Motivational Interviewing for Patients With Acute Psychosis
Phase: NA
Conditions: Psychosis, Schizophrenia
Sponsor: Psychiatric University Hospital, Zurich

 
Study protocol MIA, Version 1, 16/12/2022 
 
 
 
 
Motivational Interviewing for patients with acute psychosis. 
 
 
 
 
Study Type: 
 Other Clinical Trial according to ClinO, Chapter 4 
 
Risk Categorisation:  
Risk category A according to ClinO, Art. 61 
 
Study Registration: 
“Motivational Interviewing for patients with acute psychosis” 
(MIA) 
 
Registration intended: SNCTP (CH-Register) und clinicaltrial.gov 
 
Sponsor-Investigator: 
 University of Zurich  
Prof. Dr. med. PhD Philipp Homan 
Lenggstrasse 31 
8032 Zurich, Switzerland  
 +41 58 384 22 26 
 philipp.homan@bli.uzh.ch 
 
Study coordinator: 
 
Dr. phil. Rahel Horisberger  
 +41 58 384 26 52 
 rahel.horisberger@pukzh.ch 
 
 
Investigated Intervention: 
Psychotherapeutic intervention for patients with psychosis using 
the method of “Motivational Interviewing” on acute psychiatric 
wards. 
 
Version and Date: 
 
Version 2.0 (dated 10/02/2023) 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and the property of the Psychiatric 
University Hospital Zurich. The information may not - in full or in part - be transmitted, repro-
duced, published, or disclosed to others than the applicable Competent Ethics Committee and 
Regulatory Authority(ies) without prior written authorisation from the sponsor except to the ex-
tent necessary to obtain informed consent from those who will participate in the study. 
 
 

Study protocol MIA, Version 2, 10/02/2023 
 
 
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PROTOCOL SIGNATURE FORM    
 
 
Study Title 
Motivational Interviewing for patients with acute psychosis 
Study ID 
MIA 
 
The Sponsor-Investigator has approved the protocol version 2.0 (dated 10/02/2023) and confirm 
hereby to conduct the study according to the protocol, current version of the World Medical As-
sociation Declaration of Helsinki, and ICH-GCP guidelines as well as the local legally applicable 
requirements. 
 
 
Sponsor-Investigator: 
 
Name:   Philipp Homan 
Date:  
 _________________________      Signature: 
 ___________________________  
 
 
 
 
 

Study protocol MIA, Version 2, 10/02/2023 
 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS 
2 
GLOSSARY OF ABBREVATIONS 
3 
1 BACKGROUND AND RATIONALE 
4 
2 STUDY OBJECTIVES AND DESIGN 
5 
2.1 Hypothesis and Objectives 
5 
2.2 Primary and secondary endpoints 
5 
2.3 Study design 
6 
2.4. Study intervention 
6 
3 STUDY POPULATION AND STUDY PROCEDURES 
7 
3.1 Inclusion and exclusion criteria, justification of study population 
7 
3.2 Recruitment, screening and informed consent procedure 
8 
3.3 Study procedures 
9 
3.4 Withdrawal and discontinuation 
12 
4 STATISTICS AND METHODOLOGY 
12 
4.1. Statistical analysis plan and sample size calculation 
12 
4.2. Handling of missing data and drop-outs 
13 
5 REGULATORY ASPECTS AND SAFETY 
13 
5.1 Local regulations / Declaration of Helsinki 
13 
5.2 (Serious) Adverse Events and notification of safety and protective measures 
13 
5.3 (Periodic) safety reporting 
14 
5.4 Radiation 
14 
5.5 Pregnancy 
14 
5.6 Amendments 
14 
5.7 Notification and reporting upon completion, discontinuation or interruption of the 
study 
15 
5.8 Insurance 
15 
6 FURTHER ASPECTS 
15 
6.1 Overall ethical considerations 
15 
6.2 Risk-benefit assessment 
15 
7 QUALITY CONTROL AND DATA PROTECTION 
16 
7.1 Quality measures 
16 
7.2 Data recording and source data 
16 
7.3 Confidentiality and coding 
17 
7.4 Retention and destruction of study data and biological material 
17 
8  MONITORING AND REGISTRATION 
17 
9. FUNDING / PUBLICATION / DECLARATION OF INTEREST 
18 
10. REFERENCES 
19 
 
 

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GLOSSARY OF ABBREVATIONS 
 
AE 
Adverse Event 
ASR 
Annual Safety Repot 
BARS 
 
Brief Adherence Rating Scale 
BASEC 
Business Administration System for Ethical Committees 
ClinO 
Ordinance on Clinical Trials in Human Research (in German: KlinV) 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSM-IV 
Diagnostic and Statistical Manual of Mental Disorders, Version 4 
FADP 
Federal Act on Data Protection (in German: DSG) 
FOPH 
Federal Office of Public Health 
FPTM 
Fragebogen zur Erfassung der Psychotherapiemotivation (in English: Question-
naire to measure the motivation for psychotherapy) 
GCP 
Good Clinical Practice 
GSE  
General Self-Efficacy Scale 
G*Power 
 
G*Power Statistical Power Analyses 
HRA 
Human Research Act  
ICD-10 
International Classification of Diseases, Version 10 
ICH 
International Conference on Harmonisation  
MATRICS 
Measurement and Treatment Research to Improve Cognition in Schizophrenia 
(Consensus Cognitive Battery) 
MI 
Motivational Interviewing 
PANSS 
Positive and Negative Symptom Scale 
PUK 
Psychiatrische Universitätsklinik Zürich (in English: Psychiatric University Hospi-
tal Zurich) 
SAE 
Serious Adverse Event 
SNCTP 
 
Swiss National Clinical Trial Portal 
STAR 
 
Scale to Assess Therapeutic Relationship 
TAU 
 
Treatment as usual 
 
 
 
 
 

