
Investigational Product Dosage, Duration, and Mode of Administration: 
ALKS 3831 refers to the combination of olanzapine and samidorphan. In this study, olanzapine and 
samidorphan will be coadministered orally using separate tablets for olanzapine and samidorphan to be 
taken once daily. Commercially available olanzapine for oral administration will be dispensed by the 
investigative site. All subjects will take olanzapine for the entire duration of the study. 
Alkermes will provide samidorphan as 10 mg tablets. All subjects will take open-label ALKS 3831 for 
2 weeks prior to randomization. Subjects randomized to the double-blind treatment period will take 
ALKS 3831 (olanzapine plus samidorphan) or olanzapine plus placebo for the duration of the double-
blind period. 
Whether or not samidorphan is classified as a controlled substance varies from country to country; some 
3 


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countries have classified samidorphan as a controlled substance, but others have not. Sites will be given 
handling and storage instructions applicable to their country to ensure compliance with local regulations 
for controlled substances. 
Reference Therapy Dosage, Duration, and Mode of Administration: 
Placebo consists of tablets identical in size and appearance to the samidorphan tablets but without active 
samidorphan. Subjects who are randomized to olanzapine plus placebo will take these study drugs orally, 
once daily at the same time for 9 to 15 months. 
Duration of Study: 
The duration of the study period for a given subject will be approximately 12 to 18 months which 
includes up to 30 days for screening, a total of 6 weeks of open-label treatment, a 9 to 15 month 
double-blind treatment period, and 3 weeks for safety follow-up. 
Primary Efficacy Measure: 
The primary efficacy measure will be an event of exacerbation of disease symptoms (EEDS) based on the 
occurrence of pre-specified events indicative of exacerbation of disease symptoms, as confirmed by an 
independent adjudication committee (IAC). These events are pre-specified in the body of the protocol. 
Other Efficacy Measures: 
In addition to the primary efficacy measure, efficacy will be evaluated with the following measures: 
• 
Pre-specified psychosocial events indicative of exacerbation of disease symptoms 
• 
PANSS 
• 
CGI-S 
• 
CGI-Improvement (CGI-I) 
• 
TLFB assessment of alcohol drinking 
• 
Visual Analog Scale (VAS) for perception of desire for alcohol 
Safety Assessments: 
Safety will be evaluated with the following measures: 
• 
Adverse events (AEs) 
• 
Columbia-Suicidal Severity Rating Scale (C-SSRS) results 
• 
Vital signs 
• 
Clinical biochemistry, hematology, and urinalysis 
• 
Electrocardiograms (ECGs) 
• 
Weight 
• 
Abnormal movement rating scales results [Abnormal Involuntary Movement Scale (AIMS), 
Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS)] 


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Statistical Methods 
Efficacy: 
The efficacy analyses will be carried out using the intent-to-treat (ITT) population defined as all 
randomized subjects who receive at least 1 dose of study drug post-randomization. The primary efficacy 
endpoint is defined as the time from randomization to first occurrence of an EEDS, as defined in the 
protocol and confirmed by an IAC. The analysis comparing the 2 treatment groups will be carried out 
using a log-rank test. A Cox proportional hazard model will be used to further examine the treatment 
difference adjusting for various covariates. 
Pharmacokinetics: 
Pharmacokinetic data may be used in a subsequent population pharmacokinetic evaluation conducted 
separately. By-subject listings of plasma concentrations of olanzapine, samidorphan, and RDC-9986 
(metabolite of samidorphan) will be provided. 
Safety: 
All subjects who receive at least 1 dose of study drug (olanzapine, samidorphan, or placebo) will be 
included in the safety analysis. Safety will be evaluated based on the incidence of treatment emergent 
adverse events (TEAEs), laboratory test results, vital signs, ECG findings, C-SSRS results, change in 
weight, abnormal movement scale results, and concomitant medications. Descriptive summary statistics 
and by-subject listings will be provided for safety measures. 
Sample Size Considerations: 
The sample size calculation is based on the detection of log-hazard ratio for the first EEDS during the 
double-blind treatment period. 
Based on the previous clinical studies with olanzapine and clinical judgment, the cumulative proportion 
of EEDS by the end of a 9-month double-blind treatment period (the minimum duration for subjects in 
this study) is estimated to be 15% and 30% for the ALKS 3831 group and the olanzapine plus placebo 
group, respectively. Assuming an exponential distribution of survival time, and a 2-sided test at α=0.05, a 
total of 70 recurrent events will be required for approximately 90% power to detect a hazard ratio of 0.45 
between ALKS 3831 and olanzapine plus placebo with a randomization allocation ratio of 1:1 
(ALKS 3831:olanzapine plus placebo). An estimated 270 subjects (135 subjects per treatment group) will 
need to be randomized at Visit 8 to observe 70 total EEDS. 


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3. 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
CONTACT INFORMATION ..........................................................................................................2 
2. 
SYNOPSIS ...................................................................................................................3 
3. 
TABLE OF CONTENTS .............................................................................................7 
4. 
LIST OF ABBREVIATIONS.....................................................................................12 
5. 
INTRODUCTION ......................................................................................................14 
5.1. 
Study Population .........................................................................................................14 
5.2. 
Clinical and Nonclinical Experience ..........................................................................15 
5.2.1. 
Clinical Studies ...........................................................................................................15 
5.2.2. 
Nonclinical Studies .....................................................................................................16 
5.3. 
Dose Selection ............................................................................................................17 
6. 
OBJECTIVES .............................................................................................................18 
6.1. 
Primary Objective .......................................................................................................18 
6.2. 
Secondary Objective ...................................................................................................18 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................19 
7.1. 
Subject Inclusion Criteria ...........................................................................................19 
7.2. 
Subject Exclusion Criteria ..........................................................................................20 
7.3. 
Subject Randomization Criteria ..................................................................................24 
7.4. 
Subject Withdrawal ....................................................................................................25 
7.5. 
Replacement of Subjects .............................................................................................26 
7.6. 
Identification of Informant or Caregiver ....................................................................26 
7.7. 
Withdrawal and Replacement of Informant or Caregiver ..........................................26 
8. 
STUDY DESIGN .......................................................................................................27 
8.1. 
Overall Study Design and Plan ...................................................................................29 
8.2. 
Schedule of Visits and Assessments ...........................................................................29 
8.3. 
Study Procedures Descriptions ...................................................................................38 
8.3.1. 
Informed Consent .......................................................................................................38 
8.3.2. 
Eligibility Criteria Review ..........................................................................................38 
8.3.3. 
Demographics and Medical History ...........................................................................38 
8.3.4. 
Pregnancy Testing ......................................................................................................38 


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8.3.5. 
Drug Testing ...............................................................................................................38 
8.3.6. 
Physical Examination .................................................................................................39 
8.3.7. 
Clinical Validation Inventory for Study Admission and Ongoing Rater 
Review ........................................................................................................................39 
8.3.8. 
Mini International Neuropsychiatric Interview ..........................................................39 
8.3.9. 
Readiness to Change Questionnaire ...........................................................................39 
8.3.10. 
Positive and Negative Syndrome Scale ......................................................................39 
8.3.11. 
Clinical Global Impression .........................................................................................39 
8.3.12. 
Timeline Follow-Back ................................................................................................40 
8.3.13. 
Cigarette Use ..............................................................................................................40 
8.3.14. 
Visual Analog Scale for Perception of Desire for Alcohol ........................................40 
8.3.15. 
Exacerbation of Disease Criteria Review ...................................................................40 
8.3.16. 
Personal and Social Performance Scale ......................................................................40 
8.3.17. 
Abnormal Movement Rating Scales ...........................................................................40 
8.3.18. 
Adverse Event Monitoring .........................................................................................41 
8.3.19. 
Columbia Suicide Severity Rating Scale ....................................................................41 
8.3.20. 
Concomitant Medication Review ...............................................................................41 
8.3.21. 
Vital Signs ..................................................................................................................41 
8.3.22. 
Hematology, Biochemistry, and Urinalysis ................................................................41 
8.3.23. 
Pharmacokinetic Assessments ....................................................................................43 
8.3.24. 
Body Height, Body Weight, and Waist Circumference .............................................44 
8.3.25. 
12-Lead Electrocardiogram ........................................................................................44 
8.3.26. 
Supportive Counseling................................................................................................44 
8.3.27. 
Drug Dispensation and Reconciliation .......................................................................44 
8.3.28. 
Emergency Treatment Card ........................................................................................45 
8.4. 
Study Requirements and Restrictions .........................................................................45 
8.4.1. 
Contraception and Pregnancy .....................................................................................45 
8.4.2. 
Prohibited and Restricted Medications .......................................................................46 
8.4.3. 
Other Prohibited Substances .......................................................................................47 
8.4.4. 
Pain Management .......................................................................................................47 
8.4.5. 
Rescue Medication ......................................................................................................48 
8.5. 
Ad Hoc Study Visits ...................................................................................................48 
9. 
TREATMENT OF SUBJECTS ..................................................................................49 


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9.1. 
Study Drug Dose and Administration .........................................................................49 
9.2. 
Treatment Adherence ..................................................................................................49 
9.3. 
Randomization to Treatment ......................................................................................50 
9.4. 
Blinding ......................................................................................................................50 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................51 
10.1. 
Study Drug ..................................................................................................................51 
10.2. 
Packaging and Labeling ..............................................................................................51 
10.3. 
Storage ........................................................................................................................51 
10.4. 
Accountability .............................................................................................................51 
10.5. 
Handling and Disposal ................................................................................................51 
11. 
ASSESSMENT OF EFFICACY ................................................................................52 
11.1. 
Primary Efficacy Measure ..........................................................................................52 
11.2. 
Other Efficacy Measures ............................................................................................53 
11.3. 
Exploratory Efficacy Measures ..................................................................................53 
12. 
ASSESSMENT OF PHARMACOKINETICS AND 
PHARMACODYNAMICS ........................................................................................54 
13. 
ASSESSMENT OF SAFETY .....................................................................................55 
13.1. 
Definition of Adverse Event .......................................................................................55 
13.2. 
Definition of Serious Adverse Event ..........................................................................55 
13.3. 
Relationship to Study Drug ........................................................................................56 
13.4. 
Monitoring and Recording of Adverse Events ...........................................................58 
13.5. 
Reporting of Serious Adverse Events .........................................................................58 
14. 
STATISTICS ..............................................................................................................59 
14.1. 
Sample Size Considerations .......................................................................................59 
14.2. 
General Statistical Methodology ................................................................................59 
14.2.1. 
Study Populations .......................................................................................................59 
14.2.2. 
Demographics and Baseline Data ...............................................................................59 
14.3. 
Efficacy Analyses .......................................................................................................60 
14.3.1. 
Primary Efficacy Measure ..........................................................................................60 
14.3.2. 
Other Efficacy Endpoints ...........................................................................................60 
14.4. 
Pharmacokinetic Analyses ..........................................................................................61 
14.5. 
Safety Analyses ..........................................................................................................61 
15. 
DIRECT ACCESS TO SOURCE DATA/ DOCUMENTS........................................62 


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15.1. 
Study Monitoring ........................................................................................................62 
15.2. 
Audits and Inspections ................................................................................................62 
15.3. 
Institutional Review Board/ Independent Ethics Committee .....................................62 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................63 
16.1. 
Case Report Forms .....................................................................................................63 
16.2. 
Confidentiality of Data ...............................................................................................63 
17. 
ETHICAL CONSIDERATIONS................................................................................64 
17.1. 
Ethics Review .............................................................................................................64 
17.2. 
Ethical Conduct of the Study ......................................................................................64 
17.3. 
Written Informed Consent ..........................................................................................64 
18. 
DATA HANDLING AND RECORDKEEPING .......................................................66 
18.1. 
Data Capture ...............................................................................................................66 
18.2. 
Inspection of Records .................................................................................................66 
18.3. 
Retention of Records ..................................................................................................66 
18.4. 
Use of Information and Publication Policy ................................................................67 
19. 
REFERENCES ...........................................................................................................68 
20. 
APPENDICES ............................................................................................................70 
 
LIST OF TABLES 
Table 1: 
Schedule of Visits and Assessments for Screening and Open-label Treatment 
Periods (Visit 1-Visit 7)
 
 ..............................................................................................30
Table 2: 
Schedule of Visits and Assessments for Double-blind Treatment Period 
(Visit 8–Visit 26)
 
 ........................................................................................................32
Table 3: 
Schedule of Visits and Assessments for Continuation of Double-blind 
Treatment and Safety Follow-up Period (Visit 27―Visit 40)
 
 .....................................35
Table 4: 
Clinical Laboratory Assessments
 
 ...............................................................................43
Table 5: 
Adverse Event Causality Guidelines
 
 ..........................................................................57
 
LIST OF FIGURES 
Figure 1: 
ALK3831-401 Study Schematic
 
 .................................................................................28
 


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LIST OF APPENDICES 
Appendix A. 
Sample Mini-International Neuropsychiatric Interview 
Appendix B. 
Sample Readiness to Change Questionnaire 
Appendix C. 
Sample Positive and Negative Syndrome Scale 
Appendix D. 
Sample Clinical Global Impression-Improvement 
Appendix E. 
Sample Structured Interview Guide for Global Impressions 
Appendix F. 
Sample Visual Analog Scale 
Appendix G. 
Sample Personal and Social Performance Scale 
Appendix H. 
Sample Abnormal Involuntary Movement Scale 
Appendix I. 
Sample Barnes Akathisia Scale 
Appendix J 
Sample Simpson-Angus Scale 
Appendix K. 
Sample Columbia Suicide Severity Rating Scale 
• 
“Baseline/ Screening” Version 
• 
“Since Last Visit” Version 
Appendix L. 
Partial List of Prohibited Cytochrome P450 3A4 (CYP3A4) Inducers and 
Moderate-to-Strong Inhibitors 


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4. 
LIST OF ABBREVIATIONS 
The following abbreviations are used in this study protocol. 
Abbreviation or Term 
Explanation or Definition 
AE 
adverse event 
AIMS 
Abnormal Involuntary Movement Scale 
ALK-P 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical [classification system] 
AUC 
area under the curve 
AUC∞ 
area under the curve extrapolated to infinity 
AUD 
alcohol use disorder 
BARS 
Barnes Akathisia Rating Scale 
BUN 
blood urea nitrogen 
C-SSRS 
Columbia Suicide Severity Rating Scale 
C-VISA™ 
Clinical Validation Inventory for Study Admission 
CDT 
carbohydrate deficient transferrin 
CGI-I 
Clinical Global Impression-Improvement 
CGI-S 
Clinical Global Impression-Severity 
CPK 
creatine phosphokinase 
CSA 
Clinical Study Agreement 
DEA 
Drug Enforcement Agency 
DSM-IV-TR 
Diagnostic and Statistical Manual of Mental Disorders (4th edition, text 
revision) 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders (5th edition) 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
Electronic Data Capture 
EEDS 
event of exacerbation of disease symptoms 
ET 
early termination 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 


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Abbreviation or Term 
Explanation or Definition 
GGT 
gamma glutamyl transferase 
HbA1c 
hemoglobin A1c 
HDL 
high-density lipoprotein 
IAC 
Independent Adjudication Committee 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
LDH 
lactic dehydrogenase 
LDL 
low-density lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
MINI 
Mini-International Neuropsychiatric Interview 
PANSS 
Positive and Negative Syndrome Scale 
PI 
principal investigator 
PK 
pharmacokinetics 
PSP 
Personal and Social Performance Scale 
QTcF  
QT interval corrected using the Fridericia formula 
QTcB 
QT interval corrected using the Bazett formula 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Simpson-Angus Scale 
SCI-PANSS 
Structured Clinical Interview for the Positive and Negative Syndrome Scale 
SIGGI 
Structured Interview Guide for Global Impressions 
TEAE 
treatment-emergent adverse event 
TLFB 
Timeline Follow-Back 
TSH 
thyroid stimulating hormone 
US 
United States 
VAS 
visual analog scale 
WHO 
World Health Organization 


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5. 
INTRODUCTION 
ALKS 3831 is a combination of olanzapine and samidorphan (previously referred to as ALKS 33 
or RDC-0313) being developed for the treatment of schizophrenia. Olanzapine has been 
available in the United States (US) and Europe since 1996 and was originally approved for the 
treatment of schizophrenia [EMEA 2013;Lilly USA 2013]. Olanzapine is regarded as one of the 
most effective antipsychotics with well-recognized efficacy and other advantages such as 
decreased incidence of extrapyramidal symptoms [Lieberman, 2005]. However, its efficacy and 
safety have not been fully evaluated in patients with schizophrenia and alcohol use disorder 
(AUD). Furthermore, the use of olanzapine in treatment has been limited by adverse events 
(AEs) related to weight gain and unintended metabolic effects. 
Samidorphan is a μ-opioid receptor antagonist being developed on its own for treatment of 
reward disorders and in combination with olanzapine (ALKS 3831) for treatment of 
schizophrenia. In ALKS 3831, samidorphan has a range of potential benefits for patients with 
schizophrenia, such as reducing alcohol consumption and attenuating weight gain. Both of these 
benefits have the potential to improve long-term outcomes, such as reducing schizophrenia 
symptom severity and decreasing the frequency of events of exacerbation of disease symptoms 
(EEDS). ALK3831-401 is designed to assess efficacy of ALKS 3831 on time to EEDS after 
randomization to ALKS 3831 or olanzapine plus placebo following a recent exacerbation (within 
6 months prior to screening) in schizophrenia with AUD. A separate study (ALK3831-302) is 
ongoing to assess other potential benefits of ALKS 3831 in schizophrenia. 
5.1. 
Study Population 
The clinical presentation of schizophrenia quite often includes AUD as it occurs in this patient 
population much more frequently than in most other psychiatric disorders or the general 
population. In an epidemiological study of psychiatric disorders and AUD, approximately 1 out 
of every 3 people with schizophrenia (33.7%) were found to meet or have met criteria for AUD, 
which is nearly triple the lifetime prevalence found in the general population (13.5%) 
[Regier, 1990]. Conversely, schizophrenia is seen more than 3 times as often in people with 
AUD as in the general population (odds ratio=3.3). 
An increased risk for AUD in people with schizophrenia may be a part of a more general reward 
disorder that is part of the pathogenesis of schizophrenia and one of the core features of the 
disease. Evidence for a reward disorder includes the fact that most substance use disorders occur 
in schizophrenia more often than in the general population and often occur simultaneously 
[Regier, 1990]. In substance use disorders, the rewarding effects of a substance result in 
abnormally high levels of craving and drug-seeking with abnormally low consideration of the 
risks and negative effects of substance use. In AUD, this skewed risk/reward perception and 
alcohol drinking leads to physical and psychological effects that motivate use even when 
negative physical and psychosocial outcomes are frequently experienced (or are predictable) 
[Ahmed 2004]. Patients with schizophrenia are known to have difficulty with reward processing 
and this underlying neurobiological deficit, a pharmacologic predisposition for poor control of 
self-initiated activity, and the relative ease of access to alcohol, may explain why this population 
is particularly prone to AUD [Chambers, 2001]. Although the association between schizophrenia 


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and AUD is the strongest of nearly all psychiatric disorders, there are a substantial number of 
people with schizophrenia who may not be receiving treatment that specifically addresses their 
AUD [Drake, 1998]. 
In schizophrenia, AUD is a significant barrier to treatment and typically results in a poor disease 
course punctuated by frequent visits to “crisis settings” like jails, emergency rooms, and 
homeless shelters [Drake, 1998]. Ineffective treatments for schizophrenia with AUD directly 
contribute to the higher frequency of crisis outcomes in these patients [Dickey, 2000]. 
Schizophrenia with AUD is more strongly associated with violent behavior and incarceration; 
depression and suicide; family problems; and housing instability, all of which greatly complicate 
treatment. Poor outcomes are often the end of a long period of stable but deteriorating mental 
health as patients face the daily challenges associated with managing schizophrenia with AUD. 
Schizophrenia is a chronic condition that requires long-term coordinated care and management, 
and AUD introduces specific challenges to treating schizophrenia by affecting factors such as a 
patient’s ability to maintain stable housing and depend on caregivers. As a result, a patient’s 
functional status, stress level, and symptoms may worsen until he/she experiences a crisis 
situation and/or requires acute treatment (eg, inpatient hospitalization). 
For this study, the target population will be identified using standard diagnostic criteria for 
schizophrenia (the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text 
revision; DSM-IV-TR [American Psychiatric Association 2000]) and AUD (DSM-5 [American 
Psychiatric Association 2013]) as confirmed by the structured diagnostic interview, the 
Mini-International Neuropsychiatric Interview (MINI) [Sheehan, 1998], as well as other 
inclusion/exclusion criteria as confirmed by the Clinical Validation Inventory for Study 
Admission (C-VISA™). Subjects will have recently experienced an exacerbation of disease 
symptoms, and the primary efficacy endpoint will be time to EEDS (after randomization) using 
the pre-specified events defined in the protocol (Section 11.1) and confirmed by an independent 
adjudication committee (IAC). 
5.2. 
Clinical and Nonclinical Experience 
ALKS 3831 is being developed as a combination product containing olanzapine and 
samidorphan. In this study, olanzapine and samidorphan will be coadministered as separate 
tablets. Details of the studies summarized below are available in the ALKS 3831 Investigator’s 
Brochure. 
Samidorphan is a potent μ-opioid receptor antagonist with mixed agonist/antagonist activity at 
κ and δ receptors. To date there has not been any observed abuse potential in clinical or 
nonclinical studies. Other than binding at these human receptors, samidorphan (at 10 μM) has 
exhibited no significant receptor, transporter, or enzyme-ligand binding in [35S]GTPγS assays of 
functional activity. 
5.2.1. 
Clinical Studies 
In the clinical studies of samidorphan to date, 469 subjects have received samidorphan orally 
(1-55.7 mg) or sublingually (1–16 mg) for up to 12 weeks. Commonly reported AEs observed 
across all studies included nausea, fatigue, and somnolence. Other AEs observed in these studies 
included dry mouth, vomiting, constipation, decreased appetite, headache, dizziness, and 
anorexia. Overall, no trends or clinically meaningful changes have been observed in clinical 


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laboratory analytes, vital sign parameters, or electrocardiogram (ECG) data. No deaths have 
occurred in these studies. 
Samidorphan has been shown to block opioid agonist effects in opioid-experienced adults and 
decrease alcohol consumption in alcohol-dependent adults. In opioid-experienced adults, 
samidorphan blocked both the subjective (eg, Drug Liking measured with a visual analog scale 
[VAS]) and physiological effects (eg, pupil constriction measured with pupillometry) of the 
opioid agonists remifentanil (Study ALK33-004) and buprenorphine (Study ALK33-008). In 
adults with alcohol dependence (N=410), samidorphan (1, 2.5, or 10 mg) was associated with a 
reduction in drinking behavior (Study ALK33-005) compared with placebo; the largest reduction 
was seen with the highest samidorphan dose administered in this study (10 mg). 
In addition to the reduction of alcohol drinking, samidorphan may attenuate weight gain 
associated with olanzapine. A Phase 1 proof-of-concept study has been conducted in healthy 
adults (ALK33-301) to determine the safety, tolerability, and efficacy of samidorphan when 
taken with olanzapine to mitigate olanzapine-related weight gain. In this study, significantly less 
weight gain was seen in the ALKS 3831 treatment arm than in the olanzapine plus placebo arm. 
A Phase 2 study, ALK3831-302, is currently underway to evaluate (as a secondary outcome) 
attenuation of weight gain by ALKS 3831 compared with olanzapine plus placebo in subjects 
with schizophrenia. 
Samidorphan is a μ-opioid antagonist. Consistent with this mechanism, there has been no 
evidence of withdrawal upon discontinuation or addiction potential with samidorphan to date. In 
all studies, subjects are asked to complete a follow-up safety visit approximately 2 weeks after 
drug discontinuation, and no evidence of withdrawal has been reported after this abrupt 
discontinuation of samidorphan. The most common AEs seen with samidorphan are similar to 
those seen with naltrexone (an approved medication for addiction that is also a μ-opioid 
antagonist) and do not include AEs suggestive of addiction potential [Duramed Pharmaceuticals, 
Inc 2013]. 
Although samidorphan is a μ-opioid antagonist, agencies responsible for substance control may 
not consider a drug’s mechanism of action when determining whether an unapproved drug 
should be handled as a controlled substance. For example, the US Drug Enforcement Agency 
(DEA) has classified samidorphan as a Schedule II substance because it is derived from opium 
alkaloids. In countries where samidorphan has been designated a controlled substance, 
samidorphan (and blinded study drug) will require handling consistent with local regulations for 
drugs of this class. 
Olanzapine is regarded as one of the most effective antipsychotics with well-recognized efficacy 
and other advantages such as decreased incidence of extrapyramidal symptoms 
[Lieberman, 2005]. The safety and tolerability profile of olanzapine is well documented, and AE 
labeling is supported by an extensive safety database that includes over 8,500 adult patients. 
5.2.2. 
Nonclinical Studies 
Nonclinical data to date provide supporting (secondary pharmacology) evidence of samidorphan 
as a μ-opioid antagonist and a benefit in reduced alcohol consumption. In vivo nonclinical 
pharmacology studies have been conducted to demonstrate that samidorphan, at doses that result 
in exposure similar to therapeutically relevant doses in humans, blocks μ-opioid agonist effects 


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and reduces ethanol self-administration in rodents. In addition, these studies have demonstrated 
that, when administered alone, samidorphan is devoid of μ-opioid agonist-like properties. 
The nonclinical safety assessment program for samidorphan and ALKS 3831 is based on 
recommendations for nonclinical drug toxicity and abuse liability testing in International 
Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for 
Human Use (ICH) and US Food and Drug Administration (FDA) guidelines. A summary of 
completed GLP studies with samidorphan and ALKS 3831 can be found in the ALKS 3831 
Investigator’s Brochure. 
Nonclinical abuse liability studies examining self-administration, drug discrimination, and drug 
dependence in rats indicate that samidorphan itself has no rewarding properties and carries no 
abuse potential. Furthermore, general toxicology studies of samidorphan (exposure up to 
39 weeks: 2-week and 13-week rat/dog, 25-week rat, and 39-week dog studies) and ALKS 3831 
(39-week dog study) have included non-dosing recovery periods during which clinical 
observations were made following abrupt samidorphan or ALKS 3831 discontinuation (ie, 
without a taper period). In these studies, there have been no clinical observations noted 
suggestive of withdrawal effects following samidorphan or ALKS 3831 administration. 
Samidorphan has not been found to be genotoxic in vitro or in vivo at exposures (measured as 
area under the plasma concentration curve [AUC]) well above the ALK3831-401 samidorphan 
dose level (10 mg). General toxicology studies (referenced above) have identified findings only 
at systemic AUC∞ (AUC extrapolated to infinity) exposures far above the samidorphan dose 
level of this study. In developmental and reproductive toxicology studies conducted with 
samidorphan, dose-related effects were observed at systemic AUC∞ exposures far above the 
proposed samidorphan dose. 
Overall, nonclinical findings to date do not suggest a human safety risk as findings occurred at 
exposures significantly above dose levels used in this study and were associated with increases in 
serum transaminases that can be readily monitored in the clinic. Moreover, exclusionary criteria 
and study procedures are designed to further mitigate any potential risk. 
5.3. 
Dose Selection 
Clinical and nonclinical safety and efficacy data support the selection of a once-daily 10 mg dose 
for the samidorphan component of ALKS 3831 in this study. In a prior study in 
alcohol-dependent subjects, samidorphan 10 mg showed the largest reduction in drinking 
behavior. Furthermore, clinical trial experience to date has shown samidorphan 10 mg to be well-
tolerated. 
This study includes a 2-week open label ALKS 3831 period. This open-label ALKS 3831 period 
is included because previous clinical studies have shown that the majority of AEs associated with 
samidorphan occur within the first 2 weeks of treatment. Starting all subjects on samidorphan not 
only establishes similar pharmacological states in the 2 groups prior to randomization but also 
mitigates the risk of functional unblinding because of subjects not tolerating study drug during 
samidorphan initiation. Both open-label periods (olanzapine and ALKS 3831) will allow 
investigators to address tolerability issues prior to randomization. 
For all subjects, the once-daily olanzapine dose level throughout the study will be determined 
individually by the principal investigator (PI) or designee according to current clinical practice. 


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6. 
OBJECTIVES 
6.1. 
Primary Objective 
To evaluate the efficacy of olanzapine coadministered with samidorphan (ALKS 3831) 
compared with olanzapine coadministered with placebo in schizophrenia with alcohol use 
disorder (AUD) 
6.2. 
Secondary Objective 
The secondary objective of this study is to evaluate the safety and tolerability of ALKS 3831 in 
schizophrenia with AUD. 


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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
Each subject must meet all of the following inclusion criteria at screening, unless otherwise 
specified, to be qualified to participate in this study: 
1. Is between 18 and 65 years of age, inclusive 
2. Is willing and able to provide informed consent 
3. Is willing and able to follow the study procedures as outlined in the protocol 
4. Is fluent in the language (oral and written) in which assessments will be made and can be 
reliably rated 
5. Has a body-mass index between 18.0 and 40.0 kg/m2, inclusive, at screening and Visit 2 
6. Meets criteria for schizophrenia according to DSM-IV-TR as confirmed by the MINI 
administered by qualified site staff 
7. Meets criteria for AUD according to DSM-5 as confirmed by the C-VISA and the 
MINI 7.0 AUD module administered by qualified site staff 
8. Has experienced an acute exacerbation of schizophrenia within the past 6 months prior to 
screening that meets at least 1 of the following criteria: 
a. Was hospitalized (involuntarily or voluntarily) for symptoms of schizophrenia 
− If applicable, the total duration of any hospitalization(s) within the 30 days prior 
to Visit 2 must be ≤7 days. 
b. Committed deliberate self-injury, engaged in aggressive behavior, or displayed signs 
of suicidal or homicidal ideation deemed clinically significant by the PI 
c. Was prescribed 1 of the following changes in antipsychotic medication: 
− An increase in antipsychotic dose level due to symptom worsening 
− Change in antipsychotic due to symptom worsening 
d. Visited the emergency room or an outpatient healthcare facility (involuntarily or 
voluntarily) due to worsening of psychotic symptoms 
9. Meets the following clinical criteria at screening* and Visit 2: 
a. Has a total Positive and Negative Syndrome Scale (PANSS) score between 50 and 90, 
inclusive 
b. Has a score of ≤4 for all of the following PANSS Positive (P) Scale or General 
Psychopathology (G) items: 
− P1 (delusions) 
− P2 (conceptual disorganization) 
− P3 (hallucinatory behavior) 


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− P6 (suspiciousness/persecution) 
− P7 (hostility) 
− G8 (uncooperativeness) 
c. Has a Clinical Global Impression-Severity (CGI-S) score ≤4 
* A subject who initiated olanzapine treatment during a recent hospitalization for an 
acute exacerbation (discharged within 2 weeks prior to screening) is not required to meet 
these criteria at screening, but is required to meet them at Visit 2. 
10. In the opinion of the PI or designee, the subject is not a danger to himself/herself or 
others and has no elevated suicidal ideation or behavior at the time of screening and the 
subject answers “No” to items #4 and #5 of the Columbia Suicide Severity Scale 
(C-SSRS) for ideation and behavior in the 30 days prior to screening and Visit 2. 
• Although a recent exacerbation of symptoms is needed for inclusion in the study and 
suicidal behavior may qualify as an exacerbation, a subject who still represents a 
danger to him/herself at the time of screening is not eligible for this study. 
11. Has experienced at least 10 drinking days (a day in which the subject had at least 
1 standard alcoholic drink) within the 30 days prior to screening (as assessed by Timeline 
Follow-Back [TLFB] self-report using the TLFB definition for a standard drink) 
• At least 2 of these drinking days must be heavy drinking days, defined as 4 drinks in 
1 day for women or 5 drinks in 1 day for men. 
12. In accordance with the locally approved informed consent form (ICF), subjects at some 
sites may be required to have an informant or caregiver who meets some or all of the 
following criteria: 
a. Informant or caregiver will be in contact with the subject several times per week. 
b. If necessary, the informant or caregiver will accompany the subject to visits. 
c. Informant or caregiver will help ensure maximum subject adherence to study 
procedures. 
d. The informant or caregiver must be willing and able to provide informed consent by 
signing the caregiver ICF. 
In Bulgaria, subjects are required to have an informant or caregiver who meets criteria 
12a, 12b, 12c and 12d. 
13. Agrees to use an acceptable method of contraception for the duration of the study unless 
surgically sterile or postmenopausal 
7.2. 
Subject Exclusion Criteria 
A subject meeting any of the following criteria at screening, unless otherwise specified, will not 
qualify for participation in this study: 
1. Is pregnant (as indicated by self-report or a positive pregnancy test), planning to become 
pregnant during the study, or breastfeeding at screening or Visit 2 


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2. Is investigator-site personnel or is employed by Alkermes, 
 
(permanent, temporary contract worker, or designee responsible for the conduct of the 
study), or other third-party agents of this study or is immediate family of investigator-site 
personnel or an Alkermes, 
 or other third-party agents at screening or Visit 2 
• Immediate family is defined as a spouse, parent, child, or sibling, whether biological 
or legally adopted 
3. Had his/her first lifetime psychotic episode less than 1 year before screening or has 
experienced only a single lifetime psychotic episode 
4. Has a known or suspected intolerance, allergy, or hypersensitivity to olanzapine at 
screening or Visit 2 
5. Has current or pending legal charges with the potential for incarceration that could 
interfere with study scheduling at screening or Visit 2 
6. Has had significant blood loss (>500 mL) or has donated blood or blood components 
within 2 months prior to screening or Visit 2 
7. Is currently participating in or has participated in a clinical trial of an investigational 
product (drug, device, or biologic) within the 12 months prior to screening, has 
participated in more than 2 clinical trials within the 4 years prior to screening, or has ever 
participated in a samidorphan clinical trial 
8. Has a history or current evidence at screening or Visit 2 of a clinically significant 
condition or abnormality that in the PI’s (or designee’s) opinion could interfere with 
subject safety or complicate treatment, such as (but not limited to) the following: 
• Clinically significant renal insufficiency 
• Human immunodeficiency virus (HIV) 
• Hepatitis B 
• Hepatitis C 
• Severe alcohol withdrawal, as indicated by abrupt cessation of alcohol intake 
followed by seizures, delirium tremens, or other severe withdrawal symptoms per 
investigator judgment 
• Narrow-angle glaucoma (diagnosis or risk), or any other disease or condition 
described as a contraindication in the local Zyprexa® label  
9. Has or has had a malignant tumor within the 5 years prior to screening excluding dermal 
squamous cell carcinoma, basal cell carcinoma, and cervical carcinoma in situ 
10. Has clinically significant hypotension or hypertension not stabilized by medical therapy; a 
clinically significant cardiac arrhythmia, cardiomyopathy, or cardiac conduction defect; or 
has a clinically significant ECG abnormality at screening or Visit 2, including (but not 
limited to) the following: 
• For men, QT interval (corrected using the Fridericia formula; QTcF) 
>450 milliseconds 
PPD
PPD


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• For women, QTcF >470 milliseconds 
11. Has a history of a myocardial infarction or unstable angina, including a silent myocardial 
infarction discovered on ECG 
12. Has a positive drug screen at screening for opiates (including buprenorphine, 
norbuprenorphine, codeine, hydrocodone, hydromorphone, methadone, morphine, 
oxycodone, and oxymorphone) or meets criteria for any of the following medication 
restrictions: 
• Has taken opioid agonists (eg, codeine, oxycodone, tramadol, or morphine) within 14 
days prior to screening or anticipates needing to take opioid medication during the 
study period (eg, planned surgery) 
• Has taken opioid antagonists within 60 days before screening 
• Has received a long-acting formulation of any antipsychotic medication by 
intramuscular injection within 2 months prior to screening 
− Long-acting formulations of antipsychotics are also prohibited medications; 
therefore, administration should not occur or be planned to occur during screening 
(see Section 8.4.2) 
• Has received clozapine for more than 1 week during the past year 
• Has used naltrexone (including ReVia®/Depade® and Vivitrol®) within 2 months 
prior to screening; naloxone, acamprosate (Campral®), disulfiram (Antabuse®), or 
other medication for alcohol dependence within 14 days prior to screening; or has 
been admitted to an alcohol detoxification program within the past 3 months 
(including current treatment at screening) 
• Is currently taking an antidepressant unless the subject has been on a stable dose for 
at least 30 days prior to screening and it is anticipated that the dose will not change 
during the subject’s participation in the study. The medical monitor should be 
contacted with any questions about the appropriateness of including a subject taking 
an antidepressant medication. Antipsychotic use for depression is exclusionary. 
• Is currently receiving treatment with a hypoglycemic agent (eg, metformin, insulin, 
sulfonylurea, etc) 
• Has used an inducer or moderate to strong inhibitor of CYP3A4 (prescription 
medications, over-the-counter medications, or dietary supplements) within 30 days 
before screening. See Appendix L for a partial list of prohibited CYP3A4 inducers 
and moderate to strong inhibitors. 
• Is currently using or anticipates needing to use a prohibited medication or substance 
anytime during the study period (see Section 8.4.2 and Section 8.4.3) 


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13. Have any of the following psychiatric conditions per DSM-IV-TR criteria, unless 
otherwise specified, as assessed by the MINI (if possible). Conditions not assessable by 
the MINI should be assessed by clinical judgment or the C-VISA (if applicable): 
a. Clinically significant cognitive difficulties including dementia, delirium, or amnestic 
syndromes, or any other cognitive disorder present within the past 2 years that, in the 
opinion of the PI or designee, could interfere with participation in the study (ie, could 
potentially compromise subject safety or adversely affect the evaluation of efficacy) 
b. Substance use disorders other than AUD within the past 1 year as defined by DSM-5 
criteria for the following: 
− Hallucinogen-related disorder 
− Inhalant-related disorder 
− Opioid-related disorder 
− Sedative-, hypnotic-, or anxiolytic-related disorder 
− Stimulant-related disorder 
c. Any other psychiatric condition within the past 1 year that could, in the PI’s or 
designee’s opinion, interfere with participation in the study, especially Axis I 
(according to DSM-IV-TR criteria) disorders; established or confirmed diagnosis of 
schizoaffective disorder or bipolar disorder; or current, untreated, or unstable major 
depressive disorder 
− Subjects with current but stable depression, depressive symptoms, or major 
depressive disorder may be eligible provided schizoaffective disorder has been 
ruled out. 
14. Is planning a significant change in caffeine use or is planning to enter a smoking 
cessation program 
15. Has a history of neuroleptic malignant syndrome, has a history of clinically significant 
extrapyramidal symptoms when taking olanzapine, or has had clinically significant 
tardive dyskinesia or tardive dystonia within 30 days of screening 
16. Has unstable thyroid dysfunction within the 6 months prior to screening (eg, 
hypothyroidism, hyperthyroidism, or thyroiditis that was untreated or was discovered and 
resulted in treatment within the 6 months prior to screening) or a thyroid stimulating 
hormone (TSH) level higher than 10% above the upper limit of the normal range at 
screening.  
17. Has a neurologic condition, including (but not limited to) the following: 
• History of seizure disorder or a condition associated with seizures (excluding febrile 
seizures but including seizures associated with substance use or withdrawal) within 
the past 6 months 
• History of brain tumor, subdural hematoma, or other clinically significant 
neurological condition within the 1 year prior to screening 
• Head trauma with a loss of consciousness within 30 days prior to screening 


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• An active acute or chronic central nervous system infection 
• History of stroke or cerebrovascular infarction 
18. Has dyslipidemia (total cholesterol >280 mg/dL or triglycerides >500 mg/dL at 
screening) 
19. Has diabetes or meets any of the following criteria at screening: 
• Hemoglobin A1c (HbA1c) ≥6.5% 
• A random plasma glucose ≥200 mg/dL (11.1 mmol/L) 
20. Has a laboratory abnormality at screening, including (but not limited to) the following 
(clinical laboratory assessments may be repeated if the PI feels the test may be in error): 
• Aspartate aminotransferase or alanine aminotransferase value ≥3 times the upper limit 
of the laboratory normal reference range 
• Absolute neutrophil count ≤1.5 × 103 per μL 
• Platelet count ≤75 × 103 per μL 
• Serum creatinine >2.5 mg/dL 
21. Has no living arrangements available at screening or Visit 2, consistently lacks or loses 
housing (such that maintaining contact with the subject will be difficult), or has plans to 
leave the study site area during the study period 
• A temporary loss of living arrangements due to loss of caregiver support or other 
circumstances (eg, recent symptom exacerbation) is allowed if housing is typically 
available when schizophrenia and AUD symptoms are stable and not exacerbated. 
7.3. 
Subject Randomization Criteria 
Subjects must meet all of the following randomization inclusion criteria to be qualified to be 
randomized in this study: 
1. Meets the following PANSS criteria at Visit 6 and Visit 8: 
a. Has a total PANSS score between 50 and 80, inclusive 
b. Has a score of ≤4 for all of the following PANSS Positive (P) Scale or General 
Psychopathology (G) items: 
− P1 (delusions) 
− P2 (conceptual disorganization) 
− P3 (hallucinatory behavior) 
− P6 (suspiciousness/ persecution) 
− P7 (hostility) 
− G8 (uncooperativeness) 
2. Has a CGI-S score ≤4 at Visit 6 and Visit 8 


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Subjects must not meet any of the following randomization exclusion criteria to be qualified to 
be randomized in this study: 
1. Has a positive drug screen for opiates (including buprenorphine, norbuprenorphine, 
codeine, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and 
oxymorphone) at Visit 6 
7.4. 
Subject Withdrawal 
A completer is defined as any subject who completes the double-blind treatment period. A 
subject may be discontinued from the study at any time if the subject, PI, or Alkermes 
determines that it is not in the best interest of the subject to continue participation. Reasons for 
discontinuation include the following: 
• AE 
− Note: An absolute neutrophil count ≤1.0 × 103 per μL anytime while on 
olanzapine should be cause for discontinuing a subject. 
• Lack of efficacy 
• Lost to follow-up 
• Protocol violation (non-compliance with study drug or study procedures) 
• Withdrawal by subject (eg, withdrawn consent) 
• Pregnancy 
• Study terminated by sponsor 
• Other 
If a subject withdraws from the study at any time for any reason
In the event that a subject chooses to withdraw from the study, the PI should make a reasonable 
effort to ascertain the reason(s) for withdrawal, while fully respecting the subject’s rights. The 
subject should be encouraged to return to the study center for an early termination (ET) visit, 
which will match the procedures at Visit 38 (see Section 
, any ongoing AEs will be 
followed until resolution, until deemed stable by the PI, or until the subject is deemed by the 
investigator to be lost to follow-up. If, in the opinion of the PI or designee, it is necessary to 
monitor a subject beyond the safety follow-up visit, the follow-up period may be extended as 
necessary. In such instances, Alkermes and the PI will agree to an acceptable follow-up 
schedule. 
8), and to complete a subsequent safety 
follow-up period. The safety follow-up period for subjects who discontinue early should mirror 
the safety follow-up visits displayed in Table 3. If the subject fails or refuses to return to the 
study center, an attempt must be made to contact the subject by telephone in order to assess as 
many safety and efficacy parameters as possible. All data collected over the telephone must be 
documented and kept in the subject’s record. 
The investigator must maintain a record of all subjects who fail to complete the study. A full 
explanation of the reason for study discontinuation will be made on the appropriate electronic 
case report form (eCRF). 


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A subject will be deemed lost to follow-up after 3 attempts at contact have been made and it has 
been at least 1 month since the last subject contact. The 3rd attempt at contact must be a certified 
letter accompanied by a survey inquiring the reason for study discontinuation. All attempts at 
contact will be documented. The reason for discontinuation will be documented. If the PI 
becomes aware of a change in the subjects' status or receives more information about a subject’s 
disposition, this information will be documented. 
7.5. 
Replacement of Subjects 
Subjects who are discontinued or lost to follow-up after randomization will not be replaced. 
7.6. 
Identification of Informant or Caregiver 
In some cases a caregiver may be required for a subject to join the study (eg, by a local 
institutional review board [IRB] or independent ethics committee [IEC]). As per 
inclusion/exclusion criteria, subjects in Bulgaria are required to have an informant or caregiver 
who meets the following criteria: 
a. Informant or caregiver will be in contact with the subject several times per week. 
b. If necessary, the informant or caregiver will accompany the subject to visits. 
c. Informant or caregiver will help ensure maximum subject adherence to study 
procedures. 
In all other cases, an informant or caregiver (hereafter, caregiver) should be identified whenever 
possible. This person should be in contact with the subject and be able to help with adherence to 
study procedures (including attending study visits when needed). 
7.7. 
Withdrawal and Replacement of Informant or Caregiver 
Some sites may require the caregiver to sign a caregiver ICF (separate from a subject ICF). A 
caregiver who is required to sign a caregiver ICF may withdraw consent at any time, in which 
case he/she can no longer fill the caregiver role for this study. Any other caregiver may decide to 
stop cooperating with study staff or be lost to follow-up, in which case he/she can no longer fill 
the caregiver role for this study. If a caregiver can no longer fill the caregiver role, he/she should 
be replaced if possible. If the caregiver cannot be replaced, most subjects will be able to continue 
in the study. In Bulgaria, the caregiver must be replaced in order for the subject to continue in the 
study. If the subject must also withdraw from the study (eg, the subject is in Bulgaria, and no 
alternative caregiver is available or the caregiver provided transportation to the site and no other 
travel arrangements can be made for the subject), the PI should make a reasonable effort to 
ascertain the reason(s) for the caregiver’s withdrawal, while fully respecting the caregiver’s and 
subject’s rights. 


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8. 
STUDY DESIGN 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study designed to 
evaluate the efficacy, safety, and tolerability of ALKS 3831 in schizophrenia with AUD. 
Subjects experiencing disease symptom exacerbation (eg, inpatient hospitalization) within the 
past 6 months will be considered for screening. Assessment of eligibility is based on 
DSM-IV-TR diagnosis of schizophrenia and DSM-5 diagnosis of AUD (supported by the 
subject’s medical history, subject self-report, and caregiver or informant report of medical 
history and/or drinking behavior and confirmed via the MINI and C-VISA). Subjects must also 
meet certain clinical criteria at screening and prior to randomization. These criteria include (but 
are not limited to) having a PANSS score between 50 and 90 (inclusive) at screening and Visit 2 
and between 50 and 80 (inclusive) at Visit 6 and Visit 8; a PANSS item score of ≤4 on Positive 
(P) Scale and General Psychopathology (G) items P1, P2, P3, P6, P7, and G8; and a CGI-S score 
≤4 at screening, Visit 2, Visit 6, and Visit 8. Subjects who do not meet PANSS or CGI-S criteria 
at screening but were prescribed olanzapine during a recent hospitalization (discharged within 
the 2 weeks prior to screening) may be eligible for the study if they meet symptom severity 
criteria at Visit 2, Visit 6, and Visit 8. Other eligibility criteria assessed between screening and 
randomization are ECG (Visit 2) and drug screening (Visit 6) criteria. Complete eligibility 
criteria are given in Section 7.1 and Section 7.2, and randomization criteria are given in 
Section 7.3. 
All study visits will be outpatient visits. The olanzapine dose level throughout the study will be 
determined individually by the PI according to current clinical practice. 
Subjects who are taking an antipsychotic other than olanzapine or no antipsychotic medication at 
Visit 2 will be tapered off of current medication (if applicable) and titrated onto olanzapine 
beginning at Visit 2 (see Figure 1) according to a schedule determined by the investigator in 
accordance with current clinical practice. Subjects who are already taking olanzapine will take 
their medication as currently prescribed at Visit 2 and for a period of 4 weeks (Visits 3–5) prior 
to initiation of ALKS 3831 (Visit 6). After Visit 2, all subjects will return to the clinic weekly for 
dose adjustment, as necessary (permitted at Visits 3 and 4 only), and safety monitoring 
(Visits 3―5). A cross-taper period of up to 3 weeks is expected when switching to olanzapine and 
optimizing olanzapine dose. 
Unless a change in olanzapine dose is medically indicated, it will remain fixed for the remainder 
of the study after Visit 5. An increase in dose between Visit 5 and randomization may be a 
reason for withdrawal from the study, and an increase in dose after randomization is considered 
an EEDS (see Section 11.1). A decrease in dose is always allowed when medically indicated. If a 
dose reduction occurs after randomization, any subsequent dose must be greater than the dose at 
randomization for this increase to be considered an EEDS. 