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1 
BACKGROUND AND RATIONALE  
Psychosis includes perceptual and cognitive disturbances that are mediated, in most cases, by 
the dysregulation of dopamine and glutamate neurotransmission (Lieberman & First, 2018). The 
main symptoms of the disease have long been subdivided into positive and negative symptoms 
as well as cognitive deficits corresponding to clinical observations. Delusions, hallucinations, 
disorganized speech or behavior are described as the most common positive symptoms. Nega-
tive symptoms include a reduction or complete loss of motivation, interest, or expression (Stahl 
& Buckley, 2007).  
Psychotic disorders are among the top ten causes of long-term disability (Murray & Lopez, 
1996) and have a high chronicity potential and a high risk of invalidity (Kahn et al., 2015). Pa-
tients with psychosis are at risk for complications and derivative effects of psychosis, particularly 
suicide attempts, substance abuse, homelessness, victimization by others, and committing acts 
of violence (Lieberman & First, 2018). Especially schizophrenia, the most frequent form of psy-
chotic disorders, is associated with a more severe course of illness and poorer outcomes com-
pared to other psychotic and non-psychotic disorders (Jobe & Harrow, 2005). One-fifth of all pa-
tients with schizophrenia suffer from chronic symptoms and impairments (Owen et al., 2016), 
and the disease is associated with low long-term work performance(Rabinowitz et al., 2012), a 
high degree of all mental health care resources (Mueser & McGurk, 2004) and high socioeco-
nomic costs (Kennedy et al., 2014). These findings demonstrate the importance of sufficient 
treatment for psychotic disorders and, most importantly, point to a need for research so that 
more effective treatments can be developed in the future. 
Psychotherapeutic interventions for psychosis 
In the recent decade, various psychotherapeutic programs with cognitive-behavioral back-
ground have been developed for patients with psychosis, and their efficacy has been investi-
gated(Lincoln & Pedersen, 2019; Galderisi et al., 2021). Meta-analyses have shown superiority 
of cognitive-behavioral therapy for psychosis over standard treatment, both in combination with 
antipsychotic medication and without (Morrison et al., 2012, 2014). Many of the psychological 
approaches have focused primarily on treating the deficits associated with psychosis, as for ex-
ample cognitive remediation or social skills training (Bark et al., 2003; Aghotor et al., 2010; Puig 
et al., 2014; Mehl & Lincoln, 2014). However, these methods are not feasible in the acute set-
ting and there are only a few psychotherapeutic instruments that can be used within a short pe-
riod of time for in-patient treatment. 
The NICE-guidelines for the treatment of schizophrenia (National Institute for Health and 
Clinical Excellence, 2010) recommend a combination of antipsychotic medication and psycho-
sis-specific cognitive behavioral therapy. This includes all stages of the illness, also in the acute 
phase (Kuipers et al., 2014). The Swiss Society for Psychiatry and Psychotherapy (SGPP) has 
stated in its treatment guidelines for schizophrenia that "our group recommends a structured 
psychotherapeutic approach even in the acute phase of the disease. The best evidence cur-
rently exists for cognitive-behavioral approaches, […]. In any case, the psychotherapeutic pro-
cedure must be adapted to the circumstances of the acute phase and there is an urgent need 
for research on how this can be arranged in the setting of an acute ward.” (Kaiser et al., 2016, 
p.10). Despite this explicit recommendation, to our knowledge there have been no studies that 
have systematically investigated this in the acute setting and results of which could therefore 
inform future treatment recommendations. 
Rationale for planned project 
While recent guidelines for the treatment of psychotic disorders recommend to offer psychother-
apy right from the start of the inpatient treatment, it is well known that psychotherapeutic inter-
ventions tend to be offered to patients relatively late in the course of the hospitalization – if at 
all. On the other hand, it has been shown that a majority of symptoms that patients with a psy-
chotic disorder report as disturbing can be treated with psychotherapy (Freeman et al., 2019). 
The challenge is that there is little evidence on which mechanisms of psychotherapy are most 

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effective and applicable in the acute phase. As proposed by the SGPP, we would like to sys-
tematically test and evaluate psychotherapeutic interventions in the setting of an acute care unit 
in an initial pilot trial.  
Expected relevance 
Therapeutic alliance during the acute phase of psychotic illness is one of the most pressing ob-
stacles for successful long term recovery (e.g. Cavelti et al., 2016). In order for patients to ac-
cept much-needed medication and psychosocial therapy and not drop out prematurely, intrinsic 
motivation to adhere to therapy is crucial. Motivational Interviewing is a method, that has been 
developed and evaluated over the last three decades and that shows promising results, not only 
for patients with addiction but also for other patients who struggle with compliance and ambiva-
lence towards treatment and change of behavior. For further information on the method see 
chapter 3.4. Study intervention. 
At the same time, it is well known from clinical experience that patients are offered psychother-
apy only late during the course of hospitalizations and not when it is most needed – during the 
acute phase of their illness. Accordingly, there is a clear gap in the literature as to which inter-
ventions are particularly useful in this challenging yet crucial phase of the illness.  
We believe that the current project and the psychotherapeutic interventions tested here, can 
provide valuable data on acceptance, feasibility and effectiveness of such interventions and 
which can then be used to supplement a large multicentre trial across Switzerland. 
 
2 
STUDY OBJECTIVES AND DESIGN  
2.1 Hypothesis and Objectives 
The primary objective of the study is to investigate the impact of a brief intervention with Moti-
vational Interviewing in an acute psychiatric inpatient setting on factors that impact treatment 
outcome such as therapeutic alliance and adherence to treatment. 
The second objective is to examine if the effect of Motivational Interviewing can be measured 
in changes in symptom severity.  
The third objective is to examine secondary effects of Motivational Interviewing on motivation 
for further psychotherapeutic treatment and higher expectations of self-efficacy after discharge 
from the hospital. 
 