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Figure 1: 
ALK3831-401 Study Schematic 
 
Abbreviation: V = Study Visit; ALKS 3831=olanzapine plus samidorphan 
At Visit 6, subjects will begin a 2-week open-label ALKS 3831 (olanzapine [fixed-dose] 
coadministered with samidorphan [10 mg]) treatment period. Subjects who do not tolerate 
ALKS 3831 during this open-label period may be discontinued from the study prior to 
randomization. 
At Visit 8, subjects will be randomized in a 1:1 fashion to 1 of 2 treatment groups and will begin 
a double-blind treatment period. The 2 treatment groups are as follows: 
• ALKS 3831: (ie, olanzapine [dose determined by the PI] plus samidorphan [10 mg]) 
• Olanzapine (dose determined by the PI) plus placebo 
During the double-blind treatment period, subjects will complete an outpatient visit every 
2 weeks. As indicated in the schedule of assessments (see Table 1, Table 2, and Table 3), at some 
of these visits, subjects will complete a number of clinical assessments, receive a 15-minute 
counseling intervention (see Section 8.3.26), and will receive a 2-week study drug supply 
(including extra medication in case the subject does not return to the study site on the scheduled 
day; see Section 10). Other visits will be only drug dispensing visits during which subjects will 
only receive a 2-week study drug supply. No clinical assessments will be completed at drug 
dispensing visits. 
Subjects randomized to double-blind treatment will be followed for a minimum of 9 months and 
a maximum of 15 months. After the end of the double-blind treatment period, subjects will 
complete a 3-week safety follow-up period. The study will be stopped when the last subject 
randomized is scheduled to complete Visit 26. When the last subject is randomized, all subjects 
currently participating in the study will be informed of the target completion date of the study 
period. After the last double-blind treatment period visit, subjects will proceed to the safety 
follow-up period. 
The duration of the double-blind period will be between 9 and 15 months, depending on when 
the study is stopped. The target completion date will be based on the number of subjects 
randomized with enrollment ending when approximately 270 subjects have been randomized. 
After the last subject is randomized, the end date of the study will be set to occur approximately 
9 months later and subjects will be informed of the target completion date. Final 
3 


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samidorphan/placebo dosing for these subjects will take place the night before their final visit of 
the double-blind treatment period. A subject who is prematurely discontinued from the study will 
proceed as described in Section 7.4. 
After a subject completes an ET Visit and/or the safety-follow-up period, follow-up clinical care 
may be provided for up to 3 months if the PI determines that it is medically indicated. This care 
may include payments for medication and up to 3 clinic (outpatient) visits. 
8.1. 
Overall Study Design and Plan 
ALK3831-401 will be conducted in compliance with the protocol, ICH Good Clinical Practice 
(GCP), and applicable regulatory requirements. 
8.2. 
Schedule of Visits and Assessments 
Psychiatric symptoms, AUD, and psychosocial functioning will be assessed during study visits 
using the measures described below. 
The schedule of visits and assessments for before randomization (Visit 8) is shown in Table 1 
and the schedule after randomization is shown in Table 2 and Table 3. 
For a missed visit, the site should attempt to contact the subject to reschedule (see Section 7.4). 


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Table 1: 
Schedule of Visits and Assessments for Screening and Open-label Treatment 
Periods (Visit 1-Visit 7) 
 
Screening 
Open-label Treatment 
Olanzapine 
ALKS 3831 
Study Visit 
1 
2 
3 
4 
5 
6 
7 
Study Day 
(Visit window is ±2 days) 
-59 to -29 
-28 
-21 
-14 
-7 
1 
8 
Informed Consent1 
X 
 
 
 
 
 
 
Qualification/ Diagnostic Assessments 
Eligibility Criteria Review 
X 
X2 
 
 
 
X2 
 
Demographics and Medical/ Psychiatric History 
X 
 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
X 
 
Drug Screening 
X 
 
 
 
 
X 
 
Physical Exam3 
X 
X 
 
 
 
X 
 
Clinical Validation Inventory for Study Admission 
(C-VISA™) 
X 
 
 
 
 
 
 
Mini International Neuropsychiatric Interview (MINI) 
X 
 
 
 
 
 
 
Readiness to Change Questionnaire 
X 
 
 
 
 
 
 
Qualification/ Efficacy Measures 
Positive and Negative Syndrome Scale (PANSS)4 
X 
X 
 
 
 
X 
 
Clinical Global Impression- Severity/Improvement 
(CGI-S and CGI-I) 
X5 
X5 
 
 
 
X 
 
Timeline Follow-Back (TLFB)6 
X 
X 
 
 
 
X 
 
Cigarette Use Question 
X 
 
 
 
X 
 
Visual Analog Scale (VAS) Desire for Alcohol 
X 
 
X 
 
X 
 
X 
Personal and Social Performance Scale (PSP) 
X 
X 
 
 
 
 
 
Abnormal Involuntary Movement Scale (AIMS) 
X 
 
X 
 
X 
 
Simpson-Angus Scale (SAS) 
 
X 
 
X 
 
X 
 
Barnes Akathisia Rating Scale (BARS) 
 
X 
 
X 
 
X 
 
Qualification/ Safety Assessments 
Adverse Event (AE) monitoring 
X 
X 
X 
X 
X 
X 
X 
Columbia Suicide Severity Rating Scale (C-SSRS)7 
X 
X 
X 
X 
X 
X 
X 


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Table 1: 
Schedule of Visits and Assessments for Screening and Open-label Treatment 
Periods (Visit 1-Visit 7) (Continued) 
 
Screening 
Open-label Treatment 
Olanzapine 
ALKS 
3831 
Study Visit 
1 
2 
3 
4 
5 
6 
7 
Study Day 
(Visit window is ±2 days) 
-59 to -29 
-28 
-21 
-14 
-7 
1 
8 
Qualification/ Safety Assessments (continued) 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
Vital Signs (including orthostatic measures)8 
X 
X 
X 
X 
X 
X 
X 
Clinical labs9 
X 
X 
 
 
 
X 
 
Blood Samples for PK 
X 
X 
 
X 
 
X 
 
Body Weight, Waist Circumference, and Height10 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogram (ECG) 
X 
X 
 
 
 
X 
 
Other Study Procedures 
Open-label Olanzapine Dispensing11 
X 
X 
X 
X 
X 
X 
Open-label Samidorphan Dispensing11 
 
 
 
 
X 
X 
Dispense Emergency Treatment Card 
 
 
 
 
X 
 
Confirm Subject’s Possession of Emergency Treatment Card 
 
 
 
 
 
X 
1 Subject and informant/caregiver informed consent (when the latter is required) 
2 The criteria assessed at these visits are limited to PANSS, CGI-S, and drug screen; see Section 7.3. 
3 Full physical examination at screening; brief physical examination at all other scheduled time points 
4 At each visit, PANSS should be administered before any other clinical assessment 
5 CGI-S only at this visit, as administered using the Structured Interview Guide for Global Impressions 
6 The subject should be assisted by the same person each time he or she is asked to complete the TLFB and this 
person should not conduct the subject’s supportive counseling sessions. 
7 At screening, the “Baseline/Screening” version will be administered for assessing lifetime ideation and behavior, 
as well as ideation and behavior in the past 30 days. At all other visits, the “Since Last Visit” version will be 
administered. 
8 Orthostatic measures should not be completed at screening. 
9 Thyroid stimulating hormone and carbohydrate deficient transferrin are assessed at screening only; Hemoglobin 
A1c (HbA1c) is assessed at screening and Visit 2 only. 
10 Height at screening only 
11 The recommended time of dosing for subjects is in the evening or at bedtime. 


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Table 2: 
Schedule of Visits and Assessments for Double-blind Treatment Period (Visit 8-Visit 26) 
 
Double-blind Placebo-controlled Treatment 
Study Visit 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
261 
Study Week 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
27 
29 
31 
33 
35 
37 
39 
Qualification/Diagnostic Assessments 
Eligibility Criteria Review2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Qualification/Efficacy Measures 
PANSS3 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
CGI-S and CGI-I 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
TLFB4 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Cigarette Use Question 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
VAS Desire for Alcohol 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PSP 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Exacerbation of Disease 
Criteria Review 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
AIMS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
SAS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
BARS 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Safety Assessments 
AE Monitoring 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
C-SSRS5 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Concomitant Medications 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Medical History6 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Body Weight and Waist 
Circumference 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 


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Table 2: 
Schedule of Visits and Assessments for Double-blind Treatment Period (Visit 8-Visit 26) (Continued) 
 
Double-blind Placebo-controlled Treatment 
Study Visit 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
Study Week 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
27 
29 
31 
33 
35 
37 
39 
Brief Physical Exam 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Vital Signs (including 
orthostatic measures) 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Clinical labs7 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Electrocardiogram 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Other Study Procedures 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Supportive Counseling 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Confirm Emergency 
Treatment Card 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Blood Samples for PK 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Urine Drug Panel 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
OL OLZ Dispensing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DB S/P Dispensing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE=Adverse Event; AIMS=Abnormal Involuntary Movement Scale; BARS=Barnes Akathisia Rating Scale; CDT=Carbohydrate deficient 
transferrin; CGI-I=Clinical Global Impression – Improvement; CGI-S=Clinical Global Impression - Severity; C-SSRS=Columbia Suicide Severity Rating 
Scale; DB=double-blind; HbA1c=Hemoglobin A1c; OL=open-label; OLZ=olanzapine; PANSS=Positive and Negative Syndrome Scale; PK=pharmacokinetics; 
PSP=Personal and Social Performance Scale; S/P=samidorphan/placebo; SAS=Simpson-Angus Scale; TLFB=Timeline Follow-Back; VAS=Visual Analog 
Scale 
Shaded columns represent visits where only drug dispensing should occur. 
1 This is the end of the 9-month double-blind treatment period. Subjects who are only scheduled to complete 9 months of double-blind treatment should complete 
safety follow-up visits for Visit 39 and Visit 40 as per Table 3. 
2 PANSS and CGI-S criteria only; see Section 7.3 
3 At each visit, PANSS should be administered before any other clinical assessment. 
4 The subject should be assisted by the same person each time he or she is asked to complete the TLFB and this person should not conduct the subject’s 
supportive counseling sessions. 


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5 “Since Last Visit” version using the last administration of the C-SSRS as the “last visit” 
6 Change since last medical history assessment 
7 Except TSH; CDT should be collected at Visit 8 and 26. HbA1c should not be collected at Visit 10. 


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Table 3: 
Schedule of Visits and Assessments for Continuation of Double-blind Treatment and Safety Follow-up Period 
(Visit 27-Visit 40) 
 
Double-blind Placebo-controlled Treatment 
Safety Follow-up 
Study Visit 
27 
28 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38/ 
ET 
39 
40 
Study Week 
41 
43 
45 
47 
49 
51 
53 
55 
57 
59 
61 
63 
41/ 
65 
42/ 
66 
Efficacy Measures 
PANSS1 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
CGI-S and CGI-I 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
TLFB2 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Cigarette Use Question 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
VAS Desire for Alcohol 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PSP 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
Exacerbation of Disease 
Criteria Review 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
AIMS 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
SAS 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
BARS 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Safety Assessments 
AE Monitoring 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
C-SSRS3 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Concomitant Medications 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Medical History4 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Body Weight and Waist 
Circumference 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 


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Table 3: 
Schedule of Visits and Assessments for Continuation of Double-blind Treatment and Safety Follow-up Period 
(Visit 27-Visit 40) (Continued) 
 
Double-blind Placebo-controlled Treatment 
Safety Follow-up 
Study Visit 
27 
28 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38/  
ET 
39 
40 
Study Week 
41 
43 
45 
47 
49 
51 
53 
55 
57 
59 
61 
63 
41/ 
65 
42/ 
66 
Brief Physical Exam 
 
X 
 
 
 
X 
 
 
 
 
 
X 
Vital Signs (including orthostatic 
measures) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Clinical labs5 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
Electrocardiogram 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
Other Procedures 
Supportive Counseling 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Confirm Emergency Treatment Card 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Blood Samples for PK 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
Urine Drug Panel 
 
X 
 
 
 
X 
 
 
 
X 
 
 
OL OLZ Dispensing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
DB S/P Dispensing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Collect Emergency Treatment Card 
 
 
 
 
 
 
 
 
 
  
X 
Abbreviations: AE=Adverse Event; AIMS=Abnormal Involuntary Movement Scale; BARS=Barnes Akathisia Rating Scale; CDT=Carbohydrate deficient 
transferrin; CGI-I=Clinical Global Impression–Improvement; CGI-S=Clinical Global Impression-Severity; C-SSRS=Columbia Suicide Severity Rating Scale; 
DB=double-blind; ET=early termination; HbA1c=Hemoglobin A1c; OL=open-label; OLZ=olanzapine; PANSS=Positive and Negative Syndrome Scale; 
PK=pharmacokinetics; PSP=Personal and Social Performance Scale; S/P=samidorphan/placebo; SAS=Simpson-Angus Scale; TLFB=Timeline Follow-Back; 
VAS=Visual Analog Scale 
Shaded columns represent visits where only drug dispensing should occur. 
1 At each visit, PANSS should be administered before any other clinical assessment 
2 The subject should be assisted by the same person each time he or she is asked to complete the TLFB and this person should not conduct the subject’s 
supportive counseling sessions. 
3 “Since Last Visit” version using the last administration of the C-SSRS as the “last visit” 


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4 Change since last medical history assessment 
5 Except TSH; CDT and HbA1c are assessed at Visit 38/ET only. 


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8.3. 
Study Procedures Descriptions 
All study procedures should be administered as consistently as possible. Specifically, the subject 
should be assisted by the same person (whenever possible) each time he or she is asked to 
complete the TLFB and this person should not conduct the subject’s supportive counseling 
sessions. The TLFB and supportive counseling sessions should not be conducted by the same 
person. 
8.3.1. 
Informed Consent 
The nature of the study and its risks and benefits will be explained to the subject and caregiver 
(in Bulgaria, and other locations where required) by the investigator or designated study 
personnel as outlined in Section 17.3. When a caregiver is required (eg, in Bulgaria), the 
caregiver ICF will also be completed. Prior to the administration of any study-specific 
procedures, authorized study personnel will obtain written informed consent from each potential 
subject. 
8.3.2. 
Eligibility Criteria Review 
Eligibility for participation in the study will be confirmed as specified in Table 1 and Table 2. 
Complete inclusion and exclusion criteria are provided in Section 7.1 and Section 7.2. Additional 
criteria that must be met in order for a subject to be randomized are provided in Section 7.3. 
8.3.3. 
Demographics and Medical History 
A subject’s demographic data and medical history will be reviewed and documented at the time 
points specified in the Table 1, Table 2, and Table 3. 
At later visits, each subject’s medical and psychiatric history since the prior visit will be 
reviewed and any identified significant change will be recorded in the source documents and 
eCRF, as appropriate. 
8.3.4. 
Pregnancy Testing 
A serum or urine pregnancy test will be administered to all women at the time points specified in 
Table 1. At the screening visit, results must be negative for the subject to be eligible for the 
study. As highlighted in Section 7.4, a positive pregnancy test result at any time will necessitate 
the subject’s immediate withdrawal from the study. Additional follow-up may be required as 
detailed in Section 8.4.1. 
8.3.5. 
Drug Testing 
All subjects will undergo urine drug testing via a dipstick for a panel of substances at the time 
points specified in Table 1, Table 2, and Table 3. Results will be analyzed by the local 
laboratory. Urine drug screening may be repeated based on PI judgment. Urine drug screening 
may also be conducted at any time during the study, should the investigator feel it is warranted. 
The drug testing panel will include benzodiazepines, opiates (including buprenorphine, 
norbuprenorphine, codeine, hydrocodone, hydromorphone, methadone, morphine, oxycodone, 
and oxymorphone), amphetamine/methamphetamine, tetrahydrocannabinol, phencyclidine and 
cocaine (and its metabolite). 


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A subject is not eligible for this trial if he/she has a positive test for opiates at screening or 
Visit 6 (see Section 7.2 and 7.3). Drug testing that is not being done to determine eligibility will 
be used to collect data on substance use across the trial in support of study objectives. 
8.3.6. 
Physical Examination 
A physical examination will be performed at the time points specified in Table 1, Table 2, and 
Table 3. A full examination will occur at screening only. After screening, a brief physical exam 
will be conducted. 
8.3.7. 
Clinical Validation Inventory for Study Admission and Ongoing Rater Review 
Rater (ie, study staff) accuracy at screening on pre-specified study measures will be reviewed by 
central raters employed by 
 using the C-VISA. 
Later reviews will take place according to a pre-specified schedule (subject to change based on 
rater accuracy) after the measure has been administered using an audio recording of the 
screening interview. Rater review is necessary for mitigating inaccurate inclusion/exclusion 
assessments and inaccurate efficacy assessments. 
Rater assessments require subject interviews to be audio recorded. The audio recording will be 
disclosed and explained to the subject by study staff and will be disclosed in the ICF during the 
informed consent process. No subject will be recorded without the knowledge that a recording is 
being made. 
8.3.8. 
Mini International Neuropsychiatric Interview 
The MINI is a short, clinician-administered, structured diagnostic interview, with an 
administration time of approximately 15 minutes [Sheehan, 1998]. The MINI has been validated 
against the much longer Structured Clinical Interview for DSM Diagnoses (SCID). A sample of 
the MINI can be found in Appendix A. The MINI will be administered by qualified staff. 
8.3.9. 
Readiness to Change Questionnaire 
The Readiness to Change Questionnaire (Appendix B) [Rollnick, 1992] is a self-report measure 
that will be administered at screening. 
The Readiness to Change Questionnaire is included as an exploratory measure that may be useful 
as a potential predictor of efficacy or stratification factor for assessing efficacy in sub-groups. 
8.3.10. 
Positive and Negative Syndrome Scale 
The PI or designee will complete the PANSS [Kay, 1987] according to the schedule in Table 1, 
Table 2, and Table 3 using the Structured Clinical Interview for the PANSS (SCI-PANSS; 
[Opler, 1999]). A sample SCI-PANSS is given in Appendix C. 
8.3.11. 
Clinical Global Impression 
The PI or designee will complete the CGI-S and Clinical Global Impression-Improvement 
(CGI-I) (Appendix D) scales at the time points specified in Table 1, Table 2, and Table 3. The 
Structured Interview Guide for Global Impressions (SIGGI; see Appendix E) will be used for 
administration of CGI-S. The CGI-S measures mental illness severity and the CGI-I measures 
PPD


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total improvement compared to the first assessment [Guy 2000]. For illness severity, clinicians 
are asked to rate subjects relative to their past experience with patients in the same population as 
the individual being rated. 
8.3.12. 
Timeline Follow-Back 
Alcohol use will be recorded using the TLFB method [Sobell and Sobell 1992] at the time points 
specified in Table 1, Table 2, and Table 3. At the screening visit, alcohol use data will be 
collected for the prior 30-day period as per TLFB instructions for administration. At all other 
visits, data will be collected for the period between the last completed TLFB assessment and the 
current visit, not to exceed 30 days. The subject should be assisted by the same person each time 
he or she is asked to complete the TLFB and this person should not conduct the subject’s 
supportive counseling sessions. 
8.3.13. 
Cigarette Use 
Data on cigarette use will be collected by using the question, “How many packs of cigarettes did 
you smoke over the past 7 days?”, at the time points specified in Table 1, Table 2, and Table 3. 
8.3.14. 
Visual Analog Scale for Perception of Desire for Alcohol 
A pen and paper 1-item VAS will be presented at the timepoints specified in Table 1, Table 2, 
and Table 3. The VAS is a horizontal line with a unipolar scale, anchored on the right side with 
“No desire at all for alcohol” (marked with a “0”) and on the left side with “Strongest imaginable 
desire for alcohol” (marked with a “100” with a line connecting the two ends; see Appendix F). 
Subjects will mark the appropriate point to indicate where their “desire for alcohol” falls on this 
line. 
8.3.15. 
Exacerbation of Disease Criteria Review 
The criteria for an EEDS (see Section 11.1) should be reviewed by the PI or designee as 
indicated in Table 2 and Table 3. 
8.3.16. 
Personal and Social Performance Scale 
The PI or designee will complete the 5-point Personal and Social Performance (PSP) scale 
(Appendix G) [Morosini, 2000] according to the schedule in Table 1, Table 2, and Table 3. 
8.3.17. 
Abnormal Movement Rating Scales 
The PI or designee will complete the following abnormal movement rating scales: The Abnormal 
Involuntary Movement Scale (AIMS; see Appendix H) [Guy 1976], Barnes Akathisia Rating 
Scale (BARS; see Appendix I) [Barnes 1989], and Simpson-Angus Scale (SAS; see Appendix J) 
[Simpson and Angus 1970] at the timepoints specified in Table 1, Table 2, and Table 3. 
After administration of the first dose of study drug, if a subject complains of extrapyramidal 
symptoms on days when the abnormal movement rating scales are not scheduled to be 
performed, an unscheduled assessment should be performed. 


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8.3.18. 
Adverse Event Monitoring 
Adverse events will be monitored continuously from the time a subject signs the informed 
consent document until the completion of the final study visit (see Table 1, Table 2, and 
Table 3). Adverse events and serious adverse events (SAEs) are defined in Section 13.1 and 
13.2, respectively. Section 13.4 provides guidance on the monitoring and recording requirements 
for AEs. Section 13.5 provides guidance on the reporting requirements for SAEs. 
8.3.19. 
Columbia Suicide Severity Rating Scale 
The PI or designee will complete the C-SSRS (Appendix K) according to the schedule in 
Table 1, Table 2, and Table 3. At screening, the “Baseline/Screening” version will be 
administered [Posner, 2009a], and at all other visits, the “Since Last Visit” version will be 
administered [Posner, 2009b]. For “Since Last Visit” versions, subjects should be asked to report 
on ideation and behavior since the last scheduled C-SSRS assessment. The C-SSRS should be 
administered by a clinician trained to assess and manage suicidal ideation and behavior. 
8.3.20. 
Concomitant Medication Review 
At the time points specified in Table 1, Table 2, and Table 3, prospective subjects will be asked 
about the medications they have taken since the last visit and are currently taking, including 
prescription and nonprescription medications, vitamins, and supplements. 
The investigator will record the following data on all medications used by the subject: name, 
dose, regimen, route of administration, start date, stop date, and the indication for use. 
8.3.21. 
Vital Signs 
Vital signs (ie, blood pressure, pulse, respiratory rate, and oral body temperature) will be 
assessed at the time points specified in Table 1, Table 2, and Table 3. 
An effort will be made to consistently use the same arm (preferably the subject’s dominant arm) 
to measure blood pressure and pulse throughout the study. The blood pressure cuff will be 
calibrated per study site standard operating procedure. Automated measurement is preferred, but 
if performed manually, pulse will be measured in the brachial artery for at least 30 seconds. 
Orthostatic blood pressure, pulse, and respiration rate will be collected each time vital signs are 
measured (except at screening) in the following manner: 
• Allow subject to be in a supine position for at least 5 minutes 
• Measure blood pressure, pulse, and respiration rate 
• Have subject stand for 2 minutes 
• Measure blood pressure, pulse, and respiration rate 
Vital signs may be collected at any time during a visit where it is scheduled. 
8.3.22. 
Hematology, Biochemistry, and Urinalysis 
Blood and urine samples for laboratory assessments will be collected at the time points specified 
in Table 1, Table 2, and Table 3. Specific hematology, biochemistry, and urinalysis assessments 
are listed in Table 4. Samples will be collected in accordance with the site’s usual procedures 


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and analyzed by a central laboratory. Follow-up samples may be obtained for repeat testing as 
clinically indicated. 
An absolute neutrophil count ≤1.0 × 103 per μL anytime while on olanzapine should be cause for 
discontinuing a subject. A second test can be performed within 24 hours of availability of the 
laboratory result to confirm the finding if the investigator feels the result may be in error. 
Otherwise, the subject should be discontinued. 
For all timepoints (except screening) where samples will be collected, fasting assessments 
(fasting for at least 10 hours prior to collecting samples) should be attempted as per standard of 
care [Lilly USA 2013]. However, fasting may present challenges, including an increased 
frequency of missed visits and re-scheduling, that could negatively impact the subject’s 
treatment. Therefore, failure to fast should not be considered a protocol deviation. 
Whether or not a subject fasts and the number of hours since the subject’s last meal will be 
entered onto the appropriate eCRF. 
TSH will only be measured at screening. 


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Table 4: 
Clinical Laboratory Assessments 
Hematology 
Biochemistry 
Urinalysis 
• 
Hematocrit 
• 
Hemoglobin 
• 
Platelets 
• 
Red blood cell count 
• 
Total and differential 
(absolute) white blood cell 
count 
• 
Glycosylated hemoglobin 
(HbA1c )1 
• 
Alanine transferase (ALT) 
• 
Albumin 
• 
Albumin/globulin ratio 
• 
Alkaline phosphatase 
(ALK-P) 
• 
Aspartate transferase (AST) 
• 
Bicarbonate 
• 
Blood urea nitrogen (BUN) 
• 
Carbohydrate deficient 
transferrin (CDT)2 
• 
Creatine phosphokinase 
(CPK) 
• 
Creatinine 
• 
Gamma-glutamyl transferase 
(GGT) 
• 
Glucose3 
• 
Insulin 
• 
Lactic dehydrogenase (LDH) 
• 
Potassium 
• 
Prolactin 
• 
Sodium 
• 
Thyroid stimulating hormone 
(TSH)4 
• 
Total bilirubin 
• 
Total, HDL and LDL 
cholesterol 
• 
Total protein 
• 
Triglyceride 
• 
Color 
• 
pH 
• 
Specific gravity 
• 
Ketones 
• 
Protein 
• 
Glucose 
• 
Bilirubin 
• 
Nitrite 
• 
Urobilinogen 
• 
Occult blood 
• 
Cotinine 
• 
Microscopic examination of 
sediment, only if urinalysis 
dipstick results are abnormal 
1 Assessed at Visit 2, 8, 14, 20, 26, and 38 
2 Assessed at screening, Visit 8, 26, and 38 
3 Fasting assessments should be attempted at all visits where laboratory assessments are scheduled (except 
screening) with the time of the last meal documented on the appropriate eCRF. 
4 Assessed at screening only 
8.3.23. 
Pharmacokinetic Assessments 
Samidorphan, RDC-9986 (primary metabolite of samidorphan), and olanzapine concentrations 
will be determined from plasma samples collected according to Table 1, Table 2, and Table 3. 
The time of last study drug administration (when applicable) and the associated pharmacokinetic 
(PK) blood draw must both be recorded in a subject’s source documents. Samples for PK 


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analysis will be stored at -20°C ± 10°C. These PK data may be included in a subsequent 
population PK analysis or other post-hoc analyses conducted outside of this study. 
8.3.24. 
Body Height, Body Weight, and Waist Circumference 
Body weight (in kilograms) will be measured 3 times whenever weight is being assessed. The 
median weight will be entered into an electronic data capture system. The median is the middle 
number when the 3 measures are put in numerical order (eg, in the sequence 1, 2, 3; the median 
number is 2). Subjects should be asked to void immediately prior to the body weight 
measurement. Subjects should be weighed on the same scale for each measurement under the 
same conditions. Conditions should be as consistent across visits as possible. Subjects should 
remove all personal items, such as watches and jewelry, prior to body weight measurement. 
Subjects should be weighed in hospital gowns with a consistent amount of undergarments for 
each measurement. 
At each time that body weight is measured, waist circumference (in cm) will also be measured. 
These measurements will be made where indicated in Table 1, Table 2, and Table 3. 
Height (in cm) will be collected at screening only (see Table 1). 
8.3.25. 
12-Lead Electrocardiogram 
A 12-lead ECG will be recorded as specified in Table 1, Table 2, and Table 3. All scheduled 
ECGs must be performed after the subject has rested quietly for at least 5 minutes in the supine 
position. 
A qualified clinician will conduct ECGs and assess ECG results using equipment that has been 
calibrated according to the site’s standard operating procedures. The following ECG parameters 
will be collected: pulse, RR, PR, QRS, QT, QTcF, and QT interval corrected using the Bazett 
Formula (QTcB). 
ECGs will also be evaluated by a central reader. 
8.3.26. 
Supportive Counseling 
Supportive counseling will be provided as per investigator’s judgment as specified in Table 2, 
and Table 3. Counseling will focus on the following: 
1. Disease education 
2. Encouragement of treatment adherence 
3. Crisis intervention 
The person who conducts supportive counseling sessions should not assist the subject with 
TLFB. 
8.3.27. 
Drug Dispensation and Reconciliation 
Section 9 provides information related to drug dispensing procedures. Study drug will be 
dispensed at the time points specified in Table 1, Table 2, and Table 3. The study drug use and 
storage information will be explained to and reviewed with the subject. 


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Whether or not samidorphan is classified as a controlled substance varies from country to 
country; some countries have classified samidorphan as a controlled substance, but others have 
not. Sites will be given handling, storage, and reconciliation instructions applicable to their 
country to ensure compliance with local regulations for controlled substances. 
Olanzapine will be dispensed by the site. 
Samidorphan/placebo and olanzapine will be provided in separate containers (eg, blister cards 
and bottles). Subjects will be instructed to keep all unused tablets in their original containers and 
not combine pills into a single container. Subjects will also be instructed to return the original 
containers and any remaining study drug(s) (both olanzapine and samidorphan/placebo, as 
applicable) at each visit following dispensation. Study drug should not be re-dispensed to the 
subject after the containers have been returned. Study drug accountability will be documented as 
the number of tablets dispensed, dosed, lost/missing, or remaining. If applicable, the site will 
discuss noncompliance with the subject. 
8.3.28. 
Emergency Treatment Card 
An emergency treatment card will be distributed to each subject and collected from each subject 
at the timepoints specified in Table 1 and Table 3. The card will indicate that the subject may be 
receiving an opioid antagonist and/or olanzapine and will include the PI’s contact information, a 
suggested pain management plan, and information regarding opiate blockade. Subjects will be 
instructed to keep the emergency treatment card with them at all times. Study personnel will 
confirm that the subjects have the card in their possession at each study visit indicated on 
Table 1, Table 2, and Table 3. 
8.4. 
Study Requirements and Restrictions 
8.4.1. 
Contraception and Pregnancy 
All male and female subjects must agree to use an acceptable method of contraception for the 
duration of the study. At a minimum subjects must agree to use one of the following. Additional 
restrictions, if required, will be clarified in the locally-approved ICF or are clarified below. 
• Double-barrier protection (eg, a condom with spermicide or a diaphragm with 
spermicide) 
• Intrauterine device 
• Oral contraceptive pills and other hormonal methods (eg, a vaginal ring, 
contraceptive patch, contraceptive implant); oral contraceptives must have been 
initiated at least 30 days prior to screening 
Subjects must agree to use one of the following acceptable methods of contraception for the 
duration of the study: 
• Condom (barrier method) plus 
− Intrauterine device 
or 


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− Hormonal contraceptive (such as birth control pills or patches, a vaginal ring, or a 
contraceptive implant); oral contraceptives must have been initiated at least 
30 days prior to screening 
Subjects who are abstinent are eligible to be in this study, provided they agree to use an 
acceptable contraceptive method should they become sexually active. 
Subjects who are surgically sterile are exempt from the requirement to use contraception. 
Women who have undergone a hysterectomy, bilateral tubal ligation, or bilateral 
salpingo-oophorectomy are considered surgically sterile. Men who have undergone a vasectomy 
are considered surgically sterile. Partner vasectomy is not considered an approved acceptable 
method of contraception for a female subject. 
Women who are postmenopausal are also exempt from the requirement to use contraception. For 
the purpose of this study, postmenopausal is defined as the permanent cessation of menstruation 
for at least 12 months prior to screening in women who are 45 years of age or older. 
If any female subject becomes or is found to be pregnant while participating in the study, she 
will be discontinued from study drug immediately. The investigator must fill out a Pregnancy 
Report Form and submit the information to the sponsor within 24 hours of awareness of the 
pregnancy, irrespective of whether an adverse event has occurred. The early termination and 
safety follow-up visits will be scheduled. 
The investigator will follow the pregnancy until completion or until pregnancy termination and 
notify the outcome to the sponsor. If the outcome of the pregnancy meets the criteria for 
immediate classification as a SAE the investigator should follow the procedure of reporting 
SAEs (see Section 13.2). 
8.4.2. 
Prohibited and Restricted Medications 
The following medications are prohibited or restricted during the study period (unless otherwise 
noted) except when subjects are tapering off of the medication as described in Section 8. Trade 
names may be different outside of the US: 
• Monoamine oxidase inhibitors (eg, phenelzine, tranylcypromine, selegiline, or 
moclobemide) are prohibited. 
• Mood stabilizers (eg, lamotrigine, lithium, valproic acid, carbarmazepine) are 
prohibited (except prior to Visit 8 when medically indicated) 
• Long-acting formulations of any antipsychotic and any form of clozapine are 
prohibited during the screening and study period. 
• Benzodiazepines (except prior to Visit 8 when medically indicated) are prohibited 
• Antidepressants are prohibited if it is anticipated that the dose will change during the 
subject’s participation in the study. The medical monitor should be contacted with 
any questions about the appropriateness of including a subject taking an 
antidepressant medication. Antipsychotic use for depression is prohibited 


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• Varenicline (Chantix®) is prohibited. Other nicotine replacement therapy (eg, nicotine 
replacement patch or oral nicotine gum) is permitted if the subject regularly used the 
therapy prior to screening. 
• Alcohol-treatment-related medications including, but not limited to, the following: 
naltrexone (ReVia®/Depade®), Vivitrol®, naloxone, acamprosate (Campral®) and 
disulfiram (Antabuse®) are prohibited throughout the study period. 
• In general, the use of psychotropic medications other than study drug is discouraged 
during the study period, with the exception of the following: 
− Beta-blockers (eg, propranolol or pindolol), antihistamines, and anticholinergics 
may be used for treatment-emergent akathisia. 
− Anticholinergics may be used for extrapyramidal symptoms. 
− Non-benzodiazepine medication may be used to treat insomnia. 
• Topiramate (Topamax®) and combination products containing topiramate are 
prohibited. 
• Opioid agonists should be avoided (see Section 8.4.4 for details on pain 
management). 
• Opioid antagonists are prohibited through the follow-up period. 
• Inducers or moderate to strong inhibitors of CYP3A4 (prescription medications, over-
the-counter medications, or dietary supplements) are prohibited through the follow-up 
period. See Appendix L for a partial list of prohibited CYP3A4 inducers and 
moderate to strong inhibitors. 
• Medications that are contraindicated with olanzapine use or exhibit drug-interaction 
potential with olanzapine will be defined and prohibited at the discretion of the PI. 
8.4.3. 
Other Prohibited Substances 
Prohibited substances during the study period include amphetamines (including 
methamphetamine), cocaine, barbiturates, methadone, opiates (including morphine, oxycodone, 
methadone, and buprenorphine), and phencyclidine. Screening procedures for these substances 
are described in Section 8.3.5. Except as noted in Section 8.3.5, the PI will exercise his/her 
medical judgment as to whether or not subjects using any prohibited substances should be 
deemed ineligible or withdrawn. 
Tobacco and/or caffeine use is allowed if the daily amount used is anticipated to remain 
relatively stable throughout the study period. 
8.4.4. 
Pain Management 
Because ALKS 3831 contains samidorphan, a μ-opioid receptor antagonist, subjects may 
experience reduced or ineffective analgesia when taking an opioid analgesic agent concurrently 
with ALKS 3831, including several days after last dosing of ALKS 3831. 


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In the event of an emergency, pain management of the subject should include the following: 
• Regional analgesia or use of non-opioid analgesics 
• If opiate anesthesia or analgesia is required, the subject should be continuously 
monitored in an anesthesia care setting by persons not involved in the conduct of the 
surgical or diagnostic procedure. The opioid therapy must be provided by individuals 
specifically trained in the use of anesthetic drugs and the management of the 
respiratory effects of potent opioids, specifically the establishment and the 
maintenance of a patent airway and assisted ventilation. 
• Close monitoring by appropriately trained personnel in a setting equipped and staffed 
for cardiopulmonary resuscitation 
For subjects requiring emergency opioid analgesics prior to dosing, the study drug should not be 
administered. If opioid analgesics are required after the study drug has been dosed, it may take 
several days for opiate sensitivity to be restored, since samidorphan is an opioid antagonist and 
could interfere with opioid-mediated pain management. 
8.4.5. 
Rescue Medication 
The PI is responsible for all trial-related medical decisions for subjects enrolled at his/her site 
and can always administer rescue medication without consulting the medical monitor. 
Administering rescue medication is considered an EEDS for this trial (see Section 11.1). The PI 
or designee should document the reason(s) for the rescue medication and the designated 
treatment(s). Examples of rescue medication include (but are not limited to): 
• An increase in olanzapine dose 
• Use of a prohibited medication, such as an antipsychotic or other psychotropic 
medication (see Section 8.4.2), for psychiatric treatment 
8.5. 
Ad Hoc Study Visits 
When a subject meets a criterion for an EEDS that requires a second assessment (see 
Section 11.1), an ad hoc study visit should be scheduled for 3 days after the first assessment 
when it is possible and does not compromise subject safety. Otherwise, the ad hoc visit should be 
scheduled within 7 days of the first assessment. 
If, despite all reasonable efforts by the site, a second assessment cannot be completed within 
7 days, the event will be considered an EEDS. 
Assessments completed at the ad hoc study visit should include AE monitoring, concomitant 
medication review, C-SSRS (“Since Last Visit”), CGI-S, CGI-I, PANSS, and EEDS criteria 
review. Any assessment that needs to be confirmed from the first assessment should be 
completed before any other assessments. 


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9. 
TREATMENT OF SUBJECTS 
9.1. 
Study Drug Dose and Administration 
Study drugs include samidorphan and matching placebo tablets, and olanzapine tablets, all for 
oral administration. 
For all subjects, open-label samidorphan 10 mg will be taken once daily for 2 weeks prior to 
randomization. For subjects in the double-blind treatment period, samidorphan 10 mg (or 
placebo) will be taken once daily for up to 15 months. 
For all subjects, the dose of olanzapine will be taken once daily (to be taken at the same time as 
samidorphan/placebo) at an individualized dose level. Olanzapine initiation, including transition 
from another antipsychotic (as applicable), is a highly individualized process. Formalizing the 
potential clinical scenarios may pose undue burden and/or risk to subjects. Clinical judgment is 
essential, and for this reason, the details of this process are left to the discretion of the treating 
physician, who will follow current clinical practice. 
All subjects will be administered olanzapine for 11 to 17 months as part of this clinical trial. 
ALKS 3831 should be taken as close to bedtime as possible. Subjects should not drive or operate 
heavy machinery until they know how ALKS 3831 will affect them. 
After Visit 5, the dose level of olanzapine will be fixed, and an increase in dose level above the 
dose set at Visit 5 prior to randomization may cause the subject to be discontinued. The 
olanzapine dose level may be decreased at any time if the PI considers it medically beneficial to 
the subject, such as when a subject has stable psychiatric symptoms with side effects that may be 
reduced if the olanzapine dose level is decreased. If the PI decreases the dose level after 
randomization, only an increase above the dose level at randomization will be considered an 
EEDS. 
At study drug dispensation visits, all subjects will receive blister cards containing samidorphan 
or placebo for self-administration; subjects will also receive olanzapine in separate packaging. 
Subjects will be instructed to take 1 tablet per day from the blister card in addition to their 
olanzapine tablet(s) once daily in the evening or at bedtime. The subject will take the final 
samidorphan/placebo dose the night before the final visit of the double-blind treatment period. 
Olanzapine dosing will continue uninterrupted through the end of the study. Any subject who 
prematurely discontinues from the study will be asked to return to the clinic for an ET visit and 
2 safety follow-up visits. 
9.2. 
Treatment Adherence 
Subjects who, in the opinion of the PI or designee, have demonstrated treatment adherence 
during the open-label olanzapine and ALKS 3831 treatment period will be randomized to 
double-blind treatment (samidorphan or placebo). Study personnel may be able to identify non-
adherence during study visits (eg, based on responses during clinical assessments) and may also 
ask the subject or caregiver (if applicable) directly about adherence. Additional measures of 
adherence may be used at the sponsor’s and PI’s discretion. During the double-blind treatment 


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period, supportive counseling sessions will be used to encourage treatment adherence. Study 
staff will address non-adherence with the subject as needed. 
9.3. 
Randomization to Treatment 
At Visit 8, subjects will be randomized to receive one of the following regimens in a 1:1 ratio: 
• Olanzapine + Samidorphan (10 mg) 
• Olanzapine + Placebo 
Randomization will be performed centrally through an Interactive Web Response System 
(IWRS). A unique randomization number will be assigned by an IWRS once eligibility has been 
determined. Once a randomization number has been assigned, that number must not be used 
again if, for example, a subject is withdrawn from the study. Codes will be prepared by a third-
party biostatistician who is not otherwise involved in this study. 
9.4. 
Blinding 
All Alkermes staff, clinical staff, subjects, and caregivers will remain blinded to treatment 
assignment until the final database lock. All 
 staff will remain blinded except 
when their study function requires unblinding (eg, drug supply management, IWRS operation, 
etc). These unblinded staff will follow standard operating procedures to ensure that they do not 
bias the study. 
The PI is responsible for all trial-related medical decisions. Emergency unblinding may be done 
without contacting a medical monitor. Any premature unblinding should be promptly 
documented and explained to the medical monitor within 24 hours following disclosure of study 
drug assignment. 
If the PI is unsure whether unblinding is needed, he or she may contact the 
 or Alkermes 
medical monitor before the blind is broken. 
Breaking the blind for a single subject will not affect the blind for the remaining subjects. 
PPD
PPD


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10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Study Drug 
Commercially available olanzapine will be supplied by the investigative site. 
Samidorphan will be provided by Alkermes in 10 mg tablets. 
Placebo consists of tablets, identical in size and appearance to the samidorphan tablets. 
Subjects will take 1 tablet per day orally (either samidorphan or placebo) at the same time as 
their olanzapine. 
10.2. 
Packaging and Labeling 
Samidorphan and placebo will be packaged in blister packs. Blister cards will be provided in 
biweekly configurations. The biweekly blister card will contain 16 tablets, which provides 
2 weeks of dosing with sufficient overage to allow for 2 additional daily doses. 
Blister card labels will meet all applicable local and regulatory requirements. 
10.3. 
Storage 
Whether or not samidorphan is classified as a controlled substance varies from country to 
country; some countries have classified samidorphan as a controlled substance, but others have 
not. Sites will be given storage instructions applicable to their country to ensure compliance with 
local regulations for controlled substances. 
10.4. 
Accountability 
The clinical site is required to maintain current drug dispensation and accountability logs 
throughout the study. All unused supplies will be checked against the drug movement records 
during the study and/or at the end of the study. 
Refer to Section 8.3.27 for additional study drug reconciliation procedures. 
10.5. 
Handling and Disposal 
Following completion and verification of accountability logs, all unused and used packages must 
be destroyed. Alkermes may arrange for destruction with a third party agent operating in 
accordance with GCP. 


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11. 
ASSESSMENT OF EFFICACY 
11.1. 
Primary Efficacy Measure 
The primary efficacy measure is an EEDS, defined as any of the following occurring during the 
double-blind period and is related to worsening of disease symptoms, as confirmed by the IAC: 
1. Subject requires hospitalization due to worsening of disease symptoms including a 
psychiatric hospitalization or a hospitalization due to or for acute treatment of alcohol 
intoxication or withdrawal 
2. Subject has a ≥25% or ≥15-point increase from randomization in PANSS total score that 
is confirmed at a second, ad hoc visit shortly after the first assessment (see Section 8.5) 
3. Subject has a PANSS item score of P1, P2, P3, P6, P7, or G8 that meets one of the 
following criteria: 
• For subjects with a score ≤3 at randomization, a score ≥5 that is confirmed at a 
second, ad hoc visit shortly after the first assessment (see Section 8.5) 
• For subjects with a score of 4 at randomization, a score ≥6 that is confirmed at a 
second, ad hoc visit shortly after the first assessment (see Section 8.5) 
4. Subject commits deliberate self-injury, engages in aggressive behavior, or displays signs 
of suicidal or homicidal ideation that is clinically significant as judged by the PI 
5. Subject requires initiation of rescue medication (see Section 8.4.5), including an increase 
in prescribed olanzapine dose level, due to worsening of disease symptoms 
• For this study, the increase in olanzapine dose must be above the randomization dose 
level even if the dose level was previously decreased at some point after 
randomization. 
6. Subject requires an emergency room visit due to worsening of disease symptoms 
7.  Subject withdraws or PI discontinues the subject from the study for one of the following 
reasons: 
a. Lack of efficacy 
b. Lost to follow-up 
c. Withdrawal by subject 
8. Subject is involved in an incident leading to arrest or incarceration during the study 
period that is related to the subject’s underlying disease 
For criterion requiring a consecutive assessment, the second assessment should be scheduled 
within 3-7 days of the first occurrence and conducted as per Section 8.5. All EEDS cases will be 
reviewed by the IAC in a blinded manner. Only events confirmed by the IAC will be used for 
efficacy analyses. Further details on the functioning of the IAC will be included in the IAC 
charter. 
If no withdrawal criteria have been met, subjects experiencing an EEDS (except event #7) may 
continue in the study at the discretion of the PI. 


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11.2. 
Other Efficacy Measures 
Other efficacy measures include the following: 
• Psychosocial events indicative of exacerbation of disease include any of the EEDS 
criteria listed above in Section 11.1 and/or any of the following additional criteria*: 
1. Subject has a change in locus of care due to a worsening in disease symptoms 
2. Subject loses employment because of a worsening in disease symptoms 
3. Subject has a change in living situation because of a worsening in symptoms 
*To constitute a psychosocial event, any of the EEDS criteria must be confirmed (in a 
blinded manner) by the IAC to be related to worsening of disease symptoms. 
• PANSS 
• CGI-S 
• CGI-I 
• TLFB 
• VAS Perception of Desire for Alcohol 
11.3. 
Exploratory Efficacy Measures 
Exploratory efficacy measures for this study include the following: 
• CDT 
• PSP 
• Cigarette use 
• Other 


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12. 
ASSESSMENT OF PHARMACOKINETICS AND 
PHARMACODYNAMICS 
For all subjects, samidorphan, RDC-9986 (primary metabolite of samidorphan) and olanzapine 
concentrations will be determined from plasma samples collected according to the Table 1, 
Table 2, and Table 3. Pharmacokinetic data may be used in a subsequent population PK 
evaluation conducted outside of this study. By-subject listings of plasma concentrations will be 
provided. 


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13. 
ASSESSMENT OF SAFETY 
Safety will be assessed on the basis of: 
• Treatment-emergent adverse events (TEAEs) 
• Vital signs (ie, blood pressure, pulse, respiratory rate, and body temperature) 
• Laboratory findings (ie, hematology, chemistry, and urinalysis) 
• ECG results 
• Weight 
• C-SSRS 
• AIMS 
• BARS 
• SAS 
13.1. 
Definition of Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product. The occurrence, which may or may not have a causal 
relationship with the investigational treatment, may include any clinical or laboratory change that 
does not commonly occur in that subject and is considered clinically significant. 
Illnesses present prior to the subject signing the ICF are considered to be pre-existing conditions 
and are documented on the medical history eCRF. Pre-existing conditions that worsen during the 
study are entered on the AE eCRF. 
All out-of-range laboratory values will be deemed as clinically significant or not clinically 
significant by the investigator. Clinically significant values will be considered AEs and recorded 
as such on the eCRFs. 
Pregnancy is not considered an AE, although a subject will be withdrawn from the study if a 
pregnancy occurs. As described in Section 8.4.1, the pregnancy must be reported to Alkermes 
and additional follow-up may be required. 
13.2. 
Definition of Serious Adverse Event 
An SAE is any AE, occurring at any dose and regardless of causality that meets one or more of 
the following criteria: 
• Results in death 
• Is life-threatening, meaning the subject is at immediate risk of death from the reaction 
as it occurs. This definition of life-threatening does not include a reaction that, had it 
occurred in a more severe form, might have caused death. 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 


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• Results in disability/ incapacity (eg, a substantial disruption of a person’s ability to 
conduct normal life functions) 
• Is a congenital anomaly/ birth defect 
Important medical events that may not result in death, be immediately life threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require intervention to prevent one of the other outcomes 
listed above. 
Some outcomes of pregnancy may meet the criteria as an SAE. All neonatal deaths that occur 
within 1 month of birth should be reported as an SAE, without regard to causality. In addition, 
any infant death occurring more than 1 month after birth that the investigator assesses as possibly 
related to the in utero exposure to the study drug should be reported. See Section 8.4.1 for details 
on reporting pregnancies. 
13.3. 
Relationship to Study Drug 
The assessment of study drug relationship to each AE will be reported on the appropriate source 
document (and SAE form, in the event of an SAE) by the investigator (or designated sub 
investigator) according to his/her best clinical judgment. The criteria listed in Table 5 should be 
used to guide this assessment. Please note that not all criteria must be present to be indicative of 
a particular drug relationship. All study drugs are considered “test drugs” for the purposes of the 
definitions listed in the table. However, relationship and action taken will be assessed separately 
in the EDC (electronic data capture) system for olanzapine and samidorphan/placebo. It is 
possible that a PI may assess that a given AE is related to both study drugs (eg, possibly related 
to olanzapine and possibly related to samidorphan). 


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Table 5: 
Adverse Event Causality Guidelines 
Relationship1 
Criteria for Assessment 
Definitely related 
There is evidence of exposure to the test drug. 
AND 
The temporal sequence of the AE onset relative to administration of the test drug is 
reasonable. 
The AE is more likely explained by the test drug than by another cause. 
Dechallenge (if performed) is positive. 
Rechallenge (if feasible) is positive. 
The AE shows a pattern consistent with previous knowledge of the test drug or test 
drug class. 
Probably related 
There is evidence of exposure to the test drug. 
AND 
The temporal sequence of the AE onset relative to administration of the test drug is 
reasonable. 
The AE is more likely explained by the test drug than by another cause. 
Dechallenge (if performed) is positive. 
Possibly related 
There is evidence of exposure to the test drug. 
AND 
The temporal sequence of the AE onset relative to administration of the test drug is 
reasonable. 
The AE could have been due to another equally likely cause. 
Dechallenge (if performed) is positive. 
Probably not 
related 
There is evidence of exposure to the test drug. 
AND 
There is another more likely cause of the AE. 
Dechallenge (if performed) is negative or ambiguous. 
Rechallenge (if performed) is negative or ambiguous. 
Definitely not 
related 
The subject did not receive the test drug. 
OR 
Temporal sequence of the AE onset relative to administration of the test drug is not 
reasonable. 
OR 
There is another obvious cause of the AE. 
1 Relationship will be assessed twice: once for olanzapine and once for samidorphan/placebo 


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13.4. 
Monitoring and Recording of Adverse Events 
Adverse event data collection will begin after a subject signs the ICF and will continue until 
completion of the safety follow-up visit. Any AE or SAE having an onset after the safety follow-
up visit will not be collected or reported unless the investigator feels that the event may be 
related to the study drug. 
Subjects will be instructed by the investigator or designee to report the occurrence of any AE. 
All volunteered, elicited, and observed AEs are to be recorded on the AE eCRFs. 
The investigator will assess all AEs regardless of causal relationship to the study drug (see 
Section 13.3), the intensity (severity) of the event, action taken, and subject outcome. 
The following criteria should be used to guide the assessment of intensity (severity): 
• Mild: Causes awareness of sign or symptom, but is easily tolerated; does not interfere 
with usual activities 
• Moderate: Causes discomfort enough to interfere with usual activities 
• Severe: Is incapacitating; results in inability to work or perform usual activities 
All AEs will be followed until resolution, until deemed stable by the investigator, or until the 
subject is deemed by the investigator to be lost to follow-up. 
For clinical study safety reporting purposes, the most recent version of the ALKS 3831 
Investigator’s Brochure will be used as the reference document to designate event expectedness. 
Withdrawal from the study as a result of an AE and any therapeutic measures that are taken shall 
be at the discretion of the investigator. If a subject withdraws from the study for any reason
13.5. 
Reporting of Serious Adverse Events 
, any 
ongoing AEs will be followed until resolution, until deemed stable by the investigator, or until 
the subject is deemed by the investigator to be lost to follow-up. 
All SAEs must be reported to 
 Drug Safety within 24 hours of discovery, by 
faxing the report to the following: 
Attention: Drug Safety 
FAX Number: 
 
The written report should be submitted on the SAE form provided for this purpose. The report 
must include the investigator’s opinion as to whether the event is study drug-related. If this 
relationship is determined to be possibly, probably, or definitely related to study drug, evidence 
to support this assessment must also be provided. This assessment will be done twice as follows: 
once for olanzapine and once for samidorphan/placebo. The report submitted will include both 
assessments. 
PPD
PPD


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14. 
STATISTICS 
14.1. 
Sample Size Considerations 
The sample size calculation is based on the detection of log-hazard ratio for the first EEDS 
during the double-blind treatment period. 
Based on the previous clinical studies with olanzapine and clinical judgment, the 9-month 
cumulative proportion of subjects experiencing an EEDS will be 15% and 30% for the 
ALKS 3831 group and olanzapine plus placebo group, respectively. Assuming an exponential 
distribution of survival time, and a 2-sided test at α=0.05, a total of 70 EEDS will be required for 
approximately 90% power to detect a hazard ratio of 0.45 between ALKS 3831 and olanzapine 
plus placebo with a randomization allocation ratio of 1:1 (ALKS 3831:olanzapine plus placebo). 
Approximately 270 subjects (135 subjects per treatment group) will need to be randomized at 
Visit 8 to observe 70 total EEDS. 
14.2. 
General Statistical Methodology 
The statistical analysis methods are described below. Additional details will be provided in the 
Statistical Analysis Plan (SAP) to be finalized before database lock and unblinding. 
In general, summary statistics (n, mean, standard deviation, median, minimum, and maximum 
for continuous variables and number and percent of subjects in each category for categorical 
variables) will be provided by treatment group for all variables. 
Source data for the summary tables and statistical analyses will be presented as subject data 
listings. All statistical tests and confidence intervals, unless stated otherwise, will be 2-sided and 
will be set at α = 0.05. 
14.2.1. 
Study Populations 
The open-label olanzapine population is defined as all enrolled subjects who received at least 
1 dose of olanzapine during the open-label olanzapine treatment period. 
The open-label ALKS 3831 population is defined as all enrolled subjects who received at least 
1 dose of olanzapine or samidorphan during the open label ALKS 3831 treatment period. 
The primary safety population is defined as all randomized subjects who receive at least 1 dose 
of study drug (olanzapine, samidorphan, or placebo) during the double-blind placebo-controlled 
treatment period. The intent-to-treat (ITT) population is the same as the primary safety 
population. 
14.2.2. 
Demographics and Baseline Data 
Demographics and baseline characteristics, including but not limited to gender, age, race, weight 
and BMI will be summarized with descriptive statistics. Medical history will be summarized 
using the number and percent of subjects reporting each category. 


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14.3. 
Efficacy Analyses 
14.3.1. 
Primary Efficacy Measure 
The efficacy analyses will be carried out using the ITT population and EEDS that the IAC has 
confirmed as meeting the pre-specified criteria. The primary efficacy endpoint is defined as the 
time from randomization to an EEDS. The analysis comparing the 2 treatment groups will be 
carried out using a log-rank test. A Cox proportional hazard model will be used to further 
examine the treatment difference adjusting for various covariates. The relationship between the 
primary efficacy endpoint and alcohol intake during the double-blind placebo-controlled 
treatment period may be explored by (but not limited to) a Cox proportional hazard model. 
Additional details will be described in the SAP. 
14.3.2. 
Other Efficacy Endpoints 
Other efficacy endpoints will include (but are not limited to) the following: 
• The rate and number of EEDS 
• The proportion of subjects with psychosocial events indicative of exacerbation of 
symptoms during the double-blind treatment period 
• The rate and number of psychosocial events indicative of exacerbation of symptoms 
during the double-blind treatment period 
• Change from baseline in PANSS total and sub-scale score during the double-blind 
treatment period 
• Change from baseline in CGI-S score during the double-blind treatment period 
• CGI-I score during the double-blind treatment period 
• Complete response profile of drinking during the double-blind treatment period 
• Change from baseline in VAS score for perception of desire for alcohol during the 
double-blind treatment period 
The statistical methods include, but are not limited to, the following: Negative binomial 
regression will be used to compare treatment difference in the number and rate of EEDS and the 
number and rate of psychosocial events indicative of exacerbation symptoms during the double-
blind treatment period. Logistic regression will be used to compare treatment difference in the 
proportion of subjects with psychosocial events during the double-blind treatment period. An 
ANCOVA model with LOCF (last observation carried forward) approach will be used to 
compare treatment difference in change from baseline during the double-blind treatment period 
in PANSS total and sub-scale score, CGI-S and VAS score for perception of desire for alcohol. 
Wilcoxon rank sum test will be used to compare treatment difference in CGI-I score. Drinking 
profile will be analyzed by an Anderson-Gill model. 
Additional efficacy endpoints and analysis methods may be defined in the Statistical Analysis 
Plan. 


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14.4. 
Pharmacokinetic Analyses 
Concentrations of olanzapine, samidorphan and its metabolite (RDC-9986) will be listed. 
Pharmacokinetic concentrations may be used to assess adherence and/or as part of a subsequent 
population PK analysis to be conducted separately from this study. 
14.5. 
Safety Analyses 
Safety will be evaluated based on the incidence of TEAEs, laboratory test results, vital signs, 
ECG findings, C-SSRS results, abnormal movement rating scales results, as well as concomitant 
medications. Reported AE terms will be coded using the MedDRA (Medical Dictionary for 
Regulatory Activities) preferred terms and system organ classes. 
The incidence of TEAEs will be summarized for each study period, treatment group, and overall 
by severity and by relationship to study drug. The summary tables will include the number and 
percent of subjects with TEAEs overall, by system organ class, and by preferred terms within 
each system organ class. Additional AE summary tables will be defined in the SAP. 
Laboratory tests will be summarized by visit for the absolute value itself and for change from 
baseline by study period. Tables showing the shift from baseline will also be presented. 
Potentially clinically significant (PCS) values for each relevant parameter will be defined in the 
SAP. 
QT, QTcB, and QTcF intervals will be calculated at each ECG assessment. Interval data will be 
summarized by study period and treatment group at each time point for the absolute value and 
for changes from baseline. In addition, the number and percentages of subjects with post-
baseline results QTcB and QTcF values >450, 480, or 500 milliseconds and an increase from 
baseline of >30 or 60 milliseconds from baseline will be summarized. Other ECG variables that 
are collected will be summarized as well. 
C-SSRS will be summarized by number and percent of subjects with any abnormal findings at 
post-baseline visits by study period and treatment group. AIMS, BARS, and SAS will be 
summarized by study period and treatment group for the absolute value and for changes from 
baseline at each visit. 
Concomitant medications will be coded using World Health Organization Drug Dictionary 
Anatomical Therapeutic Chemical (WHO-ATC) class. The number and percentage of subjects 
using concomitant medications will be summarized by study period and treatment group. 


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15. 
DIRECT ACCESS TO SOURCE DATA/ DOCUMENTS 
15.1. 
Study Monitoring 
Monitoring of the study site (including, but not limited to, reviewing eCRFs for accuracy and 
completeness) will be performed by an Alkermes monitor or designee. A paper copy of the 
laboratory reports will be generated and will remain with the source documents at the site. 
15.2. 
Audits and Inspections 
By signing the protocol, the investigator agrees that, within local regulatory restrictions and 
institutional and ethical considerations, authorized representatives of Alkermes, a regulatory 
authority, and/or an IRB/Independent Ethics Committee (IEC) may visit the site to perform 
audits or inspections, including the drug storage area, study drug stocks, drug accountability 
records, subject charts and source documents, and other records relative to study conduct. The 
purpose of an Alkermes audit or inspection is to systematically and independently examine all 
study-related activities and documents (eg, laboratory reports, x-rays, workbooks, subjects’ 
medical records) to determine whether these activities were conducted, and data recorded, 
analyzed, and accurately reported according to the protocol, GCP guidelines, and any applicable 
regulatory requirements. 
The investigator should contact Alkermes immediately if contacted by a regulatory agency 
regarding an inspection. 
15.3. 
Institutional Review Board/ Independent Ethics Committee 
The PI must obtain IRB/IEC approval for the investigation. Initial IRB/IEC approval as well as 
all materials approved by the IRB/IEC for this study, including the subject and caregiver consent 
forms and recruitment materials, must be maintained by the investigator and made available for 
inspection. 


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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
This study will be conducted under GCP and all applicable regulatory requirements. To ensure 
compliance, Alkermes may conduct a quality assurance audit. Please see Section 15.2 for details 
regarding the audit process. 
16.1. 
Case Report Forms 
This study will use eCRFs. All eCRFs will be completed by the clinic staff prior to review by the 
Alkermes monitor or designated representative. 
The Alkermes monitor or designated representative will review all source records on-site and 
compare them to the data collected on the eCRF. 
16.2. 
Confidentiality of Data 
By signing this protocol, the investigator affirms to Alkermes that he/she will maintain in 
confidence information furnished to him or her by Alkermes and will divulge such information 
to his/her respective IRB or IEC under an appropriate understanding of confidentiality with such 
board. All data will be considered the sole property of Alkermes. Please refer to the Clinical 
Study Agreement (CSA) for details. 


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17. 
ETHICAL CONSIDERATIONS 
17.1. 
Ethics Review 
The clinical site’s IRB/IEC must meet all relevant regulatory requirements. The study protocol 
and ICF will be reviewed by the IRB/IEC prior to enrolling subjects into the study; written 
approval from the committee must be received by Alkermes before drug will be released to 
the investigator. The protocol must be re-approved by the IRB/IEC upon receipt of amendments 
and annually, as local regulatory requirements require. 
The PI or designee is responsible for submitting all protocol changes and SAE reports to the 
IRB/IEC according to local procedures. At a minimum, all SAEs requiring an investigational 
new drug safety report must be immediately reported. 
All relevant correspondence from the IRB/IEC will be forwarded by the respective study site to 
Alkermes in a timely fashion. 
17.2. 
Ethical Conduct of the Study 
This study will be conducted in accordance with the protocol, the ICH Guideline E6, and all 
applicable local regulatory requirements. Alkermes is committed to complying with GCP 
standards; GCP is an international ethical and scientific quality standard used for designing, 
conducting, recording, and reporting studies involving the participation of human subjects. 
Complying with these standards provide assurance that the rights, safety, and well-being of study 
subjects will be protected, consistent with the principles having their origin in the Declaration of 
Helsinki. 
17.3. 
Written Informed Consent 
The PI (or authorized designee) at each center will ensure that the subject and caregiver (in 
Bulgaria, and anywhere a caregiver is required) are given full and adequate oral and written 
information about the nature, purpose, potential and possible risks and benefits of the study. 
Each prospective subject and caregiver will receive the required, IRB/IEC-approved ICF(s) that 
summarizes all pertinent study information. The subject and caregiver will be given ample time 
to read the forms and ask questions about the study. All information is to be provided in a 
language understandable to the subject and must not include any language that waives the 
subject’s legal rights. Prospective subjects must also be informed of their right to withdraw 
consent without prejudice at any time during the study. If the subject chooses to participate, 
he/she must sign the main ICF and when required, the caregiver must sign the caregiver ICF. 
All subjects will be informed of their rights to privacy and will be made aware that the study data 
will be submitted to Alkermes, the IRB/IEC, the CRO if applicable, and to regulatory authorities 
for review and evaluation for the duration of the study and until the project has been approved 
for marketing, or is withdrawn from investigation. They will also be informed that the study 
monitor may inspect their medical records to verify the accuracy and completeness of the study 
records and results. 


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Significant changes to the protocol or product safety information may require a revision of the 
ICFs, which must be reviewed and signed by all applicable study participants. 
The time that informed consent is obtained must be documented. The PI must maintain the 
original, signed ICFs in the subject’s source documents. A copy of the signed ICF(s) must be 
given to the subject. 


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18. 
DATA HANDLING AND RECORDKEEPING 
An overview of study data handling and recordkeeping procedures and restrictions is provided in 
the subsequent sections; please refer to the CSA for further details. Principal investigators are 
responsible for handling data in a manner consistent with local and international regulations on 
personal data (including health information) collection and protection. 
18.1. 
Data Capture 
As stated in Section 16.1, this study will use eCRFs for capturing data. All entries, corrections, 
and alterations will be made by the investigator or other authorized study personnel. All data 
entries will be verified for accuracy and correctness by independent monitors. The electronic 
data capture system maintains a full audit trail. 
If available, a paper copy of all laboratory reports will remain with the source documents at the 
study site. All out of range laboratory values will be deemed as clinically significant or not 
clinically significant by the investigator. Clinically significant values will be considered AEs and 
recorded as such on the eCRFs. 
AEs and medical history conditions will be coded using MedDRA. Concomitant medications 
will be categorized using the WHO-ATC classification system. 
18.2. 
Inspection of Records 
Alkermes or its representative will be allowed to conduct site visits to the investigational 
facilities for the purpose of monitoring any aspect of the study. The investigator agrees to allow 
the monitor to inspect the drug storage area, study drug stocks, drug accountability records, 
subject charts and source documents, and other records relative to study conduct. 
18.3. 
Retention of Records 
Retention and storage of essential clinical study documents (eg, worksheets, drug accountability 
forms, and other administrative documentation) shall be governed by the terms and conditions of 
the site’s CSA. If the CSA does not state specific document retention terms, then the site shall 
keep essential clinical study documentation for the longer of: 
• Ten years after discontinuation of the study, or 
• Two years following the date a marketing application is approved for the study drug 
for the indication for which it is being investigated pursuant to the study, or 
• If no application is to be filed or if the application is not approved for such indication, 
until 2 years after the date the study is terminated. 
Subjects’ medical files should be retained in accordance with the applicable legislation and in 
accordance with the maximum period of time permitted by the hospital, institution, or private 
practice. 


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18.4. 
Use of Information and Publication Policy 
Data generated in this study are proprietary information that is the sole property of Alkermes. 
Results of the study are to be held in confidence by both the investigators and Alkermes. 
Please refer to the CSA for details on the procedures for publishing and presenting data. 


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19. 
REFERENCES 
Ahmed SH (2004) Neuroscience. Addiction as compulsive reward prediction. Science 306:1901-
1902 
American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders, 
4th ed., text revision (DSM-IV-TR). Washington, DC 
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 
5th ed. (DSM-5). Washington, DC 
Barnes TR (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154:672-676 
Chambers RA, Krystal JH, Self DW (2001) A neurobiological basis for substance abuse 
comorbidity in schizophrenia. Biol Psychiatry 50:71-83 
Dickey B, Azeni H, Weiss R, Sederer L (2000) Schizophrenia, substance use disorders and 
medical co-morbidity. J Ment Health Policy Econ 3:27-33 
Drake RE, Mercer-McFadden C, Mueser KT, McHugo GJ, Bond GR (1998) Review of 
integrated mental health and substance abuse treatment for patients with dual disorders. 
Schizophr Bull 24:589-608 
Duramed Pharmaceuticals, Inc (2013) REVIA® Package Insert 2013. 
EMEA (2013) Zyprexa: European Public Assessment Report - Product Information. 
Guy W (1976) ECDEU Assessment Manual for Psychopharmacology. Department of Health, 
Education, and Welfare, Rockville, MD 
Guy W (2000) Clinical Global Impressions (CGI) Scale. In: Rush J, Pincus HA, First MB, 
Blacker D, Endicott J, Keith SJ, Ryan ND, Smith GR, Tsuang MT, Widiger TA, Zarin DA eds. 
Handbook of Psychiatric Measures. APA, Washington, DC, pp. 100-102 
Kay S, Fiszbein A, Opler L (1987) The Positive and Negative Syndrome Scale (PANSS) for 
Schizophrenia. Schizophr Bull 13:261-276 
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, 
Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK (2005) Effectiveness of antipsychotic 
drugs in patients with chronic schizophrenia. N Engl J Med 353:1209-1223 
Lilly USA L (2013) ZYPREXA® (olanzapine): Package Insert. 
Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R (2000) Development, reliability and 
acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment 
Scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand 101:323-329 
Opler LA, Kay SR, Lindenmayer JP, Fiszbein A (1999) Structured Clinical Interview for the 
Positive and Negative Syndrome Scale. Multi-Health Systems Inc., North Tonawanda, NY, pp. 
1-16 
Posner K, Brent D, Lucas C, Gould M, Stanley B, Brown G, Fisher P, Zelazny J, Burke A, 
Oquendo M, Mann J (2009a) Columbia-Suicide Severity Rating Scale (C-SSRS): 
Baseline/Screening Version. New York State Psychiatric Institute, New York, NY 


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Posner K, Brent D, Lucas C, Gould M, Stanley B, Brown G, Fisher P, Zelazny J, Burke A, 
Oquendo M, Mann J (2009b) Columbia-Suicide Severity Rating Scale (C-SSRS): Since last visit. 
New York State Psychiatric Institute, New York, NY 
Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK (1990) 
Comorbidity of mental disorders with alcohol and other drug abuse. Results from the 
Epidemiologic Catchment Area (ECA) Study. JAMA 264:2511-2518 
Rollnick S, Heather N, Gold R, Hall W (1992) Development of a short 'readiness to change' 
questionnaire for use in brief, opportunistic interventions among excessive drinkers. Br J Addict 
87:743-754 
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, 
Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the 
development and validation of a structured diagnostic psychiatric interview for DSM-IV and 
ICD-10. J Clin Psychiatry 59 Suppl 20:22-33 
Simpson GM, Angus JW (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr 
Scand Suppl 212:11-19 
Sobell LC, Sobell MB (1992) Timeline Follow-Back: A technique for assessing self-reported 
alcohol consumption. In: Litten RZ, Allen JP eds. Measuring Alcohol Consumption: 
Psychosocial and Biological Methods. The Humana Press, Totowa, NJ, pp. 41-72 
 
 


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20. 
APPENDICES 
Appendix A. 
Sample Mini-International Neuropsychiatric Interview 
Appendix B. 
Sample Readiness to Change Questionnaire 
Appendix C. 
Sample Positive and Negative Syndrome Scale 
Appendix D. 
Sample Clinical Global Impression-Improvement 
Appendix E. 
Sample Structured Interview Guide for Global Impressions 
Appendix F. 
Sample Visual Analog Scale 
Appendix G. 
Sample Personal and Social Performance Scale 
Appendix H. 
Sample Abnormal Involuntary Movement Scale 
Appendix I. 
Sample Barnes Akathisia Scale 
Appendix J 
Sample Simpson-Angus Scale 
Appendix K. 
Sample Columbia Suicide Severity Rating Scale 
• 
“Baseline/ Screening” Version 
• 
“Since Last Visit” Version 
Appendix L 
Partial List of Prohibited Cytochrome P450 3A4 (CYP3A4) Inducers and 
Moderate-to-Strong Inhibitors 
 


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APPENDIX A. SAMPLE MINI-INTERNATIONAL 
NEUROPSYCHIATRIC INTERVIEW 
Page 71


 
	  
M.I.N.I.	  
	  
	  
	  
	  
MINI	  INTERNATIONAL	  NEUROPSYCHIATRIC	  INTERVIEW	  
	  
	  
English	  Version	  6.0.0	  	  
	  
DSM-­‐IV	  
	  
	  
	  
USA:	  	  D.	  Sheehan1,	  J.	  Janavs,	  K.	  Harnett-­‐Sheehan,	  M.	  Sheehan,	  C.	  Gray.	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  1University	  of	  South	  Florida	  College	  of	  Medicine-­‐	  Tampa,	  USA	  
	  
	  
EU:	  	  	  Y.	  Lecrubier2,	  E.	  Weiller,	  T.	  Hergueta,	  C.	  Allgulander,	  N.	  Kadri,	  D.	  Baldwin,	  C.	  Even.	  
2Centre	  Hospitalier	  Sainte-­‐Anne	  –	  Paris,	  France	  
	  
	  
	  
©	  Copyright	  1992-­‐2010	  Sheehan	  DV	  &	  Lecrubier	  Y	  
	  
	  
All	  rights	  reserved.	  	  No	  part	  of	  this	  document	  may	  be	  reproduced	  or	  transmitted	  in	  any	  form,	  or	  by	  any	  
means,	  electronic	  or	  mechanical,	  including	  photocopying,	  or	  by	  any	  information	  storage	  or	  retrieval	  
system,	  without	  permission	  in	  writing	  from	  Dr.	  Sheehan.	  	  Individual	  researchers,	  clinicians	  and	  students	  
working	   in	   nonprofit	   or	   publicly	   owned	   settings	   (including	   universities,	   nonprofit	   hospitals,	   and	  
government	  institutions)	  may	  make	  paper	  copies	  of	  a	  M.I.N.I.	  instrument	  for	  their	  personal	  clinical	  and	  
research	  use.	  
	  
	  
	  
DISCLAIMER	  
	  
Our	  aim	  is	  to	  assist	  in	  the	  assessment	  and	  tracking	  of	  patients	  with	  greater	  efficiency	  and	  accuracy.	  	  Before	  action	  is	  taken	  
on	  any	  data	  collected	  and	  processed	  by	  this	  program,	  it	  should	  be	  reviewed	  and	  interpreted	  by	  a	  licensed	  clinician.	  	  	  
	  
This	  program	  is	  not	  designed	  or	  intended	  to	  be	  used	  in	  the	  place	  of	  a	  full	  medical	  and	  psychiatric	  evaluation	  by	  a	  qualified	  
licensed	   physician	   –	   psychiatrist.	   	   It	   is	   intended	   only	   as	   a	   tool	   to	   facilitate	   accurate	   data	   collection	   and	   processing	   of	  
symptoms	  elicited	  by	  trained	  personnel.	  
	  
	  
M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
2 
Patient	  Name:	  
Patient	  Number:	  
	  
Date	  of	  Birth:	  
	  
	   Time	  Interview	  Began:	  
	  
Interviewer’s	  Name:	  
Time	  Interview	  Ended:	  
	  
Date	  of	  Interview:	  
	  
	   Total	  Time:	  
	  
	  
	  
MEETS	  
	  
	  
PRIMARY	  
	  
MODULES	  
TIME	  FRAME	  
CRITERIA	  
DSM-­‐IV-­‐TR	  
ICD-­‐10	   	  
DIAGNOSIS	  
 
A	  
MAJOR	  DEPRESSIVE	  EPISODE	  
Current	  (2	  weeks)	  
	  
❐	  
	  
	  
 
	  
	  
	  
Past	  
	  
❐	  
	  
	  
 
 
 
 
Recurrent	  
	  
❐	  
 
 
 
	  
	  
MAJOR	  DEPRESSIVE	  DISORDER	  
Current	  (2	  weeks)	  
	  
❐	  
296.20-­‐296.26	  	  Single	  
F32.x	  
	  
❐	  
	  
	  
Past	  
	  
❐	  
296.20-­‐296.26	  	  Single	  
F32.x	  
	  
❐ 
	  
	  
Recurrent	  
	  
❐	  
296.30-­‐296.36	  	  Recurrent	  
F33.x	  
❐	  
 
 
 
B	  
SUICIDALITY	  
Current	  (Past	  Month)	   	  
❐  
 
 
❐	  Low	  	  ❐	  Moderate	  	  ❐	  High	  
 
C	  
MANIC	  EPISODE	  
Current	  
	  
❐	  
	  
	  
	  
 
 
 
 
Past	  
	  
❐	  
 
HYPOMANIC	  EPISODE	  
Current	  
	  
❐	  
	  
	  
	  
 
 
 
 
Past	  
	  
❐	  
❐	  	  Not	  Explored	  
 
BIPOLAR	  I	  DISORDER	  
Current	  
	  
❐	  
296.0x-­‐296.6x	   	  
F30.x-­‐	  F31.9 
❐ 
 
 
Past	  
	  
❐	  
296.0x-­‐296.6x	   	  
F30.x-­‐	  F31.9 
❐ 
 
BIPOLAR	  II	  DISORDER	  
Current	  
	  
❐	  
296.89	  
	  
F31.8	  
❐ 
 
 
Past	  
	  
❐	  
296.89	  
	  
F31.8	  
❐ 
 
BIPOLAR	  DISORDER	  NOS	  
Current	  
	  
❐	  
296.80	  
	  
F31.9	  
❐ 
 
 
Past	  
	  
❐	  
296.80	  
	  
F31.9	  
❐ 
 
D	  
PANIC	  DISORDER	  
Current	  (Past	  Month)	   	  
❐	  
300.01/300.21	  	  
F40.01-­‐F41.0	  
❐ 
 
 
Lifetime	  
	  
❐	  
E	  
AGORAPHOBIA	  
Current	  
	  
❐	  
300.22	  
	  
F40.00 
❐ 
 
F	  
SOCIAL	  PHOBIA	  (Social	  Anxiety	  Disorder)	  
Current	  (Past	  Month)	  
	  
	  
Generalized	  
	  
❐	  
300.23	  
	  
F40.1	    
❐ 
 
 
Non-­‐Generalized	  
	  
❐	  
300.23	  
	  
F40.1	    
❐ 
 
G	  
OBSESSIVE-­‐COMPULSIVE	  DISORDER	  
Current	  (Past	  Month)	   	  
❐	  
300.3	  
	  
F42.8	    
❐ 
 
H	  
POSTTRAUMATIC	  STRESS	  DISORDER	  
Current	  (Past	  Month)	   	  
❐	  
309.81	  
	  
F43.1	   	  
❐ 
 
 
I	  
ALCOHOL	  DEPENDENCE	  
Past	  12	  Months	  
	  
❐	  
303.9	  
	  
F10.2x  
❐ 
 
ALCOHOL	  ABUSE	  
Past	  12	  Months	  
	  
❐	  
305.00	  
	  
F10.1	   	  
❐ 
J	  
SUBSTANCE	  DEPENDENCE	  (Non-­‐alcohol)	  
Past	  12	  Months	  
	  
❐	  
304.00-­‐.90/305.20-­‐.90	  
F11.2X-­‐F19.2X	  
❐ 
 
SUBSTANCE	  ABUSE	  (Non-­‐alcohol)	  
Past	  12	  Months	  
	  
❐	  
304.00-­‐.90/305.20-­‐.90	  
F11.1-­‐F19.1 
❐ 
 
K	  
PSYCHOTIC	  DISORDERS	  
Lifetime	  
	  
❐	  
295.10-­‐295.90/297.1/	  
F20.xx-­‐F29 
❐ 
 
 
Current	  
	  
❐	  
297.3/293.81/293.82/ 
F20.xx-­‐F29	  
	  
	  
	  
	  
	  
293.89/298.8/298.9	  
MOOD	  DISORDER	  WITH	  
Lifetime 
 
❐ 
296.24/296.04-­‐296.94	  
F32.3/F33.3/ 
❐	  
PSYCHOTIC	  FEATURES	  
Current  
 
❐ 
296.24/296.04-­‐296.94	  
F30.2/F31.2/F31.5	  
❐ 
 
 
 
 
 
 
F31.8/F31.9/F39 
  
L	  
ANOREXIA	  NERVOSA	  
Current	  (Past	  3	  Months)	  
❐	  
307.1	  
	  
F50.0	    
❐ 
M	  
BULIMIA	  NERVOSA	  
Current	  (Past	  3	  Months)	  
❐	  
307.51	  
	  
F50.2	    
❐ 
 
ANOREXIA	  NERVOSA,	  BINGE	  EATING/PURGING	  TYPE	  
Current	  
	  
❐	  
307.1	  
	  
F50.0	    
❐ 
 
N	  
GENERALIZED	  ANXIETY	  DISORDER	  
Current	  (Past	  6	  Months)	  
❐	  
300.02	  
	  
F41.1	    
❐ 
 
O 
MEDICAL,	  ORGANIC,	  DRUG	  CAUSE	  RULED	  OUT	  
	  
	  
❐ No      ❐ Yes	  
❐	  	  	  Uncertain	  
	  
 
P	  
ANTISOCIAL	  PERSONALITY	  DISORDER	  
Lifetime	  
	  
❐	  
301.7	  
	  
F60.2	    
❐ 
 
 
 
IDENTIFY	  THE	  PRIMARY	  DIAGNOSIS	  BY	  CHECKING	  THE	  APPROPRIATE	  CHECK	  BOX.	  
	  
(Which	  problem	  troubles	  you	  the	  most	  or	  dominates	  the	  others	  or	  came	  first	  in	  the	  natural	  history?)	  	  	  
The	  translation	  from	  DSM-­‐IV-­‐TR	  to	  ICD-­‐10	  coding	  is	  not	  always	  exact.	  For	  more	  information	  on	  this	  topic	  see	  Schulte-­‐Markwort.	  	  
Crosswalks	  ICD-­‐10/DSM-­‐IV-­‐TR.	  Hogrefe	  &	  Huber	  Publishers	  2006.	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
3 
GENERAL	  INSTRUCTIONS	  
	  
	  
The	  M.I.N.I.	  was	  designed	  as	  a	  brief	  structured	  interview	  for	  the	  major	  Axis	  I	  psychiatric	  disorders	  in	  DSM-­‐IV	  and	  ICD-­‐10.	  	  Validation	  
and	   reliability	   studies	   have	   been	   done	   comparing	   the	   M.I.N.I.	   to	   the	   SCID-­‐P	   for	   DSM-­‐III-­‐R	   and	   the	   CIDI	   (a	   structured	   interview	  
developed	  by	  the	  World	  Health	  Organization).	  	  The	  results	  of	  these	  studies	  show	  that	  the	  M.I.N.I.	  has	  similar	  reliability	  and	  validity	  
properties,	  but	  can	  be	  administered	  in	  a	  much	  shorter	  period	  of	  time	  (mean	  18.7	  ±	  11.6	  minutes,	  median	  15	  minutes)	  than	  the	  
above	  referenced	  instruments.	  	  It	  can	  be	  used	  by	  clinicians,	  after	  a	  brief	  training	  session.	  	  Lay	  interviewers	  require	  more	  extensive	  
training.	  
	  
INTERVIEW:	  
	  
In	  order	  to	  keep	  the	  interview	  as	  brief	  as	  possible,	  inform	  the	  patient	  that	  you	  will	  conduct	  a	  clinical	  interview	  that	  is	  more	  
structured	  than	  usual,	  with	  very	  precise	  questions	  about	  psychological	  problems	  which	  require	  a	  yes	  or	  no	  answer.	  
	  
GENERAL	  FORMAT:	  
	  
The	  M.I.N.I.	  is	  divided	  into	  modules	  identified	  by	  letters,	  each	  corresponding	  to	  a	  diagnostic	  category.	  
	  
•At	  the	  beginning	  of	  each	  diagnostic	  module	  (except	  for	  psychotic	  disorders	  module),	  screening	  question(s)	  corresponding	  
to	  the	  main	  criteria	  of	  the	  disorder	  are	  presented	  in	  a	  gray	  box.	  
	  
•At	  the	  end	  of	  each	  module,	  diagnostic	  box(es)	  permit	  the	  clinician	  to	  indicate	  whether	  diagnostic	  criteria	  are	  met.	  
	  
CONVENTIONS:	  
Sentences	  written	  in	  «	  normal	  font	  »	  should	  be	  read	  exactly	  as	  written	  to	  the	  patient	  in	  order	  to	  standardize	  the	  assessment	  
of	  diagnostic	  criteria.	  
	  
Sentences	  written	  in	  «	  CAPITALS	  »	  should	  not	  be	  read	  to	  the	  patient.	  	  They	  are	  instructions	  for	  the	  interviewer	  to	  assist	  in	  the	  
scoring	  of	  the	  diagnostic	  algorithms.	  
	  
Sentences	  written	  in	  «	  bold	  »	  indicate	  the	  time	  frame	  being	  investigated.	  	  The	  interviewer	  should	  read	  them	  as	  often	  as	  
necessary.	  	  Only	  symptoms	  occurring	  during	  the	  time	  frame	  indicated	  should	  be	  considered	  in	  scoring	  the	  responses.	  
	  
Answers	  with	  an	  arrow	  above	  them	  ()	  indicate	  that	  one	  of	  the	  criteria	  necessary	  for	  the	  diagnosis(es)	  is	  not	  met.	  In	  this	  
case,	  the	  interviewer	  should	  go	  to	  the	  end	  of	  the	  module,	  circle	  «	  NO	  »	  in	  all	  the	  diagnostic	  boxes	  and	  move	  to	  the	  next	  
module.	  
	  
When	  terms	  are	  separated	  by	  a	  slash	  (/)	  the	  interviewer	  should	  read	  only	  those	  symptoms	  known	  to	  be	  present	  in	  the	  
patient	  (for	  example,	  question	  G6).	  
	  
Phrases	  in	  (parentheses)	  are	  clinical	  examples	  of	  the	  symptom.	  	  These	  may	  be	  read	  to	  the	  patient	  to	  clarify	  the	  question.	  
	  
RATING	  INSTRUCTIONS:	  
	  
All	  questions	  must	  be	  rated.	  The	  rating	  is	  done	  at	  the	  right	  of	  each	  question	  by	  circling	  either	  Yes	  or	  No.	  	  Clinical	  judgment	  
by	  the	  rater	  should	  be	  used	  in	  coding	  the	  responses.	  	  Interviewers	  need	  to	  be	  sensitive	  to	  the	  diversity	  of	  cultural	  beliefs	  in	  
their	  administration	  of	  questions	  and	  rating	  of	  responses.	  The	  rater	  should	  ask	  for	  examples	  when	  necessary,	  to	  ensure	  
accurate	  coding.	  	  The	  patient	  should	  be	  encouraged	  to	  ask	  for	  clarification	  on	  any	  question	  that	  is	  not	  absolutely	  clear.	  
The	  clinician	  should	  be	  sure	  that	  each	  dimension	  of	  the	  question	  is	  taken	  into	  account	  by	  the	  patient	  (for	  example,	  time	  
frame,	  frequency,	  severity,	  and/or	  alternatives).	  
Symptoms	  better	  accounted	  for	  by	  an	  organic	  cause	  or	  by	  the	  use	  of	  alcohol	  or	  drugs	  should	  not	  be	  coded	  positive	  in	  the	  
M.I.N.I.	  	  The	  M.I.N.I.	  Plus	  has	  questions	  that	  investigate	  these	  issues.	  
	  
For	  any	  questions,	  suggestions,	  need	  for	  a	  training	  session	  or	  information	  about	  updates	  of	  the	  M.I.N.I.,	  please	  contact:	  
	  
	  
University	  of	  South	  Florida	  College	  of	  Medicine	  
Centre	  Hospitalier	  Sainte-­‐Anne	  
3515	  East	  Fletcher	  Ave,	  Tampa,	  FL	  USA	  33613-­‐4706	  
Clinique	  des	  Maladies	  Mentales	  de	  l’Encéphale	  
tel	  :	  
	  	  fax	  :	  
	  
100	  rue	  de	  la	  Santé,	  75674	  Paris	  Cedex	  14,	  France	  
e-­‐mail	  :	  
	  	  
tel	  :	  
	  	  fax	  
	  
e-­‐mail:	  
	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
4 
A. MAJOR	  DEPRESSIVE	  EPISODE	  	  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOXES,	  CIRCLE	  NO	  IN	  ALL	  DIAGNOSTIC	  BOXES,	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE) 
 
 
A1	  
a	   Were	  you	  ever	  depressed	  or	  down,	  most	  of	  the	  day,	  nearly	  every	  day,	  for	  two	  weeks?	  
	  NO	  	  	  	  	  	  	   YES	  	  	  
 
 
 
IF	  NO,	  CODE	  NO	  TO	  A1b:	  	  IF	  YES	  ASK:	  
	  
	  
b	   For	  the	  past	  two	  weeks,	  were	  you	  depressed	  or	  down,	  most	  of	  the	  day,	  nearly	  every	  day?	  
NO	  
YES	  	  	  
	  
A2	  
a	   Were	  you	  ever	  much	  less	  interested	  in	  most	  things	  or	  much	  less	  able	  to	  
NO	   	  	  	  	  	  	   YES	  	  	  
	  
	  
enjoy	  the	  things	  you	  used	  to	  enjoy	  most	  of	  the	  time,	  for	  two	  weeks?	  
	  
	  
	  
IF	  NO,	  CODE	  NO	  TO	  A2b:	  	  IF	  YES	  ASK:	  
	  
	  
b	   In	  the	  past	  two	  weeks,	  were	  you	  much	  less	  interested	  in	  most	  things	  or	  
NO	  
YES	  	  	  
	  
	  
much	  less	  able	  to	  enjoy	  the	  things	  you	  used	  to	  enjoy,	  most	  of	  the	  time?	  
 
 
 
 
 
 
IS A1a	  OR	  A2a	  CODED	  YES?	  	  
NO	  
YES	  
 
 
A3	  
	  
IF	  A1b	  OR	  A2b	  =	  YES:	  EXPLORE	  THE	  CURRENT	  AND	  THE	  MOST	  SYMPTOMATIC	  PAST	  EPISODE,	  OTHERWISE	  
	  
	  
IF	  A1b	  AND	  A2b	  =	  NO:	  EXPLORE	  ONLY	  THE	  MOST	  SYMPTOMATIC	  PAST	  EPISODE	  
	  
	  
	  
Over	  that	  two	  week	  period,	  when	  you	  felt	  depressed	  or	  uninterested:	  
	  
	  
	  
Past	  2	  Weeks	  
Past	  Episode	  
	  
	  
a	   Was	  your	  appetite	  decreased	  or	  increased	  nearly	  every	  day?	  	  Did	  your	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
weight	  decrease	  or	  increase	  without	  trying	  intentionally	  (i.e.,	  by	  ±5%	  of	  	  
	  
	  
body	  weight	  or	  ±8	  lb	  or	  ±	  3.5	  kg,	  for	  a	  160	  lb/70	  kg	  person	  in	  a	  month)?	  	  	  
	  
	  
IF	  YES	  TO	  EITHER,	  CODE	  YES.	  
	  
	  
	  
	  
b	   Did	  you	  have	  trouble	  sleeping	  nearly	  every	  night	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
(difficulty	  falling	  asleep,	  waking	  up	  in	  the	  middle	  of	  the	  night,	  	  
	  
	  
early	  morning	  wakening	  or	  sleeping	  excessively)?	  
	  
	  
c	   Did	  you	  talk	  or	  move	  more	  slowly	  than	  normal	  or	  were	  you	  fidgety,	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
restless	  or	  having	  trouble	  sitting	  still	  almost	  every	  day?	  
	  
	  
d	   Did	  you	  feel	  tired	  or	  without	  energy	  almost	  every	  day?	  
NO	  
YES	  	  
NO	  
YES	  
	  
	  
	  
	  
e	   Did	  you	  feel	  worthless	  or	  guilty	  almost	  every	  day?	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
IF	  YES,	  ASK	  FOR	  EXAMPLES.	  
	  
	  
THE	  EXAMPLES	  ARE	  CONSISTENT	  WITH	  A	  DELUSIONAL	  IDEA. Current	  Episode	   ❐ No  ❐ Yes 
 
 
 
Past	  Episode 
❐ No  ❐ Yes 
 
 
f	  
Did	  you	  have	  difficulty	  concentrating	  or	  making	  decisions	  almost	  every	  day?	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
	  
g	   Did	  you	  repeatedly	  consider	  hurting	  yourself,	  feel	  suicidal,	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
or	  wish	  that	  you	  were	  dead?	  Did	  you	  attempt	  suicide	  or	  plan	  a	  suicide?	  
	  
	  
	  
	  
	  
	  
	  
	  
IF	  YES	  TO	  EITHER,	  CODE	  YES.	  
	  
A4	  
	  
Did	  these	  symptoms	  cause	  significant	  problems	  at	  home,	  at	  work,	  socially,	  	  	  	  	  	  	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  YES	  
	  	  	  	  	  	  	  NO	   	  	  	  	  	  	  	  YES	  
	  
	  
at	  school	  or	  in	  some	  other	  important	  way?	  	  
	  
A5	  
	  
In	  between	  2	  episodes	  of	  depression,	  did	  you	  ever	  have	  an	  interval	  	  
	  
	  
of	  at	  least	  2	  months,	  without	  any	  significant	  depression	  or	  any	  significant	  loss	  of	  interest?	  
	  	  	  	  	  	  	  NO	   	  	  	  	  	  	  	  YES	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
5 
 
 
            ARE	  5	  OR	  MORE	  ANSWERS	  (A1-­‐A3)	  CODED	  YES	  AND	  IS	  A4	  CODED	  YES	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  FOR	  THAT	  TIME	  FRAME?	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  SPECIFY	  IF	  THE	  EPISODE	  IS	  CURRENT	  AND	  /	  OR	  PAST.	  
	  
IF	  A5	  IS	  CODED	  YES,	  CODE	  YES	  FOR	  RECURRENT.	  
 
 
     NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
MAJOR	  DEPRESSIVE	  
EPISODE	  
 
CURRENT                 ❐  
	  	  	  	  	  	  PAST                       ❐ 
	  	  	  	  	  	  RECURRENT              ❐ 
   
	  
A6	  
a	   How	  many	  episodes	  of	  depression	  did	  you	  have	  in	  your	  lifetime?	  	  	  	  _____	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  
	  
Between	  each	  episode	  there	  must	  be	  at	  least	  2	  months	  without	  any	  significant	  depression. 
   
 
 
 
 
 
 
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
6 
B.  SUICIDALITY 
 
 
 
 
                Points	  
 
 
In	  the	  past	  month	  did	  you:	  
	  
B1	  
	  
Have	  any	  accident?	  This	  includes	  taking	  too	  much	  of	  your	  medication	  accidentally.	  
NO	  
YES	  
0	  
	  
	  
IF	  NO	  TO	  B1,	  SKIP	  TO	  B2;	  IF	  YES,	  ASK	  B1a:	  
	  
B1a	   	  
Plan	  or	  intend	  to	  hurt	  yourself	  in	  any	  accident	  either	  actively	  or	  passively	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
(e.g.	  by	  not	  avoiding	  a	  risk)?	  
NO	  
YES	  
0	  
	  
	  
IF	  NO	  TO	  B1a,	  SKIP	  TO	  B2:	  IF	  YES,	  ASK	  B1b:	  
	  
B1b	   	  
Intend	  to	  die	  as	  a	  result	  of	  any	  accident?	  
NO	  
YES	  
0	  
	  
B2	  
	  
Feel	  hopeless?	  
NO	  
YES	  
1	  
	  
B3	  
	  
Think	  that	  you	  would	  be	  better	  off	  dead	  or	  wish	  you	  were	  dead?	  
NO	  
YES	  
1	  
	  
B4	  
	  
Think	  about	  hurting	  or	  injuring	  yourself	  or	  have	  mental	  images	  of	  harming	  yourself,	  
NO	  
YES	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  4	  
with	  at	  least	  some	  intent	  or	  awareness	  that	  you	  might	  die	  as	  a	  result?	  
	  
	  
B5	  
	  
Think	  about	  suicide	  (killing	  yourself)?	  
NO	  
YES	  
6	  
	  
	  
IF	  NO	  TO	  B5,	  SKIP	  TO	  B7.	  	  OTHERWISE	  ASK:	  
	  
Frequency	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Intensity	  
 
Occasionally     ❐   
       Mild             ❐ 
Often      
❐              Moderate     ❐ 
 
  
	  
	  
Very	  often        ❐                  Severe         ❐ 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
                                           
B6   
Have	  difficulty	  restraining	  yourself	  from	  acting	  on	  these	  impulses?	  
	  