Therefore, the study grounds on three hypotheses: 
1. Four sessions of psychotherapeutic intervention with motivational interviewing for newly ad-
mitted acute patients improves the therapeutic alliance and the adherence for treatment 
compared to supportive counseling. 
2. Four sessions of psychotherapeutic intervention with motivational interviewing for newly ad-
mitted acute patients decreases symptom severity compared to supportive counseling. 
3. Patients show higher motivation to seek psychotherapeutic treatment and have a higher 
self-efficacy expectation after leaving the inpatient stay, when they received an intervention 
with motivational interviewing compared to supportive counseling. 
2.2 Primary and secondary endpoints 
Primary endpoints are the therapeutic alliance as assessed with the Scale to Assess Therapeu-
tic Relationship STAR (McGuire-Snieckus et al., 2007) and adherence to treatment as meas-
ured with the Brief Adherence Rating Scale BARS (Byerly et al., 2008). These variables will be 
measured before and after the study intervention or control intervention. 
Secondary endpoints include changes in symptom severity as assessed with the Positive and 

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Negative Symptom Scale PANSS (Kay et al., 1987), as well as the motivation for psychotherapy 
(measured with the German version of the Questionnaire to measure the motivation for psycho-
therapy by Schulz et al., 1995) and self-efficacy (measured with the General Self-Efficacy Scale 
by Schwarzer & Jerusalem, 1995). All secondary variables will be measured before and after 
the study intervention or control intervention. 
As this study (risk category A) does not include drugs or other medical products and patients 
are hardly exposed to any more risks than in routine clinical care, no safety endpoints are de-
fined.  
2.3 Study design  
This will be an interventional study with randomized control and open label trial. A parallel-group 
design with pre- and post-measurements (longitudinal design) will be employed, using subjec-
tive and objective measurements with questionnaires and structured interviews. It is a single 
center and national project. 
The study consists of five phases: 
1. Screening: Screening will be conducted by the applicant and master’s students enrolled in 
the project who are bound to medical confidentiality, using electronic patient files at the hospital. 
The patients will be invited to the study by their treating physician or psychologist. 
2. Pre-interventional measurement (1 session within the first week, max. 60minutes): 
First, the psychopathological symptoms are to be assessed in order to decide about inclusion or 
exclusion (with PANSS; see also inclusion criteria). In addition, the therapeutic alliance and mo-
tivation for psychotherapy are measured. In order to record moderating effects or covariables, 
demographics (e.g. age, gender, education, years of illness) and two additional questionnaires 
will be added (attitude towards recovery and the individual motives). 
3. Intervention (4 sessions within two weeks, 25- 40 minutes/session):  
The patients receive either four sessions of motivational interviewing (intervention group) or four 
sessions of supportive counseling (control group). For Details see 2.4 “Study intervention”  
4. Post-interventional measurement (1 session, max. 60 minutes): At the end of the intervention 
the motives, the negative symptoms, the hope for recovery, well-being and the level of function-
ing will be measured again. 
 
The risk of bias should be kept at a minimum. Various precautions are being taken to this end.  
- 
The most important confounding variables are controlled to prevent a bias.  
- 
In order to avoid selection bias, patients are randomly assigned either to the intervention 
group or to the control group. Randomization is carried out at a 1:1 ratio, using pre-defined 
random lists (using the online randomization generator: http://www.pub-
med.de/tools/zufallsgenerator) and a block schema prepared by the principal investigator. 
- 
Block randomization ensures that the patients are distributed in the desired proportion to the 
two treatment modalities. All patients are randomized only once during the entire examina-
tion period. 
- 
For minimizing bias some patients will have to be excluded from the study (see exclusion 
criteria)  
- 
The study will be conducted as single-blind, as it is possible that the expectation towards 
one of the methods could have an impact on the outcomes. 
- 
Raters will be blinded to the intervention and will receive prior training in the application of 
the rating scales. 
2.4. Study intervention 
Motivational interviewing (MI) is an intervention that helps people identify problems as such, 
build and maintain a commitment to change specific behaviors, and actually do so (Miller & 
Rollnick, 2002). It combines elements of behavior analysis with the principles of client-centered 
therapy, in which the patient learns to talk about his or her problems in empathetic but strategic 

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conversations. The therapeutic alliance plays a central role in this process. Ambivalence is not 
seen as resistance, but is respected and explored as a natural phenomenon, in order to support 
the patient's individual decision regarding the pros and cons. MI includes several techniques to 
help to manage ambivalence and decision making. If necessary, the patient is made aware of 
the ambivalences he or she has toward a specific topic (Barkhof et al., 2006).  
In psychosis patients, there are several risk behaviors for relapse described in the literature, 
with the biggest problem of non-adherence to antipsychotic medication (Kane et al., 2013) 
which is consistent with our experience in clinical practice. The goal here is to guide patients to 
identify and increase their own motivation to change their behavior, and ultimately to ensure that 
psychiatric treatment is and remains effective. Accordingly, the overall goal of the intervention is 
to enter into a therapeutic alliance with the patient so that the patient's inner motivation to partic-
ipate in treatment can be increased and the process can begin from within rather than being im-
posed from without.  
Clinician-delivered motivational interviewing has been identified as effective for enhancing ad-
herence among patients with psychosis (Kemp et al., 1996; Chien et al., 2016). Nevertheless, 
the literature also points to a lack of evidence. Although previous studies have shown that MI 
can positively influence important aspects of disease-related impairments, such as medication 
adherence, frequency and severity of psychotic relapses, duration of hospitalization, functional 
level, insight into the disease, and cognitive rehabilitation, data are still insufficient in schizo-
phrenic patients (Reimer et al., 2019). 
 
In our study intervention, patients should receive four session of motivational interviewing 
within two weeks. Throughout the MI sessions, interviewers use common MI techniques includ-
ing open-ended questions, affirmations, reflections, summaries, asking permission, expressing 
empathy, supporting self-efficacy, etc. Interviewers are clinical psychologists who received MI 
training immediately prior to the study. 
 