	  
	  
NO	  
YES	  
8	  
 
B7	  	   	  
Have	  a	  suicide	  method	  in	  mind	  (e.g.	  how)?	   	  
	  
	  	  	  
	  
	  
	  
NO	  
YES   
8	  
	  
B8	  	   	  
Have	  a	  suicide	  plan	  in	  mind	  (e.g.	  when	  or	  where)?	  
	  
	   	  	  
	  
	  
	  
NO	  
YES   
8	  
 
 
  
 
 
 
 
 
B9	  
	  
Intend	  to	  act	  on	  thoughts	  of	  killing	  yourself?	  
NO	  
YES	  
8	  
	  
B10	   	  
Intend	  to	  die	  as	  a	  result	  of	  a	  suicidal	  act?	  	  
NO	  
YES	  
8	  
	  
B11	   	  
Take	  any	  active	  steps	  to	  prepare	  to	  injure	  yourself	  or	  to	  prepare	  for	  	  
	  
	  
a	  suicide	  attempt	  in	  which	  you	  expected	  or	  intended	  to	  die?	  
NO	  
YES	  	  
9	  
	  
This	  includes	  times	  when	  you	  were	  going	  to	  kill	  yourself,	  but	  were	  
	  
interrupted	  or	  stopped	  yourself,	  before	  harming	  yourself.	  
	  
	  
IF	  NO	  TO	  B11,	  SKIP	  TO	  B12.	  
	  
B11a	  	  
Take	  active	  steps	  to	  prepare	  to	  kill	  yourself,	  but	  you	  did	  not	  start	  the	  suicide	  attempt?	  
NO	  
YES	  
	  
	  
	  
B11b	  	  
Start	  a	  suicide	  attempt,	  but	  then	  you	  stopped	  yourself	  before	  
	  
	  
harming	  yourself	  (aborted	  attempt)?	  
NO	  
YES	  
	  
B11c	  	  
Start	  a	  suicide	  attempt,	  but	  then	  someone	  or	  something	  stopped	  you	  before	  	  
	  
	  
harming	  yourself	  (interrupted	  attempt)?	  
NO	  
YES	  
	  
B12	   	  
Injure	  yourself	  on	  purpose	  without	  intending	  to	  kill	  yourself?	  
NO	  
YES	  
4	  
	  
B13	   	  
Attempt	  suicide	  (to	  kill	  yourself)?	  	  
	  
NO	  
YES	  
10	  
	  
	  
	  
A	  suicide	  attempt	  means	  you	  did	  something	  where	  you	  could	  possibly	  be	  injured,	  
	  
with	  at	  least	  a	  slight	  intent	  to	  die.	  
	  
	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
7 
	  
IF	  NO,	  SKIP	  TO	  B14:	  	  
	  
	  
 
Hope	  to	  be	  rescued	  /	  survive        ❐ 
 
 
Expected	  /	  intended	  to	  die            ❐ 
 
 
 
 
In	  your	  lifetime:	  
	  
B14	   	  
Did	  you	  ever	  make	  a	  suicide	  attempt	  (try	  to	  kill	  yourself)?	  
NO	  
YES	  
4	  
	  
	  
	  
“A	  suicide	  attempt	  is	  any	  self	  injurious	  behavior,	  with	  at	  least	  some	  intent	  (>	  0)	  to	  die	  as	  a	  result	  or	  if	  intent	  can	  be	  inferred,	  
e.g.	  if	  it	  is	  clearly	  not	  an	  accident	  or	  the	  individual	  thinks	  the	  act	  could	  be	  lethal,	  even	  though	  denying	  intent.”	  	  
	  
	  
(C-­‐CASA	  definition).	  	  Posner	  K	  et	  al.	  Am	  J	  Psychiatry	  164:7,	  July	  2007.	  
	  
	  
 
 
 
   IS	  AT	  LEAST	  1	  OF	  THE	  ABOVE	  (EXCEPT	  B1)	  CODED	  YES?	  
	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  IF	  YES,	  ADD	  THE	  TOTAL	  POINTS	  FOR	  THE	  ANSWERS	  (B1-­‐B14)	  	  
CHECKED	  ‘YES’	  AND	  SPECIFY	  THE	  SUICIDALITY	  SCORE	  AS	  INDICATED	  IN	  THE	  DIAGNOSTIC	  BOX:	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  
	  	  MAKE	  ANY	  ADDITIONAL	  COMMENTS	  ABOUT	  YOUR	  ASSESSMENT	  OF	  THIS	  PATIENT’S	  CURENT	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
AND	  NEAR	  FUTURE	  SUICIDALITY	  IN	  THE	  SPACE	  BELOW:	  	  
            
 
	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
SUICIDALITY	  
CURRENT	  
 
   1-­‐8	  points	  	  	  	  	  Low               ❐ 
   9-­‐16	  points	  	  	  Moderate     ❐ 
   >	  17	  points	  	  	  High              ❐ 
 
 
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
8 
C. MANIC	  AND	  HYPOMANIC	  EPISODES 
 
( MEANS	  :  GO	  TO	  THE	  DIAGNOSTIC	  BOXES,	  CIRCLE	  NO	  IN	  MANIC	  AND	  HYPOMANIC	  DIAGNOSTIC	  BOXES,	  AND	  MOVE	  TO	  NEXT	  MODULE) 
 
Do	  you	  have	  any	  family	  history	  of	  manic-­‐depressive	  illness	  or	  bipolar	  disorder,	  
or	  any	  family	  member	  who	  had	  mood	  swings	  treated	  with	  a	  medication	  like	  lithium,	  
NO	  
	  	  	  	  	  	  	  	  	  	  YES	  
	  
	  	  
	  
sodium	  valproate	  (Depakote)	  or	  lamotrigine	  (Lamictal)?	  	  	  
	  
	  
THIS	  QUESTION	  IS	  NOT	  A	  CRITERION	  FOR	  BIPOLAR	  DISORDER,	  BUT	  IS	  ASKED	  TO	  INCREASE	  	  
	  
	  
THE	  CLINICIAN’S	  VIGILANCE	  ABOUT	  THE	  RISK	  FOR	  BIPOLAR	  DISORDER.	  
IF	  YES,	  PLEASE	  SPECIFY	  WHO:________________________________________	  	  	  	  
	  
	  
C1	  
a	   Have	  you	  ever	  had	  a	  period	  of	  time	  when	  you	  were	  feeling	  'up'	  or	  'high'	  or	  ‘hyper’	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  NO	  	  	  	  	  	  	   YES	  	  	  
	  
	  
or	  so	  full	  of	  energy	  or	  full	  of	  yourself	  that	  you	  got	  into	  trouble,	  -­‐	  or	  that	  
	  
	  
other	  people	  thought	  you	  were	  not	  your	  usual	  self?	  	  (Do	  not	  consider	  
	  
	  
times	  when	  you	  were	  intoxicated	  on	  drugs	  or	  alcohol.)	  
	  
	  
	  
IF	  PATIENT	  IS	  PUZZLED	  OR	  UNCLEAR	  ABOUT	  WHAT	  YOU	  MEAN	  	  
	  
	  
BY	  'UP'	  OR	  'HIGH'	  OR	  ‘HYPER’,	  CLARIFY	  AS	  FOLLOWS:	  	  By	  'up'	  or	  'high'	  or	  ‘hyper’	  	  
	  
	  
I	  mean:	  having	  elated	  mood;	  increased	  energy;	  needing	  less	  sleep;	  having	  rapid	  	  
	  
	  
thoughts;	  being	  full	  of	  ideas;	  having	  an	  increase	  in	  productivity,	  motivation,	  
	  
	  
creativity,	  or	  impulsive	  behavior;	  phoning	  or	  working	  excessively	  or	  spending	  more	  money.	  
	  
	  
	  
IF	  NO,	  CODE	  NO	  TO	  C1b:	  	  IF	  YES	  ASK:	  
	  
	  
b	   Are	  you	  currently	  feeling	  ‘up’	  or	  ‘high’	  or	  ‘hyper’	  or	  full	  of	  energy?	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
NO	  
YES	  	  	  
	  
C2	  
a	   Have	  you	  ever	  been	  persistently	  irritable,	  for	  several	  days,	  so	  that	  you	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
NO	   	  	  	  	  	  	   YES	  	  	  
	  
	  
had	  arguments	  or	  verbal	  or	  physical	  fights,	  or	  shouted	  at	  people	  outside	  
	  
	  
your	  family?	  	  Have	  you	  or	  others	  noticed	  that	  you	  have	  been	  more	  irritable	  
	  
	  
or	  over	  reacted,	  compared	  to	  other	  people,	  even	  in	  situations	  that	  you	  felt	  
	  
	  
were	  justified?	  
	  
	  
	  
IF	  NO,	  CODE	  NO	  TO	  C2b:	  	  IF	  YES	  ASK:	  
	  
	  
b	   Are	  you	  currently	  feeling	  persistently	  irritable?	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
NO	  
YES   
 
 
 
 
	  
	  
IS	  C1a	  OR	  C2a	  CODED	  YES?	  	  
NO	  
YES	  
 
 
C3	  
	  
IF	  C1b	  OR	  C2b	  =	  YES:	  EXPLORE	  THE	  CURRENT	  AND	  THE	  MOST	  SYMPTOMATIC	  PAST	  EPISODE,	  OTHERWISE	  
	  
	  
IF	  C1b	  AND	  C2b	  =	  NO:	  EXPLORE	  ONLY	  THE	  MOST	  SYMPTOMATIC	  PAST	  EPISODE	  
	  
	  
During	  the	  times	  when	  you	  felt	  high,	  full	  of	  energy,	  or	  irritable	  did	  you:	  
	  
	  
	  
Current	  Episode	  
Past	  Episode	  
	  
	  
a	   Feel	  that	  you	  could	  do	  things	  others	  couldn't	  do,	  or	  that	  you	  were	  an	  
NO	  
YES	  
NO	  
YES	  
	  
	  
especially	  important	  person?	  IF	  YES,	  ASK	  FOR	  EXAMPLES.	  
	  
	  
THE	  EXAMPLES	  ARE	  CONSISTENT	  WITH	  A	  DELUSIONAL	  IDEA.	  
Current	  Episode ❐ No ❐ Yes 
 
 
 
Past	  Episode 
❐ No ❐ Yes 
 
 
b	   Need	  less	  sleep	  (for	  example,	  feel	  rested	  after	  only	  a	  few	  hours	  sleep)?	  
NO	  
YES	  
NO	  
YES	  
	  
	  
c	   Talk	  too	  much	  without	  stopping,	  or	  so	  fast	  that	  people	  had	  difficulty	  
NO	  
YES	  
NO	  
YES	  
	  
	  
understanding?	  
	  
	  
d	   Have	  racing	  thoughts?	  
NO	  
YES	  	  
NO	  
YES	  
	  
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Current	  Episode	  
Past	  Episode	  
 
	  
e	   Become	  easily	  distracted	  so	  that	  any	  little	  interruption	  could	  distract	  you?	  
NO	  
YES	  
NO	  
YES	  
	  
	  
f	  
Have	  a	  significant	  increase	  in	  your	  activity	  or	  drive,	  at	  work,	  at	  school,	  
NO	  
YES	  
NO	  
YES	  
	  
	  
socially	  or	  sexually	  or	  did	  you	  become	  physically	  or	  mentally	  restless?	  
	  
	  
g	   Want	  so	  much	  to	  engage	  in	  pleasurable	  activities	  that	  you	  ignored	  the	  risks	  or	   NO	  
YES	  
NO	  
YES	  
	  
	  
consequences	  (for	  example,	  spending	  sprees,	  reckless	  driving,	  or	  sexual	  	  
	  
	  
indiscretions)?	  
 
 
 
 
 
 
C3	  	  SUMMARY:	  	  WHEN	  RATING	  CURRENT	  EPISODE:	  
NO	  
YES	  
NO	  
YES	  
	  
	  
	  
IF	  C1b	  IS	  NO,	  ARE	  4	  OR	  MORE	  C3	  ANSWERS	  CODED	  YES?	  	  
	  
	  
	  
IF	  C1b	  IS	  YES,	  ARE	  3	  OR	  MORE	  C3	  ANSWERS	  CODED	  YES?	  
	  
	  
	  
WHEN	  RATING	  PAST	  EPISODE:	  
	  
	  
	  
IF	  C1a	  IS	  NO,	  ARE	  4	  OR	  MORE	  C3	  ANSWERS	  CODED	  YES?	  	  
	  
	  
	  
IF	  C1a	  IS	  YES,	  ARE	  3	  OR	  MORE	  C3	  ANSWERS	  CODED	  YES?	  
	  
	  
	  
CODE	  YES	  ONLY	  IF	  THE	  ABOVE	  3	  OR	  4	  SYMPTOMS	  OCCURRED	  DURING	  THE	  SAME	  TIME	  PERIOD.	  	  
	  
	  
	  
	  
	  
RULE:	  	  ELATION/EXPANSIVENESS	  REQUIRES	  ONLY	  THREE	  C3	  SYMPTOMS,	  WHILE	  	  
	  
	  
IRRITABLE	  MOOD	  ALONE	  REQUIRES	  4	  OF	  THE	  C3	  SYMPTOMS.	  
	  
	  
	  
	  
	  
C4	  
	  
What	  is	  the	  longest	  time	  these	  symptoms	  lasted?	  
a) 3	  days	  or	  less	  
❐    
❐ 
b) 4	  to	  6	  days	  
❐    
❐ 
c) 7	  days	  or	  more	  
❐    
❐ 
	  
C5	  
	  
Were	  you	  hospitalized	  for	  these	  problems?	  
NO	  
YES	  
NO	  
YES	  
	  
IF	  YES,	  CIRCLE	  YES	  IN	  MANIC	  EPISODE	  FOR	  THAT	  TIME	  FRAME	  AND	  GO	  TO	  C7.	  	  
	  
C6	  
	  
Did	  these	  symptoms	  cause	  significant	  problems	  at	  home,	  at	  work,	  socially	  	  
NO	  
YES	  
NO	  
YES	  
	  
	  
in	  your	  relationships	  with	  others,	  at	  school	  or	  in	  some	  other	  important	  way?	  
	  
 
 
            ARE	  C3	  SUMMARY	  AND	  C5	  AND	  C6	  CODED	  YES?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  OR	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  ARE	  C3	  SUMMARY	  AND	  C4c	  AND	  C6	  CODED	  YES	  AND	  IS	  C5	  CODED	  NO?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  SPECIFY	  IF	  THE	  EPISODE	  IS	  CURRENT	  AND	  /	  OR	  PAST. 
 
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
MANIC	  EPISODE	  
 
CURRENT                 ❐  
PAST                       ❐   
 
 
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
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IS	  C3	  SUMMARY	  CODED	  YES	  AND	  ARE	  C5	  AND	  C6	  CODED	  NO	  AND	  IS	  EITHER	  C4b	  OR	  C4C	  CODED	  YES?	  
	  
OR	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  ARE	  C3	  SUMMARY	  AND	  C4b	  AND	  C6	  CODED	  YES	  AND	  IS	  C5	  CODED	  NO?	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  SPECIFY	  IF	  THE	  EPISODE	  IS	  CURRENT	  AND	  /	  OR	  PAST.	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
IF	  YES	  TO	  CURRENT	  MANIC	  EPISODE,	  THEN	  CODE	  CURRENT	  HYPOMANIC	  EPISODE	  AS	  NO.	  	  
	  
IF	  YES	  TO	  PAST	  MANIC	  EPISODE,	  THEN	  CODE	  PAST	  HYPOMANIC	  EPISODE	  AS	  NOT	  EXPLORED.	  
	  
 
 
HYPOMANIC	  EPISODE	  
	  
 
CURRENT    ❐ 	  NO 
              ❐  YES 	  
	  
PAST         ❐ 	  NO 
              ❐ 	  YES	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  ❐  NOT	  EXPLORED    
 
 
 
 
          ARE	  C3	  SUMMARY	  AND	  C4a	  CODED	  YES	  AND	  IS	  C5	  CODED	  NO?	  
	  	  	  	  	  	  	  	  	  	  	  	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  SPECIFY	  IF	  THE	  EPISODE	  IS	  CURRENT	  AND	  /	  OR	  PAST.	  
	  
IF	  YES	  TO	  CURRENT	  MANIC	  EPISODE	  OR	  HYPOMANIC	  EPISODE,	  	  
THEN	  CODE	  CURRENT	  HYPOMANIC	  SYMPTOMS	  AS	  NO.	  	  
	  
IF	  YES	  TO	  PAST	  MANIC	  EPISODE	  OR	  YES	  TO	  PAST	  HYPOMANIC	  EPISODE,	  	  
THEN	  CODE	  PAST	  HYPOMANIC	  SYMPTOMS	  AS	  NOT	  EXPLORED.	  
 
 
 
	  HYPOMANIC	  SYMPTOMS	  
	  
 
CURRENT    ❐ 	  NO 
              ❐  YES	  
	  
PAST         ❐ 	  NO 
              ❐  YES    
              ❐ NOT	  EXPLORED 	  
 
	  
	  
C7	  
a)	  IF	  MANIC	  EPISODE	  IS	  POSITIVE	  FOR	  EITHER	  CURRENT	  OR	  PAST	  ASK:	  
Did	  you	  have	  2	  or	  more	  of	  these	  (manic)	  episodes	  lasting	  7	  days	  or	  more	  (C4c)	  in	  your	  	  
lifetime	  (including	  the	  current	  episode	  if	  present)?	  	  	  	  	  	  
NO	  	  	  	  	  	  YES	  
	  
	  
	   	  
	  
b)	  IF	  MANIC	  OR	  HYPOMANIC	  EPISODE	  IS	  POSITIVE	  FOR	  EITHER	  CURRENT	  OR	  PAST	  ASK:	  
Did	  you	  have	  2	  or	  more	  of	  these	  (hypomanic)	  episodes	  lasting	  just	  4	  to	  6	  days	  (C4b)	  	  
in	  your	  lifetime	  (including	  the	  current	  episode)?	  	  	  	  	  	  	  	  	  	  	  	  	  	  
NO	  	  	  	  	  	  YES	  
	  
	  
	  
	  
c)	  IF	  THE	  PAST	  “HYPOMANIC	  SYMPTOMS”	  CATEGORY	  IS	  CODED	  POSITIVE	  ASK:	  
	  
Did	  you	  have	  these	  hypomanic	  symptoms	  lasting	  only	  1	  to	  3	  days	  (C4a)	  2	  or	  more	  times	  	  
in	  your	  lifetime,	  (including	  the	  current	  episode	  if	  present)?	  	  	  
NO	  	  	  	  	  YES
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  
	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
11
	  
D.  PANIC	  DISORDER 
 
( MEANS	  :	  	  CIRCLE	  NO	  IN	  D5,	  D6	  AND	  D7	  AND	  	  SKIP	  TO	  E1)	  
 
 
 
 
 
D1	  
a	   Have	  you,	  on	  more	  than	  one	  occasion,	  had	  spells	  or	  attacks	  when	  you	  suddenly	  
NO	  
YES	  
	  
	  
	  
felt	  anxious,	  frightened,	  uncomfortable	  or	  uneasy,	  even	  in	  situations	  where	  most	  
	  
	  
people	  would	  not	  feel	  that	  way?	  	  	  
 
 
 
 
 
b	   Did	  the	  spells	  surge	  to	  a	  peak	  within	  10	  minutes	  of	  starting?	  
NO	  
YES 
 
 
 
 
 
 
 
 
D2	  
	  
At	  any	  time	  in	  the	  past,	  did	  any	  of	  those	  spells	  or	  attacks	  come	  on	  unexpectedly	  
NO	  
YES	  
	  
or	  occur	  in	  an	  unpredictable	  or	  unprovoked	  manner?	  
 
D3	  
Have	  you	  ever	  had	  one	  such	  attack	  followed	  by	  a	  month	  or	  more	  of	  persistent	   	  
	  
NO	  
YES	  
	  
concern	  about	  having	  another	  attack,	  or	  worries	  about	  the	  consequences	  of	  the	  attack	  -­‐	  
or	  did	  you	  make	  a	  significant	  change	  in	  your	  behavior	  because	  of	  the	  attacks	  (e.g.,	  shopping	  
only	  with	  a	  companion,	  not	  wanting	  to	  leave	  your	  house,	  visiting	  the	  emergency	  
room	  repeatedly,	  or	  seeing	  your	  doctor	  more	  frequently	  because	  of	  the	  symptoms)?	  	  	  
	  
D4	  
	  
During	  the	  worst	  attack	  that	  you	  can	  remember:	  
	  
	  
	  
	  
a	   Did	  you	  have	  skipping,	  racing	  or	  pounding	  of	  your	  heart?	  
NO	  
YES	  
	  
	  
	  
	  
	  
b	   Did	  you	  have	  sweating	  or	  clammy	  hands?	  
NO	  
YES	  
	  
	  
	  
	  
	  
c	   Were	  you	  trembling	  or	  shaking?	  
NO	  
YES	  
	  
	  
	  
d	   Did	  you	  have	  shortness	  of	  breath	  or	  difficulty	  breathing?	  
NO	  
YES	  
	  
	  
	  
	  
	  
e	   Did	  you	  have	  a	  choking	  sensation	  or	  a	  lump	  in	  your	  throat?	  
NO	  
YES	  
	  
	  
	  
	  
	  
f	  
Did	  you	  have	  chest	  pain,	  pressure	  or	  discomfort?	  
NO	  
YES	  
	  
	  
	  
	  
	  
g	   Did	  you	  have	  nausea,	  stomach	  problems	  or	  sudden	  diarrhea?	  
NO	  
YES	  
	  
	  
	  
	  
	  
h	   Did	  you	  feel	  dizzy,	  unsteady,	  lightheaded	  or	  faint?	  
NO	  
YES	  
	  
	  
	  
	  
	  
i	  
Did	  things	  around	  you	  feel	  strange,	  unreal,	  detached	  or	  unfamiliar,	  or	  did	  	  
NO	  
YES	  
	  
you	  feel	  outside	  of	  or	  detached	  from	  part	  or	  all	  of	  your	  body?	  
	  
	  
	  
	  
j	  
Did	  you	  fear	  that	  you	  were	  losing	  control	  or	  going	  crazy?	  
NO	  
YES	  
	  
	  
	  
	  
	  
k	   Did	  you	  fear	  that	  you	  were	  dying?	  
NO	  
YES	  
	  
	  
	  
	  
l	  
Did	  you	  have	  tingling	  or	  numbness	  in	  parts	  of	  your	  body?	  
NO	  
YES	  
	  
	  
	  
	  
	  
m	   Did	  you	  have	  hot	  flushes	  or	  chills?	  
NO	  
YES	  
	  
	  
	  
	  
D5	  
	  
ARE	  BOTH	  D3,	  AND	  4	  OR	  MORE	  D4	  ANSWERS,	  CODED	  YES?	  
NO	  
YES	  
IF	  YES	  TO	  D5,	  SKIP	  TO	  D7.	  	  
	  
PANIC	  DISORDER	  
LIFETIME	  
	  
D6	  
	  
IF	  D5	  =	  NO,	  ARE	  ANY	  D4	  ANSWERS	  CODED	  YES?	  
NO	  
YES	  
	  
	  
	  
THEN	  SKIP	  TO	  E1.	  
	  
LIMITED	  SYMPTOM	  
	  
	  
	  
	  
ATTACKS	  LIFETIME	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
12
	  
	  
D7	  
	  
In	  the	  past	  month,	  did	  you	  have	  such	  attacks	  repeatedly	  (2	  or	  more),	  and	  did	  you	  have	  
NO	  
YES	  
	  
	  
persistent	  concern	  about	  having	  another	  attack,	  or	  worry	  about	  the	  consequences	  
	  
PANIC	  DISORDER	  
	  	  
of	  the	  attacks,	  or	  did	  you	  change	  your	  behavior	  in	  any	  way	  because	  of	  the	  attacks?	  
	  
CURRENT	  
	  
	  
E.  AGORAPHOBIA 
 
 
E1	  
	  
Do	  you	  feel	  anxious	  or	  uneasy	  in	  places	  or	  situations	  where	  help	  might	  not	  be	  available	  	  
	  
	  
or	  escape	  might	  be	  difficult,	  like	  being	  in	  a	  crowd,	  standing	  in	  a	  line	  (queue),	  when	  you	  
	  
	  
are	  alone	  away	  from	  home	  or	  alone	  at	  home,	  or	  when	  crossing	  a	  bridge,	  or	  traveling	  
	  
	  
in	  a	  bus,	  train	  or	  car	  or	  where	  you	  might	  have	  a	  panic	  attack	  or	  the	  panic-­‐like	  
NO	  
YES	  
	  
	  
	  
symptoms	  we	  just	  spoke	  about?	  
	  
	  
	  
	  
IF	  E1	  =	  NO,	  CIRCLE	  NO	  IN	  E2.	  
	  
E2	  
	  
Do	  you	  fear	  these	  situations	  so	  much	  that	  you	  avoid	  them,	  or	  suffer	  
NO	  
YES	  
	  
	  
	  
through	  them,	  or	  need	  a	  companion	  to	  face	  them?	  
	  	  	  	  	  	  	  	  	  	  	  	  AGORAPHOBIA	  	  
	  
	  
	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  CURRENT	  	  
	  
	  
	  
	  
	  
	  
IS	  E2	  (CURRENT	  AGORAPHOBIA)	  CODED	  YES	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  IS	  D7	  (CURRENT	  PANIC	  DISORDER)	  CODED	  YES?	  
	    
	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
PANIC	  DISORDER	  
with	  Agoraphobia	  
CURRENT	    
 
	  
	  
	  
	  
IS	  E2	  (CURRENT	  AGORAPHOBIA)	  CODED	  NO	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  IS	  D7	  (CURRENT	  PANIC	  DISORDER)	  CODED	  YES?	  
	    
	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
PANIC	  DISORDER	  
without	  Agoraphobia	  
CURRENT	    
	  
	  
	  
	  
	  	  	  	  	  IS	  E2	  (CURRENT	  AGORAPHOBIA)	  CODED	  YES	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  IS	  D5	  (PANIC	  DISORDER	  LIFETIME)	  CODED	  NO?	  
	    
	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
AGORAPHOBIA,	  CURRENT	  
without	  history	  of	  
Panic	  Disorder	    
	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
13
F.  SOCIAL	  PHOBIA	  (Social	  Anxiety	  Disorder)	  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOX,	  CIRCLE	  NO	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE)	  
 
 
 
 
 
F1	  
	  
In	  the	  past	  month,	  did	  you	  have	  persistent	  fear	  and	  significant	  anxiety	  at	  being	  watched,	  
NO	  
YES	  
	  
	  
	  
being	  the	  focus	  of	  attention,	  or	  of	  being	  humiliated	  or	  embarrassed?	  	  This	  includes	  things	  like	  	  
	  
	  
speaking	  in	  public,	  eating	  in	  public	  or	  with	  others,	  writing	  while	  someone	  watches,	  	  
	  
	  
or	  being	  in	  social	  situations.	  
 
 
 
 
 
 
F2	  
	  
Is	  this	  social	  fear	  excessive	  or	  unreasonable	  and	  does	  it	  almost	  always	  make	  you	  anxious?	  
NO	  
YES	  
	  
 
 
 
 
 
F3	  
	  
Do	  you	  fear	  these	  social	  situations	  so	  much	  that	  you	  avoid	  them	  or	  suffer	  
NO	  
YES	  
	  
	  
	  
through	  them	  most	  of	  the	  time?	  
 
 
 
F4	  
Do	  these	  social	  fears	  disrupt	  your	  normal	  work,	  school	  or	  social	  functioning	  or	  cause	  	  	  	  	  	  	      
you	  significant	  distress?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  
SUBTYPES	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  Do	  you	  fear	  and	  avoid	  4	  or	  more	  social	  situations?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  If	  YES	  
Generalized	  social	  phobia	  (social	  anxiety	  disorder)	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  If	  NO	  
Non-­‐generalized	  social	  phobia	  (social	  anxiety	  disorder)	   	  
	  
EXAMPLES	  OF	  SUCH	  SOCIAL	  SITUATIONS	  TYPICALLY	  INCLUDE	  	  
• 
INITIATING	  OR	  MAINTAINING	  A	  CONVERSATION,	  	  
• 
PARTICIPATING	  IN	  SMALL	  GROUPS,	  	  
• 
DATING,	  	  
• 
SPEAKING	  TO	  AUTHORITY	  FIGURES,	  	  
• 
ATTENDING	  PARTIES,	  	  
• 
PUBLIC	  SPEAKING,	  	  
• 
EATING	  IN	  FRONT	  OF	  OTHERS,	  	  
• 
URINATING	  IN	  A	  PUBLIC	  WASHROOM,	  ETC.	  
	  
NOTE	  TO	  INTERVIEWER:	  PLEASE	  ASSESS	  WHETHER	  THE	  SUBJECT’S	  FEARS	  ARE	  RESTRICTED	  TO	  NON-­‐
GENERALIZED	  (“ONLY	  1	  OR	  SEVERAL”)	  SOCIAL	  SITUATIONS	  OR	  EXTEND	  TO	  GENERALIZED	  (“MOST”)	  SOCIAL	  
SITUATIONS.	  	  “MOST”	  SOCIAL	  SITUATIONS	  IS	  USUALLY	  OPERATIONALIZED	  TO	  MEAN	  4	  OR	  MORE	  SOCIAL	  
SITUATIONS,	  ALTHOUGH	  THE	  DSM-­‐IV	  DOES	  NOT	  EXPLICITLY	  STATE	  THIS. 
                                           
     NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
SOCIAL	  PHOBIA	  
(Social	  Anxiety	  Disorder)	  
CURRENT 
 
 
GENERALIZED       ❐ 
  
    NON-­‐GENERALIZED    ❐        
   
 
 
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
14
G.  OBSESSIVE-­‐COMPULSIVE	  DISORDER 
 
( MEANS:	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOX,	  CIRCLE	  NO	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE)	  
 
 
 
 
 
G1	  
	  
In	  the	  past	  month,	  have	  you	  been	  bothered	  by	  recurrent	  thoughts,	  impulses,	  or	  
NO	  
YES	  
	  
 
 
images	  that	  were	  unwanted,	  distasteful,	  inappropriate,	  intrusive,	  or	  distressing?	  -­‐ 
↓  
 
 
 
(For	  example,	  the	  idea	  that	  you	  were	  dirty,	  contaminated	  or	  had	  germs,	  or	  fear	  of	  	  
SKIP	  TO	  G4	  
	  
	  
contaminating	  others,	  or	  fear	  of	  harming	  someone	  even	  though	  it	  disturbs	  or	  distresses	  	  
	  
	  
you,	  or	  fear	  you	  would	  act	  on	  some	  impulse,	  or	  fear	  or	  superstitions	  that	  you	  would	  	  
	  
	  
be	  responsible	  for	  things	  going	  wrong,	  or	  obsessions	  with	  sexual	  thoughts,	  images	  
	  
	  
or	  impulses,	  or	  hoarding,	  collecting,	  or	  religious	  obsessions.)	  
	  
	  
	  
	  
	  
(DO	  NOT	  INCLUDE	  SIMPLY	  EXCESSIVE	  WORRIES	  ABOUT	  REAL	  LIFE	  PROBLEMS.	  	  DO	  NOT	  	  
	  
	  
INCLUDE	  OBSESSIONS	  DIRECTLY	  RELATED	  TO	  EATING	  DISORDERS,	  SEXUAL	  DEVIATIONS,	  	  
	  
	  
PATHOLOGICAL	  GAMBLING,	  OR	  ALCOHOL	  OR	  DRUG	  ABUSE	  BECAUSE	  THE	  PATIENT	  MAY	  	  
	  
	  
DERIVE	  PLEASURE	  FROM	  THE	  ACTIVITY	  AND	  MAY	  WANT	  TO	  RESIST	  IT	  ONLY	  BECAUSE	  OF	  	  
	  
	  
ITS	  NEGATIVE	  CONSEQUENCES.)	  
	  
 
G2	  
	  
Did	  they	  keep	  coming	  back	  into	  your	  mind	  even	  when	  you	  tried	  to	  ignore	  or	  	  
NO	  
YES	  
	  
	  
	  
get	  rid	  of	  them? 
↓  
 
 
 
 
SKIP	  TO	  G4	  
 
G3	  
	  
Do	  you	  think	  that	  these	  obsessions	  are	  the	  product	  of	  your	  own	  mind	  and	  that	  
NO	  
YES	  
	  
	  
they	  are	  not	  imposed	  from	  the	  outside? 
 
obsessions 	  	  	   
 
 
 
G4	  
	  
In	  the	  past	  month,	  did	  you	  do	  something	  repeatedly	  without	  being	  able	  to	  
NO	  
YES	  
	  
	  
resist	  doing	  it,	  like	  washing	  or	  cleaning	  excessively,	  counting	  or	  checking	  	  
	  
compulsions 	  	  	  	  
	  
	  
things	  over	  and	  over,	  or	  repeating,	  collecting,	  arranging	  things,	  or	  other	  
	  
	  
superstitious	  rituals?	  
	  
 
 
 
 
 
 
IS	  G3	  OR	  G4	  CODED	  YES? 
NO	  
YES 
 
 
 
 
G5	   	  
At	  any	  point,	  did	  you	  recognize	  that	  either	  these	  obsessive	  thoughts	  or	  these	  	  
NO	  
YES	  
	  
	  
	  
compulsive	  behaviors	  were	  excessive	  or	  unreasonable?	  
	  
	  
	  
	  
G6	  	  	  	  	  	  	  	  	  In	  the	  past	  month,	  did	  these	  obsessive	  thoughts	  and/or	  compulsive	  behaviors	  
significantly	  interfere	  with	  your	  normal	  routine,	  your	  work	  or	  school,	  your	  usual	  	  	  	  	  
social	  activities,	  or	  relationships,	  or	  did	  they	  take	  more	  than	  one	  hour	  a	  day?	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
O.C.D.	  
CURRENT	  
	  
 
SAMPLE
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
15
H.  POSTTRAUMATIC	  STRESS	  DISORDER	  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOX,	  CIRCLE	  NO,	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE) 
 
 
 
 
 
 
 
H1	  
	  
Have	  you	  ever	  experienced	  or	  witnessed	  or	  had	  to	  deal	  with	  an	  extremely	  traumatic	  
NO	  
YES	  
	  
	  
	  
event	  that	  included	  actual	  or	  threatened	  death	  or	  serious	  injury	  to	  you	  or	  someone	  else?	  
	  
	  
	  
EXAMPLES	  OF	  TRAUMATIC	  EVENTS	  INCLUDE:	  SERIOUS	  ACCIDENTS,	  SEXUAL	  OR	  PHYSICAL	  	  
	  
	  
ASSAULT,	  A	  TERRORIST	  ATTACK,	  BEING	  HELD	  HOSTAGE,	  KIDNAPPING,	  FIRE,	  DISCOVERING	  	  
	  
	  
A	  BODY,	  WAR,	  OR	  NATURAL	  DISASTER,	  	  WITNESSING	  THE	  VIOLENT	  OR	  SUDDEN	  DEATH	  OF	  	  
	  
	  
SOMEONE	  CLOSE	  TO	  YOU,	  OR	  A	  LIFE	  THREATENING	  ILLNESS.	  
 
 
 
 
H2	  
	  
Did	  you	  respond	  with	  intense	  fear,	  helplessness	  or	  horror?	  
NO	  
YES	  
	  
 
 
 
 
 
 
 
H3	  
	  
During	  the	  past	  month,	  have	  you	  re-­‐experienced	  the	  event	  in	  a	  distressing	  way	  
NO	  
YES	  
	  
	  
	  
(such	  as	  in	  dreams,	  intense	  recollections,	  flashbacks	  or	  physical	  reactions)	  or	  did	  you	  
	  
	  
have	  intense	  distress	  when	  you	  were	  reminded	  about	  the	  event	  or	  exposed	  to	  a	  similar	  event?	  
	  
 
H4	  
	  
In	  the	  past	  month:	  
	  
	  
a	   Have	  you	  avoided	  thinking	  about	  or	  talking	  about	  the	  event	  ?	  
NO	  
YES	  
	  
	  
	  
b	   Have	  you	  avoided	  activities,	  places	  or	  people	  that	  remind	  you	  of	  the	  event?	  
NO	  
YES	  
	  
	  
	  
	  
	  
c	   Have	  you	  had	  trouble	  recalling	  some	  important	  part	  of	  what	  happened?	  
NO	  
YES	  
	  
	  
	  
d	   Have	  you	  become	  much	  less	  interested	  in	  hobbies	  or	  social	  activities?	  
NO	  
YES	  
	  
	  
	  
e	   Have	  you	  felt	  detached	  or	  estranged	  from	  others?	  
NO	  
YES	  
	  
	  
	  
f	  
Have	  you	  noticed	  that	  your	  feelings	  are	  numbed?	  
NO	  
YES	  
	  
	  
	  
g	   Have	  you	  felt	  that	  your	  life	  will	  be	  shortened	  or	  that	  you	  will	  die	  sooner	  than	  other	  people?	  
NO	  
YES 
 
 
 
 
 
 
 
ARE	  3	  OR	  MORE	  H4	  ANSWERS	  CODED	  YES?	  
NO	  
YES	  
	  
H5	  
	  
In	  the	  past	  month:	  
	  
	  
a	   Have	  you	  had	  difficulty	  sleeping?	  
NO	  
YES	  
	  
	  
	  
b	   Were	  you	  especially	  irritable	  or	  did	  you	  have	  outbursts	  of	  anger?	  
NO	  
YES	  
	  
	  
	  
c	   Have	  you	  had	  difficulty	  concentrating?	  
NO	  
YES	  
	  
	  
	  
d	   Were	  you	  nervous	  or	  constantly	  on	  your	  guard?	  
NO	  
YES	  
	  
	  
	  
e	   Were	  you	  easily	  startled?	  
NO	  
YES	  
	  
 
 
 
 
 
 
ARE	  2	  OR	  MORE	  H5	  ANSWERS	  CODED	  YES?	  
NO	  
YES	  
	  
	  
	  
	  
	  
H6	  
	  	  	  	  	  	  	  During	  the	  past	  month,	  have	  these	  problems	  significantly	  interfered	  with	  
	  
	  	  	  	  	  	  	  your	  work,	  school	  or	  social	  activities,	  or	  caused	  significant	  distress?	  
	  	  	  	  	  	  	  	  	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
POSTTRAUMATIC	  
	  STRESS	  DISORDER	  
CURRENT	  
SAMPLE
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
16
I.  ALCOHOL	  DEPENDENCE	  /	  ABUSE	  	  
 
( MEANS:	  	  GO	  TO	  DIAGNOSTIC	  BOXES,	  CIRCLE	  NO	  IN	  BOTH	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE) 
 
 
 
 
 
  
 
 
I1	  
	  
In	  the	  past	  12	  months,	  have	  you	  had	  3	  or	  more	  alcoholic	  drinks,	  -­‐	  within	  a	  
NO	  
YES	  
	  
	  
	  
3	  hour	  period,	  -­‐	  on	  3	  or	  more	  occasions?	  
 
 
I2	  
	  
In	  the	  past	  12	  months:	  
	  
	  
a	   Did	  you	  need	  to	  drink	  a	  lot	  more	  in	  order	  to	  get	  the	  same	  effect	  that	  you	  got	  when	  you	  first	  
NO	  
YES	  
	  
	  
	  
started	  drinking	  or	  did	  you	  get	  much	  less	  effect	  with	  continued	  use	  of	  the	  same	  amount?	  
	  
	  
b	   When	  you	  cut	  down	  on	  drinking	  did	  your	  hands	  shake,	  did	  you	  sweat	  or	  feel	  agitated?	  	  Did	  
NO	  
YES	  
	  
	  
	  
you	  drink	  to	  avoid	  these	  symptoms	  (for	  example,	  "the	  shakes",	  sweating	  or	  agitation)	  
	  
	  
or	  to	  avoid	  being	  hungover?	  	  	  
	  
	  
IF	  YES	  TO	  ANY,	  CODE	  YES.	  
	  
	  
c	   During	  the	  times	  when	  you	  drank	  alcohol,	  did	  you	  end	  up	  drinking	  more	  than	  
NO	  
YES	  
	  
	  
	  
you	  planned	  when	  you	  started?	  
	  
	  
d	   Have	  you	  tried	  to	  reduce	  or	  stop	  drinking	  alcohol	  but	  failed?	  
NO	  
YES	  
	  
	  
	  
e	   On	  the	  days	  that	  you	  drank,	  did	  you	  spend	  substantial	  time	  obtaining	  
NO	  
YES	  
	  
	  
	  
alcohol,	  drinking,	  or	  recovering	  from	  the	  effects	  of	  alcohol?	  
	  
	  
f	  
Did	  you	  spend	  less	  time	  working,	  enjoying	  hobbies,	  or	  being	  with	  others	  
NO	  
YES	  
	  
	  
	  
because	  of	  your	  drinking?	  
	  
g	   	  If	  your	  drinking	  caused	  you	  health	  or	  mental	  problems,	  
NO	  
YES	  
	  
	  
	  
did	  you	  still	  keep	  on	  drinking?	  
	  
 
 
           ARE	  3	  OR	  MORE	  I2	  ANSWERS	  CODED	  YES?	  
 
                * IF	  YES,	  SKIP	  I3	  QUESTIONS	  AND	  GO	  TO	  NEXT	  MODULE.	  “DEPENDENCE	  PREEMPTS	  ABUSE”	  
IN	  DSM	  IV	  TR.      
                                       
     NO                      YES* 
	  
ALCOHOL	  DEPENDENCE	  
CURRENT	  
 
I3	  
	  
In	  the	  past	  12	  months:	  
	  
	  
a	   Have	  you	  been	  intoxicated,	  high,	  or	  hungover	  more	  than	  once	  when	  you	  had	  other	  	  
NO	  
YES	  
	  
	  
	  
responsibilities	  at	  school,	  at	  work,	  or	  at	  home?	  	  Did	  this	  cause	  any	  problems?	  	  	  
	  
	  
(CODE	  YES	  ONLY	  IF	  THIS	  CAUSED	  PROBLEMS.)	  
	  
	  
b	   Were	  you	  intoxicated	  more	  than	  once	  in	  any	  situation	  where	  you	  were	  physically	  at	  risk,	  
NO	  
YES	  
	  
	  
	  
for	  example,	  driving	  a	  car,	  riding	  a	  motorbike,	  using	  machinery,	  boating,	  etc.?	  
	  
	  
	  
	  
c	   Did	  you	  have	  legal	  problems	  more	  than	  once	  because	  of	  your	  drinking,	  for	  example,	  
NO	  
YES	  
	  
	  
	  
an	  arrest	  or	  disorderly	  conduct?	  
	  
	  
d	   If	  your	  drinking	  caused	  problems	  with	  your	  family	  or	  other	  people,	  
NO	  
YES	  
	  
	  
	  
did	  you	  still	  keep	  on	  drinking?	  
	  
SAMPLE
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
17
	  
	  
	  	  	  	  	  	  	   	  
	  
	  
ARE	  1	  OR	  MORE	  I3	  ANSWERS	  CODED	  YES?	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
ALCOHOL	  ABUSE	  
CURRENT	  
SAMPLE
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
18
J. 	  SUBSTANCE	  DEPENDENCE	  /	  ABUSE	  (NON-­‐ALCOHOL) 
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOXES,	  CIRCLE	  NO	  IN	  ALL	  DIAGNOSTIC	  BOXES,	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE) 
 
 
 
 
 
 
Now	  I	  am	  going	  to	  show	  you	  /	  read	  to	  you	  a	  list	  of	  street	  drugs	  or	  medicines.	  
	  
 
 
 
 
  
 
 
J1	  
a	   In	  the	  past	  12	  months,	  did	  you	  take	  any	  of	  these	  drugs	  more	  than	  once,	  	  
NO	  
YES	  
	  
	  
to	  get	  high,	  to	  feel	  elated,	  to	  get	  “a	  buzz”	  or	  to	  change	  your	  mood?	  
 
 
 
 
 
CIRCLE	  EACH	  DRUG	  TAKEN:	  
	  
	  
Stimulants:	  	  amphetamines,	  "speed",	  crystal	  meth,	  “crank”,	  "rush",	  Dexedrine,	  Ritalin,	  diet	  pills.	  
	  
	  
Cocaine:	  	  snorting,	  IV,	  freebase,	  crack,	  "speedball".	  	  	  
	  
	  
Narcotics:	  	  heroin,	  morphine,	  Dilaudid,	  opium,	  Demerol,	  methadone,	  Darvon,	  codeine,	  Percodan,	  Vicodin,	  OxyContin.	  	  	  
	  
	  
Hallucinogens:	  	  LSD	  ("acid"),	  mescaline,	  peyote,	  psilocybin,	  STP,	  "mushrooms",	  “ecstasy”,	  MDA,	  MDMA.	  
	  
	  
Phencyclidine:	  	  PCP	  ("Angel	  Dust",	  "Peace	  Pill",	  “Tranq”,	  “Hog”),	  or	  ketamine	  (“Special	  K”).	  
	  
	  
Inhalants:	  	  "glue",	  ethyl	  chloride,	  “rush”,	  nitrous	  oxide	  ("laughing	  gas"),	  amyl	  or	  butyl	  nitrate	  ("poppers").	  
	  
	  
Cannabis:	  	  marijuana,	  hashish	  ("hash"),	  THC,	  "pot",	  "grass",	  "weed",	  "reefer".	  	  	  
	  
	  
Tranquilizers:	  	  Quaalude,	  Seconal	  ("reds"),	  Valium,	  Xanax,	  Librium,	  Ativan,	  Dalmane,	  Halcion,	  barbiturates,	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
Miltown,	  GHB,	  Roofinol,	  “Roofies”.	  	  	  
	  
	  
Miscellaneous:	  	  steroids,	  nonprescription	  sleep	  or	  diet	  pills.	  	  Cough	  Medicine?	  Any	  others?	  	  
	  
	  
SPECIFY	  THE	  MOST	  USED	  DRUG(S):	  	  	  
	  
WHICH	  DRUG(S)	  CAUSE	  THE	  BIGGEST	  PROBLEMS?:	  	  	  
	  
FIRST	  EXPLORE	  THE	  DRUG	  CAUSING	  THE	  BIGGEST	  PROBLEMS	  AND	  MOST	  LIKELY	  TO	  MEET	  DEPENDENCE	  /	  ABUSE	  CRITERIA.	  
IF	  MEETS	  CRITERIA	  FOR	  ABUSE	  OR	  DEPENDENCE,	  SKIP	  TO	  THE	  NEXT	  MODULE.	  	  OTHERWISE,	  EXPLORE	  THE	  NEXT	  MOST	  PROBLEMATIC	  DRUG.	  
	  
	  
	  
	  
	  
J2	  
	  
Considering	  your	  use	  of	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED),	  in	  the	  past	  12	  months:	  
	  
	  
a	   Have	  you	  found	  that	  you	  needed	  to	  use	  much	  more	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED)	  
NO	  
YES	  
	  
	  
	  
	  to	  get	  the	  same	  effect	  that	  you	  did	  when	  you	  first	  started	  taking	  it?	  
	  
	  
b	   When	  you	  reduced	  or	  stopped	  using	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED),	  did	  you	  have	  	  
NO	  
YES	  
	  
	  
	  
withdrawal	  symptoms	  (aches,	  shaking,	  fever,	  weakness,	  diarrhea,	  nausea,	  sweating,	  	  
	  
	  
heart	  pounding,	  difficulty	  sleeping,	  or	  feeling	  agitated,	  anxious,	  irritable,	  or	  depressed)?	  
	  
	  
Did	  you	  use	  any	  drug(s)	  to	  keep	  yourself	  from	  getting	  sick	  (withdrawal	  symptoms)	  or	  so	  	  
	  
	  
that	  you	  would	  feel	  better?	  	  	  
	  