In the control intervention patients should also be given four sessions, in which no MI tech-
niques take place. They will be carried out in the sense of supportive conversations. Supportive 
conversations aim to promote stabilization of the patient's current state without pursuing a goal 
set by the therapist. Supportive therapy includes tasks such as assistance with everyday re-
quirements, emotional relief in the event of problems, or the provision of a reliable relationship. 
The topics are preferably defined by the patient. The clarification and processing of conflicts and 
problems that underlie the psychopathology is not usually the subject of therapy (Weierstall & 
Schonauer, 2016).   
Since we want to check whether the patients really benefit from the specific intervention and not 
from getting more speaking time, the patient in the control group will also be given four conver-
sations. It is known that supportive conversations can have a certain effect on the well-being 
and recovery process of patients, as the therapeutic relationship, i.e. appreciation, attention 
and/or attention, is an important efficacy factor (e. g. Grawe, 1995). 
 
 
3 
STUDY POPULATION AND STUDY PROCEDURES 
3.1 Inclusion and exclusion criteria, justification of study population 
As the aim of the study is to improve psychotherapeutic treatment in the acute phase of psycho-
sis, the inclusion of patients suffering from this disorder is necessary and cannot be studied in 
healthy people.  
We will recruit newly admitted inpatients from the Psychiatric University Hospital with a diagno-
sis of a psychotic spectrum disorder (schizophrenia, schizoaffective disorder, acute psychotic 

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disorder, psychosis not otherwise specified, bipolar disorder with psychotic features, major de-
pression with psychotic features). Patients are recruited within the first three days of hospitaliza-
tion to test psychotherapeutic interventions in the acute phase of illness. 
 
Patients fulfilling all of the following inclusion criteria may be enrolled in the study: 
- 
Informed consent as documented by signature  
- 
Male and female patients from PUK inpatient units between 18 and 65 years of age  
- 
ICD-10 diagnosis of psychosis (F2) meeting DSM-IV criteria 
- 
Fluent in German and able to understand the instructions 
 
The presence of any one of the following exclusion criteria will lead to exclusion of the partici-
pant: 
- 
Organic schizophrenia-like disorder (ICD: F0.6) 
- 
Cognitive impairments: strongly below average values in more than two cognitive tests (per-
centage rank < 5) 
- 
Drug or alcohol abuse during treatment 
- 
Previous enrolment in the current study 
- 
Enrolment of the investigator, his/her family members, employees and other dependent per-
sons. 
- 
During study: Complete stop of taking antipsychotic medications without the consent of the 
attending physician. 
3.2 Recruitment, screening and informed consent procedure 
Recruitment of patients will take place at the Psychiatric University Hospital Zurich in the form of 
ongoing recruitment by the study coordinator in the clinical setting as well as by other physi-
cians and psychologists at the hospital. The study is presented and reminded to them in regular 
intervals at internal clinic reports. 
The investigators will explain to each participant the nature of the study, its purpose, the proce-
dures involved, the expected duration, the potential risks and benefits and any discomfort it may 
entail. Each participant will be informed that the participation in the study is voluntary and that 
he or she may withdraw from the study at any time and that withdrawal of consent will not affect 
his or her subsequent medical assistance and treatment.  
The participant will be informed that his or her medical records may be examined by authorised 
individuals other than their treating physician. 
All participants for the study will be provided a participant information sheet and a consent form 
describing the study and providing sufficient information for participant to make an informed de-
cision about their participation in the study. Enough time (one to five days) will be given to the 
participant to decide whether to participate or not.  
The formal consent of a participant, using the approved consent form, will be obtained before 
the participant is submitted to any study procedure.   
The consent form will be signed and dated by the investigator or his designee at the same time 
as the participant sign. A copy of the signed informed consent will be given to the study partici-
pant. The consent form will be retained as part of the study records. The informed consent pro-
cess must be documented in the patient file and any discrepancy to the process described in 
the protocol must be explained.  
In the case of incapacity to judge or if there is doubt about the capacity to judge, a separate pro-
cedure takes place: 
The study information must be explained verbally to the interested patient in any case. Handing 
over the written study information alone is not sufficient. The patient should be able to describe 
in general terms what participation in the study entails and what the patient's rights are. 
If there are doubts about the patient's ability to judge, either because he/she is unable to repro-
duce what is contained in the study information, or because of critical comments by the health 

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care personnel and/or trusted persons of the patient, an evaluation is carried out using the "U-
Doc" (Hermann et al., 2020; Trachsel & Biller-Andorno, 2022). The information for this is col-
lected on an interdisciplinary basis and discussed with the patient's legal representative and/or 
a close confidant. Any conflicts of interest in the evaluation can be critically reflected upon and 
transparently documented in U-Doc. Both the patient and his/her representative have the right 
to inspect this documentation at any time and can also refuse it. 
If an incapacitated person explicitly wishes to participate in the study, we will conduct a detailed 
information session about the study, at which not only the patient but also the legal representa-
tive must be present. It is desirable to have a conversation on site, in exceptional cases the con-
versation can take place by telephone conference. If there is no legal representative, the law 
prescribes a cascade of possible representatives (spouse, partner, offspring, parents, siblings). 
The conversation is recorded (in the CRF). The documentation of the conversation is accessible 
to the patient and her representative at all times. It is important to note that incapacity is rele-
vant in relation to the decision on medical measures. 
Participants will receive financial compensation after completing the study (after post-measure-
ment). A payment of 40 swiss francs per participant is calculated in the budget. 
3.3 Study procedures 
Time schedule 
The study will last from October 2022 to September 2023.  
 
From October to December 2022, the study will be planned, and the ethics application 
will be written and submitted.  
 
From January, the concrete preparations will take place and  
 
from February 2023, the implementation will take place. The survey phase will last until 
August 2023.  
 
From August to October 2023, the study is to be evaluated, completed and the data ana-
lysed. 
 
As can be seen in Table 2, the duration for each patient is between 13 and max. 16 days during 
their inpatient stay. The goal is to start with the study intervention as soon as possible after en-
tering the psychiatric hospital. 
 
Table 1: Study Flow Chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening / 
Informed consent
Pre
Measurement
MI - Session
Post 
Measurement
MI - Session
MI - Session
MI - Session
Screening / 
Informed consent
Pre
Measurement
Supportive 
Counseling
Post 
Measurement
Supportive 
Counseling
Supportive 
Counseling
Supportive 
Counseling
Measurements by
study team
Interventions by
clinical
professionals
Initial interview by 
study coordinator

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Table 2: Overview study procedure 
* If questions / need for feedback occur after the last visit, an additional visit shall be provided 
 
Detailed description of the planned intervention 
Motivational Interviewing is a technique that aims in particular to promote intrinsic motivation 
and to make ambivalences visible and reduce them. It involves a therapeutic attitude based on 
the humanistic approach as well as on person-centred psychotherapy according to Carl Rogers. 
The original founders of MI defined five basic principles: 1. make clear, consensual agreements, 
2. show empathy, 3. develop the will to change and clarify discrepancies, 4. redirect resistance, 
5. promote self-confidence and responsibility. In addition, MI compliant skills such as active lis-
tening, supporting positive behaviours, asking open-ended questions, summarizing and reflect-
ing, supporting self-motivating statements are applied. The concept of MI is that the conversa-
tion with the patient goes through different phases of decision making and motivation building. 
The therapist always addresses and emphasizes the patient's stated desires, reasons, or abili-
ties to change. This is called "change talk." In the same way, however, doubts and counterargu-
ments are also addressed ("sustain talk") and appreciated. The aim is to increase the patient's 
 
Re-
cruit-
ment 
Pre-
Meas-
ure-
ment 
Intervention phase 
Post-Measure-
ment 
 
Visits  
1 
max.  
30min. 
2 
max. 
60min. 
3 
25- 
40min
. 
4 
25- 
40min
. 
5 
25- 
40min
. 
6 
25- 
40min
. 
7 
max. 
60min. 
Follow 
up 
max. 
60min. 
Time (days) 
-3 
+/-2d 
0 
2 
+/-1d 
4 
+/-1d 
6 
+/-1d 
8 
+/-1d 
10 
+/-1d 
60 
+/5d 
Check with treating physi-
cian or psychologist 
x 
 
 
 
 
 
 
 
Patient Information and In-
formed Consent 
x 
 
 
 
 
 
 
 
Randomization  
x 
 
 
 
 
 
 
 
Demographics and infor-
mation about current treat-
ment 
x 
 
 
 
 
 
 
 
Examination of symptoms 
with PANSS and MATRICS 
 
x 
 
 
 
 
x 
x 
Control of In- and Exclusion 
Criteria 
  
x 
 
 
 
 
 
 
Measurements of secondary 
outcome variables 
 
x 
 
 
 
 
x 
 
MI-Intervention (intervention 
group) or  
supportive conversations 
(controls) 
 
 
x 
x 
x 
x 
 
 
Possibility for patients to 
ask questions and give a 
feedback 
 
 
 
 
 
 
x* 
 

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discrepancy in a trustworthy and empathic way, so that he or she moves on to the phase of ac-
tual decision-making and finally to goal-directed behaviour on the basis of self-developed argu-
ments. 
Four interviews will be conducted using this method as part of the study intervention. The con-
tent of these will be about participation in treatment. In order to make the intervention measura-
ble, the conversations will be recorded on an audio device and subsequently evaluated by two 
independent raters according to the number of MI principles and techniques applied. 
 
Psychometric tests used in the study 
Primary diagnosis at point of admittance and medical history are assessed by physicians and 
psychologists at PUK and documented electronically. The applicant and master’s students en-
rolled in the project will use this available data and document them in specific study protocols. 
These assessments are part of standard assessments at the hospital by physicians and psy-
chologists. For primary psychiatric diagnoses the International Classification of Diseases (ICD-
10) is used.  
- 
Psychotic symptoms are assessed with the Positive and Negative Syndrome Scale 
(PANSS). This is a structured interview, which consists of four scales measuring positive 
and negative syndromes of schizophrenia, their differential, and general severity of illness. 
- 
Two cognitive tests: Letter-Number-Span (LNS), Symbol-Coding-Test (SCT) from MATRICS 
(Measurement and Treatment Research to Improve Cognition in Schizophrenia, Consensus 
Cognitive Battery; Nuechterlein et al., 2008) 
- 
The Brief Adherence Rating Scale BARS (Byerly et al, 2008) is a brief, pencil-paper, clini-
cian-administered adherence assessment instrument. It consists of 4 items: 3 questions and 
an overall visual analog rating scale to assess the proportion of doses taken by the patient 
in the past month (0%–100%). 
- 
The therapeutic relationship will be evaluated with the Scale to Assess Therapeutic Rela-
tionship STAR (McGuire-Snieckus et al., 2007). The patient (STAR-P) and clinician scales 
(STAR-C) each have 12 items comprising three subscales: positive collaboration and posi-
tive clinician input in both versions, non-supportive clinician input in the patient version, and 
emotional difficulties in the clinician version. 
- 
Motivation for psychotherapy will be measured with the Fragebogen zur Erfassung der Psy-
chotherapiemotivation (FPTM; engl: “Questionnaire to measure the motivation for psycho-
therapy “) by Schulz, Nübling und Rüddel (1995), a 4-point Likert-scale with 39 items. 
 
- 
Self-efficacy is measured with the German version of the General Self-Efficacy Scale (GSE) 
by Schwarzer & Jerusalem (1995), an instrument that has been proved with a sample of 
more than 19’000 persons in 25 countries and shows good psychometric properties. 
 
Expected biases to the study 
There are several risks for biases as already described in chapter 2.3 Study design. With regard 
to the method, it must be noted that the effect of psychotherapy is multifactorial and thus difficult 
to control whether any effects are only due to the difference of the specific method (MI) com-
pared to supportive talks (as a control intervention). In order to control for other possible influ-
encing factors, the level of training of the therapists will be included and controlled for. The de-
gree of motivation for psychotherapy of the patients before the beginning of the intervention as 
well as the attitude towards recovery on the therapist's side can also influence the outcome of a 
psychotherapeutic intervention, independent of the method. These specific variables will also be 
included in our calculations. In addition, it is possible that expectation or attitude toward one of 
the two therapy methods may have an effect on the outcomes. We will therefore blind the study 
so that patients do not know which group they belong to ("single-blind"). 