	  
	  
IF	  YES	  TO	  EITHER,	  CODE	  YES.	  
	  
	  
c	   Have	  you	  often	  found	  that	  when	  you	  used	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED),	  	  
NO	  
YES	  
	  
	  
	  
you	  ended	  up	  taking	  more	  than	  you	  thought	  you	  would?	  
	  
	  
d	   Have	  you	  tried	  to	  reduce	  or	  stop	  taking	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED)	  but	  failed?	  
NO	  
YES	  
	  
	  
	  
e	   On	  the	  days	  that	  you	  used	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED),	  did	  you	  spend	  substantial	  	  
NO	  
YES	  
	  
	  
	  
time	  (>2	  HOURS),	  obtaining,	  using	  or	  recovering	  from	  the	  drug,	  or	  thinking	  about	  the	  drug?	  
	  
f	  
Did	  you	  spend	  less	  time	  working,	  enjoying	  hobbies,	  or	  being	  with	  family	  
NO	  
YES	  
	  
	  
	  
or	  friends	  because	  of	  your	  drug	  use?	  
	  
	  
g	   If	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED)	  caused	  you	  health	  or	  mental	  problems,	  
NO	  	  	  	  	  	  	  	  YES	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
did	  you	  still	  keep	  on	  using	  it?	  
	  
	  
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	  	  	  	  	  	  	  	  	  	  	  	  	  	  ARE	  3	  OR	  MORE	  J2	  ANSWERS	  CODED	  YES?	  	  	  
	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  SPECIFY	  DRUG(S):	  __________________________________ 
            
*	  IF	  YES,	  SKIP	  J3	  QUESTIONS,	  MOVE	  TO	  NEXT	  DISORDER.	  	  	  
“DEPENDENCE	  PREEMPTS	  ABUSE”	  IN	  DSM	  IV	  TR.	  	  
	  	  	  	  	  
	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  *	  
	  
SUBSTANCE	  DEPENDENCE	  
CURRENT	  
	  
	  
	  
 
 
Considering	  your	  use	  of	  (NAME	  THE	  DRUG	  CLASS	  SELECTED),	  in	  the	  past	  12	  months:	  
	  
J3	  
a	   Have	  you	  been	  intoxicated,	  high,	  or	  hungover	  from	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED)	  	  
NO	  
YES	  
	  
	  
	  
more	  than	  once,	  when	  you	  had	  other	  responsibilities	  at	  school,	  at	  work,	  or	  at	  home?	  	  	  
	  
	  
Did	  this	  cause	  any	  problem?	  
	  
	  
	  
	  
	  
(CODE	  YES	  ONLY	  IF	  THIS	  CAUSED	  PROBLEMS.)	  
	  
	  
b	   Have	  you	  been	  high	  or	  intoxicated	  from	  (NAME	  OF	  DRUG	  /	  DRUG	  CLASS	  SELECTED)	  
NO	  
YES	  
	  
	  
	  
more	  than	  once	  in	  any	  situation	  where	  you	  were	  physically	  at	  risk	  (for	  example,	  	  
	  
	  
driving	  a	  car,	  riding	  a	  motorbike,	  using	  machinery,	  boating,	  etc.)?	  
	  
	  
c	   Did	  you	  have	  legal	  problems	  more	  than	  once	  because	  of	  your	  drug	  use,	  for	  example,	  
NO	  
YES	  
	  
	  
	  
an	  arrest	  or	  disorderly	  conduct?	  
	  
	  
d	   If	  (NAME	  OF	  DRUG	  /	  	  DRUG	  CLASS	  SELECTED)	  caused	  problems	  
NO	  	  	  	  	  	  	  	  	  YES	  
	  
	  
with	  your	  family	  or	  other	  people,	  did	  you	  still	  keep	  on	  using	  it?	  
 
 
  
 
 
       ARE	  1	  OR	  MORE	  J3	  ANSWERS	  CODED	  YES?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  SPECIFY	  DRUG(S): __________________________________ 
            
                                              
     NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
SUBSTANCE	  ABUSE	  
CURRENT	  
 
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K. PSYCHOTIC	  DISORDERS	  AND	  MOOD	  DISORDER	  WITH	  PSYCHOTIC	  FEATURES 
 
ASK	  FOR	  AN	  EXAMPLE	  OF	  EACH	  QUESTION	  ANSWERED	  POSITIVELY.	  	  CODE	  YES	  ONLY	  IF	  THE	  EXAMPLES	  CLEARLY	  SHOW	  A	  DISTORTION	  OF	  THOUGHT	  OR	  OF	  PERCEPTION	  OR	  IF	  THEY	  ARE	  NOT	  
CULTURALLY	  APPROPRIATE.	  	  BEFORE	  CODING,	  INVESTIGATE	  WHETHER	  DELUSIONS	  QUALIFY	  AS	  "BIZARRE".	  
	  
DELUSIONS	  ARE	  "BIZARRE"	  IF:	  CLEARLY	  IMPLAUSIBLE,	  ABSURD,	  NOT	  UNDERSTANDABLE,	  AND	  CANNOT	  DERIVE	  FROM	  ORDINARY	  LIFE	  EXPERIENCE.	  
HALLUCINATIONS	  ARE	  SCORED	  "BIZARRE"	  IF:	  A	  VOICE	  COMMENTS	  ON	  THE	  PERSON'S	  THOUGHTS	  OR	  BEHAVIOR,	  OR	  WHEN	  TWO	  OR	  MORE	  VOICES	  ARE	  CONVERSING	  WITH	  EACH	  OTHER.	  
THE	  PURPOSE	  OF	  THIS	  MODULE	  IS	  TO	  EXCLUDE	  PATIENTS	  WITH	  PSYCHOTIC	  DISORDERS.	  THIS	  MODULE	  NEEDS	  EXPERIENCE.	  
	  
	  
	  
Now	  I	  am	  going	  to	  ask	  you	  about	  unusual	  experiences	  that	  some	  people	  have.	  
	  
BIZARRE	   	  
	  
	  
	  
	  
	  
	  
K1	  
a	   Have	  you	  ever	  believed	  that	  people	  were	  spying	  on	  you,	  or	  that	  someone	  
NO	  
YES	  
YES	  
	  
	  
	  
	  
was	  plotting	  against	  you,	  or	  trying	  to	  hurt	  you?	  
	  
	  
	  
	  
	  
	  
NOTE:	  	  ASK	  FOR	  EXAMPLES	  TO	  RULE	  OUT	  ACTUAL	  STALKING.	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
b	  
IF	  YES	  OR	  YES	  BIZARRE:	  do	  you	  currently	  believe	  these	  things?	  
NO	  
YES	  
YES	  
 
 
 
 
 
 
 
  9	  K6  
 
 
 
 
 
 
 
 
K2	  
a	   Have	  you	  ever	  believed	  that	  someone	  was	  reading	  your	  mind	  or	  could	  hear	  
NO	  
YES	  
YES	  
	  
	  
	  
	  
your	  thoughts,	  or	  that	  you	  could	  actually	  read	  someone’s	  mind	  or	  hear	  what	  	  
	  
	  
	  
	  
	  
	  
another	  person	  was	  thinking?	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
b	  
IF	  YES	  OR	  YES	  BIZARRE:	  do	  you	  currently	  believe	  these	  things?	  
NO	  
YES	  
YES 
 
 
 
 
 
 
 
  9	  K6  
	  
	  
	  
	  
	  
	  
	  
K3	  
a	   Have	  you	  ever	  believed	  that	  someone	  or	  some	  force	  outside	  of	  yourself	  	  
NO	  
YES	  
YES	  
	  
	  
	  
	  
put	  thoughts	  in	  your	  mind	  that	  were	  not	  your	  own,	  or	  made	  you	  act	  in	  a	  
	  
	  
	  
	  
	  
	  
way	  that	  was	  not	  your	  usual	  self?	  	  Have	  you	  ever	  felt	  that	  you	  were	  
	  
	  
	  
	  
	  
	  
possessed?	  
	  
	  
	  
	  
	  
	  
CLINICIAN:	  	  ASK	  FOR	  EXAMPLES	  AND	  DISCOUNT	  ANY	  THAT	  ARE	  NOT	  PSYCHOTIC.	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
b	  
IF	  YES	  OR	  YES	  BIZARRE:	  do	  you	  currently	  believe	  these	  things?	  
NO	  
YES	  
YES 
 
 
 
 
 
 
 
  9	  K6  
 
 
 
 
 
 
  
K4	  
a	   Have	  you	  ever	  believed	  that	  you	  were	  being	  sent	  special	  messages	  through	  
NO	  
YES	  
YES	  
	  
	  
	  
	  
the	  TV,	  radio,	  internet,	  newspapers,	  books,	  or	  magazines	  or	  that	  a	  person	  
	  
	  
	  
	  
	  
	  
you	  did	  not	  personally	  know	  was	  particularly	  interested	  in	  you?	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
b	  
IF	  YES	  OR	  YES	  BIZARRE:	  do	  you	  currently	  believe	  these	  things?	  
NO	  
YES	  
YES 
 
 
 
 
 
 
 
  9	  K6  
 
 
 
 
 
 
 
K5	  
a	   Have	  your	  relatives	  or	  friends	  ever	  considered	  any	  of	  your	  beliefs	  odd	  
NO	  
YES	  
YES	  
	  
	  
	  
	  
or	  unusual?	  
	  
	  
	  
	  
	  
	  
INTERVIEWER:	  ASK	  FOR	  EXAMPLES.	  ONLY	  CODE	  YES	  IF	  THE	  EXAMPLES	  ARE	  CLEARLY	  	  
	  
	  
	  
	  
	  
	  
DELUSIONAL	  IDEAS	  NOT	  EXPLORED	  IN	  QUESTIONS	  K1	  TO	  K4,	  FOR	  EXAMPLE,	  SOMATIC	  OR	  RELIGIOUS	  
	  
	  
	  	  
	  
	  
	  
DELUSIONS	  OR	  DELUSIONS	  OF	  GRANDIOSITY,	  JEALOUSY,	  GUILT,	  RUIN	  OR	  DESTITUTION,	  ETC.	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
b	  
IF	  YES	  OR	  YES	  BIZARRE:	  do	  they	  currently	  consider	  your	  beliefs	  strange?	  
NO	  
YES	  
YES	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
K6	  
a	   Have	  you	  ever	  heard	  things	  other	  people	  couldn't	  hear,	  such	  as	  voices?	  
NO	  
YES	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
IF	  YES	  TO	  VOICE	  HALLUCINATION:	  Was	  the	  voice	  commenting	  on	  your	  
NO	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	   YES	  
	  	  
	  
	  
thoughts	  or	  behavior	  or	  did	  you	  hear	  two	  or	  more	  voices	  talking	  to	  each	  other?	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
b	  
IF	  YES	  OR	  YES	  BIZARRE	  TO	  K6a:	  have	  you	  heard	  sounds	  /	  voices	  in	  the	  past	  month?	  	  
NO	  
YES	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
IF	  YES	  TO	  VOICE	  HALLUCINATION:	  Was	  the	  voice	  commenting	  on	  your	  thoughts	  
NO	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	   YES	  
	  
or	  behavior	  or	  did	  you	  hear	  two	  or	  more	  voices	  talking	  to	  each	  other?	  
	  
	  
 9	  K8b  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
21
	  
K7	  
a	   Have	  you	  ever	  had	  visions	  when	  you	  were	  awake	  or	  have	  you	  ever	  seen	  things	  	  
NO	  
YES	  
	  
	  
	  
other	  people	  couldn't	  see?	  	  
	  
	  
CLINICIAN:	  CHECK	  TO	  SEE	  IF	  THESE	  ARE	  CULTURALLY	  INAPPROPRIATE.	  
	  
	  
b	  
IF	  YES:	  	  have	  you	  seen	  these	  things	  in	  the	  past	  month?	  
NO	  
YES	  
	  
	  
	  
	  
CLINICIAN'S	  JUDGMENT	  
	  
K8	  
b	  
IS	  THE	  PATIENT	  CURRENTLY	  EXHIBITING	  INCOHERENCE,	  DISORGANIZED	  	  
NO	  
YES	  
	  
	  
	  
SPEECH,	  OR	  MARKED	  LOOSENING	  OF	  ASSOCIATIONS?	  
	  
K9	  
b	  
IS	  THE	  PATIENT	  CURRENTLY	  EXHIBITING	  DISORGANIZED	  OR	  CATATONIC	  	  
NO	  
YES	  
	  
	  
	  
BEHAVIOR?	  
	  
K10	   b	  
ARE	  NEGATIVE	  SYMPTOMS	  OF	  SCHIZOPHRENIA,	  E.G.	  SIGNIFICANT	  AFFECTIVE	  	  
NO	  
YES	  
	  
	  
	  
FLATTENING,	  POVERTY	  OF	  SPEECH	  (ALOGIA)	  OR	  AN	  INABILITY	  TO	  INITIATE	  	  	  
	  
	  
OR	  PERSIST	  IN	  GOAL-­‐DIRECTED	  ACTIVITIES	  (AVOLITION),	  PROMINENT	  DURING	  	  
	  
	  
THE	  INTERVIEW?	  
	  
K11	   a	  
ARE	  1	  OR	  MORE	  «	  a	  »	  QUESTIONS	  FROM	  K1a	  TO	  K7a	  CODED	  YES	  OR	  YES	  BIZARRE	  	  
	  
	  
AND	  IS	  EITHER:	  
	  
	  
	  
	  
	  
MAJOR	  DEPRESSIVE	  EPISODE,	  (CURRENT,	  RECURRENT	  OR	  PAST)	  
	  
	  
	  
OR	  
	  
	  
	  
	  	  
MANIC	  OR	  HYPOMANIC	  EPISODE,	  (CURRENT	  OR	  PAST)	  CODED	  YES?	  
NO	  
YES	  
 
 
 
9	  	  K13 
 
	  
IF	  NO	  TO	  K11	  a,	  CIRCLE	  NO	  IN	  BOTH	  ‘MOOD	  DISORDER	  WITH	  PSYCHOTIC	  	  
	  
	  
FEATURES’	  DIAGNOSTIC	  BOXES	  AND	  MOVE	  TO	  K13.	  
 
	  
	  
	  	  	  	  	  	  	  	  b	  	  	  You	  told	  me	  earlier	  that	  you	  had	  period(s)	  when	  you	  felt	  (depressed/high/persistently	  	  
	  	  	  	  	  	  	  	  	  	  	  	  irritable).	  
	  
	  	  	  	  	  	  	  	  	  	  	  Were	  the	  beliefs	  and	  experiences	  you	  just	  described	  (SYMPTOMS	  CODED	  YES	  FROM	  K1a	  TO	  K7a)	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  restricted	  exclusively	  to	  times	  when	  you	  were	  feeling	  depressed/high/irritable?	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  	  	  	  	  	  	  	  	  IF	  THE	  PATIENT	  EVER	  HAD	  A	  PERIOD	  OF	  AT	  LEAST	  2	  WEEKS	  OF	  HAVING	  THESE	  BELIEFS	  OR	  EXPERIENCES	  
(PSYCHOTIC	  SYMPTOMS)	  WHEN	  THEY	  WERE	  NOT	  DEPRESSED/HIGH/IRRITABLE,	  CODE	  NO	  TO	  THIS	  DISORDER.	  	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  IF	  THE	  ANSWER	  IS	  NO	  TO	  THIS	  DISORDER,	  ALSO	  CIRCLE	  NO	  TO	  K12	  AND	  MOVE	  TO	  K13	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
	  
MOOD	  DISORDER	  WITH	  
	  	  	  	  PSYCHOTIC	  FEATURES	  
	  
LIFETIME	  
	  
	  
	  
K12	   a	  
ARE	  1	  OR	  MORE	  «	  b	  »	  QUESTIONS	  FROM	  K1b	  TO	  K7b	  CODED	  YES	  OR	  YES	  BIZARRE	  AND	  IS	  EITHER:	  
	  
	  
	  
	  
	  
MAJOR	  DEPRESSIVE	  EPISODE,	  (CURRENT)	  
	  
	  
	  
OR	  
	  
	  
	  	  
MANIC	  OR	  HYPOMANIC	  EPISODE,	  (CURRENT)	  CODED	  YES?	  
	  
	  
IF	  THE	  ANSWER	  IS	  YES	  TO	  THIS	  DISORDER	  (LIFETIME	  OR	  CURRENT),	  CIRCLE	  NO	  TO	  K13	  AND	  K14	  AND	  MOVE	  TO	  
THE	  NEXT	  MODULE.	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
	  
MOOD	  DISORDER	  WITH	  
	  	  	  	  PSYCHOTIC	  FEATURES	  
	  
CURRENT	  
 
 
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
22
	  
	  
	  K13	   	  	  	  	  	  ARE	  1	  OR	  MORE	  «	  b	  »	  QUESTIONS	  FROM	  K1b	  TO	  K6b,	  CODED	  YES	  BIZARRE?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  OR	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  ARE	  2	  OR	  MORE	  «	  b	  »	  QUESTIONS	  FROM	  K1b	  TO	  K10b,	  CODED	  YES	  (RATHER	  THAN	  YES	  BIZARRE)?	  
	  
	  
	  
AND	  DID	  AT	  LEAST	  TWO	  OF	  THE	  PSYCHOTIC	  SYMPTOMS	  OCCUR	  DURING	  THE	  SAME	  1	  MONTH	  PERIOD?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
PSYCHOTIC	  DISORDER	  
CURRENT	  
	  
	  
	  
	  
	  
	  K14	   	  	  	  	  IS	  K13	  CODED	  YES	  	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  OR	  	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  ARE	  1	  OR	  MORE	  «	  a	  »	  QUESTIONS	  FROM	  K1a	  TO	  K6a,	  CODED	  YES	  BIZARRE?	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  OR	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  ARE	  2	  OR	  MORE	  «	  a	  »	  QUESTIONS	  	  FROM	  K1a	  TO	  K7a,	  CODED	  YES	  (RATHER	  THAN	  	  YES	  BIZARRE)	  
	  
	  
	            
	  	  	  	  	  	  	  	  	  	  	  	  AND	  DID	  AT	  LEAST	  TWO	  OF	  THE	  PSYCHOTIC	  SYMPTOMS	  OCCUR	  DURING	  THE	  SAME	  1	  MONTH	  PERIOD?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
	  
	  
PSYCHOTIC	  DISORDER	  
LIFETIME	  
	  
	  
	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
23
L.  ANOREXIA	  NERVOSA  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOX,	  CIRCLE	  NO,	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE) 
 
L1	  
a	   How	  tall	  are	  you? 
❏ft ❏❏in. 
 
 
 
❏ ❏ ❏cm          
 
b.	  	  What	  was	  your	  lowest	  weight	  in	  the	  past	  3	  months? 
❏ ❏ ❏lb 
   
❏ ❏ ❏kg 
 
 
 
 
 
 
 
 
c	  
IS	  PATIENT’S	  WEIGHT	  EQUAL	  TO	  OR	  BELOW	  THE	  THRESHOLD	  CORRESPONDING	  TO	  
NO	  
YES	  
	  
	  
	  
	  
HIS	  /	  HER	  HEIGHT?	  	  (SEE	  TABLE	  BELOW) 
 
 
 
 
 
 
 
 
In	  the	  past	  3	  months:	  
	  
	  
	  
 
L2	  
	  
In	  spite	  of	  this	  low	  weight,	  have	  you	  tried	  not	  to	  gain	  weight?	  
NO	  
YES	  
	  
 
 
 
 
L3	  
	  
Have	  you	  intensely	  feared	  gaining	  weight	  or	  becoming	  fat,	  even	  though	  you	  were	  underweight?	   NO	  
YES	  
	  
 
L4	  
a	   Have	  you	  considered	  yourself	  too	  big	  /	  fat	  or	  that	  part	  of	  your	  body	  was	  too	  big	  /	  fat?	  
NO	  
YES	  
	  
	  
	  
b	   Has	  your	  body	  weight	  or	  shape	  greatly	  influenced	  how	  you	  felt	  about	  yourself?	  
NO	  
YES	  
	  
	  
	  
c	   Have	  you	  thought	  that	  your	  current	  low	  body	  weight	  was	  normal	  or	  excessive?	  
NO	  
YES	  
	  
 
 
 
 
L5	  
	  
ARE	  1	  OR	  MORE	  ITEMS	  FROM	  L4	  CODED	  YES?	  
NO	  
YES	  
 
 
 
 
L6	  
	  
FOR	  WOMEN	  ONLY:	  	  During	  the	  last	  3	  months,	  did	  you	  miss	  all	  your	  menstrual	  
NO	  
YES	  
	  
	  
	  
periods	  when	  they	  were	  expected	  to	  occur	  (when	  you	  were	  not	  pregnant)?	  
 
	  
	  
	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  FOR	  WOMEN:	  	  	  	  	  	  	  	  	  ARE	  L5	  AND	  L6	  CODED	  YES?	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  FOR	  MEN:	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  IS	  L5	  CODED	  YES?	  
	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
ANOREXIA	  NERVOSA	  
CURRENT	  
	  
HEIGHT	  /	  WEIGHT	  TABLE	  CORRESPONDING	  TO	  A	  BMI	  THRESHOLD	  OF	  17.5	  KG/M2	  	  
	  
Height/Weight	  
ft/in	  
4'9	  
4'10	  
4'11	  
5'0	  
5'1	  
5'2	  
5'3	  
5'4	  
5'5	  
5'6	  
5'7	  
5'8	  
5'9	  
5'10	  
lb	  
81	  
84	  
87	  
89	  
92	  
96	  
99	  
102	  
105	  
108	  
112	  
115	  
118	  
122	  
cm	  
145	  
147	  
150	  
152	  
155	  
158	  
160	  
163	  
165	  
168	  
170	  
173	  
175	  
178	  
kg	  
37	  
38	  
39	  
41	  
42	  
43	  
45	  
46	  
48	  
49	  
51	  
52	  
54	  
55	  
	  
	  
	  
	  
	  
Height/Weight	  
	  
ft/in	  
5'11	  
6'0	  
6'1	  
6'2	  
6'3	  
lb	  
125	  
129	  
132	  
136	  
140	  
	  
cm	  
180	  
183	  
185	  
188	  
191	  
	  
kg	  
57	  
59	  
60	  
62	  
64	  
The	  weight	  thresholds	  above	  are	  calculated	  using	  a	  body	  mass	  index	  (BMI)	  equal	  to	  or	  below	  17.5	  kg/m2	  for	  the	  patient's	  height.	  	  This	  is	  the	  
threshold	  guideline	  below	  which	  a	  person	  is	  deemed	  underweight	  by	  the	  DSM-­‐IV	  and	  the	  ICD-­‐10	  Diagnostic	  Criteria	  for	  Research	  for	  Anorexia	  
Nervosa.	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
24
M.	  	  BULIMIA	  NERVOSA	  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOXES,	  CIRCLE	  NO	  IN	  ALL	  DIAGNOSTIC	  BOXES,	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE)	  
 
 
 
 
 
M1	   	  
In	  the	  past	  three	  months,	  did	  you	  have	  eating	  binges	  or	  times	  when	  you	  ate	  	  
NO	  
YES	  
 
 
a	  very	  large	  amount	  of	  food	  within	  a	  2-­‐hour	  period?	  
	  
 
 
 
 
M2	   	  
In	  the	  last	  3	  months,	  did	  you	  have	  eating	  binges	  as	  often	  as	  twice	  a	  week?	  
NO	  
YES	  
	  
 
 
 
 
 
M3	   	  
During	  these	  binges,	  did	  you	  feel	  that	  your	  eating	  was	  out	  of	  control?	  
NO	  
YES	  
	  
 
 
 
 
M4	   	  
Did	  you	  do	  anything	  to	  compensate	  for,	  or	  to	  prevent	  a	  weight	  gain	  from	  these	  	  	  
NO	  
YES	  
	  
	  
	  
binges,	  like	  vomiting,	  fasting,	  exercising	  or	  taking	  laxatives,	  enemas,	  diuretics	  	  
	  
	  
(fluid	  pills),	  or	  other	  medications?	  
	  
	  
 
 
M5	   	  
Does	  your	  body	  weight	  or	  shape	  greatly	  influence	  how	  you	  feel	  about	  yourself?	  
NO	  
YES	  
	  
 
M6	   	  
DO	  THE	  PATIENT’S	  SYMPTOMS	  MEET	  CRITERIA	  FOR	  ANOREXIA	  NERVOSA?	  
NO	  
YES	  
	  
 
 
 
↓ 
 
 
 
Skip	  to	  M8	  
	  
	  
M7	   	  
Do	  these	  binges	  occur	  only	  when	  you	  are	  under	  (	  	  	  	  	  	  	  	  	  	  lb/kg)?	  
NO	  
YES	  
	  
	  
	  
INTERVIEWER:	  WRITE	  IN	  THE	  ABOVE	  PARENTHESIS	  THE	  THRESHOLD	  WEIGHT	  FOR	  THIS	  PATIENT’S	  	  
	  
	  
HEIGHT	  FROM	  THE	  HEIGHT	  /	  WEIGHT	  TABLE	  IN	  THE	  ANOREXIA	  NERVOSA	  MODULE.	  	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  
	  M8	  	  	  	  	  	  	  IS	  M5	  CODED	  YES	  AND	  IS	  EITHER	  M6	  OR	  M7	  CODED	  NO?	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
BULIMIA	  NERVOSA	  
CURRENT	  
	  
	  
	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  IS	  M7	  CODED	  YES?	  
	  
	  	  	  	  	  	  	  	  
	  
	  
	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	      
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
ANOREXIA	  NERVOSA	  
Binge	  Eating/Purging	  Type	  
CURRENT	  
	  
SAMPLE
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
25
N.	  	  GENERALIZED	  ANXIETY	  DISORDER	  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOX,	  CIRCLE	  NO,	  AND	  MOVE	  TO	  THE	  NEXT	  MODULE)	  
 
 
 
 
 
 
N1	  
a	   	  
Were	  you	  excessively	  anxious	  or	  worried	  about	  several	  routine	  things,	  
NO	  
YES	  
	  
	  
	  
	  
over	  the	  past	  6	  months?	  	  
	  
	  
	  
IN	  ENGLISH,	  IF	  THE	  PATIENT	  IS	  UNCLEAR	  ABOUT	  WHAT	  YOU	  MEAN,	  PROBE	  
	  
	  
	  
BY	  ASKING	  (Do	  others	  think	  that	  you	  are	  a	  “worry	  wart”?)	  AND	  GET	  EXAMPLES. 
 
 
 
 
 
 
	  
b	   	  
Are	  these	  anxieties	  and	  worries	  present	  most	  days?	  
NO	  
YES	  
 
 
 
 
 
 
 
 
 
 
ARE	  THE	  PATIENT’S	  ANXIETY	  AND	  WORRIES	  RESTRICTED	  EXCLUSIVELY	  	  
NO	  
YES	  
	  
	  
	  
	  
TO,	  OR	  BETTER	  EXPLAINED	  BY,	  ANY	  DISORDER	  PRIOR	  TO	  THIS	  POINT?	  
	  
 
 
 
 
 
N2	  
	  
	  
Do	  you	  find	  it	  difficult	  to	  control	  the	  worries?	  
NO	  
YES	  
	  
 
 
 
N3	  
	  
	  
FOR	  THE	  FOLLOWING,	  CODE	  NO	  IF	  THE	  SYMPTOMS	  ARE	  CONFINED	  TO	  	  
	  
	  
	  
FEATURES	  OF	  ANY	  DISORDER	  EXPLORED	  PRIOR	  TO	  THIS	  POINT.	  
	  
	  
	  
	  
	  
	  
	  
When	  you	  were	  anxious	  over	  the	  past	  6	  months,	  did	  you,	  most	  of	  the	  time:	  	  	  
	  
	  
	  
a	   Feel	  restless,	  keyed	  up	  or	  on	  edge?	  
NO	  
YES	  
	  
	  
	  
	  
b	   Have	  muscle	  tension?	  
NO	  
YES	  
	  
	  
	  
	  
c	   Feel	  tired,	  weak	  or	  exhausted	  easily?	  
NO	  
YES	  
	  
	  
	  
	  
d	   Have	  difficulty	  concentrating	  or	  find	  your	  mind	  going	  blank?	  
NO	  
YES	  
	  
	  
	  
	  
e	   Feel	  irritable?	  
NO	  
YES	  
	  
	  
	  
	  
f	   Have	  difficulty	  sleeping	  (difficulty	  falling	  asleep,	  waking	  up	  in	  the	  middle	  
NO	  
YES	  
	  
	  
	  
	  
of	  the	  night,	  early	  morning	  wakening	  or	  sleeping	  excessively)?	  
 
 
 
 
 
	  
	  
	  
ARE	  3	  OR	  MORE	  N3	  ANSWERS	  CODED	  YES?	  
NO	  
YES	  
	  
 
 
N4	  	   	  
Do	  these	  anxieties	  and	  worries	  disrupt	  your	  normal	  work,	  school	  or	  	  
	  
	  
social	  functioning	  or	  cause	  you	  significant	  distress?  
            
                                           
	  	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
GENERALIZED	  ANXIETY	  
DISORDER	  
CURRENT 
	  
O.	  	  RULE	  OUT	  MEDICAL,	  ORGANIC	  OR	  DRUG	  CAUSES	  FOR	  ALL	  DISORDERS	  
	  
	  
IF	  THE	  PATIENT	  CODES	  POSITIVE	  FOR	  ANY	  CURRENT	  DISORDER	  ASK:	  
	  
Just	  before	  these	  symptoms	  began:	  
	  
	  
O1a	  
Were	  you	  taking	  any	  drugs	  or	  medicines? 
❐ No      ❐ Yes	  
❐ Uncertain 
 
 
 
 
 
O1b	  
Did	  you	  have	  any	  medical	  illness? 
❐ No      ❐ Yes	  
❐ Uncertain 
 
 
 
 
 
 
IN	  THE	  CLINICIAN’S	  JUDGMENT:	  ARE	  EITHER	  OF	  THESE	  LIKELY	  TO	  BE	  DIRECT	  CAUSES	  OF	  THE	  PATIENT'S	  DISORDER?	  
	  
	  
IF	  NECESSARY	  ASK	  ADDITIONAL	  OPEN-­‐ENDED	  QUESTIONS.	  
	  
	  
	  
	  
	  
O2	  	  
SUMMARY:	  HAS	  AN	  ORGANIC	  CAUSE	  BEEN	  RULED	  OUT? 
 
❐ No      ❐ Yes      ❐ Uncertain	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
26
 
P.	  ANTISOCIAL	  PERSONALITY	  DISORDER	  	  
 
( MEANS	  :	  	  GO	  TO	  THE	  DIAGNOSTIC	  BOX	  AND	  CIRCLE	  NO) 
 
P1	  
	  
Before	  you	  were	  15	  years	  old,	  did	  you:	  
	  
	  
a	   	  repeatedly	  skip	  school	  or	  run	  away	  from	  home	  overnight?	  
NO	  
YES	  
	  
	  
	  
b	   	  repeatedly	  lie,	  cheat,	  "con"	  others,	  or	  steal?	  
NO	  
YES	  
	  
	  
	  
c	   	  start	  fights	  or	  bully,	  threaten,	  or	  intimidate	  others?	  
NO	  
YES	  
	  
	  
	  
d	   	  deliberately	  destroy	  things	  or	  start	  fires?	  
NO	  
YES	  
	  
	  
	  
e	   	  deliberately	  hurt	  animals	  or	  people?	  
NO	  
YES	  
	  
	  
	  
f	  
	  force	  someone	  to	  have	  sex	  with	  you?	  
NO	  
YES	  
	  
 
 
 
 
 
 
ARE	  2	  OR	  MORE	  P1	  ANSWERS	  CODED	  YES?	  	  
NO	  
YES	  
	  
	  
	  
	  
DO	  NOT	  CODE	  YES	  TO	  THE	  BEHAVIORS	  BELOW	  IF	  THEY	  ARE	  EXCLUSIVELY	  	  
	  
	  
POLITICALLY	  OR	  RELIGIOUSLY	  MOTIVATED.	  
	  
P2	  
	  
Since	  you	  were	  15	  years	  old,	  have	  you:	  
	  
	  
a	   repeatedly	  behaved	  in	  a	  way	  that	  others	  would	  consider	  irresponsible,	  like	  
NO	  
YES	  
	  
	  
	  
failing	  to	  pay	  for	  things	  you	  owed,	  deliberately	  being	  impulsive	  or	  deliberately	  
	  
	  
not	  working	  to	  support	  yourself?	  	  	  
	  
	  
b	   done	  things	  that	  are	  illegal	  even	  if	  you	  didn't	  get	  caught	  (for	  example,	  destroying	  
NO	  
YES	  
	  
	  
	  
property,	  shoplifting,	  stealing,	  selling	  drugs,	  or	  committing	  a	  felony)?	  
	  
	  
c	   been	  in	  physical	  fights	  repeatedly	  (including	  physical	  fights	  with	  your	  
NO	  
YES	  
	  
	  
	  
spouse	  or	  children)?	  
	  
	  
d	   often	  lied	  or	  "conned"	  other	  people	  to	  get	  money	  or	  pleasure,	  or	  lied	  just	  	  
NO	  
YES	  
	  
	  
	  
for	  fun?	  
	  
	  
e	   exposed	  others	  to	  danger	  without	  caring?	  
NO	  
YES	  
	  
	  
	  
f	  
felt	  no	  guilt	  after	  hurting,	  mistreating,	  lying	  to,	  or	  stealing	  from	  others,	  or	  
NO	  
YES	  
	  
	  
	  
after	  damaging	  property?	  
	  
	  
	  
	  
	  
	  
	  
ARE	  3	  OR	  MORE	  P2	  QUESTIONS	  CODED	  YES?	  
	  
	  
	  	  	  	  	  	  	  	  
	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	        
	  	  	  	  NO	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  YES	  
	  
ANTISOCIAL	  PERSONALITY	  
DISORDER	  
LIFETIME	  
	  
	  
	  
THIS	  CONCLUDES	  THE	  INTERVIEW	  
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
27
REFERENCES	  
	  
Sheehan	  DV,	  Lecrubier	  Y,	  Harnett-­‐Sheehan	  K,	  Janavs	  J,	  Weiller	  E,	  Bonara	  LI,	  Keskiner	  A,	  Schinka	  J,	  Knapp	  E,	  Sheehan	  MF,	  Dunbar	  GC.	  	  Reliability	  and	  
Validity	  of	  the	  MINI	  International	  Neuropsychiatric	  Interview	  (M.I.N.I.):	  According	  to	  the	  SCID-­‐P.	  	  European	  Psychiatry.	  1997;	  12:232-­‐241.	  	  
	  
Lecrubier	  Y,	  Sheehan	  D,	  Weiller	  E,	  Amorim	  P,	  Bonora	  I,	  Sheehan	  K,	  Janavs	  J,	  Dunbar	  G.	  	  The	  MINI	  International	  Neuropsychiatric	  Interview	  (M.I.N.I.)	  
A	  Short	  Diagnostic	  Structured	  Interview:	  Reliability	  and	  Validity	  According	  to	  the	  CIDI.	  European	  Psychiatry.	  	  1997;	  12:	  224-­‐231.	  
	  
Sheehan	  DV,	  Lecrubier	  Y,	  Harnett-­‐Sheehan	  K,	  Amorim	  P,	  Janavs	  J,	  Weiller	  E,	  Hergueta	  T,	  Baker	  R,	  Dunbar	  G:	  The	  Mini	  International	  Neuropsychiatric	  
Interview	  (M.I.N.I.):	  The	  Development	  and	  Validation	  of	  a	  Structured	  Diagnostic	  Psychiatric	  Interview.	  J.	  Clin	  Psychiatry,	  1998;59(suppl	  20):22-­‐33.	  
	  
Amorim	   P,	   Lecrubier	   Y,	   Weiller	   E,	   Hergueta	   T,	   Sheehan	   D:	   DSM-­‐III-­‐R	   Psychotic	   Disorders:	   procedural	   validity	   of	   the	   Mini	   International	  
Neuropsychiatric	  Interview	  (M.I.N.I.).	  	  Concordance	  and	  causes	  for	  discordance	  with	  the	  CIDI.	  	  European	  Psychiatry.	  	  1998;	  13:26-­‐34.	  
	  
Scientific	  committee	  for	  the	  MINI	  6.0.0:	  
A.	  Carlo	  Altamura,	  Milano,	  Italy	  
Cyril	  Hoschl,	  Praha,	  Czech	  Republic	  
George	  Papadimitriou,	  Athens,	  Greece	  
Hans	  Ågren,	  Göteborg,	  Sweden	  
Hans-­‐Jürgen	  Möller,	  München,	  Germany	  
Hans-­‐Ulrich	  Wittchen,	  Dresden,	  Germany	  
István	  Bitter,	  Budapest,	  Hungary	  
Jean-­‐Pierre	  Lépine,	  Paris,	  France	  
Jules	  Angst,	  Zurich,	  Switzerland	  
Julio	  Bobes,	  Oviedo,	  Spain	  
Luciano	  Conti,	  Pisa,	  Italy	  
Marelli	  Colon-­‐Soto	  MD,	  Puerto	  Rico,	  United	  States	  
Michael	  Van	  Ameringen	  MD,	  Toronto,	  Canada	  
Rosario	  Hidalgo	  MD,	  Tampa,	  United	  States	  
Siegfried	  Kasper,	  Vienna,	  Austria	  
Thomas	  Schlaepfer,	  Bonn,	  Germany	  
	  
	  
M.I.N.I.	  4.6/5.0,	  M.I.N.I.	  Plus	  4.6/5.0	  	  
Translations	  
M.I.N.I.	  4.4	  or	  earlier	  versions	  	  
	  
and	  M.I.N.I.	  Screen	  5.0:	  	  	  
Afrikaans	  	  
R.	  Emsley,	  W.	  Maartens	  
Arabic	  
	  
	  
O.	  Osman,	  E.	  Al-­‐Radi	  
Bengali	  
	  
	  
H.	  Banerjee,	  A.	  Banerjee	  
Braille	  (English)	  
Brazilian	  Portuguese	   	  P.	  Amorim	  
P.	  Amorim	  
Bulgarian	  	  
L.G.	  Hranov	  
Chinese	   	  
	  
L.	  Carroll,	  Y-­‐J.	  Lee,	  Y-­‐S.	  Chen,	  C-­‐C.	  Chen,	  C-­‐Y.	  Liu,	  	  
	  
	  
	  
C-­‐K.	  Wu,	  H-­‐S.	  Tang,	  K-­‐D.	  Juang,	  Yan-­‐Ping	  Zheng.	  	  	  
Czech	  
	  
	  
P.	  Svlosky	  
Danish	  
	  
P.	  Bech	  
P.	  Bech,	  T.	  Schütze	  
Dutch/Flemish	  
E.	  Griez,	  K.	  Shruers,	  T.	  Overbeek,	  K.	  Demyttenaere	  
I.	  Van	  Vliet,	  H.	  Leroy,	  H.	  van	  Megen	  
English	  
	  
D.	  Sheehan,	  J.	  Janavs,	  R.	  Baker,	  K.	  Harnett-­‐Sheehan,	  	  
D.	  Sheehan,	  R.	  Baker,	  J.	  Janavs,	  K.	  Harnett-­‐Sheehan,	  
	  
	  
E.	  Knapp,	  M.	  Sheehan	  
M.	  Sheehan	  
Estonian	   	  
	  
J.	  Shlik,	  A.	  Aluoja,	  E.	  Khil	  
Farsi/Persian	  
	  
K.	  Khooshabi,	  A.	  Zomorodi	  
Finnish	  	   	  
M.	  Heikkinen,	  M.	  Lijeström,	  O.	  Tuominen	  
M.	  Heikkinen,	  M.	  Lijeström,	  O.	  Tuominen	  
French	  
	  
Y.	  Lecrubier,	  E.	  Weiller,	  I.	  Bonora,	  P.	  Amorim,	  J.P.	  Lepine	  
Y.	  Lecrubier,	  E.	  Weiller,	  P.	  Amorim,	  T.	  Hergueta	  
German	   	  
I.	  v.	  Denffer,	  M.	  Ackenheil,	  R.	  Dietz-­‐Bauer	  	  
G.	  Stotz,	  R.	  Dietz-­‐Bauer,	  M.	  Ackenheil	  	  	  
Greek	  
	  
S.	  Beratis	  
T.	  Calligas,	  S.	  Beratis,	  GN	  Papidimitriou,	  T	  Matsoukas	  
	  
	  
	  
CR	  Soldatos	  
Gujarati	   	  
	  
M.	  Patel,	  B.	  Patel,	  Organon	  
Hebrew	   	  
J.	  Zohar,	  Y.	  Sasson	  
R.	  Barda,	  I.	  Levinson,	  A.	  Aviv	  
Hindi	  
	  
	  
C.	  Mittal,	  K.	  Batra,	  S.	  Gambhir,	  Organon	  
Hungarian	  
I.	  Bitter,	  J.	  Balazs	  	  
I.	  Bitter,	  J.	  Balazs	  
Icelandic	   	  
	  
J.G.	  Stefansson	  
Italian	  
	  
I.	  Bonora,	  L.	  Conti,	  M.	  Piccinelli,	  M.	  Tansella,	  G.	  Cassano,	  
L.	  Conti,	  A.	  Rossi,	  P.	  Donda	  
	  
	  
Y.	  Lecrubier,	  P.	  Donda,	  E.	  Weiller	  
Japanese	  	  
	  
T.	  Otsubo,	  H.	  Watanabe,	  H.	  Miyaoka,	  K.	  Kamijima,	  
	  
J.Shinoda,	  K.Tanaka,	  Y.	  Okajima	  
	  
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28
	  
Kannada	   	  
	  
Organon	  
Korean	  
	  
	  
K.S.	  Oh	  and	  Korean	  Academy	  of	  Anxiety	  Disorders	  	  
Latvian	  
	  
V.	  Janavs,	  J.	  Janavs,	  I.	  Nagobads	  
V.	  Janavs,	  J.	  Janavs	  
Lithuanian	  
	  
A.	  Bacevicius	  
Luganda	   	  
	  
WW.	  Muhweziosal,	  H.	  Agren	  
Malayalam	  
	  
Organon	  
Marathi	   	  
	  
Organon	  
Norwegian	  
G.	  Pedersen,	  S.	  Blomhoff	  
K.A.	  Leiknes	  ,	  U.	  Malt,	  E.	  Malt,	  S.	  Leganger	  
Polish	  
	  
M.	  Masiak,	  E.	  Jasiak	  
M.	  Masiak,	  E.	  Jasiak	  	  
Portuguese	  
P.	  Amorim	  
P.	  Amorim,	  T.	  Guterres	  
Punjabi	   	  
	  
A.	  Gahunia,	  S.	  Gambhir	  
Romanian	  
	  
O.	  Driga	  
Russian	   	  
	  
	  
A.	  Bystritsky,	  E.	  Selivra,	  M.	  Bystritsky,	  L.	  Shumyak,	  	  
	  
	  
	  
M.	  Klisinska.	  	  	  
Serbian	   	  
I.	  Timotijevic	  
I.	  Timotijevic	  
Setswana	  	  
K.	  Ketlogetswe	  
Slovenian	  	  	  
M.	  Kocmur	  
Spanish	   	  
L.	  Ferrando,	  J.	  Bobes-­‐Garcia,	  J.	  Gilbert-­‐Rahola,	  Y.	  Lecrubier	  
L.	  Ferrando,	  L.	  Franco-­‐Alfonso,	  M.	  Soto,	  J.	  Bobes-­‐	  
	  
	  
	  
	  
Garcia,	  O.	  Soto,	  L.	  Franco,	  G.	  Heinze,	  C.	  Santana,	  
	  
	  
	  
R.	  Hidalgo	  
Swedish	   	  
M.	  Waern,	  S.	  Andersch,	  M.	  Humble	  
C.	  Allgulander,	  H.	  Agren	  M.	  Waern,	  A.	  Brimse,	  M.	  Humble.	  
Tamil	  
	  
	  
Organon	  
Telugu	  
	  
	  
Organon	  
Thai	  	  
	  
	  
	  
P.	  Kittirattanapaiboon,	  S.	  Mahatnirunkul,	  P.	  Udomrat,	  	  
	  
	  
	  
	  
P.	  Silpakit,,	  M.	  Khamwongpin,	  S.	  Srikosai.	  
Turkish	  
	  
T.	  Örnek,	  A.	  Keskiner,	  I.	  Vahip	  
T.	  Örnek,	  A.	  Keskiner,	  A.Engeler	  
Urdu	  
	  
	  
S.	  Gambhir	  
Yiddish	  
	  
	  
	  
	  
	  
	  
	  
	  
J.	  Goldman,	  Chana	  Pollack,	  Myrna	  Mniewski	  
	  
A	  validation	  study	  of	  this	  instrument	  was	  made	  possible,	  in	  part,	  by	  grants	  from	  SmithKline	  Beecham	  and	  the	  European	  Commission.	  
The	  authors	  are	  grateful	  to	  Dr.	  Pauline	  Powers	  for	  her	  advice	  on	  the	  modules	  on	  Anorexia	  Nervosa	  and	  Bulimia.	  
	  
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29
 
MOOD	  DISORDERS:	  DIAGNOSTIC	  ALGORITHM	  
	  
	  
Consult	  Modules:	  
A	  
Major	  Depressive	  Episode	  
	  
	  
C	  
(Hypo)manic	  Episode	  
	  
	  
K	  
Psychotic	  Disorders	  
	  
	  
	  
MODULE	  K:	  
	  
	  
1a	   	   IS	  K11b	  CODED	  YES?	  
NO	  
YES	  
	  
	  
1b	  
IS	  K12a	  CODED	  YES?	  
NO	  
YES	  
	  
	  
	  
	  
	  
	  
	  
MODULES	  A	  and	  C:	  
Current	  
Past	  
	  
2	  
a	   CIRCLE	  YES	  IF	  A	  DELUSIONAL	  IDEA	  IS	  IDENTIFIED	  IN	  A3e 
YES 
YES 
 
 
	  	  	  	  	  	  	  	  	  b	  	  	  	  CIRCLE	  YES	  IF	  A	  DELUSIONAL	  IDEA	  IS	  IDENTIFIED	  IN	  C3a 
YES 
YES 
 
	  
	  	  	  	  	  	  
c	  	  	  	  Is	  a	  Major	  Depressive	  Episode	  coded	  YES	  (current	  or	  past)?	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  is	  Manic	  Episode	  coded	  NO	  (current	  and	  past)?	  
and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  is	  Hypomanic	  Episode	  coded	  NO	  (current	  and	  past)?	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  is	  “Hypomanic	  Symptoms”	  coded	  NO	  (current	  and	  past)?	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Specify:	  	  
• If	  the	  depressive	  episode	  is	  current	  or	  past	  or	  both	  
	  	  
• With	  Psychotic	  Features	  Current:	  If	  1b	  or	  2a	  (current)	  =	  YES	  	  
With	  Psychotic	  Features	  Past:	  If	  1a	  or	  2a	  (past)	  =	  YES	  	                                          
	  
MAJOR	  DEPRESSIVE	  
DISORDER	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  current	  	  	  	  past	  
MDD 
❏        ❏ 
	  
With	  Psychotic	  Features	  
Current 
 ❏ 
Past  
 ❏ 
 
 
 
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30
 
	  
	  
	  
d	  	  	  	  Is	  a	  Manic	  Episode	  coded	  YES	  (current	  or	  past)?	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
	  
	  	  	  Specify:	  
	  
• If	  the	  Bipolar	  I	  Disorder	  is	  current	  or	  past	  or	  both	  
	  
• With	  Single	  Manic	  Episode:	  If	  Manic	  episode	  (current	  or	  past)	  	  =	  YES	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  MDE	  (current	  and	  past)	  =	  NO	  
	  
• With	  Psychotic	  Features	  Current:	  If	  1b	  or	  2a	  (current)	  or	  2b	  (current)	  =	  YES	  	  
With	  Psychotic	  Features	  Past:	  If	  1a	  or	  2a	  (past)	  or	  2b	  (past)	  =	  YES	  	  
	  
• If	  the	  most	  recent	  episode	  is	  manic,	  depressed,	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  mixed	  or	  hypomanic	  or	  unspecified	  (all	  mutually	  exclusive)	  
	  
• Unspecified	  if	  the	  Past	  Manic	  Episode	  is	  coded	  YES	  AND	  	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Current	  (C3	  Summary	  AND	  C4a	  AND	  C6	  AND	  O2)	  are	  coded	  YES	  	  
	  
BIPOLAR	  I	  
DISORDER	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  current	  	  	  past	  
Bipolar	  I	  Disorder 
❏     ❏ 
Single	  Manic	  Episode ❏     ❏ 
	  
With	  Psychotic	  Features	  
Current 
 ❏ 
Past  
 ❏ 
 
Most	  Recent	  Episode	  
Manic 
 ❏ 
Depressed   
 ❏ 
Mixed 
 ❏ 
Hypomanic 
 ❏ 
Unspecified 
 ❏ 
 
 
 
	  	  	  	  	  	  	  	  	  	  e	  	  	  	  	  	  Is	  Major	  Depressive	  Episode	  coded	  YES	  (current	  or	  past)	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  
	  	  	  Is	  Hypomanic	  Episode	  coded	  YES	  (current	  or	  past)	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Is	  Manic	  Episode	  coded	  NO	  (current	  and	  past)?	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Specify:	  
	  
• If	  the	  Bipolar	  Disorder	  is	  current	  or	  past	  or	  both	  
	  	  
• If	  the	  most	  recent	  mood	  episode	  is	  hypomanic	  or	  depressed	  (mutually	  exclusive)	  
 
BIPOLAR	  II	  
DISORDER	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  current	  	  	  past	  
Bipolar	  II	  Disorder 
❏     ❏ 
 
Most	  Recent	  Episode	  
 
Hypomanic 
❏ 
Depressed	    
❏ 
 
 
 
 
	  
	  
f	  	  	  	  	  	  	  Is	  MDE	  coded	  NO	  (current	  and	  past)	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  
	  	  Is	  Manic	  Episode	  coded	  NO	  (current	  and	  past	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Is	  C4b	  coded	  YES	  for	  the	  appropriate	  time	  frame	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  	  
Is	  C7b	  coded	  YES?	  
___________________________________________________	  	  	  	  	  	  
	  
or	  
___________________________________________________	  
	  
Is	  Manic	  Episode	  coded	  NO	  (current	  and	  past)	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  
	  	  Is	  Hypomanic	  Episode	  coded	  NO	  (current	  and	  past)	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Is	  C4a	  coded	  YES	  for	  the	  appropriate	  time	  frame	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  and	  	  
Is	  C7c	  coded	  YES?	  
	  
Specify	  if	  the	  Bipolar	  Disorder	  NOS	  is	  current	  or	  past	  or	  both.   
	  
BIPOLAR	  	  
DISORDER	  NOS	  
	  
	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  current	  	  	  	  past	  
	  
Bipolar	  Disorder	  NOS ❏      ❏ 
 
SAMPLE
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M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
31
	  
M.I.N.I.	  PLUS	  
	  
The	  shaded	  modules	  below	  are	  additional	  modules	  available	  in	  the	  MINI	  PLUS	  beyond	  what	  is	  available	  in	  the	  standard	  MINI.	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  
The	  un-­‐shaded	  modules	  below	  are	  in	  the	  standard	  MINI.	  	  
	  
These	  MINI	  PLUS	  modules	  can	  be	  inserted	  into	  or	  used	  in	  place	  of	  the	  standard	  MINI	  modules,	  as	  dictated	  by	  the	  
specific	  needs	  of	  any	  study.	  
	  
	  
	  
	  
MODULES	  
TIME	  FRAME	  
	  
 
A	  
MAJOR	  DEPRESSIVE	  EPISODE	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
	  
Past	  
	  
	  
 
 
 
Recurrent	  
	  
	  
	  
	  
	  
MAJOR	  DEPRESSIVE	  DISORDER	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
Past	  
	  
	  
	  
	  
	  
Recurrent	  
	  
	  
	  
	  
	  
	  
MDE	  WITH	  MELANCHOLIC	  FEATURES	  	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
MDE	  WITH	  CATATONIC	  FEATURES	  	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
MDE	  WITH	  ATYPICAL	  FEATURES	  	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
	  
MAJOR	  DEPRESSIVE	  DISORDER	  WITH	  PSYCHOTIC	  FEATURES	  	  
Current	  
	  
	  
	  
	  
	  
Past	  
	  
	  
	  
 
	  
MINOR	  DEPRESSIVE	  DISORDER	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
(DEPRESSIVE	  DISORDER	  NOS)	  
Past	  
	  
	  
 
 
 
Recurrent	  
	  
	  
 
	  
 
 
MOOD DISORDER DUE TO A GENERAL MEDICAL CONDITION	  	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
	  
Past	  
	  
	  
 
 
 
SUBSTANCE INDUCED MOOD DISORDER	  	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
	  
Past	  
	  
	  
	  
AY	  
DYSTHYMIA	  
Current	  
	  
	  
	  
 
B	  
SUICIDALITY	  
Current	  (Past	  Month)	   	  
  
 
 
❏	  Low	  	  ❏	  Moderate	  	  ❏	  High	  
 
C	  
MANIC	  EPISODE	  
Current	  
	  
	  
	  
	  
	  
 
 
 
 
Past	  
	  
	  
 
HYPOMANIC	  EPISODE	  
Current	  
	  
	  
	  
	  
	  
 
 
 
 
Past	  
	  
	  
 
 
 
BIPOLAR	  I	  DISORDER	  
Current	  
	  
 
 
 
Past	  
	  
 
 
 
 
BIPOLAR	  II	  DISORDER	  
Current	  
	  
 
 
 
Past	  
	  
 
 
 
 
BIPOLAR	  DISORDER	  NOS	  
Current	  
	  
 
 
 
Past	  
	  
	  
	  
	  
	  
BIPOLAR	  I	  DISORDER	  WITH	  PSYCHOTIC	  FEATURES	  
Current	  
	  
	  
	  
	  
Past	  
	  
	  
 
 
 
MANIC EPISODE DUE TO A GENERAL MEDICAL CONDITION	  	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
Past	  
	  
	  
 
 
 
HYPOMANIC EPISODE DUE TO A GENERAL MEDICAL CONDITION	  	  Current	  (2	  weeks)	  
	  
	  
	  
	  
Past	  
	  
	  
 
 
 
SUBSTANCE INDUCED MANIC EPISODE	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
Past	  
	  
	  
 
 
 
 
 
SAMPLE
Page 102


M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
32
 
 
SUBSTANCE INDUCED HYPOMANIC EPISODE	  
Current	  (2	  weeks)	  
	  
	  
	  
	  
Past	  
	  
	  
	  
	  
MOOD	  DISORDER	  NOS	  
Lifetime	  	  
	  
	  
	  
D	  
PANIC	  DISORDER	  
Current	  (Past	  Month)	   	  
 
 
 
Lifetime	  
	  
	  
 
 
 
ANXIETY DISORDER WIITH PANIC ATTACKS DUE TO	  
	  
	  
A GENERAL MEDICAL CONDITION	  
Current	  
	  
	  
 
 
 
SUBSTANCE INDUCED ANXIETY DISORDER WITH PANIC ATTACKS	  Current	  
	  
	  
 
E	  
AGORAPHOBIA	  
Current	  
	  
 
	  
F	  
SOCIAL	  PHOBIA	  (Social	  Anxiety	  Disorder)	  
Current	  (Past	  Month)	  
	  
	  
Generalized	  
	  
 
 
 
Non-­‐Generalized	  
	  
 
 
FA	   SPECIFIC	  PHOBIA	  
Current	  
	  
 
	  
G	  
OBSESSIVE-­‐COMPULSIVE	  DISORDER	  (OCD)	  
Current	  (Past	  Month)	   	  
	  
	  
 
OCD DUE TO A GENERAL MEDICAL CONDITION	  	  
Current	  	  
	  
	  
	  
	  
	  
 
SUBSTANCE INDUCED OCD	  
Current	  
	  
	  
	  
	  
	  
H	  
POSTTRAUMATIC	  STRESS	  DISORDER	  
Current	  (Past	  Month)	   	  
	  
HL	   POSTTRAUMATIC	  STRESS	  DISORDER	  
Lifetime	  
	  
	  
 
 
I	  
ALCOHOL	  DEPENDENCE	  
Past	  12	  Months	  
	  
	  
 
ALCOHOL	  ABUSE	  
Past	  12	  Months	  
	  
	  
	  
IL	  
ALCOHOL	  DEPENDENCE	  
Lifetime	  	  
	  
	  
	  
ALCOHOL	  ABUSE	  
Lifetime	  	  
	  
	  
 
J	  
SUBSTANCE	  DEPENDENCE	  (Non-­‐alcohol)	  
Past	  12	  Months	  
	  
	  
	  
SUBSTANCE	  ABUSE	  (Non-­‐alcohol)	  
Past	  12	  Months	  
	  
	  
 
JL 
SUBSTANCE	  DEPENDENCE	  (Non-­‐alcohol)	  
Lifetime	  
	  
	  
	  
SUBSTANCE	  ABUSE	  (Non-­‐alcohol)	  
Lifetime	  	  
	  
 
	  
K	  
PSYCHOTIC	  DISORDERS	  
Lifetime	  	  
	  
	  
	  
	  
Current	  
	  
	  
 
 
 
 
	  
 
MOOD	  DISORDER	  WITH	  PSYCHOTIC	  FEATURES	  
Current 
 
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
MOOD	  DISORDER	  WITH	  PSYCHOTIC	  FEATURES	  
Lifetime 
 
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
SCHIZOPHRENIA	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
SCHIZOAFFECTIVE	  DISORDER	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
SCHIZOPHRENIFORM	  DISORDER	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
BRIEF	  PSYCHOTIC	  DISORDER	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
DELUSIONAL	  DISORDER	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
PSYCHOTIC	  DISORDER	  DUE	  TO	  A	  GENERAL	  MEDICAL	  CONDITION	  	   Current	  
	  
	  
	  
	  
Lifetime	  
	  
	  
SAMPLE
Page 103


M.I.N.I.	  6.0.0	  (October	  10,	  2010)	  (10/10/10)	  
33
	  
	  
	  
	  
	  
	  
SUBSTANCE	  INDUCED	  PSYCHOTIC	  DISORDER	  
Current	  
	  
	  
	  
	  
Lifetime	  
	  
	  
	  
	  
PSYCHOTIC	  DISORDER	  NOS	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
L	  
ANOREXIA	  NERVOSA	  
Current	  (Past	  3	  Months)	  
 
	  
M	  
BULIMIA	  NERVOSA	  
Current	  (Past	  3	  Months)	  
	  
	  
	  
BULMIA	  NERVOSA,	  PURGING	  TYPE	  
Current	  
	  
	  
	  
	  
BULMIA	  NERVOSA,	  NON-­‐PURGING	  TYPE	  
Current	  
	  
 
 
 
ANOREXIA	  NERVOSA,	  BINGE	  EATING/PURGING	  TYPE	  
Current	  
	  
	  
	  
 
ANOREXIA	  NERVOSA,	  RESTRICTING	  TYPE	  
Current	  
	  
	  
 
N	  
GENERALIZED	  ANXIETY	  DISORDER	  (GAD)	  
Current	  (Past	  6	  Months)	  
	  
	  
 
GAD DUE TO A GENERAL MEDICAL CONDITION	  	  
Current	  
	  
 
 
SUBSTANCE INDUCED GAD	  
Current	  
	  
	  
	  
O	  
SOMATIZATION	  DISORDER	  
Current	  
	  
	  
	  
	  
Lifetime	  	  
	  
	  
	  
	  
	  
P	  
HYPOCHONDRIASIS	  
Current	  
	  
	  
	  
Q	  
BODY	  DYSMORPHIC	  DISORDER	  
Current	  
	  
	  
	  
R	  
PAIN	  DISORDER	  
Current	  
	  
	  
	  
S	  
CONDUCT	  DISORDER	  
Current	  (past	  12	  months)	   	  
	  
T	  
ATTENTION	  DEFICIT/	  HYPERACTIVITY	  DISORDER	  
Current	  (Past	  6	  months)	  (Children	  /Adolescents)	  
	  
	  
	  
ADHD	  COMBINED   
 
 
 
 
 
 
ADHD	  INATTENTIVE   
 
 
 
 
 
 
ADHD	  HYPERACTIVE	  /	  IMPULSIVE   
 
 
 
 
TA	   ATTENTION	  DEFICIT/	  HYPERACTIVITY	  DISORDER	  
Current	  (Past	  6	  months)	  (Adults)	  
 
 
 
ADHD	  COMBINED   
 
 
 
 
 
 
ADHD	  INATTENTIVE   
 
 
 
 
 
 
ADHD	  HYPERACTIVE	  /	  IMPULSIVE   
 
 
 
	  
U	  
PREMENSTRUAL	  	  DYSPHORIC	  DISORDER	  
Current	  
	  
	  
 
V	  
MIXED	  ANXIETY	  DEPRESSIVE	  DISORDER	  
Current	  
	  
	  
 
W	  	   ADJUSTMENT	  DISORDERS	  
Current	  
	  
 
 
X 
MEDICAL,	  ORGANIC,	  DRUG	  CAUSE	  RULED	  OUT	  
	  
	  
	  
	  
 
Y	  
ANTISOCIAL	  PERSONALITY	  DISORDER	  
Lifetime	  
	  
 
 
 
SAMPLE
Page 104


Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX B. SAMPLE READINESS TO CHANGE QUESTIONNAIRE 
Page 105


 
SAMPLE READINESS TO CHANGE QUESTIONNAIRE 
0=strongly agree; 1=agree; 2=unsure; 3=disagree; 4=strongly disagree 
1. I don’t think I drink too much 
0  
1  
2  
3  
4 
 
2. I am trying to drink less than I used to 
0  
1  
2  
3  
4 
 
3. I enjoy my drinking, but sometimes  
0  
1  
2  
3  
4 
I drink too much 
 
4. Sometimes I think I should cut  
0  
1  
2  
3  
4 
down on my drinking 
 
5. It’s a waste of time thinking about my drinking 
0  
1  
2  
3  
4 
 
6. I have just recently changed my drinking habits 
0  
1  
2  
3  
4 
 
7. Anyone can talk about wanting to do something 
0  
1  
2  
3  
4 
about drinking, but I am actually doing 
something about it 
 
8. I am at the stage where I should think about 
drinking alcohol less 
0  
1  
2  
3  
4 
 
9. My drinking is a problem sometimes 
0  
1  
2  
3  
4 
 
10. There is no need for me to think about  
0  
1  
2  
3  
4 
changing my drinking 
 
11. I am actually changing my  
0  
1  
2  
3  
4 
drinking habits right now 
 
12. Drinking less alcohol would be pointless for me 
0  
1  
2  
3  
4 
SAMPLE
Page 106


Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX C. SAMPLE POSITIVE AND NEGATIVE SYNDROME 
SCALE 
Page 107


Lewis A. Opler, M.D., Ph.D.
Stanley R. Kay, Ph.D.
J.P. Lindenmayer, M.D., &
Abraham Fiszbein, M.D.
Structured Clinical Interview –
Positive and Negative
Syndrome Scale
S C I - P A N S S
SCI-PANSS
SAMPLE
Page 108


Page 2
SCI–PANSS BOOKLET
PAGE 2
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 1-800-456-3003.
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 1-800-268-6011. Internationally, +1-416-492-2627. Fax, +1-416-492-3343 or 1-888-540-4484.
SAMPLE
Page 109


Page 3
SCI–PANSS BOOKLET
PAGE 3
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
Structured Clinical Interview for the Positive and Negative Syndrome Scale
SCI-PANSS
L. A. Opler, M.D., Ph.D.        S. R. Kay, Ph.D.        J. P. Lindenmayer, M.D.      A. Fiszbein, M.D.
Patient Name or ID: ______________________________________________________________________
Interviewer: ____________________________________________________   Date: _____ / _____ / _____
Data on “Lack of Spontaneity and Flow of Conversation” (N6),
“Poor Rapport” (N3), and “Conceptual Disorganization” (P2)
Hi, I’m ... We’re going to be spending the next 30 to 40 minutes talking about you and your reasons for being here. Maybe you
can start out by telling me something about yourself and your background?
(Instruction to interviewer: Allow at least 5 minutes for a non-directive phase serving to establish rapport in the context of an
overview before proceeding to the specific questions listed below.)
Data on “Anxiety” (G2)
1.
Have you been feeling worried or nervous in the past week? _________________________________
IF YES, skip to question 3. IF NO, continue.
2.
Would you say that you’re usually calm and relaxed? ______________________________________
IF YES, skip to question 8. IF NO, continue.
3.
What’s been making you feel nervous (worried, not calm, not relaxed)? ________________________
4.
Just how nervous (worried, etc.) have you been feeling? ____________________________________
5.
Have you been shaking at times, or has your heart been racing? ______________________________
6.
Do you get into a state of panic? _______________________________________________________
7.
Has your sleep, eating, or participation in activities been affected? ____________________________
Data on “Delusions (General)” (PI) and “Unusual Thought Content” (G9)
8.
Have things been going well for you? ___________________________________________________
9.
Has anything been bothering you lately? _________________________________________________
10.
Can you tell me something about your thoughts on life and its purpose? ________________________
SAMPLE
Page 110
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PPD
PPD
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Page 4
SCI–PANSS BOOKLET
PAGE 4
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
11.
Do you follow a particular philosophy (any special rules, teachings, or religious doctrine)? ____________
12.
Some people tell me they believe in the Devil; what do you think? ____________________________
IF NO (i.e., he/she doesn’t believe in the Devil), skip to question 14.
IF YES (i.e., he/she does believe), continue.
13.
Can you tell me more about this?_______________________________________________________
14.
Can you read other people’s minds? ____________________________________________________
IF NO, skip to question 16. IF YES, continue.
15.
How does that work? ________________________________________________________________
16.
Can others read your mind? ___________________________________________________________
IF NO, skip to question 19. IF YES, continue.
17.
How can they do that? _______________________________________________________________
18.
Is there any reason that someone would want to read your mind? _____________________________
19.
Who controls your thoughts? __________________________________________________________
Data on “Suspiciousness/Persecution” (P6) and “Poor Impulse Control” (GI4)
20.
How do you spend your time these days? ________________________________________________
21.
Do you prefer to be alone? ____________________________________________________________
22.
Do you join in activities with others? ___________________________________________________
IF YES, skip to question 25. IF NO, continue.
23.
Why not? ... Are you afraid of people, or do you dislike them? _______________________________
IF NO, skip to question 26. IF YES, continue.
24.
Can you explain?
__________________________________________________________________
Skip to question 26.
25.
Tell me about it.
__________________________________________________________________
26.
Do you have many friends? ___________________________________________________________
IF YES, skip to question 30. IF NO, continue.
27.
Just a few?
__________________________________________________________________
IF YES, skip to question 29. IF NO, continue.
SAMPLE
Page 111
PPD
PPD
PPD
PPD


Page 5
SCI–PANSS BOOKLET
PAGE 5
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
28.
Any? .... Why?
__________________________________________________________________
Skip to question 32.
29.
Why just a few friends? ______________________________________________________________
30.
Close friends?
__________________________________________________________________
IF YES, skip to question 32. IF NO, continue.
31.
Why not?
__________________________________________________________________
32.
Do you feel that you can trust most people? ______________________________________________
IF YES, skip to question 34. IF NO, continue.
33.
Why not?
__________________________________________________________________
34.
Are there some people in particular who you don’t trust? ____________________________________
IF NO to question 34 and YES to question 32, skip to question 41.
IF NO to question 34 and NO to question 32, skip to question 36.
IF YES to question 34, continue.
35.
Can you tell me who they are? _________________________________________________________
36.
Why don’t you trust people (or name specific person)? _____________________________________
IF “DON’T KNOW” OR “DON’T WANT TO SAY,” continue. Otherwise, skip to question 41.
37.
 Do you have a good reason not to trust ...?
               ______________________________________________________________________________
38.
Is there something that .... did to you? ___________________________________________________
39.
Perhaps something that ... might do to you now? __________________________________________
IF NO, skip to question 41. IF YES, continue.
40.
Can you explain to me? ______________________________________________________________
41.
Do you get along well with others? _____________________________________________________
IF YES, skip to question 43. IF NO, continue.
42.
What’s the problem? ________________________________________________________________
43.
Do you have a quick temper? __________________________________________________________
SAMPLE
Page 112
PPD
PPD
PPD
PPD


Page 6
SCI–PANSS BOOKLET
PAGE 6
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
44.
Do you get into fights? _______________________________________________________________
IF NO, skip to question 48. IF YES, continue.
45.
How do these fights start? ____________________________________________________________
46.
Tell me about these fights. ____________________________________________________________
47.
How often does this happen? __________________________________________________________
48.
Do you sometimes lose control of yourself? ______________________________________________
IF NO, skip to question 50. IF YES, continue.
49.
What happens when you lose control of yourself? _________________________________________
50.
Do you like most people? _____________________________________________________________
IF YES, skip to question 52. IF NO, continue.
51.
Why not?
__________________________________________________________________
52.
Are there perhaps some people who don’t like you? ________________________________________
IF NO, skip to question 54. IF YES, continue.
53.
For what reason?
__________________________________________________________________
54.
Do others talk about you behind your back? ______________________________________________
IF NO, skip to question 57. IF YES, continue.
55.
What do they say about you? __________________________________________________________
56.
Why?_____________________________________________________________________________
57.
Does anyone ever spy on you or plot against you? _________________________________________
58.
Do you sometimes feel in danger? ______________________________________________________
IF NO, skip to question 64. IF YES, continue.
59.
Would you say that your life is in danger? _______________________________________________
60.
Is someone thinking of harming you or even perhaps thinking of killing you? ___________________
61.
Have you gone to the police for help? ___________________________________________________
62.
Do you sometimes take matters into your own hands or take action against those who might harm you?
__________________________________________________________________________________
IF NO, skip to question 64. IF YES, continue.
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Page 7
SCI–PANSS BOOKLET
PAGE 7
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
63.
What have you done? ________________________________________________________________
Data on “Hallucinatory Behavior” (P3) and associated delusions
64.
Do you once in a while have strange or unusual experiences? ________________________________
65.
Sometimes people tell me that they can hear noises or voices inside their head that others can’t hear.
What about you?
__________________________________________________________________
IF YES, skip to question 68. IF NO, continue.
66.
Do you sometimes receive personal communications from the radio or TV? _____________________
IF YES, skip to question 68. IF NO, continue.
67.
From God or the Devil?: _____________________________________________________________
IF NO, skip to question 83. IF YES, continue.
68.
What do you hear? __________________________________________________________________
69.
Are these as clear and loud as my voice?_________________________________________________
70.
How often do you hear these voices, noises, messages, etc.? _________________________________
71.
Does this happen at a particular time of day or all the time? __________________________________
IF HEARING NOISES ONLY, skip to question 80. IF HEARING VOICES, continue.
72.
Can you recognize whose voices these are? ______________________________________________
73.
What do the voices say? ______________________________________________________________
74.
Are the voices good or bad? ___________________________________________________________
75.
Pleasant or unpleasant? ______________________________________________________________
76.
Do the voices interrupt your thinking or your activities? ____________________________________
77.
Do they sometimes give you orders or instructions? ________________________________________
IF NO, skip to question 80. IF YES, continue.
78.
For example?
__________________________________________________________________
79.
Do you usually obey these orders (instructions)? __________________________________________
80.
What do you make of these voices (or noises); where do they really come from? _________________
81.
Why do you have these experiences?____________________________________________________
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Page 8
SCI–PANSS BOOKLET
PAGE 8
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
82.
Are these normal experiences?_________________________________________________________
83.
Do ordinary things sometimes look strange or distorted to you?_______________________________
84.
Do you sometimes have “visions” or see things that others can’t see? __________________________
IF NO, skip to question 88. IF YES, continue.
85.
For example?
__________________________________________________________________
86.
Do these visions seem very real or life-like? ______________________________________________
87.
How often do you have these experiences? _______________________________________________
88.
Do you sometimes smell things that are unusual or that others don’t smell? _____________________
IF NO, skip to question 90. IF YES, continue.
89.
Please explain.
__________________________________________________________________
90.
Do you get any strange or unusual sensations from your body? _______________________________
IF NO, skip to question 92. IF YES, continue.
91.
Tell me about this. __________________________________________________________________
Data on “Somatic Concern” (GI)
92.
How have you been feeling in terms of your health?________________________________________
IF OTHER THAN “GOOD,” skip to question 94. IF “GOOD,” continue.
93.
Do you consider yourself to be in top health? _____________________________________________
IF YES, skip to question 95. IF NO, continue.
94.
What has been troubling you? _________________________________________________________
95.
Do you have any medical illness or disease? ______________________________________________
96.
Has any part of your body been troubling you? ____________________________________________
IF YES, skip to question 98. IF NO, continue.
97.
How is your head?  Your heart?  Stomach?  The rest of your body? ___________________________
98.
Could you explain?__________________________________________________________________
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Page 9
SCI–PANSS BOOKLET
PAGE 9
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
99.
Has your head or body changed in shape or size? __________________________________________
IF NO, skip to question 102. IF YES, continue.
100. Please explain.
__________________________________________________________________
101. What is causing these changes? ________________________________________________________
Data on “Depression” (G6)
102. How has your mood been in the past week: mostly good, mostly bad? _________________________
IF “MOSTLY BAD,” skip to question 104. IF “MOSTLY GOOD,” continue.
103. Have there been times in the past week when you were feeling sad or unhappy? _________________
IF NO, skip to question 114. IF YES, continue.
104.  Is there something in particular that is making you sad? ____________________________________
105. How often do you feel sad? ___________________________________________________________
106. Just how sad have you been feeling? ____________________________________________________
107. Have you been crying lately? __________________________________________________________
108. Has your mood in any way affected your sleep? ___________________________________________
109. Has it affected your appetite?__________________________________________________________
110. Do you participate less in activities on account of your mood? _______________________________
111. Have you had any thoughts of harming yourself? __________________________________________
IF NO, skip to question 114. IF YES, continue.
112. Any thoughts about ending your life? ___________________________________________________
IF NO, skip to question 114. IF YES, continue.
113. Have you attempted suicide? __________________________________________________________
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Page 10
SCI–PANSS BOOKLET
PAGE 10
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
Data on “Guilt Feelings” (G3) and “Grandiosity” (P5)
114. If you were to compare yourself to the average person, how would you come out: a little better, maybe
a little worse, or about the same? _______________________________________________________
IF “BETTER,” skip to question 117.
IF “ABOUT THE SAME,” skip to question 118.
IF “WORSE,” continue.
115. Worse in what ways? ________________________________________________________________
116. Just how do you feel about yourself? ____________________________________________________
Skip to question 120.
117. Better in what ways? ________________________________________________________________
Skip to question 120.
118. Are you special in some ways? ________________________________________________________
IF NO, skip to question 120. IF YES, continue.
119. In what ways?
__________________________________________________________________
120. Would you consider yourself gifted? ____________________________________________________
121. Do you have talents or abilities that most people don’t have?_________________________________
IF NO, skip to question 123. IF YES, continue.
122. Please explain.
__________________________________________________________________
123. Do you have any special powers? ______________________________________________________
IF NO, skip to question 126. IF YES, continue.
124. What are these?
__________________________________________________________________
125. Where do these powers come from? ____________________________________________________
126. Do you have extrasensory perception (ESP), or can you read other people’s minds?_______________
127. Are you very wealthy? _______________________________________________________________
IF NO, skip to question 129. IF YES, continue.
128. Explain please.
__________________________________________________________________
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PAGE 11
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
129. Can you be considered to be very bright? ________________________________________________
IF NO, skip to question 131. IF YES, continue.
130. Why would you say so? ______________________________________________________________
131. Would you describe yourself as famous?_________________________________________________
132. Would some people recognize you from TV, radio, or the newspaper? _________________________
IF NO, skip to question 134. IF YES, continue.
133. Can you tell me about it? _____________________________________________________________
134. Are you a religious person? ___________________________________________________________
IF NO, skip to question 140. IF YES, continue.
135. Are you close to God? _______________________________________________________________
IF NO, skip to question 140. IF YES, continue.
136. Did God assign you some special role or purpose? _________________________________________
137. Can you be one of God’s messengers or angels? ___________________________________________
IF NO, skip to question 139. IF YES, continue.
138. What special powers do you have as God’s messenger (angel)? _______________________________
139. Do you perhaps consider yourself to be God? _____________________________________________
140. Do you have some special mission in life? _______________________________________________
IF NO, skip to question 143. IF YES, continue.
141. What is your mission? _______________________________________________________________
142. Who assigned you to that mission? _____________________________________________________
143. Did you ever do something wrong — something you feel bad or guilty about? ___________________
IF NO, skip to question 149. IF YES, continue.
144. Just how much does that bother you now?________________________________________________
145. Do you feel that you deserve punishment for that? _________________________________________
IF NO, skip to question 149. IF YES, continue.
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SCI–PANSS BOOKLET
PAGE 12
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
146. What kind of punishment would you deserve? ____________________________________________
147. Have you at times thought of punishing yourself?__________________________________________
IF NO, skip to question 149. IF YES, continue.
148. Have you ever acted on those thoughts of punishing yourself? ________________________________
 Data on “Disorientation” (GlO)
149. Can you tell me today’s date (i.e., the day, month, and year)? ________________________________
IF YES, skip to question 151. IF NO, continue.
150. Can you tell me what day of the week it is? ______________________________________________
151. What is the name of the place that you are in now?_________________________________________
IF NOT HOSPITALIZED, skip to question 154. IF HOSPITALIZED, continue.
152. What ward are you on?_______________________________________________________________
153. What is the address of where you’re now staying? _________________________________________
IF ABLE TO TELL, skip to question 155. IF NOT ABLE TO TELL, continue.
154. Can you tell me your home address? ____________________________________________________
IF NOT HOSPITALIZED, skip to question 156. IF HOSPITALIZED, continue.
155. If someone had to reach you by phone, what number would that person call? ____________________
156. If someone had to reach you at home, what number would that person call? _____________________
157. What is the name of the doctor who is treating you? ________________________________________
IF NOT HOSPITALIZED, skip to question 159. IF HOSPITALIZED, continue.
158. Can you tell me who else is on the staff and what they do? __________________________________
159. Do you know who is currently the president (prime minister, etc.)? ____________________________
160. Who is our governor (premier, etc.)? ____________________________________________________
161. Who is the mayor (town supervisor, etc.) of this city (town, etc.)? _____________________________
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Page 13
SCI–PANSS BOOKLET
PAGE 13
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
Data on “Difficulty in Abstract Thinking” (N5)
I’m going to now say a pair of words, and I’d like you to tell me in what important way they’re alike.  Let’s start, for example, with the words
“apple” and “banana.” How are they alike — what do they have in common? IF THE RESPONSE IS THAT “THEY’RE BOTH FRUIT”,
THEN SAY:  Good.  Now what about ...?  (Select three other items from the Similarities list at varying levels of difficulty from Appendix A.)
IF AN ANSWER IS GIVEN THAT IS CONCRETE, TANGENTIAL, OR IDIOSYNCRATIC (E.G., “THEY BOTH HAVE SKINS,”
“YOU CAN EAT THEM,” “THEY’RE SMALL,” OR “MONKEYS LIKE THEM”), THEN SAY:  OK, but they’re both fruit.  Now
how about ... and ... : how are these alike?  (Select three other items from the Similarities list at varying levels of difficulty from Appendix A.)
APPENDIX A
Items for Similarities in the evaluation of “Difficulty in Abstract Thinking”
1. How are a ball and an orange alike?
2. Apple and banana ?
3. Pencil and pen?
4. Nickel and dime?
     ______________
5. Table and chair?
6. Tiger and elephant?
7. Hat and shirt?
8. Bus and train?
     ______________
9.  Arm and leg?
10. Rose and tulip?
11. Uncle and cousin?
12. The sun and the moon?
      _______________
13. Painting and poem?
14. Hilltop and valley?
15. Air and water?
16. Peace and prosperity?
You’ve probably heard the expression, “Carrying a chip on the shoulder.” What does that really mean? There’s a very old saying,
“Don’t judge a book by its cover.” What is the deeper meaning of this proverb? (Select two other proverbs from the list in Appendix
B at varying levels of difficulty.)
APPENDIX B
Items for assessing PROVERB INTERPRETATION in the evaluation of “Difficulty in Abstract Thinking”
What does the saying mean:
1. “Plain as the nose on your face”
2. “Carrying a chip on your shoulder”
3. “Two heads are better than one”
4. “Too many cooks spoil the broth”
      ___________________
5. “Don’t judge a book by its cover”
6. “One man’s food is another man’s poison”
7. “All that glitters is not gold”
8. “Don’t cross the bridge until you come to it”
     ____________________
9.  “What’s good for the goose is good for the gander”
10. “The grass always looks greener on the other side”
11. “Don’t keep all your eggs in one basket”
12. “One swallow does not make a summer”
     ____________________
13. “A stitch in time saves nine”
14. “A rolling stone gathers no moss”
15. “The acorn never falls far from the tree”
16. “People who live in glass houses should not throw stones at others”
Note on Appendix A: Similarities are generally assessed by sampling
four items at different levels of difficulty (i.e., one item selected from
each quarter of the full set). When using the PANSS longitudinally,
items should be systematically altered with successive interviews so
as to provide different selections from the various levels of difficulty
and thus minimize repetition.
Notes on Similarities responses:
________________________________________________
________________________________________________
________________________________________________
________________________________________________
Circle the Similarities Used
Note on Appendix B: Proverb interpretation is generally assessed by
sampling four items at different levels of difficulty (i.e., one item
selected from each quarter of the full set). When using the PANSS
longitudinally, items should be systematically altered with succes-
sive interviews so as to provide different selections from the various
levels of difficulty and thus minimize repetition.
Notes on Proverb responses:
________________________________________________
________________________________________________
________________________________________________
________________________________________________
Circle the Proverbs Used
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Page 14
SCI–PANSS BOOKLET
PAGE 14
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
Data on “Lack of Judgment and Insight” (G12)
162. How long have you been in the hospital (clinic, etc.)?__________________________________________
163. Why did you come to the hospital (clinic, etc.)? ___________________________________________
164. Did you need to be in a hospital (clinic, etc.)? _____________________________________________
IF YES, skip to question 167. IF NO, continue.
165. Did you have a problem that needed treatment? ___________________________________________
IF NO, skip to question 169. IF YES, continue.
166. Would you say that you had a psychiatric or mental problem? ________________________________
IF NO, skip to question 169. IF YES, continue.
167. Why?....would you say that you had a psychiatric or mental problem? _________________________
IF NO, skip to question 169. IF YES, continue.
168. Can you tell me about it and what it consisted of? _________________________________________
169. In your own opinion, do you need to be taking medicine? ___________________________________
IF YES, skip to question 171.
IF NO and unmedicated, skip to question 172.
IF NO and medicated, continue.
170. Why then are you taking medicines? ____________________________________________________
Skip to question 172.
171. Why?... Does the medicine help you in any way? __________________________________________
172. Do you at this time have any psychiatric or mental problems? ________________________________
IF YES, skip to question 174. IF NO, continue.
173. For what reason are you at the hospital (clinic, etc.)? _______________________________________
Skip to question 175.
174. Please explain
__________________________________________________________________
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Page 15
SCI–PANSS BOOKLET
PAGE 15
Copyright © 1992, 1999, Multi-Health Systems Inc. All rights reserved. In the U.S.A., P.O. Box 950, North Tonawanda, NY 14120-0950, 
In Canada, 3770 Victoria Park Ave., Toronto, ON  M2H 3M6, 
 Internationally, 
 Fax, 
175. Just how serious are these problems? _____________________________________________________
IF UNHOSPITALIZED, skip to question 178.
IF HOSPITALIZED, continue.
176. Are you ready yet for discharge from the hospital? _________________________________________
177. Do you think you’ll be taking medicine for your problems after discharge? _____________________
178. What are your future plans? ___________________________________________________________
179. What about your longer-range goals? ___________________________________________________
Well, that’s about all I have to ask of you now.  Are there any questions that you might like to ask of me?
Thank you for your cooperation.
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Multi-Health Systems Inc.
In the U.S.A...
P.O. Box 950
North Tonawanda, NY 14120-0950
In Canada...
3770 Victoria Park Avenue
Toronto, ON  M2H 3M6
Local and International: 
Fax: 
www.mhs.com
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX D. SAMPLE CLINICAL GLOBAL IMPRESSION - 
IMPROVEMENT 
Page 124


Clinical Global Impression – Improvement of Illness (CGI-I) 
 
Global Improvement (CGI-I) 
Rate total improvement whether or not in your judgment it is due entirely to drug 
treatment.  Compared to his/her condition at admission, how much has he/she 
changed? 
0 = Not assessed 
1 = Very much improved 
2 = Much improved 
3 = Minimally improved 
4 = No change 
5 = Minimally worse 
6 = Much worse 
7 = Very much worse 
 
 
SAMPLE
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX E. SAMPLE STRUCTURED INTERVIEW GUIDE FOR 
GLOBAL IMPRESSIONS 
Page 126


 
Structured Interview Guide for Global Impressions (SIGGI) 
 2014 
ALK3831-401 
This interview guide explores the global impact of identified “targeted” symptoms of interest on behavior and 
function within the PAST SEVEN DAYS. To be eligible for this study (ALK3831-401), subjects must meet DSM-IV-TR 
or DSM-5 criteria for Schizophrenia 
Instructions for Raters 
AND
 
 DSM-5 criteria for Alcohol Use Disorder (AUD).  In this study, subjects may 
have mild to moderate symptoms of schizophrenia and symptoms of AUD that overall cause minimal, mild, or 
moderate impact on behavior or function.   
Generally, the SIGGI interview follows a review of the psychiatric history, the administration of a symptomatic 
questionnaire that identifies current clinically relevant symptoms, and collection of any collateral information from 
reliable informants.  USE ALL AVAILABLE CLINICAL INFORMATION TO COMPLETE THIS FORM. 
 
The interview proceeds as follows: 
1. 
EXPLANATION: Explain the purpose of the interview and obtain the subjects consent to participate. 
2. 
SYMPTOM IDENTIFICATION: Inquire about (and/or confirm) the presence of relevant symptoms of 
schizophrenia and AUD
3. 
IMPACT ASSESSMENT: Inquire about the amount of current distress (if any) or interference that the 
 that have been present within the past week (PAST 7 DAYS). 
specific “targeted” symptoms have caused for the subject in the past week (PAST 7 DAYS). 
4. SCORE AND DOCUMENT: Using the scoring anchors provided, determine the most appropriate global 
score and provide written documentation to support the derived score. 
 
1. EXPLANATION AND CONSENT 
I’d like to ask you some questions about some of the symptoms that you have experienced within the past week. 
Some of these questions may have already been asked and others will be new questions. 
 
I’m interested in how much the symptoms that you’ve experienced in the past week have affected you at home, 
at work, at school, in your relationships with others, or while you pursue your usual interests or activities (such 
as hobbies). 
 
Is that okay with you? 
2. SYMPTOM IDENTIFICATION 
Let’s begin by listing the most troubling symptoms that you have experienced within the past week (7 days). Can 
you describe them? How long have you had these symptoms (describe each specific symptom)?  
(includes BOTH Schizophrenia and Alcohol Use Disorder) 
SYMPTOM 
 
LISTING (Identify SYMPTOM and DURATION) 
1.   
 
Duration:   
 
 
2.   
 
Duration:   
 
 
3.   
 
Duration:   
 
 
4.   
 
Duration:   
 
 
5.   
 
Duration:   
 
 
NOTE TO RATER:  Please include any relevant symptoms identified from any other sources beyond this interview that may be 
present within the PAST SEVEN days. Summarize and confirm each symptom and its duration before proceeding 
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3. IMPACT ASSESSMENT 
 
A. Have any of these symptoms interfered with your ability to function? 
YES 
NO 
 
 
INQUIRE ABOUT RELEVANT ACTIVITIES: work, study, pursuit of hobbies or interests, participation in social 
events, or attending school. 
 
IF SUBJECT RESPONDS YES, ASK: In what way have the symptoms interfered?  
DOCUMENT RESPONSES IN THE SUBJECT’S OWN WORDS (with examples): 
 
B. Have any of these symptoms interfered with your relationships? 
YES 
NO  
 
INQUIRE ABOUT: friendships, social or work relationships, and interactions with family members. 
 
IF SUBJECT RESPONDS YES, ASK: In what way have the symptoms interfered with your relationships in the past 
week? DOCUMENT RESPONSES IN THE SUBJECT’S OWN WORDS (with examples): 
 
 
 
 
 
 
IF THE SUBJECT RESPONDS YES TO EITHER OF THE ABOVE IMPACT QUERIES (A or B), ASK THE FOLLOWING 
QUESTIONS: 
 
Regarding these symptoms, how troubling or distressing have these symptoms been for you? 
 
 
Can you give me an example? DOCUMENT RESPONSES IN THE SUBJECT’S OWN WORDS (with examples): 
QUANTIFICATION
 
 (RATER: refer to queries A or B above) 
How many DAYS in the past week have these symptoms disturbed you or interfered with your behavior or 
function? ______________days 
 
How much of the time during the day (or night) have these symptoms disturbed you or interfered with your 
behavior or function? ______________ % of time 
 
 
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4. SCORE AND DOCUMENT 
 
CGI SEVERITY ASSESSMENT: ______________ (1-7) 
 
(use scoring guide/anchors provided for specific study/evaluation) 
 
DOCUMENT JUSTIFICATION FOR DERIVED SCORE FROM ALL AVAILABLE CLINICAL DATA: 
 
CGI-S SCORING GUIDELINES 
1 
Normal, not at all 
ill 
Symptoms of disorder have not been present in the past seven days 
2 
Borderline 
mentally ill 
Subtle or suspected pathology present within the past seven days 
3 
Mildly ill 
Clearly established symptoms causing minimal, if any, distress for the 
subject or difficulty in social and occupational function 
4 
Moderately ill 
Overt symptoms causing 
 
noticeable, but modest, functional impairment 
or distress for the subject;   
Some symptoms may warrant adjustment of medication 
5 
Markedly ill 
Intrusive symptoms that 
 
distinctly impair social/occupational function 
or cause intrusive levels of distress for the subject 
There is overt behavioral or social dysfunction that is obvious to others 
6 
Severely ill 
Disruptive pathology; behavior and function are frequently influenced by 
symptoms; Extent of overt dysfunction may require intervention from 
others 
7 
Among the most 
extremely ill 
patients 
Pathology drastically interferes in many life functions; patient may be 
hospitalized 
 
SAMPLE
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX F. SAMPLE VISUAL ANALOG SCALE 
Page 130


 
VISUAL ANALOG SCALE – Desire for Alcohol 
 
 
 
Instructions:
 
 Below is a question regarding your desire for alcohol. We would like to know 
how strong your desire for alcohol has been during this past week. Please indicate your 
answer by placing a vertical mark ( l ) somewhere on the line between 0 and 100 to indicate 
how strong your desire for alcohol has been this past week. 
 
Correct:  
 
 
 
 
 
Incorrect: 
 
 
 
 
 
 
 
If you make a mistake, cross out your answer, initial and date it, and place a new vertical mark 
on the line.  
 
 
 
 
 
Please indicate how strong your desire for alcohol has been during this past week below:  
 
 
 
 
My desire for 
alcohol 
 
 
 
 
 
 
 
 
 
 
 
 
      
                      0                                                                                                    100 
                   No desire at                                                                     Strongest imaginable  
                   all for alcohol                                                                    desire for alcohol 
             0 
   No desire at 
   all for alcohol 
             100  
     Strongest imaginable  
     desire for alcohol 
 X 
             0 
   No desire at 
   all for alcohol 
             100  
     Strongest imaginable  
     desire for alcohol 
SAMPLE
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX G. SAMPLE PERSONAL AND SOCIAL PERFORMANCE 
SCALE 
Page 132


P ers o n al  a n d  S o ci al  Perf or m a n c e  ( P S P) S c al e  a n d  p oi nts  s c al e. 
( 1) M a k e  n ot e  of   t h e p ati e nt ’s l e v el of   d ysf u n cti o n  d uri n g  t h e p ast  m o nt h  f or  t h e  4 m ai n  ar e as  b el o w. T h e f u ncti o ni n g crit eri a 
b el o w  m ust  b e  us e d  t o d et er mi n e  t h e l e v el of  d ysf u n cti o n. N ot e  t h at t h er e ar e  s o m e c o m m o n  crit eri a  f or ar e as a - c a n d  
ot h er  crit eri a  s p e cifi c all y f or ar e a  d.  
 