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3.4 Withdrawal and discontinuation 
Participants have the right to abort the study at any point and without providing a reason. The 
principal investigator and the co-investigator have the right to withdraw participants if they know-
ingly provide incorrect information, withdraw consent, do not adhere to protocol requirements 
(i.e. missing appointments, ignoring instructions) or if the disease has progressed (see exclu-
sion criteria). 
If participants do not finish the experiment, the data will be stored properly and taken into analy-
sis as far as possible and useful. Additional participants will be recruited to replace the with-
drawn participants.  
Since they are inpatients, there is a very low risk of missed appointments. If this is still the case, 
the appointments can be made up on the following day.  
If participants are discharged before the end of the study, they may attend the remaining ap-
pointments as outpatients if the majority of the study has already taken place (at least 3 psycho-
therapy sessions must have taken place during inpatient treatment). 
 
4 
STATISTICS AND METHODOLOGY 
4.1. Statistical analysis plan and sample size calculation 
Hypothesis 1: Four sessions of motivational interviewing for newly admitted acute patients 
(within the first 7 days of hospitalization) improve the therapeutic alliance and the adherence for 
treatment compared to supportive counseling. 
Statistical analysis for hypothesis 1: To apply the statistically most sensitive test, we will use an 
ANCOVA to analyze the treatment effect of motivational interviewing compared to supportive 
counseling, with baseline values used as covariates. 
 
Hypothesis 2: Four sessions of motivational interviewing for newly admitted acute patients de-
creases symptom severity compared to supportive counseling. 
Statistical analysis for hypothesis 2: We will use an ANCOVA to analyze the treatment effect of 
motivational interviewing compared to supportive counseling, with baseline values used as co-
variates. 
 
Hypothesis 3: Patients show higher motivation to seek psychotherapeutic treatment and have a 
higher self-efficacy expectation after leaving the inpatient stay, when they received an interven-
tion with motivational interviewing compared to supportive counseling. 
Statistical analysis for hypothesis 3: We will use an ANCOVA to analyze the treatment effect of 
motivational interviewing compared to supportive counseling, with baseline values used as co-
variates. 
 
Additional calculations: We also want to investigate how the number of hospitalization days and 
the severity of symptoms at the beginning of the intervention have an influence on the therapy 
outcome. We calculate this with a multiple regression with days of hospitalization and/or the 
PANSS total score as independent variables. The treatment outcome is defined as the delta be-
tween symptoms before and after the intervention and serves as dependent variable. 
 
General statistical considerations: We will use routine procedures of data processing and use 
data transformation if necessary (in case of non-normal distribution). Standard statistical calcu-
lations will be computed. The level of significance will be set to p < 0.05 (two tailed). Effect sizes 
will be calculated for significant results. The IBM® SPSS Statistics® statistical software as well 
as the program R will be used. 

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Sample size justification: Comparable studies found effect sizes that were moderate (Cohen’s d 
= 0.3 - 0.5). An effect sizes of f = 0.25 will require us to recruit at least 64 patients per group to 
achieve 80% power and to detect such an effect with reasonable certainty at an alpha level of 
0.05. We therefore plan to include a minimum of N = 128 patients (calculated with G*Power 
3.1). 
Analysis population: There is only one analysis population for all hypothesis. For inclusion crite-
ria see chapter 4.1. 
Analysis of gender differences: Analyses of gender differences are not planned because there 
is no research evidence to suggest that gender may be a determining variable. However, it is 
planned to conduct a group comparison between patients who benefit strongly from MI and 
those who benefit little, and to investigate possible discriminatory factors as part of this. 
4.2. Handling of missing data and drop-outs 
All patients who completed the study will be taken into analysis. All collected data will be 
checked at each study assessment, and missing data will thus be avoided as much as possible. 
If missing data nevertheless does occur, data has to be excluded.  
 
5 
REGULATORY ASPECTS AND SAFETY 
5.1 Local regulations / Declaration of Helsinki 
This study is conducted in compliance with the protocol, the current version of the Declaration of 
Helsinki, the ICH-GCP, the HRA as well as other locally relevant legal and regulatory require-
ments.  
 
5.2 (Serious) Adverse Events and notification of safety and protective measures 
An Adverse Event (AE) is any untoward medical occurrence in a patient or a clinical investiga-
tion subject which does not necessarily have a causal relationship with the trial procedure. An 
AE can therefore be any unfavourable or unintended finding, symptom, or disease temporally 
associated with a trial procedure, whether or not related to it. 
A Serious Adverse Event (SAE) (ClinO, Art. 63) is any untoward medical occurrence that 
- 
Results in death or is life-threatening, 
- 
Requires in-patient hospitalisation or prolongation of existing hospitalisation, 
- 
Results in persistent or significant disability or incapacity, or 
- 
Causes a congenital anomaly or birth defect  
Both Investigator and Sponsor-Investigator make a causality assessment of the event to the trial 
intervention, (see table below based on the terms given in ICH E2A guidelines). Any event as-
sessed as possibly, probably or definitely related is classified as related to the trial intervention. 
Relationship 
Description 
Definitely 
Temporal relationship 
Improvement after dechallenge* 
Recurrence after rechallenge 
(or other proof of drug cause) 
Probably 
Temporal relationship 
Improvement after dechallenge 
No other cause evident 

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Possibly 
Temporal relationship 
Other cause possible 
Unlikely 
Any assessable reaction that does not fulfil the above conditions 
Not related 
Causal relationship can be ruled out 
*Improvement after dechallenge only taken into consideration, if applicable to reaction 
 