A bs e nt  
Mil d  
M a nif est  
M ar k e d  
S e v er e  
V er y s e v er e  
a)  
S elf -c ar e  
 
 
 
 
 
 
b)  
P ers o n al  a n d  s o ci al r el ati o ns hi ps 
 
 
 
 
 
 
c)  
S o ci all y  us ef ul a cti viti es,  i n cl u di n g w or k  a n d  st u d y 
 
 
 
 
 
 
d)  
Dist ur bi n g  a n d  a g gr essi v e  b e h a vi or  
 
 
 
 
 
 
L e v el  of  s e v erit y: ar e as a- c 
(i) A bs e nt  
(ii) Mil d:  o nl y  r e c o g nis e d b y  s o m e o n e w h o is v er y  cl os e  t o t h e p ers o n  
(iii) M a nif est:  diffi c ulti es  t h at ar e  cl e arl y  visi bl e  t o a n y b o d y, alt h o u g h t h e y d o  n ot  s u bst a nti all y i nt erf er e wit h t h e  p ers o n ’s 
a bilit y  t o p erf or m  a r ol e i n t his ar e a,  t a ki n g i nt o a c c o u nt  his / h er  s o ci o-c ult ur al  c o nt e xt,  a g e, s e x  a n d  l e v el of  e d u c ati o n.  
(i v) M ar k e d:  diffi c ulti es  c o nsi d er a bl y  hi n d er t h e p ers o n  fr o m p erf or mi n g  his / h er  r ol e i n t his ar e a.  T h e p ers o n  is still c a p a bl e 
of  p erf or mi n g  s o m e t as ks, alt h o u g h i ns uffi ci e ntl y a n d  o c c asi o n all y, wit h o ut pr of essi o n al  or  s o ci al h el p. If  t h e p ers o n  is 
h el p e d  b y  s o m e o n e, s / h e m a y  q u alif y  f or t h e pr e vi o us  l e v el of  f u n cti o ni n g. 
( v) S e v er e:  diffi c ulti es  t h at m a k e  t h e p ers o n  u n a bl e t o p erf or m  a n y  r ol e i n t his ar e a  if n ot  h el p e d  b y  a pr of essi o n al, or  t h e 
p ers o n  h as  a d estr u cti v e  r ol e, h o w e v e r, t h er e ar e  n o s ur vi v al ris ks 
( vi)  Ver y  s e v er e: d et eri or ati o n  a n d  e xtr e m e  diffi c ulti es  w hi c h  m a y  p ut t h e p ers o n ’s s ur vi v al at  ris k 
L e v els  of  s e v erit y: ar e a  d 
(i) A bs e nt  
(ii) Mil d:  b ei n g  r u d e, u ns o ci a bl e  or  sli g ht c o m pl ai nts  
(iii) M a nif est:  s p e a ki n g t o o l o u dl y or  s p e a ki n g t o ot h ers  i n a t o o f a mili ar m a n n er, or  e ati n g  i n a s o ci all y u n a c c e pt a bl e w a y  
(i v) M ar k e d:  i ns ulti n g ot h er  p e o pl e  i n p u bli c,  br e a ki n g  o r t hr o wi n g o bj e cts,  fr e q u e ntl y b e h a vi n g  i n a s o ci all y u n a c c e pt a bl e 
w a y, b ut n ot  d a n g er o us w a y  ( e. g. u n dr essi n g  or  uri n ati n g  i n p u bli c)  
( v) S e v er e:  fr e q u e nt v er b al  t hr e ats or  p h ysi c al  att a c ks  wit h o ut i nt e nti o n or  p ossi bl e  s eri o us i nj uri es 
( vi)  Ver y  s e v er e: fr e q u e nt a g gr essi v e  a cts,  ai m e d  t o c a us e  s eri o us i nj uri es 
( 2) C h o os e  a 1 0 -p oi nt  r a n g e. T h e 1 0 -p oi nt  r a n g e is b as e d  o n  t h e l e v el of  d ysf u n cti o n f or t h e 4 m ai n  ar e as:  ( a) s o ci all y us ef ul 
a cti viti es,  i n cl u di n g w or k  a n d  st u d y; ( b) p ers o n al  a n d  s o ci al r el ati o ns hi ps; ( c) s elf-c ar e;  a n d  ( d) dist ur bi n g  a n d  a g gr essi v e  
b e h a vi or.  
1 0 0 -9 1  
E x c ell e nt  f u n cti o ni n g i n all  4 ar e as.  T h e p ers o n  is h el d  i n hi g h  c o nsi d er ati o n  f or his / h er  g o o d  q u aliti es, 
a d e q u at el y  c o p es  wit h  lif e’s pr o bl e ms,  a n d  is i n v ol v e d i n a wi d e  r a n g e of  i nt er ests a n d  a cti viti es  
9 0 -8 1  
G o o d  f u n cti o ni n g i n all  4 ar e as,  o nl y  h as  c o m m o n  pr o bl e ms  or  diffi c ulti es  
8 0 -7 1  
Mil d  diffi c ulti es  f or 1 or  m or e  a- c ar e as  
7 0 -6 1  
M a nif est  b ut n ot  m ar k e d  diffi c ulti es  i n 1 or  m or e  a- c ar e as  or  mil d  diffi c ulti es  i n d 
6 0 -5 1  
M ar k e d  diffi c ulti es  f or 1 or  m or e  a- c ar e as  or  m a nif est  diffi c ulti es  i n d 
5 0 -4 1  
M ar k e d  diffi c ulti es  i n 2 or  m or e  ar e as,  or  s e v er e diffi c ulti es  i n 1 or  m or e  a- c ar e as,  wit h  or  wit h o ut m ar k e d 
diffi c ulti es  i n d 
4 0 -3 1  
S e v er e  diffi c ulti es  i n 1 ar e a  a n d  m ar k e d  diffi c ulti es  i n at  l e ast 1 of  t h e a- c ar e as,  or  m ar k e d  diffi c ulti es  i n d 
3 0 -2 1  
S e v er e  diffi c ulti es  i n 2 a- c ar e as,  or  s e v er e diffi c ulti es  i n d,  wit h  or  wit h o ut d et eri or ati o n  i n a- c ar e as  
2 0 -1 1  
S e v er e  diffi c ulti es  i n all  a- d ar e as  or  v er y  s e v er e diffi c ulti es  i n d wit h  or  wit h o ut d et eri or ati o n  i n g e n er al a - c ar e as.  
If t h e p ers o n  r e a cts t o pr o v o c ati v e  sti m uli, t h e s u g g est e d r ati n g is 2 0 -1 6;  if n ot,  1 5 -1 1.  
1 0 - 1 
L a c k  of  i n d e p e n d e n c e f or b asi c  f u n ctio ni n g, wit h  e xtr e m e  b e h a vi o u r, b ut wit h  n o ris k t o s ur vi v al ( 6-1 0)  or  wit h  ris k 
t o s ur vi v al, e. g.  d e at h  ris k d u e  t o m al n utriti o n,  d e h y dr ati o n, i nf e cti o ns, i n a bilit y t o r e c o g nis e m a nif est d a n g er o us 
sit u ati o ns ( 1-5)  
( 3) A dj ust m e nt  wit hi n  t h e 1 0 -p oi nt  r a n g e 
•  
T h e l e v el of  d ysf u n cti o n i n ot h er  ar e as  s h o ul d b e  t a k e n i nt o c o nsi d er ati o n,  a d di n g  p oi nts  wit hi n  t h e 1 0 -p oi nt  r a n g e 
( e. g. fr o m 3 1  t o 4 0).  C o nsi d er:  
 
T a ki n g  c ar e  of  p h ysi c al  a n d  ps y c h ol o gi c al  h e alt h  
 
A c c o m m o d ati o n,  pl a c e  of  r esi d e n c e, l o o ki n g aft er  li vi n g s p a c e 
 
C o ntri b uti n g t o h o us e k e e pi n g a cti viti es,  p arti ci p ati n g  i n f a mil y lif e or  at  d a y  c e ntr e / h alls  of  r esi d e n c e 
 
P ers o n al  a n d  s e x u al r el ati o ns hi ps 
 
L o o ki n g  aft er  c hil dr e n  
 
S o ci al  n et w or k,  fri e n ds a n d  c o -w or k ers  
 
A dj usti n g  t o s o ci al n or ms  
 
G e n er al  int er ests  
 
Usi n g  tr a ns p ort, t el e p h o n e 
 
Str at e gi es  f or c o pi n g  wit h  crisis  sit u ati o ns 
•  
Ris k  a n d  s ui ci d al b e h a vi o ur  ar e  n ot  t a k e n i nt o a c c o u nt  o n  t his s c al e 
( 4) Writ e  t h e fi n al s c or e ( 0-1 0 0): _ _ _ _ _ _ _ _  
S A M P L E
Pa ge 1 3 3


Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX H. SAMPLE ABNORMAL INVOLUNTARY MOVEMENT 
SCALE 
Page 134


 
Guy, W. ed. ECDEU Assessment Manual for Psychopharmacology. US Dept 
of HEW, Publication No. (Adm): 76-338, 1976 
 Version 1.6 June, 2011 
 
 
 
Page 1 of 1 
 
Abnormal Involuntary Movement Scale (AIMS) 
Movement ratings: Rate highest severity observed. Rate movements that occur upon activation 
one less than those observed spontaneously. 
Code: 
0 = None 
1 = Minimal, may be extreme normal 
2 = Mild 
3 = Moderate 
4 = Severe 
 
(Circle One) 
FACIAL AND 
ORAL 
MOVEMENTS: 
1. MUSCLES OF FACIAL EXPRESSION e.g movements of forehead, eyebrows, 
periorbital area, cheeks, including frowning, blinking, smiling, grimacing 
0 
1 
2 
3 
4 
2. LIPS AND PERIORAL AREA e.g. puckering, pouting, smacking 
0 
1 
2 
3 
4 
3. JAW e.g. biting, clenching, chewing, mouth opening, lateral movement 
0 
1 
2 
3 
4 
4. TONGUE Rate only increases in movement both in and out of mouth. NOT 
inability to sustain movement 
0 
1 
2 
3 
4 
EXTREMITY 
MOVEMENTS: 
5. UPPER (ARMS, WRISTS, HANDS, FINGERS) Include choreic movements (i.e. 
rapid, objectively purposeless, irregular, spontaneous), athetoid movements (i.e. 
slow, irregular, complex, serpentine). Do NOT include tremor (i.e. repetitive, 
regular, rhythmic) 
0 
1 
2 
3 
4 
6. LOWER (LEGS, KNEES, ANKLES, TOES) e.g. lateral knee movement, foot 
tapping, heel dropping, foot squirming, inversion and eversion of foot 
0 
1 
2 
3 
4 
TRUNK 
MOVEMENTS: 
7. NECK, SHOULDERS, HIPS e.g.rocking, twisting, squirming, pelvic gyrations 
0 
1 
2 
3 
4 
GLOBAL 
JUDGMENT: 
8. SEVERITY OF ABNORMAL MOVEMENTS 
None, normal     0  
 
Minimal     1  
 
Mild     2  
 
Moderate     3  
 
Severe     4 
9. INCAPACITATION DUE TO ABNORMAL MOVEMENTS 
None, normal     0  
 
Minimal     1  
 
Mild     2  
 
Moderate     3  
 
Severe     4 
10.  PATIENT’S AWARENESS OF ABNORMAL MOVEMENTS. RATE ONLY 
PATIENT’S REPORT 
 
No awareness     0 
 
Aware, no distress     1  
 
Aware, mild distress     2  
 
Aware, moderate distress     3  
 
Aware, severe distress     4 
DENTAL 
STATUS: 
11. Current problems with teeth and/or dentures? 
No     0  
Yes    1 
12. Does patient usually wear dentures? 
No     0 
Yes    1 
 
Rater Signature: _______________________ 
Date: _________________________ 
 
SAMPLE
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX I. SAMPLE BARNES AKATHISIA SCALE 
Page 136


 
Reproduced from: Barnes TR: A Rating Scale for Drug-Induced Akathisia. 
British Journal of Psychiatry 154:672-676, 1989.  
 Version 1.6 June, 2011 
 
Page 1 of 1 
Barnes Akathisia Rating Scale (BARS) 
 
Instructions: Patient should be observed while they are seated, and then standing while engaged in neutral conversation (for a 
minimum of two minutes in each position). Symptoms observed in other situations, for example, while engaged in activity on the 
ward, may also be rated. Subsequently, the subjective phenomena should be elicited by direct questioning.  
Please circle the appropriate scores. 
 
Objective 
 
0 
Normal, occasional fidgety movements of the limbs 
1 
Presence of characteristic restless movements: shuffling or tramping movements of the legs/feet, or swinging of 
one leg while sitting, and/or rocking from foot to foot or “walking on the spot” when standing, but movements 
present for less than half the time observed 
2 
Observed phenomena, as described in (1) above, which are present for at least half the observation period 
3 
Patient is constantly engaged in characteristic restless movements, and/or has the inability to remain seated or 
standing without walking or pacing, during the time observed 
 
Subjective 
 
Awareness of restlessness 
0 
Absence of inner restlessness 
1 
Non-specific sense of inner restlessness 
2 
The patient is aware of an inability to keep the legs still, or a desire to move the legs, and/or complains of inner 
restlessness aggravated specifically by being required to stand still 
3 
Awareness of an intense compulsion to move most of the time and/or reports strong desire to walk or pace most 
of the time 
 
Distress related to restlessness 
0 
No distress 
1 
Mild 
2 
Moderate 
3 
Severe 
 
Global Clinical Assessment of Akathisia 
0 
Absent. No evidence of awareness of restlessness. Observation of characteristic movements of akathisia in the 
absence of a subjective report of inner restlessness or compulsive desire to move the legs should be classified 
as pseudoakathisia 
1 
Questionable. Non-specific inner tension and fidgety movements 
2 
Mild akathisia. Awareness of restlessness in the legs and/or inner restlessness worse when required to stand 
still. Fidgety movements present, but characteristic restless movements of akathisia not necessarily observed. 
Condition causes little or no distress 
3 
Moderate akathisia. Awareness of restlessness as described for mild akathisia above, combined with 
characteristic restless movements such as rocking from foot to foot when standing. Patient finds the condition 
distressing 
4 
Marked akathisia. Subjective experience of restlessness includes a compulsive desire to walk or pace. 
However, the patient is able to remain seated for at least five minutes. The condition is obviously distressing. 
5 
Severe akathisia. The patient reports a strong compulsion to pace up and down most of the time. Unable to sit 
or lie down for more than a few minutes. Constant restlessness which is associated with intense distress and 
insomnia. 
 
Rater Signature: _______________________ 
Date: _________________________ 
 
 
Scoring the Barnes Akathisia Rating Scale (BARS)  
 
The Barnes Akathisia Rating Scale is scored as follows:  
Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness are rated on a 
4-point scale from 0 – 3 and are summed yielding a total score ranging from 0 to 9.  
 
The Global Clinical Assessment of Akathisia uses a 5-point scale ranging from 0 – 4.  
 
SAMPLE
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX J. SAMPLE SIMPSON-ANGUS SCALE 
Page 138


Modified from: Simpson GM, Angus JWS: A rating scale for 
extrapyramidal side effects. Acta Psychiatrica Scandinavica 212:11-19, 
1970. Revised 
 Version 1.5 June, 2011 
 
Page 1 of 3 
 
SIMPSON ANGUS RATING SCALE  
 
Circle the appropriate score for each item
 
: 
1. 
GAIT 
The patient is examined as he walks into the examining room: his gait, the swing of arms, his 
general posture; all form the basis for an overall score for this item. This is rated as follows: 
0 
Normal 
1 
Mild diminution in swing while the patient is walking 
2 
Obvious diminution in swing suggesting shoulder rigidity 
3 
Stiff gait with little or no arm swing noticeable 
4 
Rigid gait with arms slightly pronated; or stopped-shuffling gait with propulsion and retropulsion 
2. 
ARM DROPPING 
The patient and the examiner both raise their arms to shoulder height and let them fall to their 
sides. In a normal subject a stout slap is heard as the arms hit the sides. In the patient with 
extreme Parkinson’s syndrome, the arms fall very slowly. 
0 
Normal, free fall with loud slap and rebound 
1 
Fall slowed slightly with less audible contact and little rebound 
2 
Fall slowed, no rebound 
3 
Marked slowing, no slap at all 
4 
Arms fall as though against resistance; as though through glue 
3. 
SHOULDER SHAKING 
The subject’s arms are bent at a right angle at the elbow and are taken one at a time by the 
examiner who grabs one hand and also clasps the other around the patient’s elbow. The subject’s 
upper arm is pushed to and fro and the humerus is externally rotated. The degree of resistance 
from normal to extreme rigidity is scored as follows: 
0 
Normal 
1 
Slight stiffness and resistance 
2 
Moderate stiffness and resistance 
3 
Marked rigidity with difficulty in passive movement 
4 
Extreme stiffness and rigidity with almost a frozen joint 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAMPLE
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Subject ID No.________    Visit No.________ 
Modified from: Simpson GM, Angus JWS: A rating scale for 
extrapyramidal side effects. Acta Psychiatrica Scandinavica 212:11-19, 
1970. Revised 
 Version 1.6 June, 2011 
 
Page 2 of 3 
4. 
ELBOW RIGIDITY 
The elbow joints are separately bent at right angles and passively extended and flexed, with the 
subject’s biceps observed and simultaneously palpated. The resistance to this procedure is rated. 
(The presence of cogwheel rigidity is noted separately.) 
0 
Normal 
1 
Slight stiffness and resistance 
2 
Moderate stiffness and resistance 
3 
Marked rigidity with difficulty in passive movement 
4 
Extreme stiffness and rigidity with almost a frozen joint 
5. 
WRIST RIGIDITY OR FIXATION OF POSITION 
The wrist is held in one hand and then the fingers held by the examiner’s other hand with the wrist 
moved to extension, and both ulnar and radial deviation. The resistance to this procedure is rated: 
 
0 
Normal 
1 
Slight stiffness and resistance 
2 
Moderate stiffness and resistance 
3 
Marked rigidity with difficulty in passive movement 
4 
Extreme stiffness and rigidity with almost a frozen joint 
6. 
LEG PENDULOUSNESS 
The patient sits on a table with his legs hanging down and swinging free. The ankle is grasped by 
the examiner and raised until the knee is partially extended. It is then allowed to fall. The 
resistance to falling and the lack of swinging form the basis for the score on this item: 
0 
The legs swing freely 
1 
Slight diminution in the swing of the legs 
2 
Moderate resistance to swing 
3 
Marked resistance and damping of swing 
4 
Complete absence of swing 
7. 
HEAD ROTATION 
The patient sits or stands and is told that you are going to move his head side to side, that it will 
not hurt and that he should try and relax. (Questions about pain in the cervical area or difficulty in 
moving his head should be obtained to avoid causing any pain.) Clasp the patient’s head between 
the two hands with fingers on back of the neck. Gently rotate the head in a circular motion 3 times 
and evaluate the muscular resistance to the movement. 
0 
Loose, no resistance 
1 
Slight resistance to movement although the time to rotate may be normal 
2 
Resistance is apparent and time of rotation is slowed 
3 
Resistance is obvious and rotation is slowed 
4 
Head appears stiff and rotation is difficult to carry out 
 
 
 
 
SAMPLE
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Subject ID No.________    Visit No.________ 
Modified from: Simpson GM, Angus JWS: A rating scale for 
extrapyramidal side effects. Acta Psychiatrica Scandinavica 212:11-19, 
1970. Revised 
 Version 1.6 June, 2011 
 
Page 3 of 3 
8. 
GLABELLA TAP 
Subject is told to open his eyes and not to blink. The glabella region is tapped at a steady, rapid 
speed. The number of times patient blinks in succession is noted: 
0 
0-5 blinks 
1 
6-10 blinks 
2 
11-15 blinks 
3 
16-20 blinks 
4 
21 and more blinks 
9. 
TREMOR 
Patient is observed walking into examining room and then is examined for this item: 
0 
Normal 
1 
Mild finger tremor, obvious to sight and touch 
2 
Tremor of hand or arm occurring spasmodically 
3 
Persistent tremor of one or more limbs 
4 
Whole body tremor 
10. 
SALIVATION 
Patient is observed while talking and then asked to open his mouth and elevate his tongue. The 
following ratings are given: 
0 
Normal 
1 
Excess salivation so that pooling takes place if the mouth is open and the tongue raised 
2 
Excess salivation is present and might occasionally result in difficulty in speaking 
3 
Speaking with difficulty because of excess salivation 
4 
Frank drooling 
 
 
Rater Signature: _______________________ 
Date: _________________________ 
 
 
 
SAMPLE
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Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX K. SAMPLE COLUMBIA SUICIDE SEVERITY RATING 
SCALE 
• “Baseline/ Screening” Version 
• “Since Last Visit” Version 
Page 142


 
 
 
 
 
 
 
 
 
COLUMBIA-SUICIDE SEVERITY 
RATING SCALE 
(C-SSRS)  
Baseline/Screening Version 
Version 1/14/09 
 
  
Posner, K.; Brent, D.; Lucas, C.; Gould, M.; Stanley, B.; Brown, G.; Fisher, P.; Zelazny, J.; 
Burke, A.; Oquendo, M.; Mann, J.  
 
 
Disclaimer: 
This scale is intended for use by trained clinicians. The questions contained in the Columbia-Suicide Severity Rating Scale 
are suggested probes. Ultimately, the determination of the presence of suicidality depends on clinical judgment. 
 
 
 
Definitions of behavioral suicidal events in this scale are based on those used in The Columbia Suicide History Form, 
developed by John Mann, MD and Maria Oquendo, MD, Conte Center for the Neuroscience of Mental Disorders 
(CCNMD), New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032. (Oquendo M. A., 
Halberstam B. & Mann J. J., Risk factors for suicidal behavior: utility and limitations of research instruments. In M.B. First 
[Ed.] Standardized Evaluation in Clinical Practice, pp. 103 -130, 2003.) 
 
 For reprints of the C-SSRS contact 
 New York State Psychiatric Institute, 1051 Riverside Drive, New 
York, New York, 10032; inquiries and training requirements contact 
  
 
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SUICIDAL IDEATION 
Ask questions 1 and 2.  If both are negative, proceed to “Suicidal Behavior” section. If the answer to 
question 2 is “yes,” ask questions 3, 4 and 5.  If the answer to question 1 and/or 2 is “yes”, complete 
“Intensity of Ideation” section below. 
Lifetime: Time 
He/She Felt 
Most Suicidal 
Past __ 
Months 
1.  Wish to be Dead  
Subject endorses thoughts about a wish to be dead or not alive anymore, or wish to fall asleep and not wake up.  
Have you wished you were dead or wished you could go to sleep and not wake up?  
 
If yes, describe: 
 
Yes       No 
□    □ 
 
Yes     No 
□   □ 
2.  Non-Specific Active Suicidal Thoughts 
General non-specific thoughts of wanting to end one’s life/commit suicide (e.g. “I’ve thought about killing myself”) without thoughts 
of ways to kill oneself/associated methods, intent, or plan during the assessment period.  
Have you actually had any thoughts of killing yourself? 
 
If yes, describe: 
 
    Yes       No 
   □    □ 
 
Yes     No 
□   □ 
3.  Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act 
Subject endorses thoughts of suicide and has thought of at least one method during the assessment period. This is different than a 
specific plan with time, place or method details worked out (e.g.  thought of method to kill self but not a specific plan).  Includes person 
who would say, “I thought about taking an overdose but I never made a specific plan as to when, where or how I would actually do 
it…..and I would never go through with it”.  
Have you been thinking about how you might do this? 
 
If yes, describe: 
 
 
    Yes      No 
 □    □ 
 
Yes     No 
□   □ 
4.  Active Suicidal Ideation with Some Intent to Act, without Specific Plan 
Active suicidal thoughts of killing oneself and subject reports having some intent to act on such thoughts, as opposed to “I have the 
thoughts but I definitely will not do anything about them”. 
Have you had these thoughts and had some intention of acting on them?  
 
If yes, describe: 
 
 
   Yes      No 
□    □ 
 
Yes     No 
□   □ 
5.  Active Suicidal Ideation with Specific Plan and Intent 
Thoughts of killing oneself with details of plan fully or partially worked out and subject has some intent to carry it out. 
Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan? 
   
If yes, describe: 
 
 
   Yes       No 
 □    □ 
 
Yes     No 
□   □ 
INTENSITY OF IDEATION 
The following features should be rated with respect to the most severe type of ideation (i.e.,1-5 from above, with 1 being 
the least severe and 5 being the most severe ). For prior to study entry, ask about time he/she was feeling the most 
suicidal.  
                                   
Lifetime -           Most Severe Ideation:  _______                  ________________________________________ 
                                                                       Type # (1-5)                                                 Description of  Ideation 
 
Past X Months - Most Severe Ideation:  _______                   ________________________________________ 
                                                                      Type # (1-5)                                                 Description of  Ideation 
Most  
Severe 
Most 
Severe 
Frequency 
How many times have you had these thoughts?  
(1) Less than once a week    (2) Once a week   (3)  2-5 times in week    (4) Daily or almost daily    (5) Many times each day 
 
 
____ 
 
 
____ 
Duration 
When you have the thoughts how long do they last? 
(1) Fleeting - few seconds or minutes                                                 (4) 4-8 hours/most of day 
(2) Less than 1 hour/some of the time                                                 (5) More than 8 hours/persistent or continuous 
(3) 1-4 hours/a lot of time 
____ 
____ 
Controllability 
Could /can you stop thinking about killing yourself or wanting to die if you want to? 
(1) Easily able to control thoughts                                                      (4) Can control thoughts  with a lot of difficulty 
(2) Can control thoughts with little difficulty                                     (5) Unable to control thoughts 
(3) Can control thoughts with some difficulty                                    (0) Does not attempt to control thoughts 
____ 
____ 
Deterrents 
Are there things - anyone or anything (e.g. family, religion, pain of death) - that stopped you from wanting to 
die or acting on thoughts of committing suicide? 
(1) Deterrents definitely stopped you from attempting suicide            (4) Deterrents most likely did not stop you  
(2) Deterrents probably stopped you                                                    (5) Deterrents definitely did not stop you  
(3) Uncertain that deterrents stopped you                                             (0) Does not apply 
____ 
____ 
Reasons for Ideation 
What sort of reasons did you have for thinking about wanting to die or killing yourself?  Was it to end the pain 
or stop the way you were feeling (in other words you couldn’t go on living with this pain or how you were 
feeling) or was it to get attention, revenge or a reaction from others? Or both? 
(1) Completely to get attention, revenge or a reaction from others.       (4) Mostly to end or stop the pain (you couldn’t go on 
(2) Mostly to get attention, revenge or a reaction from others.                     living with the pain or how you were feeling). 
(3) Equally to get attention, revenge or a reaction from others               (5) Completely to end or stop the pain (you couldn’t go on  
       and to end/stop the pain.                                                                         living with the pain or  how you were feeling). 
                                                                                                                 (0)  Does not apply 
 
 
 
 
____ 
 
 
____ 
 
Version 1/14/09 
SAMPLE
Page 144


SUICIDAL BEHAVIOR 
(Check all that apply, so long as these are separate events; must ask about all types) 
Lifetime 
Past __ 
Years 
Actual Attempt:  
A potentially self-injurious act committed with at least some wish to die, as a result of act. Behavior was in part thought of as method to kill 
oneself. Intent does not have to be 100%.  If there is any intent/desire to die associated with the act, then it can be considered an actual suicide 
attempt. There does not have to be any injury or harm, just the potential for injury or harm. If person pulls trigger while gun is in 
mouth but gun is broken so no injury results, this is considered an attempt.   
Inferring Intent: Even if an individual denies intent/wish to die, it may be inferred clinically from the behavior or circumstances. For example, a 
highly lethal act that is clearly not an accident so no other intent but suicide can be inferred (e.g. gunshot to head, jumping from window of a 
high floor/story). Also, if someone denies intent to die, but they thought that what they did could be lethal, intent may be inferred.  
Have you made a suicide attempt? 
Have you done anything to harm yourself? 
Have you done anything dangerous where you could have died? 
What did you do? 
Did you______ as a way to end your life?  
Did you want to die (even a little) when you_____?  
Were you trying to end your life when you _____? 
Or Did you think it was possible you could have died from_____? 
Or did you do it purely for other reasons / without ANY intention of killing yourself (like to relieve stress, feel better,  
get sympathy, or get something else to happen)?  (Self-Injurious Behavior without suicidal intent) 
If yes, describe: 
 
Has subject engaged in Non-Suicidal Self-Injurious Behavior? 
Yes     No 
□   □ 
 
 
 
 
 
 
 
Total # of 
Attempts 
 
______ 
 
 
 
 
 
 
 
Yes     No 
□   □ 
Yes     No 
□   □ 
 
 
 
 
 
 
Total # of 
Attempts 
 
______ 
 
 
 
 
 
 
 
Yes     No 
□   □ 
Interrupted Attempt:   
When the person is interrupted (by an outside circumstance) from starting the potentially self-injurious act (if not for that, actual attempt would 
have occurred). 
Overdose: Person has pills in hand but is stopped from ingesting.  Once they ingest any pills, this becomes an attempt rather than an interrupted 
attempt. Shooting: Person has gun pointed toward self, gun is taken away by someone else, or is somehow prevented from pulling trigger. Once 
they pull the trigger, even if the gun fails to fire, it is an attempt. Jumping: Person is poised to jump, is grabbed and taken down from ledge. 
Hanging: Person has noose around neck but has not yet started to hang - is stopped from doing so. 
Has there been a time when you started to do something to end your life but someone or something stopped you before 
you actually did anything? 
If yes, describe: 
 
Yes      No 
□   □ 
 
 
 
Total # of 
interrupted 
 
______ 
 
Yes     No 
□   □ 
 
 
Total # of 
interrupted 
 
______ 
 
Aborted Attempt:   
When person begins to take steps toward making a suicide attempt, but stops themselves before they actually have engaged in any self-
destructive behavior. Examples are similar to interrupted attempts, except that the individual stops him/herself, instead of being stopped by 
something else. 
Has there been a time when you started to do something to try to end your life but you stopped yourself before you 
actually did anything? 
If yes, describe: 
 
Yes      No 
□   □ 
 
 
Total # of 
aborted 
 
______ 
Yes     No 
□   □ 
 
Total # of 
aborted 
 
______ 
Preparatory Acts or Behavior: 
Acts or preparation towards imminently making a suicide attempt. This can include anything beyond a verbalization or thought, such as 
assembling a specific method (e.g. buying pills, purchasing a gun) or preparing for one’s death by suicide (e.g. giving things away, writing a 
suicide note).  
Have you taken any steps towards making a suicide attempt or preparing to kill yourself (such as collecting pills, 
getting a gun, giving valuables away or writing a suicide note)? 
If yes, describe: 
 
 
 
Yes      No 
□   □ 
 
 
Yes     No 
□   □ 
Suicidal Behavior: 
Suicidal behavior was present during the assessment period? 
Yes      No 
□   □ 
Yes     No 
□   □ 
Answer for Actual Attempts Only 
Most Recent 
Attempt 
Date: 
Most Lethal        
Attempt 
Date: 
Initial/First 
Attempt 
Date: 
Actual Lethality/Medical Damage:   
0.  No physical damage or very minor physical damage (e.g. surface scratches). 
1.  Minor physical damage (e.g. lethargic speech; first-degree burns; mild bleeding; sprains). 
2.  Moderate physical damage; medical attention needed (e.g. conscious but sleepy, somewhat responsive; second-degree 
burns; bleeding of major vessel). 
3.  Moderately severe physical damage; medical hospitalization and likely intensive care required (e.g. comatose with reflexes 
intact; third-degree burns less than 20% of body; extensive blood loss but can recover; major fractures). 
4.  Severe physical damage; medical hospitalization with intensive care required (e.g. comatose without reflexes; third-degree 
burns over 20% of body; extensive blood loss with unstable vital signs; major damage to a vital area). 
5.  Death 
 
Enter Code 
 
 
 
______ 
 
 
 
 
Enter Code 
 
 
 
______ 
 
 
 
 
Enter Code 
 
 
 
______ 
 
 
 
Potential Lethality: Only Answer if Actual Lethality=0 
Likely lethality of actual attempt if no medical damage (the following examples, while having no actual medical damage, had 
potential for very serious lethality: put gun in mouth and pulled the trigger but gun fails to fire so no medical damage; laying 
on train tracks with oncoming train but pulled away before run over). 
 
0 = Behavior not likely to result in injury 
1 = Behavior likely to result in injury but not likely to cause death 
2 = Behavior likely to result in death despite available medical care 
 
Enter Code 
 
 
 
______ 
 
 
Enter Code 
 
 
 
______ 
 
 
Enter Code 
 
 
 
______ 
 
SAMPLE
Page 145


 
 
 
 
 
 
 
 
 
COLUMBIA-SUICIDE SEVERITY 
RATING SCALE 
(C-SSRS) 
Since Last Visit 
Version 1/14/09 
 
Posner, K.; Brent, D.; Lucas, C.; Gould, M.; Stanley, B.; Brown, G.; Fisher, P.; Zelazny, J.; 
Burke, A.; Oquendo, M.; Mann, J.  
 
 
Disclaimer: 
This scale is intended for use by trained clinicians. The questions contained in the Columbia-Suicide Severity Rating Scale 
are suggested probes. Ultimately, the determination of the presence of suicidality depends on clinical judgment. 
 
 
 
Definitions of behavioral suicidal events in this scale are based on those used in The Columbia Suicide History 
Form, developed by John Mann, MD and Maria Oquendo, MD, Conte Center for the Neuroscience of Mental Disorders 
(CCNMD), New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032. (Oquendo M. A., 
Halberstam B. & Mann J. J., Risk factors for suicidal behavior: utility and limitations of research instruments. In M.B. First 
[Ed.] Standardized Evaluation in Clinical Practice, pp. 103 -130, 2003.) 
 
 For reprints of the C-SSRS contact 
 New York State Psychiatric Institute, 1051 Riverside Drive, New 
York, New York, 10032; inquiries and training requirements contact 
  
SAMPLE
Page 146
PPD
PPD


SUICIDAL IDEATION 
Ask questions 1 and 2.  If both are negative, proceed to “Suicidal Behavior” section. If the answer to question 2 is “yes,” 
ask questions 3, 4 and 5.  If the answer to question 1 and/or 2 is “yes”, complete “Intensity of Ideation” section below. 
 
Since Last 
Visit 
1.  Wish to be Dead  
Subject endorses thoughts about a wish to be dead or not alive anymore, or wish to fall asleep and not wake up.  
Have you wished you were dead or wished you could go to sleep and not wake up?  
 
If yes, describe: 
 
 
Yes       No 
 □    □ 
2.  Non-Specific Active Suicidal Thoughts 
General, non-specific thoughts of wanting to end one’s life/commit suicide (e.g. “I’ve thought about killing myself”) without thoughts of ways to kill 
oneself/associated methods, intent, or plan during the assessment period.  
Have you actually had any thoughts of killing yourself? 
 
If yes, describe: 
 
 Yes      No 
 □    □ 
3.  Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act 
Subject endorses thoughts of suicide and has thought of at least one method during the assessment period. This is different than a specific plan with time, 
place or method details worked out (e.g.  thought of method to kill self but not a specific plan).  Includes person who would say, “I thought about taking an 
overdose but I never made a specific plan as to when, where or how I would actually do it…..and I would never go through with it”.  
Have you been thinking about how you might do this? 
 
If yes, describe: 
 
 
 Yes      No 
 □    □ 
4.  Active Suicidal Ideation with Some Intent to Act, without Specific Plan 
Active suicidal thoughts of killing oneself and subject reports having some intent to act on such thoughts, as opposed to “I have the thoughts but I 
definitely will not do anything about them”. 
Have you had these thoughts and had some intention of acting on them?  
 
If yes, describe: 
 
 
Yes       No 
 □    □ 
5.  Active Suicidal Ideation with Specific Plan and Intent 
Thoughts of killing oneself with details of plan fully or partially worked out and subject has some intent to carry it out. 
Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan? 
   
If yes, describe: 
 
 
 Yes      No 
 □    □ 
INTENSITY OF IDEATION 
The following features should be rated with respect to the most severe type of ideation (i.e.,1-5 from above, with 1 being the least severe 
and 5 being the most severe ).  
                                             
Most Severe Ideation:             _____                      _________________________________________________ 
                                               
                                                                                                           Type # (1-5)                                         Description of  Ideation 
Most 
Severe 
Frequency 
How many times have you had these thoughts?  
(1) Less than once a week    (2) Once a week   (3)  2-5 times in week    (4) Daily or almost daily    (5) Many times each day 
 
____ 
Duration 
When you have the thoughts, how long do they last? 
(1) Fleeting - few seconds or minutes                                                 (4) 4-8 hours/most of day 
(2) Less than 1 hour/some of the time                                                 (5) More than 8 hours/persistent or continuous 
(3) 1-4 hours/a lot of time                                                                    
____ 
Controllability 
Could /can you stop thinking about killing yourself or wanting to die if you want to? 
(1) Easily able to control thoughts                                                      (4) Can control thoughts with a lot of difficulty 
(2) Can control thoughts with little difficulty                                     (5) Unable to control thoughts 
(3) Can control thoughts with some difficulty                                    (0) Does not attempt to control thoughts 
____ 
Deterrents 
Are there things - anyone or anything (e.g. family, religion, pain of death) - that stopped you from wanting to die or acting on 
thoughts of committing suicide? 
(1) Deterrents definitely stopped you from attempting suicide            (4) Deterrents most likely did not stop you  
(2) Deterrents probably stopped you                                                    (5) Deterrents definitely did not stop you  
(3) Uncertain that deterrents stopped you                                             (0) Does not apply 
____ 
Reasons for Ideation 
What sort of reasons did you have for thinking about wanting to die or killing yourself?  Was it to end the pain or stop the way 
you were feeling (in other words you couldn’t go on living with this pain or how you were feeling) or was it to get attention, 
revenge or a reaction from others? Or both? 
(1) Completely to get attention, revenge or a reaction from others.       (4) Mostly to end or stop the pain (you couldn’t go on 
(2) Mostly to get attention, revenge or a reaction from others.                     living with the pain or how you were feeling). 
(3) Equally to get attention, revenge or a reaction from others               (5) Completely to end or stop the pain (you couldn’t go on  
       and to end/stop the pain.                                                                         living with the pain or  how you were feeling). 
                                                                                                                 (0)  Does not apply 
 
 
 
 
____ 
Version 1/14/09 
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Page 147


SUICIDAL BEHAVIOR 
(Check all that apply, so long as these are separate events; must ask about all types) 
Since Last 
Visit 
Actual Attempt:  
A potentially self-injurious act committed with at least some wish to die, as a result of act. Behavior was in part thought of as method to kill oneself. Intent 
does not have to be 100%.  If there is any intent/desire to die associated with the act, then it can be considered an actual suicide attempt. There does not 
have to be any injury or harm, just the potential for injury or harm. If person pulls trigger while gun is in mouth but gun is broken so no injury results, 
this is considered an attempt.   
Inferring Intent: Even if an individual denies intent/wish to die, it may be inferred clinically from the behavior or circumstances. For example, a highly 
lethal act that is clearly not an accident so no other intent but suicide can be inferred (e.g. gunshot to head, jumping from window of a high floor/story). 
Also, if someone denies intent to die, but they thought that what they did could be lethal, intent may be inferred.  
Have you made a suicide attempt? 
Have you done anything to harm yourself? 
 
Have you done anything dangerous where you could have died? 
What did you do? 
Did you______ as a way to end your life?  
Did you want to die (even a little) when you_____?  
Were you trying to end your life when you _____? 
Or did you think it was possible you could have died from_____? 
Or did you do it purely for other reasons / without ANY intention of killing yourself (like to relieve stress, feel better, get 
sympathy, or get something else to happen)?  (Self-Injurious Behavior without suicidal intent) 
If yes, describe: 
 
 
Has subject engaged in Non-Suicidal Self-Injurious Behavior? 
 
Yes      No 
□   □ 
 
 
 
 
 
 
 
Total # of 
Attempts 
 
______ 
 
 
 
 
 
 
 
Yes     No 
□   □ 
Interrupted Attempt:   
When the person is interrupted (by an outside circumstance) from starting the potentially self-injurious act (if not for that, actual attempt would have 
occurred). 
Overdose: Person has pills in hand but is stopped from ingesting.  Once they ingest any pills, this becomes an attempt rather than an interrupted attempt. 
Shooting: Person has gun pointed toward self, gun is taken away by someone else, or is somehow prevented from pulling trigger. Once they pull the trigger, 
even if the gun fails to fire, it is an attempt. Jumping: Person is poised to jump, is grabbed and taken down from ledge. Hanging: Person has noose around 
neck but has not yet started to hang - is stopped from doing so. 
Has there been a time when you started to do something to end your life but someone or something stopped you before you 
actually did anything? 
If yes, describe: 
 
Yes      No 
□   □ 
 
 
Total # of 
interrupted 
 
______ 
 
Aborted Attempt:   
When person begins to take steps toward making a suicide attempt, but stops themselves before they actually have engaged in any self-destructive behavior. 
Examples are similar to interrupted attempts, except that the individual stops him/herself, instead of being stopped by something else. 
Has there been a time when you started to do something to try to end your life but you stopped yourself before you 
actually did anything? 
If yes, describe: 
 
 
Yes      No 
□   □ 
 
Total # of 
aborted 
 
______ 
Preparatory Acts or Behavior: 
Acts or preparation towards imminently making a suicide attempt. This can include anything beyond a verbalization or thought, such as assembling a 
specific method (e.g. buying pills, purchasing a gun) or preparing for one’s death by suicide (e.g. giving things away, writing a suicide note).  
Have you taken any steps towards making a suicide attempt or preparing to kill yourself (such as collecting pills, getting a gun, 
giving valuables away or writing a suicide note)? 
If yes, describe: 
 
 
Yes      No 
□   □ 
Suicidal Behavior: 
Suicidal behavior was present during the assessment period? 
Yes      No 
□   □ 
Completed Suicide: 
   Yes    No 
□   □ 
Answer for Actual Attempts Only 
Most Lethal 
Attempt 
Date: 
Actual Lethality/Medical Damage:   
0.  No physical damage or very minor physical damage (e.g. surface scratches). 
1.  Minor physical damage (e.g. lethargic speech; first-degree burns; mild bleeding; sprains). 
2.  Moderate physical damage; medical attention needed (e.g. conscious but sleepy, somewhat responsive; second-degree burns; bleeding of major vessel). 
3.  Moderately severe physical damage; medical hospitalization and likely intensive care required (e.g. comatose with reflexes intact; third-degree burns less 
than 20% of body; extensive blood loss but can recover; major fractures). 
4.  Severe physical damage; medical hospitalization with intensive care required (e.g. comatose without reflexes; third-degree burns over 20% of body; 
extensive blood loss with unstable vital signs; major damage to a vital area). 
5.  Death 
 
Enter Code 
 
 
 
______ 
Potential Lethality: Only Answer if Actual Lethality=0 
Likely lethality of actual attempt if no medical damage (the following examples, while having no actual medical damage, had potential for very serious 
lethality: put gun in mouth and pulled the trigger but gun fails to fire so no medical damage; laying on train tracks with oncoming train but pulled away 
before run over). 
 
0 = Behavior not likely to result in injury 
1 = Behavior likely to result in injury but not likely to cause death 
2 = Behavior likely to result in death despite available medical care  
 
Enter Code 
 
 
 
______ 
 
SAMPLE
Page 148


Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
APPENDIX L. PARTIAL LIST OF PROHIBITED CYTOCHROME P450 
3A4 (CYP3A4) INDUCERS AND MODERATE-TO-
STRONG INHIBITORS 
Partial List of CYP3A4 Inhibitors and Inducers (This is not an all inclusive list.) 
Moderate to Strong CYP3A4 inhibitors: 
Amprenavir 
Aprepitant 
Atazanavir 
Boceprevir 
Ciprofloxacin 
Clarithromycin 
Conivaptan 
Crizotinib 
Darunavir/ ritonavir 
Diltiazem 
Erythromycin 
Fosamprenavir 
Fluconazole 
Imatinib 
Indinavir 
Itraconazole 
Ketoconazole 
Lopinavir/ ritonavir 
Nefazodone 
Nelfinavir 
Posaconazole 
Ritonavir 
Saquinavir 
Telaprenavir 
Telithromycin 
Troleandomycin 
Verapamil 
Voriconazole 
Page 149


Protocol Amendment #6 
CONFIDENTIAL 
Alkermes, Inc. 
01 Mar 2016 
ALK3831-401 
 
Partial List of Moderate to Strong CYP3A4 inducers: 
Bosentan 
Carbamazepine 
Efavirenz 
Etravirine 
Modafinil 
Nafcillin 
Nevirapine 
Phenobarbital 
Phenytoin 
Rifampin 
Rifabutin 
St. John’s Wort 
Page 150

SAP_001.pdf: 
A Phase 2, Efficacy, Safety, and Tolerability Study of ALKS 
3831 in Schizophrenia with Alcohol Use Disorder 
 
 
Unique Protocol ID: 
ALK3831-401 
NCT Number: 
NCT02161718 
Date of Statistical Analysis 
Plan:  
20 Jan 2017 
 


 
Date: 20 JAN 2017 
 
Page 1 of 28 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
ALK3831-401 
 
Study Title: 
A Phase 2, Efficacy, Safety, and Tolerability Study of ALKS 3831 in 
Schizophrenia with Alcohol Use Disorder 
Document Status: 
Final Version 1.0 
Document Date: 
20 January 2017 
Based on: 
Protocol Amendment 6: 01 Mar 2016 
Sponsor: 
Alkermes, Inc. 
852 Winter Street 
Waltham, MA 02451 
USA 
 
 
 
 
 
CONFIDENTIAL 
Information and data in this document contain trade secrets and privileged or confidential information, 
which is the property of Alkermes, Inc. No person is authorized to make it public without the written 
permission of Alkermes, Inc. These restrictions or disclosures will apply equally to all future information 
supplied to you that is indicated as privileged or confidential. This study is being conducted in 
compliance with good clinical practice, including the archiving of essential documents. 


Alkermes, Inc. 
ALK3831-401: Statistical Analysis Plan 
 
Date: 20 JAN 2017 
 
Page 2 of 28 
TABLE OF CONTENTS 
ABBREVIATIONS .........................................................................................................................5 
1. 
INTRODUCTION ........................................................................................................7 
1.1. 
Study Objectives ...........................................................................................................7 
1.2. 
Summary of the Study Design ......................................................................................7 
2. 
SAMPLE SIZE CONSIDERATION ............................................................................8 
3. 
DATA ANALYSIS ......................................................................................................9 
3.1. 
General Statistical Methodology ..................................................................................9 
3.2. 
Definitions of Analysis Populations .............................................................................9 
3.2.1. 
Open-label Olanzapine Population ...............................................................................9 
3.2.2. 
Open-label ALKS 3831 Population ..............................................................................9 
3.2.3. 
Safety Population ..........................................................................................................9 
3.2.4. 
Efficacy Population ......................................................................................................9 
3.3. 
Disposition ....................................................................................................................9 
3.4. 
Demographics and Baseline Characteristics ...............................................................10 
3.5. 
Prior and Concomitant Medication .............................................................................10 
3.6. 
Treatment Adherence Rate and Extent of Exposure ...................................................10 
3.6.1. 
Treatment Adherence Rate .........................................................................................10 
3.6.2. 
Extent of Exposure .....................................................................................................10 
3.7. 
Efficacy Analyses .......................................................................................................11 
3.7.1. 
General Considerations ...............................................................................................11 
3.7.2. 
Primary Efficacy Endpoint .........................................................................................11 
3.7.2.1. 
Primary Analysis of the Primary Efficacy Endpoint ..................................................12 
3.7.2.2. 
Sensitivity Analysis of the Primary Efficacy Endpoint ..............................................12 
3.7.2.3. 
Additional Analysis of the Primary Efficacy Endpoint ..............................................12 
3.7.2.4. 
Examination of Subgroups .........................................................................................12 
3.7.3. 
Secondary Efficacy Endpoints ....................................................................................13 
3.7.3.1. 
Rate and Number of EEDS .........................................................................................13 
3.7.3.2. 
Proportion of Subjects with at least 1 Level Decrease in World Health 
Organization (WHO) Drinking Risk Level from Baseline to Week 24 of 
Double-blind Treatment (Study Week 27) .................................................................14 
3.7.4. 
Other Efficacy Endpoints ...........................................................................................15 


Alkermes, Inc. 
ALK3831-401: Statistical Analysis Plan 
 
Date: 20 JAN 2017 
 
Page 3 of 28 
3.7.4.1. 
Proportion of Subjects with Psychosocial Events Indicative of Exacerbation 
of Symptoms during the Double-blind Treatment period ...........................................15 
3.7.4.2. 
Rate and Number of Psychosocial Events Indicative of Exacerbation of 
Symptoms during the Double-blind Treatment Period ...............................................15 
3.7.4.3. 
Change from Baseline in PANSS Total Score, Positive Score, Negative 
Score, and General Psychopathology Score during the Double-blind 
Treatment Period ........................................................................................................15 
3.7.4.4. 
Change from Baseline in CGI-S Score during the Double-blind Treatment 
Period ..........................................................................................................................16 
3.7.4.5. 
Clinical Global Impression–Improvement (CGI-I) Score during the double-
blind Treatment Period ...............................................................................................16 
3.7.4.6. 
Complete Response Profile of Drinking during the Double-blind Treatment 
Period ..........................................................................................................................16 
3.7.4.7. 
Change from Baseline in Visual Analogue Score (VAS) for Perception of 
Desire for Alcohol during the Double-blind Treatment Period ..................................18 
3.7.5. 
Exploratory Endpoints ................................................................................................18 
3.8. 
Safety Analysis ...........................................................................................................18 
3.8.1. 
Adverse Events ...........................................................................................................18 
3.8.2. 
Other significant adverse events .................................................................................19 
3.8.3. 
Clinical Laboratory Parameters ..................................................................................19 
3.8.4. 
Weight, Body Mass Index, Waist Circumferences and Vital Signs ...........................21 
3.8.4.1. 
Weight, Body Mass Index, Waist Circumferences .....................................................21 
3.8.4.2. 
Vital Signs ..................................................................................................................22 
3.8.5. 
Electrocardiograms .....................................................................................................22 
3.8.6. 
Abnormal Movement Scales .......................................................................................23 
3.8.7. 
Columbia Suicide Severity Rating Scale (C-SSRS) ...................................................24 
3.9. 
Pharmacokinetic/Pharmacodynamic Data Analysis ...................................................24 
4. 
INTERIM ANALYSES ..............................................................................................24 
5. 
CHANGES IN CONDUCT OR PLANNED ANALYSES FROM THE 
PROTOCOL ...............................................................................................................25 
6. 
DEFINITIONS AND CONVENTIONS FOR HANDLING OF THE DATA ..........25 
6.1. 
Analysis Visit Windows .............................................................................................25 
6.2. 
Handling of Partial Dates of Concomitant Medication ..............................................27 
6.3. 
Handling of Safety Data .............................................................................................27 
7. 
GENERAL STATISTICAL METHODOLOGY .......................................................27 


Alkermes, Inc. 
ALK3831-401: Statistical Analysis Plan 
 
Date: 20 JAN 2017 
 
Page 4 of 28 
7.1. 
Reporting Precision ....................................................................................................27 
8. 
PROGRAMMING SPECIFICATIONS .....................................................................28 
9. 
MOCK TABLE LISTING AND FIGURES (TLF) ....................................................28 
10. 
REFERENCES ...........................................................................................................28 
 
LIST OF TABLES 
Table 1: 
Criteria for risk of alcohol consumption on a single drinking day .............................14 
Table 2: 
Criteria of Potentially Clinically Significant (PCS) Abnormality for Selected 
Analytes ......................................................................................................................20 
Table 3: 
Potentially Clinically Significant Results Criteria for Hematology ...........................21 
Table 4: 
Criteria for Potentially Clinically Significant (PCS) Changes from Baseline 
in Body Weight ...........................................................................................................21 
Table 5: 
Criteria for Potentially Clinically Significant (PCS) Blood Pressure or Pulse 
Rate .............................................................................................................................22 
Table 6: 
Criteria for Potentially Clinically Significant (PCS) QTcB and QTcF ......................23 
Table 7: 
C-SSRS Categories for Analysis ................................................................................24 
Table 8: 
Visit Window Definition .............................................................................................25 
Table 9: 
Degree of Precision .....................................................................................................27 
 
LIST OF FIGURES 
Figure 1: 
ALK3831-401 Study Schematic ...................................................................................8 
 
 


Alkermes, Inc. 
ALK3831-401: Statistical Analysis Plan 
 
Date: 20 JAN 2017 
 
Page 5 of 29 
ABBREVIATIONS 
Abbreviation or Term 
Explanation or Definition 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BMI 
Body Mass Index 
CGI-S 
Clinical Global Impression–Severity 
CGI-I 
Clinical Global Impression–Improvement 
CI 
Confidence Interval 
CRF 
Case Report Form 
C-SSRS 
Columbia Suicide Severity Rating Scale 
ET 
Early Termination 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EEDS 
Event of Exacerbation of Disease Symptom 
HbA1c 
Hemoglobin A1c 
HDL 
High Density Lipoprotein 
HR 
Heart Rate 
ITT 
Intention to Treat 
LDL 
Low Density Lipoprotein 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
PANSS 
Positive and Negative Syndrome Scale 
PBO 
Placebo 
PD 
Pharmacodynamic 
PK 
Pharmacokinetics 
PSP 
Personal and Social Performance 
PT 
Preferred Term 
QTcB 
QTcB – Bazett’s correction formula 
QTcF 
QTcF – Fridericia’s correction formula 
SAE 
Serious Adverse Event 


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SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TLF 
Table, Listing, and Figure 
TLFB 
Timeline Follow-Back 
TEAE 
Treatment-Emergent Adverse Event 
WHO 
World Health Organization 
WHO-ATC 
World Health Organization Anatomical Therapeutic Chemical 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical methods to be used for analyses and 
data presentation for reporting efficacy and safety results for study ALK3831-401. This 
document has been prepared based on Alkermes ALK3831-401 Study Protocol Amendment 61 
(dated 01 Mar 2016). 
1.1. 
Study Objectives 
Primary: 
• To evaluate the efficacy of olanzapine coadministered with samidorphan 
(ALKS 3831) compared with olanzapine coadministered with placebo in 
schizophrenia with alcohol use disorder (AUD) 
Secondary: 
• To evaluate the safety and tolerability of ALKS 3831 in schizophrenia with AUD 
1.2. 
Summary of the Study Design 
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study designed to 
evaluate the efficacy, safety, and tolerability of ALKS 3831 in schizophrenia with AUD. 
ALKS 3831 is a combination of olanzapine, an approved antipsychotic treatment for 
schizophrenia, and samidorphan, a new molecular entity. 
Potential subjects for this study are adults with a diagnosis of schizophrenia (based on the 
Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision [DSM-IV-TR]) 
and AUD (based on DSM 5th edition [DSM-5]). Subjects must have recently (within the last 
6 months) experienced an exacerbation of disease symptoms (eg, hospitalization) but cannot 
exceed a pre-defined level of symptom severity at the time of screening (as measured by the 
Positive and Negative Syndrome Scale [PANSS] and Clinical Global Impression-Severity 
[CGI-S]). 
All study visits will be outpatient visits. After informed consent and screening, subjects will 
begin a 4-week open-label olanzapine dosing period followed by a 2-week open-label 
ALKS 3831 period (see Figure 1). Once-daily, open-label olanzapine dosing will begin at Visit 2 
with the dose level determined by the principal investigator (PI). Once daily open-label 
ALKS 3831 dosing (olanzapine coadministered with 10 mg samidorphan using separate tablets) 
will begin at Visit 6 and last until Visit 8 (randomization). ALKS 3831 treatment will consist of a 
once-daily dose of olanzapine (with dose level determined by the PI) plus samidorphan 10 mg to 
be taken at the same time (ie, coadministered) using separate tablets. 
At Visit 8, subjects will be randomized in a 1:1 fashion to 1 of 2 treatment groups as follows: 
• ALKS 3831 (ie, olanzapine [dose determined by the PI] plus samidorphan [10 mg]) 
• Olanzapine (dose determined by the PI) plus placebo 


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Subjects randomized to double-blind treatment will be followed for a minimum of 9 months and 
a maximum of 15 months. Visits during the double-blind period will be every 2 weeks. Each 
visit will consist of clinical assessments plus drug dispensing or drug dispensing only. After the 
end of the double-blind treatment period, subjects will complete a 3-week safety follow-up 
period. 
Figure 1: 
ALK3831-401 Study Schematic 
 
Abbreviation: V = Study Visit; ALKS 3831=olanzapine + samidorphan 
The schedule of visits and assessments for before randomization (Visit 8) and after 
randomization are shown in Table 1, Table 2, and Table 3 of the protocol 
(Study ALK3831-4011). 
2. 
SAMPLE SIZE CONSIDERATION 
The sample size calculation is based on the detection of hazard ratio for the first event of 
exacerbation of disease symptoms (EEDS) during the double-blind treatment period. 
Based on the previous clinical studies with olanzapine and clinical judgment, the 9-month 
cumulative proportion of subjects experiencing an event of exacerbation of disease symptoms 
(EEDS) will be 15% and 30% for the ALKS 3831 group and olanzapine plus placebo group, 
respectively. Assuming an exponential distribution of survival time, and a 2-sided test at α=0.05, 
a total of 70 EEDS will be required for approximately 90% power to detect a hazard ratio of 0.45 
between ALKS 3831 and olanzapine plus placebo with a randomization allocation ratio of 1:1 
(ALKS 3831:olanzapine plus placebo). Approximately 270 subjects (135 subjects per treatment 
group) will need to be randomized at Visit 8 to observe 70 total EEDS. 
3 


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3. 
DATA ANALYSIS 
3.1. 
General Statistical Methodology 
The baseline for each efficacy and safety parameter in a period is defined as the last assessment 
made on or before the first dose of study drug in that period. That is, baseline for open-label 
Olanzapine and ALKS 3831 period is defined as the last non-missing observation on or before 
the first dose of study drug for the open-label period at Visit 2 and 6, respectively; baseline for 
double-blind period is defined as the last non-missing observation on or before the date of the 
first dose of study drug for double-blind period at Visit 8. 
Unless specified otherwise, the efficacy parameters will be summarized for the double-blind 
period and the safety parameters will be summarized for the open-label, double-blind and safety 
follow-up periods. 
Continuous variables will be summarized by number of subjects and mean, SD, median, 
minimum, and maximum values. Categorical variables will be summarized by number and 
percentage of subjects. 
3.2. 
Definitions of Analysis Populations 
3.2.1. 
Open-label Olanzapine Population 
The open-label olanzapine population is defined as all enrolled subjects who received at least 
1 dose of olanzapine during the open-label olanzapine treatment period. 
3.2.2. 
Open-label ALKS 3831 Population 
The open-label ALKS 3831 population is defined as all enrolled subjects who received at least 
1 dose of olanzapine or samidorphan during the open-label ALKS 3831 treatment period. 
3.2.3. 
Safety Population 
The safety population is defined as all randomized subjects who receive at least 1 dose of study 
drug (olanzapine, samidorphan or placebo) during the double-blind placebo-controlled treatment 
period. 
Follow-up safety population is defined as subjects who entered into the follow-up period or have 
any newly emergent adverse events (Section 3.8.1).  
3.2.4. 
Efficacy Population 
The intent-to-treat (ITT) population is the same as the safety population. 
3.3. 
Disposition 
The number and percentage of subjects completing or prematurely discontinuing during the 
open-label olanzapine period and the open-label ALKS 3831 period will be summarized. For the 
safety population, the number and percentage of subjects completing or prematurely 


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discontinuing the study and reason for discontinuation will be summarized by treatment group; 
and overall.  
3.4. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics, including but not limited to, sex, age, race, 
ethnicity, region, weight, BMI, PANSS, CGI-S and drinking status will be summarized for the 
open-label populations and by treatment group and overall for the safety population. 
Assignment of the stage of readiness to change will be based on the quick method3. The scale 
score is the sum of the item scores. The highest scale score represents the stage of change 
designation. The score of the precontemplation scale is reversed to compare with the 
contemplation and action scales. If two scale scores are equal, the scale farther along the 
continuum of change (ie precontemplation - contemplation - action) represents the subject's stage 
of change designation.  
Medical history will be summarized for the open-label olanzapine population (overall) and for 
the safety population (by treatment group and overall). 
3.5. 
Prior and Concomitant Medication 
Prior medications are defined as medications taken prior to the first dose of open-label 
olanzapine. Concomitant medications are defined as medications taken on or after the first dose 
of open-label olanzapine. All medications as documented by the investigator will be coded using 
the World Health Organization Anatomical Therapeutic Chemical (WHO-ATC) drug dictionary 
Version March 2015. 
Prior and concomitant medications will be summarized by the preferred term and treatment 
group for the safety population. Concomitant medications that are taken during the double-blind 
treatment period will be included in the summary table. All reported medications (including 
those initiated after the last dose of double-blind study medication) will be included in the listing. 
For the summary tables, if a subject has taken a prior or concomitant medication more than once, 
the subject will be counted only once for the medication. 
3.6. 
Treatment Adherence Rate and Extent of Exposure 
3.6.1. 
Treatment Adherence Rate 
Treatment adherence to the daily dosing schedule of samidorphan and placebo during the 
double-blind period will be summarized by treatment group for the safety population. Treatment 
adherence will be calculated as follows: 
100 × 
Total tablets dispensed – total tablets returned – total tablets lost 
Total tablets scheduled to be taken 
3.6.2. 
Extent of Exposure 
Exposure (days) on study drug is defined as the number of days from the date of the first dose of 
study drug taken to the date of the last dose taken, inclusive, for the relevant period. Exposure to 


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study drug will be summarized for each population; overall for the open-label periods and by 
treatment group for the double-blind period. 
The olanzapine dose level at the start of the double-blind treatment period (V8) will be 
summarized by treatment group and overall. 
3.7. 
Efficacy Analyses 
3.7.1. 
General Considerations 
All statistical tests will be 2-sided hypothesis tests performed at the 5% significance level. All 
confidence intervals will be 2-sided 95% confidence intervals, unless specified otherwise.  
3.7.2. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is defined as the time from randomization to the first EEDS. 
An EEDS is defined as any of the following occurring during the double-blind period and is 
related to worsening of disease symptoms, as confirmed by the IAC (protocol section 11.11): 
1. Subject requires hospitalization due to worsening of disease symptoms including a 
psychiatric hospitalization or a hospitalization due to or for acute treatment of alcohol 
intoxication or withdrawal 
2. Subject has a ≥25% or ≥15-point increase from randomization in PANSS total score that 
is confirmed at a second, ad hoc visit shortly after the first assessment 
3. Subject has a PANSS item score of P1, P2, P3, P6, P7, or G8 that meets one of the 
following criteria: 
• For subjects with a score ≤3 at randomization, a score ≥5 that is confirmed at a 
second, ad hoc visit shortly after the first assessment 
• For subjects with a score of 4 at randomization, a score ≥6 that is confirmed at a 
second, ad hoc visit shortly after the first assessment 
4. Subject commits deliberate self-injury, engages in aggressive behavior, or displays signs 
of suicidal or homicidal ideation that is clinically significant as judged by the PI 
5. Subject requires initiation of rescue medication, including an increase in prescribed 
olanzapine dose level, due to worsening of disease symptoms 
• For this study, the increase in olanzapine dose must be above the randomization dose 
level even if the dose level is previously decreased at some point after randomization. 
6. Subject requires an emergency room visit due to worsening of disease symptoms 
7. Subject withdraws or PI discontinues the subject from the study for one of the following 
reasons: 
a. Lack of efficacy 
b. Lost to follow-up 
c. Withdrawal by subject 


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8. Subject is involved in an incident leading to arrest or incarceration during the study 
period that is related to the subject’s underlying disease 
For criterion requiring a consecutive assessment, the second assessment should be scheduled 
within 3-7 days of the first occurrence and conducted as per Section 8.5 of the protocol1. All 
EEDS cases will be reviewed by the IAC in a blinded manner. Only events confirmed by the 
IAC will be used for efficacy analyses. Further details on the functioning of the IAC are included 
in the IAC charter2. 
Subjects who completed or discontinued the double-blind period without an EEDS will be 
censored at the last EEDS assessment date. For all other subjects with EEDS, the date of first 
EEDS will be counted as event date. 
3.7.2.1. 
Primary Analysis of the Primary Efficacy Endpoint 
For the primary analysis of time to the first EEDS, comparison of the 2 treatment groups will be 
carried out using a log rank test. The Cox proportional hazards model will be used to obtain an 
estimate of the hazard ratio for the ALKS 3831 group to the olanzapine group adjusting for the 
baseline PANSS total score and drinking status. A 95% confidence interval will be computed for 
the hazard ratio. 
Kaplan-Meier estimates of EEDS rate will be generated and the Kaplan-Meier plot of time to 
first EEDS will be presented by the treatment group. 
3.7.2.2. 
Sensitivity Analysis of the Primary Efficacy Endpoint 
As sensitivity analysis, if the first adjudicated EEDS only satisfies the discontinuation criterion, 
(either satisfies 7b or 7c criteria in EEDS definition, or if IAC doesn’t specify a criterion), it will 
be censored at the last EEDS assessment date. Analysis will be the same as the primary analysis 
of EEDS. 
Additional sensitivity analysis will be performed to assess the potential impact of informative 
censoring. 10%, 20% and 30% of subjects who discontinued from the study without any EEDS 
will be randomly assigned as having EEDS one day after the discontinuation. Twenty 
imputations will be carried out. The generated datasets will be analyzed similarly as the primary 
analysis using the cox proportional hazard model. Rubin’s rule will be used to combine the 
treatment effect estimates and standard errors across imputations. 
3.7.2.3. 
Additional Analysis of the Primary Efficacy Endpoint 
Exploratory analysis will be performed to analyze the relationship of the primary endpoint to the 
drinking profiles during the double-blind treatment period. Percent of heavy drinking days 
during the double-blind treatment period will be subset into quantiles and used as the factor in 
the Cox proportional hazards model. The model will also adjust for the baseline PANSS total 
score. Kaplan-Meier estimates of EEDS rate will be generated. 
3.7.2.4. 
Examination of Subgroups 
The following subgroup category will be examined for the primary efficacy endpoint:  
• Male vs. Female 


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• Black vs. non-Black 
• US vs. Non-US 
• Prior olanzapine exposure (subjects on olanzapine at Visit 1 vs. subjects not on 
olanzapine at Visit 1) 
• Baseline PANSS (≥70 vs. <70) 
• Baseline alcohol consumption risk category (medium, high or very high risk vs. 
abstinence or low risk) 
• Baseline AUD severity (severe vs. mild or moderate) 
• Baseline number of prior hospitalizations or ER visits for the underlying disease in 
the last 12 months (≥1 vs. 0) 
For each subgroup category, the Cox proportional hazards model will be used to obtain an 
estimate of the hazard ratio of the ALKS 3831 group to the olanzapine group. The model will 
include treatment group, subgroup, and treatment by subgroup interaction as factors and adjust 
for the relevant baseline covariates/factors when appropriate.  
3.7.3. 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints include:  
• The rate and number of EEDS 
• Proportion of subjects with at least 1 level decrease in World Health Organization 
(WHO) drinking risk level from baseline to week 24 of the double-blind treatment 
(study week 27) 
3.7.3.1. 
Rate and Number of EEDS 
3.7.3.1.1. Primary Analysis on the Rate and Number of EEDS 
Considering EEDS as recurrent events, an Andersen-Gill mean/rate intensity model will be 
employed to analyze the time-to-recurrent EEDS. This model will allow for an arbitrary 
dependence structure of the recurrent events within the same subject by using a robust 
“sandwich” estimate of the covariance matrix. The model will also adjust for the baseline 
PANSS total score and drinking status. The estimated hazard ratio (and 95% confidence interval) 
of the ALKS 3831 group to the olanzapine group will be calculated under the Anderson-Gill 
mean/rate intensity model. 
3.7.3.1.2. Sensitivity Analysis on the Rate and Number of EEDS 
Annualized EEDS rate will be analyzed by a negative binomial regression model. The 
logarithmic transformation of the time from the first dose of the double-blind study drug to the 
last EEDS assessment visit will be included in the model as the “offset” parameter. The model 
will adjust the baseline PANSS total score and drinking status. If the data are underdispersed, or 
if the negative binomial regression model does not converge, a Poisson regression model will be 
used instead of the negative binomial regression model. Dispersion will be evaluated from the 


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Pearson Chi-Square statistic. If the ratio of the Pearson Chi-Square statistic to the degrees of 
freedom is ≤ 1 which indicates no overdispersion, then a Poisson regression model will be used.  
The descriptive statistics for the annualized rate of EEDS for each treatment group will be 
calculated as the total number of EEDS experienced in the group divided by the total number of 
subject-years on study. The descriptive statistics for the annualized rate of EEDS rate for an 
individual subject will be calculated as the number of EEDS for that subject divided by the 
number of subject-years and presented by the treatment group. 
3.7.3.1.3. Additional Analysis on the Rate and Number of EEDS 
Since the EEDS consists of a series of individual criteria, number and percent of subjects who 
met each individual criterion will be provided. The treatment groups will be compared by the 
logistic regression model adjusting for the baseline PANSS total score and drinking status.  
In addition, the duration of IAC confirmed hospitalizations related to the underlying disease will 
be summarized by treatment group. 
3.7.3.2. 
Proportion of Subjects with at least 1 Level Decrease in World Health 
Organization (WHO) Drinking Risk Level from Baseline to Week 24 of Double-
blind Treatment (Study Week 27) 
The alcohol consumption per day at each visit will calculated based on the number of drinks per 
day as follows.  
 
Alcohol consumption per day = 
total number of drinks × 14 gram 
total number of days 
The risk of the alcohol consumption will be categorized based on the alcohol consumption per 
day using the criteria in Table 1. Proportion of subjects with at least 1 level decrease in World 
Health Organization (WHO) drinking risk level3 from baseline to week 24 of double-blind 
treatment (study week 27) will be compared between two treatment groups using the logistic 
regression model based on LOCF (last observation carried forward) imputation for the missing 
data, that is, the last observed non-missing post-baseline value will be carried forward for the 
missing post baseline assessments. The model will include the treatment group as factor and 
adjust for the baseline PANSS total score and drinking status. 
Table 1: 
Criteria for risk of alcohol consumption on a single drinking day 
Risk Category 
Males 
Females 
Abstinence 
0 g 
0 g 
Low Risk 
1 to 40 g 
1 to 20 g 
Medium Risk 
41 to 60 g 
21 to 40 g 
High Risk 
61 to 100 g 
41 to 60 g 
Very High Risk 
≥101 g 
≥61 g 


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3.7.4. 
Other Efficacy Endpoints 
Other efficacy endpoints for the double-blind treatment period are: 
• The proportion of subjects with psychosocial events indicative of exacerbation of 
symptoms during the double-blind treatment period 
• The rate and number of psychosocial events indicative of exacerbation of symptoms 
during the double-blind treatment period 
• Change from baseline in PANSS total Score, Positive Score, Negative Score, and 
General Psychopathology Score during the double-blind treatment period 
• Change from baseline in Clinical Global Impression–Severity (CGI-S) score during 
the double-blind treatment period 
• Clinical Global Impression–Improvement (CGI-I) score during the double-blind 
treatment period 
• Complete response profile of drinking during the double-blind treatment period 
• Change from baseline in visual analogue score (VAS) for perception of desire for 
alcohol during the double-blind treatment period 
3.7.4.1. 
Proportion of Subjects with Psychosocial Events Indicative of Exacerbation of 
Symptoms during the Double-blind Treatment period 
The proportion of subjects with psychosocial events indicative of exacerbation of symptoms 
(defined in study protocol section 11.21) will be analyzed similarly as the primary analysis of the 
primary efficacy endpoint (Section 3.7.2.1). The incidence rate will be estimated by Kaplan-
Meier estimate. The treatment comparison will be performed using the log-rank test and hazard 
ratio will be estimated by the Cox proportional hazards model. 
3.7.4.2. 
Rate and Number of Psychosocial Events Indicative of Exacerbation of 
Symptoms during the Double-blind Treatment Period 
The annualized rate and number of psychosocial events indicative of exacerbation of symptoms 
will be analyzed in the same way as the rate and number of EEDS (Section 3.7.3.1). 
3.7.4.3. 
Change from Baseline in PANSS Total Score, Positive Score, Negative Score, 
and General Psychopathology Score during the Double-blind Treatment Period 
Change from baseline of double-blind period in PANSS total score and subscale scores will be 
analyzed using ANCOVA (analysis of covariance) model with treatment group as factor and 
corresponding baseline value as the covariates for the ITT population. The ANCOVA model will 
be based on the LOCF imputation.  
In addition, PANSS total score will be summarized by visit for the open-label olanzapine 
population. Plot of mean PANSS total score over time from the open-label periods (as overall) 
and through the double-blind period (by treatment group) will be provided for the open-label 
olanzapine population.  


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3.7.4.4. 
Change from Baseline in CGI-S Score during the Double-blind Treatment 
Period 
The analysis of change from baseline in CGI-S score during the double-blind treatment period 
will be ANCOVA and LOCF method for the ITT population, similar to Section 3.7.4.3.  
3.7.4.5. 
Clinical Global Impression–Improvement (CGI-I) Score during the double-blind 
Treatment Period 
CGI-I scores will be analyzed based on the subject’s by-visit responder status (≤2 versus >2) 
using the logistic regression model based on LOCF imputation for missing data. The model will 
include the treatment group as factor and the baseline PANSS as the covariate.  
3.7.4.6. 
Complete Response Profile of Drinking during the Double-blind Treatment 
Period 
Complete response profile of drinking during the double-blind treatment period will be analyzed 
by the following endpoints: 
• Proportion of subjects with at least 1 level decrease in World Health Organization 
(WHO) drinking risk level from baseline by visit 
• Proportion of subjects with at least 2 levels decrease in World Health Organization 
(WHO) drinking risk level from baseline by visit 
• Proportion of subjects abstinent from heavy drinking days from randomization 
through week 24 of the double-blind treatment period (study week 27) 
• Proportion of subjects abstinent from heavy drinking days by visit 
• Proportion of subjects abstinent from drinking days by visit 
• Number and rate of heavy drinking days 
• Number and rate of drinking days 
• Percent of heavy drinking days cumulatively from baseline through weeks 12, 24, 36, 
48 and 60 of the double-blind treatment period 
• Percent of drinking days cumulatively from baseline through weeks 12, 24, 36, 48 
and 60 of the double-blind treatment period 
• Percent of heavy drinking days by visit during the double-blind treatment period 
• Percent of drinking days by visit during the double-blind treatment period 
• Number of drinks per day by visit during the double-blind treatment period 
• Number of drinks per drinking day by visit during the double-blind treatment period 
In general for the TLFB assessment, by-visit result is defined as the drinking assessments 
between previous and current visits. It will be 2 weeks of drinking assessments for Visit 9 Week 
5 and Visit 10 Week 7, and monthly thereafter. 


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3.7.4.6.1. Categorical endpoints for the Complete Response Profile of Drinking 
The following categorical endpoints for the complete response profile of drinking during the 
double-blind treatment period will be analyzed using a logistic regression model. 
• Proportion of subjects with at least 1 level decrease in World Health Organization 
(WHO) drinking risk level from baseline by visit 
• Proportion of subjects with at least 2 levels decrease in World Health Organization 
(WHO) drinking risk level from baseline by visit 
• Proportion of subjects abstinent from heavy drinking days from randomization 
through week 24 of the double-blind treatment period (study week 27) 
• Proportion of subjects abstinent from heavy drinking days by visit 
• Proportion of subjects abstinent from drinking days by visit 
The model will include treatment as factor and adjust for baseline PANSS and drinking status. 
LOCF imputation will be used for the by-visit summary. 
3.7.4.6.2. Number and Rate of Heavy Drinking Days or Drinking Days 
Considering heavy alcohol drinking days or drinking days as recurrent events, an Anderson-Gill 
model will be used to analyze the time-to-recurrent events, similar to Section 3.7.3.1.1. 
Weekly alcohol drinking and heavy drinking rate will be summarized by treatment groups and 
compared by the negative binomial model, similar to Section 3.7.3.1.2. 
3.7.4.6.3. Percent of Heavy Drinking Days or Drinking Days Cumulatively through Weeks 
12, 24, 36, 48 and 60 of the Double-blind Treatment Period 
Percent of heavy drinking days or drinking days cumulatively through weeks 12, 24, 36, 48 and 
60 of the double-blind treatment period (corresponding to study weeks 15, 27, 39, 51 and 63) 
will be compared between two treatment groups using the Wilcoxon rank sum test.  
Cumulative frequency distributions of percent of heavy drinking days or drinking days through 
week 60 of the double-blind treatment period will be presented by treatment group with 
horizontal axis as percent of heavy drinking days and vertical axis as corresponding proportion 
of subjects in each treatment group.  
Two sensitivity analyses will be conducted. First analysis will exclude any drinking records after 
the discontinuation of the double-blind study drug or after any forced abstinence to control for 
carryover effects. Forced abstinence is defined as greater than 4 days of hospitalization or any 
incarceration. Additional sensitivity analysis will exclude any drinking records after 
discontinuation of the double-blind study drug or incarceration or 1 week of drinking records 
after greater than 4 days of hospitalization.  
3.7.4.6.4. Percent of Heavy Drinking Days or Drinking Days by Visit during the Double-
blind Treatment Period 
Percent of alcohol heavy drinking days or drinking days will be presented by visit and by 
treatment groups. In addition, plot of mean percent of heavy drinking days or drinking days by 


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visit from the open-label periods (as overall) and through the double-blind period (by treatment 
group) will be provided for the open-label olanzapine population. 
3.7.4.6.5. Number of Drinks Per Day and Per Drinking Day by Visit during the Double-
blind Treatment Period 
Number of drinks per day and per drinking day during the double-blind treatment period will be 
summarized by the treatment group and by visit.  
3.7.4.7. 
Change from Baseline in Visual Analogue Score (VAS) for Perception of Desire 
for Alcohol during the Double-blind Treatment Period 
The analysis of change from baseline in VAS score for perception of desire for alcohol during 
the double-blind treatment period will be ANCOVA and LOCF method, similar to 
Section 3.7.4.3.  
3.7.5. 
Exploratory Endpoints 
Exploratory endpoints during the double-blind treatment period are:  
• Change from baseline in cigarette use questionnaire during the double-blind treatment 
period 
• Change from baseline in Personal and Social Performance (PSP) score during the 
double-blind treatment period 
• Time from randomization to the discontinuation of the study drug during the 
double-blind treatment period 
Cigarette use questionnaire and PSP score (results and change from baseline) will be 
summarized using descriptive statistics at each visit in the double-blind treatment period.  
Time from randomization to the discontinuation of the study drug during the double-blind 
treatment period will be compared between ALKS 3831 and olanzapine for the safety 
population, similar to Section 3.7.2.1.  
3.8. 
Safety Analysis 
3.8.1. 
Adverse Events 
Adverse events will be coded by System Organ Class and Preferred Term using the Medical 
Dictionary for Regulatory Activities Version 18.0 (MedDRA®). The verbatim term will be 
included in the AE listings. 
An AE (classified by preferred term) will be considered as treatment-emergent AE (TEAE) if the 
event is newly occurring or worsening on or after the first dose of study drug.  
A TEAE will be summarized for the open-label olanzapine population in the open-label 
olanzapine period, and for the ALKS 3831 populations in the ALKS 3831 period.  
TEAE will be summarized by treatment group for the safety population in the double-blind 
period. A TEAE will be summarized in the double-blind period if it starts between the date of the 


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first dose of study drug (inclusive) and the date of the last dose of samidorphan or placebo in the 
double-blind period.  
The number and percentage of subjects reporting TEAEs in each treatment group during the 
double-blind period will be presented by treatment group and the following categories: 
• system organ class and preferred term 
• preferred terms in decreasing frequency 
• system organ class, preferred term, and severity 
• system organ class, preferred term, and relationship 
• system organ class, preferred term for drug-related TEAEs 
If more than one AE is coded to the same preferred term for the same subject for the same 
period, the subject will be counted only once for that preferred term using the most severe and 
most related occurrence for the summarization by severity and by relationship to the study drug. 
The incidence of most frequently reported (≥ 5% of subjects in any treatment group) TEAEs for 
the double-blind period will be summarized by system organ class, preferred term, and treatment 
group and will be sorted by decreasing frequency for ALKS 3831 group. It will also be 
summarized by the olanzapine dose level at randomization.  
Newly-emergent AEs (NEAEs), defined as AEs that started or worsened after the date of the last 
dose of study drug during the treatment period will also be summarized for the follow-up safety 
population. 
The number and percentage of subjects who have serious adverse events (SAE) will be 
summarized by preferred term and overall for open-label periods. It will be summarized by 
preferred term and treatment group for the double-blind period and will be sorted by decreasing 
frequency for ALKS 3831 group. A listing of subjects with SAEs for entire study will be 
provided by period. The number and percentage of subjects who have AEs leading to premature 
discontinuation from the study will be summarized in the same way as SAEs. 
3.8.2. 
Other significant adverse events 
In addition, incidence of selected subset of relevant AEs in this class of drugs, including 
extrapyramidal symptom (EPS) TEAEs, AEs associated with abuse potential and suicide related 
events, etc. will be summarized by treatment group and preferred term. The selection of AEs will 
be based on Standardized MedDRA queries (SMQs). 
3.8.3. 
Clinical Laboratory Parameters 
Laboratory parameters will be presented in conventional units. Only scheduled laboratory 
parameters will be included in the summaries. All laboratory data, including those collected at 
unscheduled visits, will be included in the listings. 
Laboratory results (baseline and change from baseline) for chemistry and hematology parameters 
will be summarized as overall for open-label periods and by treatment group for the double-blind 
period. 


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Clinical laboratory test values, scheduled or unscheduled, will be considered potentially 
clinically significant (PCS) if they meet PCS criteria listed in Table 2. The number and 
percentage of subjects who have PCS post baseline clinical laboratory values will be tabulated by 
treatment group for the double-blind period. The percentages will be calculated relative to the 
number of subjects with available non-PCS baseline values and at least 1 post baseline 
assessment for the double-blind treatment period. The numerator will be the total number of 
subjects with available non-PCS baseline values and at least 1 PCS post baseline value for the 
double-blind treatment period. A supportive tabular display of subjects with PCS post baseline 
values will be provided, including the subject ID number, study center number, baseline, and all 
post baseline (including non-PCS) values. 
Table 2: 
Criteria of Potentially Clinically Significant (PCS) Abnormality for Selected 
Analytes 
Parameters 
Criteria 
Albumin 
<2.5 g/dL 
Alkaline phosphatase (U/L) 
≥3 × ULN 
Alanine aminotransferase (U/L) 
≥3 × ULN 
Aspartate aminotransferase (U/L) 
≥3 × ULN 
Bilirubin, total 
≥2.0 mg/dL 
Blood urea nitrogen 
>30 mg/dL 
Cholesterol, random 
>300 mg/dL 
Cholesterol, fasting 
≥240 mg/dL 
Cholesterol, HDL fasting 
≤30 mg/dL 
Cholesterol, LDL fasting 
≥160 mg/dL 
Creatine kinase (U/L) 
≥3 × ULN 
Creatinine 
≥2.0 mg/dL 
Glucose, random 
<50 mg/dL or 
≥200 mg/dL 
Glucose, fasting 
≥126 mg/dL 
Potassium 
<3 mmol/L or 
>5.5 mmol/L 
Lactate dehydrogenase (U/L) 
>3 × ULN 
Phosphate 
<2 mg/dl or 
>5 mg/dl 
Prolactin (female) 
>30 ng/mL 
Prolactin (male) 
>20 ng/mL 
Sodium 
<130 mmol/L or 
>150 mmol/L 


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Table 2: 
Criteria of Potentially Clinically Significant (PCS) Abnormality for Selected 
Analytes (Continued) 
Parameters 
Criteria 
Triglycerides, fasting (female) 
≥120 mg/dL 
Triglycerides, fasting (male) 
≥160 mg/dL 
 
Table 3: 
Potentially Clinically Significant Results Criteria for Hematology 
Parameters 
Criteria 
Eosinophils 
>1.0 × 103/μL 
Hematocrit (female) 
≤32% 
Hematocrit (male) 
≤37% 
Neutrophils, absolute 
<1.5 × 103/μL 
Platelets 
<75.0 × 103 cells/μL or 
≥ 700.0 × 103 cells/μL 
Leukocytes 
≤ 2.8 × 103/μL or 
≥ 16.0 x103/μL 
Shift tables for metabolic parameters (glucose, total cholesterol, LDL, HDL, triglycerides, and 
HbA1c will be presented. 
3.8.4. 
Weight, Body Mass Index, Waist Circumferences and Vital Signs 
3.8.4.1. 
Weight, Body Mass Index, Waist Circumferences 
Weight (kg), BMI (kg/m2) and waist circumferences (baseline and change from baseline) for 
each visit will be summarized as overall for the open-label periods and by treatment group for 
the double-blind periods. Height (cm) will be measured at screening visit and this value will be 
used for the calculation of the BMI. All weight and BMI data will be listed. 
Number and percentage of subjects with weight change values considered as PCS occurring at 
any post-baseline visit will be summarized by treatment group for the double-blind period. 
Criteria for PCS are presented below. The percentages will be calculated relative to the number 
of subjects in the safety population. A supportive listing will present all body weight for a 
subject and parameter for cases where at least one value was potentially significant. 
Table 4: 
Criteria for Potentially Clinically Significant (PCS) Changes from Baseline 
in Body Weight 
Parameter 
Criteria 
Body Weight 
Decrease from Baseline ≥7% 
Increase from Baseline ≥7% 


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3.8.4.2. 
Vital Signs 
Descriptive statistics for vital signs and changes from baseline values at each scheduled time 
point will be presented as overall for the open-label periods and by treatment group for the 
double-blind period. 
Vital sign values will be considered PCS if they meet both the observed-value criteria and the 
change-from-baseline criteria listed in Table 5. The number and percentage of subjects with PCS 
post baseline values will be tabulated by treatment group for the double-blind period. The 
percentages will be calculated relative to the number of subjects with available baseline values 
and at least 1 post baseline assessment for the double-blind period. The numerator will be the 
total number of subjects with available baseline values and at least 1 PCS post baseline value for 
double-blind period. A supportive tabular display of subjects with PCS post baseline values will 
be provided, including the subject ID number, study center number, and baseline and all post 
baseline (including non-PCS) values. 
All vital signs will be presented in the subject data listing. 
Orthostatic hypotension (20/10) is defined as a fall in systolic blood pressure of at least 
20 mmHg and a fall in the diastolic blood pressure of at least 10 mmHg upon standing from 
supine. Orthostatic hypotension (30) is defined as a fall in systolic blood pressure of at least 
30 mmHg upon standing from supine. 
Orthostatic tachycardia is defined as a heart rate increase of 30 beats per minute (bpm) or more 
upon standing from supine, or over 120 bpm upon standing. 
The number and percentage of subjects with orthostatic hypotension or orthostatic tachycardia 
occurring at any post-baseline visit will also be summarized by treatment group for the 
double-blind period. 
Table 5: 
Criteria for Potentially Clinically Significant (PCS) Blood Pressure or Pulse 
Rate 
Parameter 
Criteria 
Supine Systolic Blood Pressure 
≤90 and decrease ≥20 mm Hg 
≥180 and increase ≥20 mm Hg 
Supine Diastolic Blood Pressure 
≤50 and decrease ≥15 mm Hg 
≥105 and increase ≥15 mm Hg 
Supine Heart Rate 
≤50 and decrease ≥15 bpm 
≥120 and increase ≥15 bpm 
3.8.5. 
Electrocardiograms 
Descriptive statistics for ECG parameters (heart rate, PR interval, QRS interval, QT interval, and 
QTc interval) at baseline and change from baseline values at each assessment time point will be 
presented as overall for the open-label periods and by treatment group for the double-blind 
period. QTc interval will be calculated using both Bazett (QTcB = QT/(RR)½) and Fridericia 
(QTcF = QT/(RR)⅓) corrections; if RR is not available, it will be replaced with 60/HR in the 
correction formula. 


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Electrocardiogram parameter values are considered PCS if they meet or exceed the higher-limit 
PCS criteria listed in Table 6. The number and percentage of subjects with PCS post baseline 
ECG values will be tabulated by treatment group for the double-blind treatment period. The 
percentages will be calculated relative to the number of subjects with available non-PCS baseline 
values and at least 1 post baseline assessment for the double-blind treatment period. The 
numerator is the total number of subjects with available non-PCS baseline values and at least 
1 PCS post baseline value for the double-blind treatment period. A supportive tabular display of 
subjects with PCS post baseline values will be provided, including the subject ID number, study 
center number, baseline, all post baseline (including non-PCS) values, and change from baseline. 
Table 6: 
Criteria for Potentially Clinically Significant (PCS) QTcB and QTcF 
Parameter 
Criteria 
QTcB and QTcF 
>450 to ≤480 msec 
 
and change from baseline ≤30 msec 
 
and change from baseline >30 to ≤60 msec 
 
and change from baseline >60 msec 
>480 to ≤500 msec 
 
and change from baseline ≤30 msec 
 
and change from baseline >30 to ≤60 msec 
 
and change from baseline >60 msec 
>500 msec 
 
and change from baseline ≤30 msec 
 
and change from baseline >30 to ≤60 msec 
 
and change from baseline >60 msec 
Change from baseline >30 to ≤60 msec 
Change from baseline >60 msec 
3.8.6. 
Abnormal Movement Scales 
Extra pyramidal symptoms (EPS) will be evaluated as AEs and also as assessed by abnormal 
movement scales. Abnormal movement scales will include the following: Abnormal Involuntary 
Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale 
(SAS). 
For all abnormal movement scales, total scores and subscale scores will be summarized by 
treatment group at each visit for the absolute value and for changes from baseline. 
Number and percentage of subjects meeting the criteria for treatment emergent Parkinsonism 
(SAS total score>3), for treatment emergent akathisia (BARS global clinical assessment of 
akathisia score ≥2), for treatment emergent dyskinesia (AIMS score ≥3 on any of the first 
7 items, or a score ≥2 on two or more of any of the first 7 items) at any post-baseline visit will be 
summarized by treatment group.  


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A listing will be provided for every abnormal movement scale. Listing for treatment emergent 
EPS will be provided.  
3.8.7. 
Columbia Suicide Severity Rating Scale (C-SSRS) 
The C-SSRS is a questionnaire used to measure the presence and intensity of suicidal ideation 
and behavior. 
Suicidal behavior and suicidal ideation will be summarized descriptively. The number of 
subjects with suicidal ideation and suicidal behavior at lifetime history, open-label periods and 
double-blind treatment period and safety follow-up period will be summarized by overall or by 
treatment group when applicable. 
Supportive tabular display of subjects with all values will be provided, including subject ID 
number, treatment group, visit number, intensity of suicidal ideation, suicidal behavior type, and 
lethality of suicidal behavior. 
Table 7: 
C-SSRS Categories for Analysis  
Category 
C-SSRS Item response is "YES"  
Suicidal behavior 
• 
Preparatory acts or behavior 
• 
Aborted attempt 
• 
Interrupted attempt 
• 
Actual attempt 
• 
Complete suicide 
Suicidal ideation 
• 
Wish to be dead 
• 
Non-specific active suicidal thoughts 
• 
Active suicidal ideation with any methods (not 
plan) without intent to act 
• 
Active suicidal ideation with some intent to act, 
without specific plan 
• 
Active suicidal ideation with specific plan and 
intent 
3.9. 
Pharmacokinetic/Pharmacodynamic Data Analysis 
Subject listings for PK sampling time, prior drug dosing time, and plasma concentrations of 
olanzapine, samidorphan, and RDC-9986 (metabolite of samidorphan) will be provided. Plasma 
concentration data obtained from this study may be included in a subsequent population PK 
analysis or other post-hoc analyses. 
4. 
INTERIM ANALYSES 
Not applicable.  


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5. 
CHANGES IN CONDUCT OR PLANNED ANALYSES FROM 
THE PROTOCOL 
Two endpoints, which have been included in the study protocol as the other endpoints, are 
elevated to the secondary endpoints in the SAP (Section 3.7.3).  
Three exploratory endpoints, which have not been specified in the protocol, are included in the 
SAP (Section 3.7.5). 
6. 
DEFINITIONS AND CONVENTIONS FOR HANDLING OF THE 
DATA 
Dataset specifications will be provided in a separate document. 
6.1. 
Analysis Visit Windows 
Scheduled analysis visits are visits upon scheduled time points as specified in the protocol 
(Table 1-3 Schedule of Visits and Assessments). 
Scheduled analysis visits during the study period will be the same as the nominal visits collected 
in eCRF. There will be one valid value of assessment kept for each scheduled analysis visit 
in summary/analysis statistics. 
Unscheduled visits are visits with data not collected on the scheduled time point. Unscheduled 
visits will not be used for by-visit summary/analysis statistics unless specified otherwise. 
All unscheduled visits will be included as collected in eCRF in listings. 
The V38/ET visit can be mapped to a scheduled visit and be used for analysis and summaries 
only if there is no valid value already at the mapped visit. 
A mapped V38/ET visit will be treated as a scheduled visit to be included in table summaries. 
Otherwise, it will be treated as an unscheduled visit. 
Four rules will be used to map an ET visit. 
• First, a 7-day (inclusive) window (≤ last dose date + 7) will be used to determine if 
the assessment at the ET visit is considered to be an on-treatment result. If an ET visit 
is within 7 days after the last dose of samidorphan/placebo, it will be considered as a 
valid on-treatment visit. 
• Second, visit windows (inpatient stay is excluded) will be applied to determine to 
which visit a V38/ET valid on-treatment assessment can be mapped to. Visit windows 
are defined in Table 8 below. 
Table 8: 
Visit Window Definition 
Analysis Visit to be 
Mapped to 
Target Study Day 
Visit Day 
Visit Window 
Visit 2 
Study day -28 
Day -28 
[-28, -25] 
Visit 3 
Study day -21 
Day -21 
[-24,-18] 


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Table 8: 
Visit Window Definition (Continued) 
Analysis Visit to be 
Mapped to 
Target Study Day 
Visit Day 
Visit Window 
Visit 4 
Study day -14 
Day -14 
[-17,-11] 
Visit 5 
Study day -7 
Day -7 
[-10, 0] 
Visit 6 
Study day 1 
Day 1 
1 
Visit 7 
Study day 8 
Day 8 
[2, 11] 
Visit 8 
Week 3 
Day 15 
[12, 21] 
Visit 9 
Week 5 
Day 29 
[22, 35] 
Visit 10 
Week 7 
Day 43 
[36, 57] 
Visit 12 
Week 11 
Day 71 
[58, 85] 
Visit 14 
Week 15 
Day 99 
[86, 113] 
Visit 16 
Week 19 
Day 127 
[114, 141] 
Visit 18 
Week 23 
Day 155 
[142, 169] 
Visit 20 
Week 27 
Day 183 
[170, 197] 
Visit 22 
Week 31 
Day 211 
[198, 225] 
Visit 24 
Week 35 
Day 239 
[226, 253] 
Visit 26 
Week 39 
Day 267 
[254, 281] 
Visit 28 
Week 43 
Day 295 
[282, 309] 
Visit 30 
Week 47 
Day 323 
[310, 337] 
Visit 32 
Week 51 
Day 351 
[338, 365] 
Visit 34 
Week 54 
Day 379 
[366, 393] 
Visit 36 
Week 59 
Day 407 
[394, 421] 
Visit 38 
Week 63 
Day 435 
[422, Day of Safety follow-up -1] 
Visit Day is calculated as visit date – date of the first dose of ALKS 3831 (scheduled on Visit 6) 
+ 1. 
• Third, V38/ET visit can only be mapped to the same treatment period as the last 
scheduled visit. Otherwise, ET visit will be considered as unscheduled visit. 
Additionally, V38/ET visit can only be mapped to a scheduled visit that a particular 
assessment is taken based on the protocol.  
• Four, for subjects who discontinued before visit 6, an on-treatment V38/ET results as 
defined above, will be mapped to the next scheduled visit, if within the same 
treatment period as the last scheduled visit.  
Last post baseline values are defined as the last valid post baseline values collected for each 
subject during the treatment period or a specified reporting period.  


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6.2. 
Handling of Partial Dates of Concomitant Medication 
Partial start dates of prior and concomitant medications will be assumed to be the earliest 
possible date consistent with the partial date. Partial stop dates of prior and concomitant 
medications will be assumed to be the latest possible date consistent with the partial date. In 
the case of completely missing stop date, medication will be assumed to be ongoing. 
6.3. 
Handling of Safety Data 
All efforts should be made to obtain the missing information from the investigator. For C-SSRS, 
vital signs, laboratory testing (chemistry, hematology, urinalysis), and 12-lead ECGs, only 
observed data will be used for analyses, and missing data will not be imputed. 
7. 
GENERAL STATISTICAL METHODOLOGY 
In general, summary statistics (n, mean, standard deviation [SD], median, minimum, and 
maximum for continuous variables, and number and percentage of subjects in each category for 
categorical variables) will be provided by treatment group. All summary tables will be based on 
observed data, and missing values will not be imputed unless otherwise indicated. Measurements 
collected from unscheduled visits or repeated assessments will not be included in the by-visit 
summary tables or figures, or the derivation of the last post-baseline value during treatment, but 
will be included in the analyses for the PCS post-baseline values, and subject listings. Source 
data for the summary tables and statistical analyses will be presented as subject data listings. 
7.1. 
Reporting Precision 
Summary statistics will be presented to the following degree of precision, unless otherwise 
specified: 
Table 9: 
Degree of Precision 
Statistics 
Degree of Precision 
Mean, Median, Confidence limit boundaries 
One more than the raw data, up to 3 decimal places. 
Standard deviation, Standard error 
One more than the mean, up to 3 decimal places 
Minimum, Maximum 
The same as the raw data, up to 2 decimal places 
p-value 
Rounded to 3 decimal places and therefore presented as 
0.xxx; p-values smaller than 0.001 as ‘<0.001’; p-values 
greater than 0.999 as ‘>0.999’. 
Percentage 
One decimal place. A percentage of 100% will be reported 
as 100%. Percentages of zero will be reported as 0. 
Fractional numeric values will be presented with a zero to the left of the decimal point (for 
example, 0.12 – 0.30). 
For weight, height, and body mass index (BMI), one decimal place will be used for summary 
statistics. 


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8. 
PROGRAMMING SPECIFICATIONS 
Programming specifications will be provided in a separate document. 
9. 
MOCK TABLE LISTING AND FIGURES (TLF) 
Mock-up tables and listings will be provided in a separate document. 
10. 
REFERENCES 
1. Alkermes ALK3831-401 Study Protocol Amendment 6 (dated 01 March 2016) 
2. Independent Adjudication Committee Charter Version 0.6 (dated 01 March 2016)  
3. Heather N and Rollnick S. Readiness to change questionnaire: user’s manual (revised 
version) 1993. 
4. Witkiewitz K, Hallgren KA et al. Clinical validation of reduced alcohol consumption 
after treatment for alcohol dependence using the World Health Organization risk drinking 
level. Alcoholism: Clinical and Experimental Research 2017; 41: 179-186