Both Investigator and Sponsor-Investigator make a severity assessment of the event as mild, 
moderate or severe. Mild means the complication is tolerable, moderate means it interferes with 
daily activities and severe means it renders daily activities impossible.  
Reporting of SAEs (see ClinO, Art. 63): All SAEs are documented and reported immediately 
(within a maximum of 24 hours) to the Sponsor-Investigator of the study. If it cannot be ex-
cluded that the SAE occurring in Switzerland is attributable to the intervention under investiga-
tion, the Investigator reports it to the Ethics Committee via BASEC within 15 days. 
Exceptions to expedited reporting are possible if the SAE is either a clear consequence of the 
underlying illness or known before onset: In this study, exacerbation of psychotic symptoms 
may occur, possibly accompanied by unwillingness to treat and leading to coercive measures. 
Similarly, suicidal behaviors may occur in the course of acute psychoatric treatment, which are 
usually an expression of a subjectively stressful situation and are not directly related to the 
study.  
Follow up of (Serious) Adverse Events: Participants terminating the study (either regularly or 
prematurely) with reported ongoing SAE, or any ongoing AEs of laboratory values or of vital 
signs being beyond the alert limit will return for a follow-up investigation. This visit will take place 
up to 30 days after terminating the treatment period. Follow-up information on the outcome will 
be recorded on the respective SAE page in the CRF.  
Follow-up investigations may also be necessary according to the investigator’s medical judg-
ment even if the participant has no SAE at the end of the study. However, information related to 
these investigations does not have to be documented in the CRF but must be noted in the 
source documents. 
Notification of safety and protective measures (see ClinO, Art 62, b): If immediate safety 
and protective measures have to be taken during the conduct of the study, the investigator noti-
fies the Ethics committee of these measures, and of the circumstances necessitating them, 
within 7 days. 
5.3 (Periodic) safety reporting 
An annual safety report (ASR) is submitted once a year to the local Ethics Committee by the In-
vestigator (ClinO, Art. 43 Abs 1). 
5.4 Radiation 
Not applicable. 
5.5 Pregnancy 
This study (risk category A) does not include drugs or other medical products and is based ex-
clusively on psychotherapeutic intervention. Pregnancy is therefore not an exclusion criterion 
and there are no risks for pregnant women to participate in the study, but it will be noted in the 
CRF. 
5.6 Amendments 
Substantial changes to the study setup and study organization, the protocol and relevant study 

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documents are submitted to the Ethics Committee for approval before implementation. Under 
emergency circumstances, deviations from the protocol to protect the rights, safety and well-be-
ing of human subjects may proceed without prior approval of the Ethics Committee. Such devia-
tions shall be documented and reported to the Ethics Committee as soon as possible. 
Substantial amendments are changes that affect the safety, health, rights and obligations of 
participants, changes in the protocol that affect study objective(s) or central research topic, 
changes of study site(s) or of study leader and sponsor (ClinO, Art. 29). 
A list of all non-substantial amendments will be submitted once a year to the competent EC to-
gether with the ASR. 
5.7 Notification and reporting upon completion, discontinuation or interruption of the 
study 
Upon regular study completion, the Ethics Committee is notified via BASEC within 90 days 
(ClinO, Art. 38).  
The Sponsor-Investigator may terminate the study prematurely according to certain circum-
stances, e.g. 
- 
Ethical concerns, 
- 
Insufficient participant recruitment, 
- 
When the safety of the participants is doubtful or at risk (e.g. when the benefit-risk as-
sessment is no longer positive), 
- 
Alterations in accepted clinical practice that make the continuation of the study unwise, 
or 
- 
Early evidence of harm or benefit of the experimental intervention 
Upon premature study termination or study interruption, the Ethics Committee is notified via 
BASEC within 15 days (ClinO, Art. 38). 
When the study is finished the datasheet with the patient-identification number will be printed 
and then deleted from the clinic server. The encoded datasheet and the printed form of the 
datasheet with the patient-identification number and the corresponding identification-number will 
be stored and secured. 
A final report is submitted to the Ethics Committee via BASEC within a year after completion or 
discontinuation of the study, unless a longer period is specified in the protocol (ClinO, Art. 38). 
5.8 Insurance 
In the event of project-related damage or injuries, the liability of the University Hospital of Psy-
chiatry Zurich provides compensation, except for claims that arise from misconduct or gross 
negligence. 
 
6 
FURTHER ASPECTS 
6.1 Overall ethical considerations 
This study (risk category A) does not include drugs or other medical products and is based ex-
clusively on a psychotherapeutic intervention. Patients are hardly exposed to any more risks 
than in routine clinical care, so no safety measures are required. The time commitment for par-
ticipants is limited to six sessions of 25 to 60 minutes. Participants may benefit from additional 
discussions in both conditions: either MI sessions or supportive conversations, but both groups 
have more support than patients who do not participate in the study. In addition, participants will 
receive financial compensation for their participation.  
6.2 Risk-benefit assessment  

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We have identified several risks to this project, including the risk of unauthorized data access or 
inadvertent identification of project participants. We have taken appropriate measures for both 
(see section 7.2 Data recording and source data) 
This is a standard psychotherapy study, and participants generally tolerate this type of study 
very well, as they are exposed to almost no additional risks during the psychotherapy interven-
tion itself. Although there will be no immediate benefit to the project participant, the results of 
the pilot project will form the basis for further and larger-scale psychotherapy studies, and these 
in turn should benefit future patients by providing more effective psychotherapeutic treatment for 
psychosis in the acute stage of the illness. 
 
7 
QUALITY CONTROL AND DATA PROTECTION 
7.1 Quality measures  
The study coordinator is implementing and maintaining quality assurance and quality control 
systems including written working instructions to ensure that trials are conducted, and data are 
generated, documented, and reported in compliance with the protocol.  
The study will strictly follow the protocol. If any changes become necessary, they must be laid 
down in an amendment to the protocol. For quality assurance the sponsor, the Ethics Commit-
tee or an independent trial monitor may visit the research sites. Direct access to the source data 
and all study related files is granted on such occasions.  
Study personnel will be trained in diagnostic skills by the study coordinator, including PANSS 
training. Clinical psychologists participating in the study and delivering the interventions with pa-
tients will receive an update (if they have previous experience with MI) or training (if they do not 
have experience) in MI. 
The study coordinator will present interim data as well as organizational and feasibility findings 
to the Sponsor-Investigator at regular intervals. 
We will take several measures for quality control regarding the data such as double data entry 
and independent data review.  
7.2 Data recording and source data 
All acquired data will be stored at the University Hospital of Psychiatry and will be treated strictly 
confidential. The data and the decoding list will be archived separately. Only researchers who 
are involved in the study will have access to the project plan, dataset, statistical code, etc. dur-
ing and after the research project. The results of the study will be published in an anonymized 
manner.  
For each participant a paper CRF is maintained. CRFs do not identify participants by their name 
or birth date but provide appropriate coded identification. CRF's are filled in manually and trans-
ferred to a SPSS file by the study staff and checked by another person. The file is stored in a 
folder on the clinic server, which is only accessible to study staff. CRFs must be kept current to 
reflect participant status at each phase during the course of study. An audit trail ensures that all 
changes to the original data are documented and apparent. 
 
Source data must be available at the site to document the existence of the study participants 
and substantiate the integrity of study data collected. Source data must include the original doc-
uments relating to the study, as well as the medical treatment and medical history of the partici-
pant. The following information will be included in the source documents: 
 
Demographic data (age, sex, education, work situation) and relevant information about dis-
ease (year of onset, number of psychotic episodes, medication, other diagnosis) 
 
Inclusion and Exclusion Criteria details  
 
Participation in study and signed and dated Informed Consent Forms  
 
Visit dates  

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 
Key efficacy and safety data  
 
SAEs (related) and concomitant medication  
 
Results of relevant examinations (questionnaires, observations) 
 
Reason for premature discontinuation  
 
Randomization number 
We will not collect any data during the daily practice (routinely collected). 
7.3 Confidentiality and coding 
Trial and participant data will be handled with uttermost discretion and is only accessible to au-
thorized personnel (study team) who require the data to fulfil their duties within the scope of the 
study.  
On the CRFs and other study specific documents, participants are only identified by a unique 
participant number. The participant identification list will be stored in a locked closet at the Uni-
versity Psychiatric Hospital. Only the Sponsor-Investigator and the study coordinator do have 
access. When a patient is enrolled in the study, they are assigned a number by the study coor-
dinator. The patient is added to the participant identification list and the list is then locked again. 
There must be no name on any documents, only the participant number. It must be assured that 
any authorized person, who may perform data entries and changes in the CRF, can be identi-
fied. A list with signatures and initials of all authorized persons will be filed in the study site file 
and the trial master file, respectively. 
Electronic data are stored on the University Psychiatric Hospital server, which is password pro-
tected and accessible only to the study team. 
7.4 Retention and destruction of study data and biological material 
All study data are archived for 10 years after study termination (planned for September 2023) or 
premature termination of the study. Location of storage is the Psychiatric University Hospital. 
Data could potentially be shared with other researchers to promote Open Science for a longer 
period than 10 years, i.e., for meta analyses or secondary analyses. However, we will only 
share deidentified data with other researchers. 
 
8  
MONITORING AND REGISTRATION 
Monitoring visits at the investigator’s site at the start and during the course of the study will help 
to follow up the progress of the clinical study, to assure utmost accuracy of the data and to de-
tect possible errors at an early time point. The Sponsor-Investigator organizes professional in-
dependent monitoring for the study and will therefore collaborate with other research groups 
from the Psychiatric University Hospital. 
All original data including all patient files, progress notes and copies of laboratory and medical 
test results will be available for monitoring. The monitor will review all or a part of the CRF and 
written informed consents. The accuracy of the data will be verified by reviewing the above ref-
erenced documents.  
The monitoring plan for this study includes: 
pre-study visit 
- 
Initiation / first visit  
January 2023 
Visits  
One visit during the study intervention phase in April 2023  
Review of key data 
 
Existence and consent in 100% of patients  
 
100% of the other key data (if available at the time of the visit) in 
at least 20% of the patients  
 
One 100%-source data comparison is performed for one patient 

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The study will be registrated in the Swiss National Clinical Trial Portal (SNCTP via BASEC) and 
clinicaltrial.gov. 
 
9. FUNDING / PUBLICATION / DECLARATION OF INTEREST 
The Psychiatric University Hospital provides rooms, electronic equipment (computer, telephone, 
photocopier), test batteries and administrative material (paper, pens, folders, etc.). The master's 
students work free of charge as part of their academic training. 
This study is funded by the «Stiftung zur Förderung von Psychiatrie und Psychotherapie» (Zu-
rich, Switzerland). There is no conflict of interest. 
Publication policy of the study: After the statistical analysis of this trial the sponsor will make 
every endeavor to publish the data in a scientific journal.  
If gender effects are observed, they will be published in the final study report. If an analysis is 
performed but no gender effects are observed, this will also be published. 
 
 
 
from the sample  
Additional contacts 
Additional contacts by phone and/or e-mail will be made as required. 
Final visit 
August 2023  

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10. REFERENCES 
Online-Documents and Sources (in order of appearance): 
1. 
Common Terminology Criteria for Adverse Events (CTCAE) 
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2. 
Declaration of Helsinki 
https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medi-
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3. 
Federal Act on Data Protection (FADP) 
https://www.admin.ch/opc/en/classified-compilation/19920153/index.html 
4. 
Human Research Act (HRA) 
https://www.admin.ch/opc/de/classified-compilation/20061313/index.html 
5. 
International Conference on Harmonization (ICH) E6(R2) Guideline for Good Clinical Prac-
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http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Effi-
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6. 
International Conference on Harmonization (ICH) E2A Clinical Safety Data Management: 
Definitions and Standards for Expedited Reporting 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guide-
line/2009/09/WC500002749.pdf 
7. 
Ordinance on Clinical Trials in Human Research (ClinO) 
https://www.admin.ch/opc/de/classified-compilation/20121176/index.html 
 
 
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