VA/DoD CLINICAL PRACTICE GUIDELINE FOR 

THE MANAGEMENT OF SUBSTANCE USE 

DISORDERS 

Department of Veterans Affairs

Department of Defense

QUALIFYING STATEMENTS

The Department of Veterans Affairs and the Department of Defense guidelines are based upon the best 

information available at the time of publication. They are designed to provide information and assist 

decision making. They are not intended to define a standard of care and should not be construed as one.

Neither should they be interpreted as prescribing an exclusive course of management. 

This Clinical Practice Guideline is based on a systematic review of both clinical and epidemiological 

evidence. Developed by a panel of multidisciplinary experts, it provides a clear explanation of the logical 

relationships between various care options and health outcomes while rating both the quality of the 

evidence and the strength of the recommendation. 

Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of 

individual patients, available resources, and limitations unique to an institution or type of practice. Every 

healthcare professional making use of these guidelines is responsible for evaluating the appropriateness of 

applying them in the setting of any particular clinical situation.

These guidelines are not intended to represent TRICARE policy. Further, inclusion of recommendations for 

specific testing and/or therapeutic interventions within these guidelines does not guarantee coverage of 

civilian sector care. Additional information on current TRICARE benefits may be found at www.tricare.mil 

or by contacting your regional TRICARE Managed Care Support Contractor.

Version 3.0 – 2015
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Prepared by:

The Management of Substance Use Disorders

Work Group

With support from:

The Office of Quality, Safety and Value, VA, Washington, DC

& 

Office of Evidence Based Practice, U.S. Army Medical Command

Version 3.0 – 2015 

Based on evidence reviewed through January 2015
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Table of Contents

I. Introduction..................................................................................................................................... 6

II. Background...................................................................................................................................... 6

A. Description of Substance Use Disorders............................................................................................. 6

B. Epidemiology and Impact.................................................................................................................... 8

C. Factors Affecting Risk of Substance Use Disorders............................................................................ 8

D. Substance Use Disorders in the Department of Veterans Affairs and the Department of 

Defense ................................................................................................................................................ 8

E. Working Toward Successful Substance Use Disorders Treatment.................................................... 9

III. About this Clinical Practice Guideline ............................................................................................... 9

A. Methods............................................................................................................................................... 9

a. Grading Recommendations...................................................................................................................... 10

b. Reconciling 2009 Clinical Practice Guideline Recommendations............................................................ 11

c. Peer Review Process................................................................................................................................. 12

B. Conflict of Interest.............................................................................................................................13

C. Scope of this Clinical Practice Guideline ...........................................................................................13

D. Highlighted Features of this Clinical Practice Guideline...................................................................14

E. Patient-centered Care .......................................................................................................................14

F. Shared Decision Making ....................................................................................................................15

G. Engagement Strategies......................................................................................................................15

H. Addiction-focused Medical Management........................................................................................16

I. Accreditation Standards ....................................................................................................................17

J. Management of Substance Use Disorders in Department of Defense Healthcare Settings..........17

K. Substance Use Disorders and Co-occurring Conditions...................................................................19

a. Substance Use Disorder and Tobacco Use............................................................................................... 19

b. Patients with Multiple Substance Use Disorders..................................................................................... 19

c. Substance Use Disorder and Other Co-occurring Conditions.................................................................. 19

L. Implementation................................................................................................................................. 20

IV. Guideline Work Group ................................................................................................................... 21

V. Algorithm ...................................................................................................................................... 22

A. Module A: Screening and Treatment................................................................................................23

B. Module B: Stabilization......................................................................................................................24

VI. Recommendations......................................................................................................................... 25

A. Screening............................................................................................................................................29
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B. Brief Alcohol Intervention .................................................................................................................31

C. Determination of Treatment Setting ................................................................................................32

D. Treatment..........................................................................................................................................33

a. Alcohol Use Disorder ................................................................................................................................ 33

b. Opioid Use Disorder.................................................................................................................................. 38

c. Cannabis Use Disorder ............................................................................................................................. 47

d. Stimulant Use Disorder............................................................................................................................. 48

E. Promoting Group Mutual Help Involvement....................................................................................50

F. Co-occurring Mental Health Conditions and Psychosocial Problems..............................................52

G. Follow-up ...........................................................................................................................................52

H. Stabilization and Withdrawal ............................................................................................................55

a. Assessment ............................................................................................................................................... 55

b. Alcohol Use Disorder Stabilization and Withdrawal................................................................................ 58

c. Opioid Use Disorder Stabilization and Withdrawal................................................................................. 60

d. Sedative Hypnotic Use Disorder Stabilization and Withdrawal .............................................................. 62

VII. Knowledge Gaps and Recommended Research.............................................................................. 63

A. Determination of Treatment Setting ................................................................................................63

B. Pharmacotherapy ..............................................................................................................................63

a. Opioid Use Disorder.................................................................................................................................. 63

b. Stimulant Use Disorder............................................................................................................................. 63

C. Psychosocial Interventions................................................................................................................64

a. Substance Use Disorders.......................................................................................................................... 64

b. Opioid Use Disorder.................................................................................................................................. 64

D. Follow-up ...........................................................................................................................................64

E. Stabilization and Withdrawal ............................................................................................................64

F. Telehealth ..........................................................................................................................................64

Appendix A: Evidence Review Methodology....................................................................................... 65

A. Developing the Scope and Key Questions........................................................................................65

a. Population(s)............................................................................................................................................. 65

b. Interventions............................................................................................................................................. 65

c. Outcomes.................................................................................................................................................. 66

B. Conducting the Systematic Review...................................................................................................67

a. Criteria for Study Inclusion/Exclusion....................................................................................................... 70

b. Literature Search Strategy........................................................................................................................ 71

C. Convening the Face-to-face Meeting................................................................................................71

D. Grading Recommendations...............................................................................................................72

E. Recommendation Categorization .....................................................................................................75

a. Recommendation Categories and Definitions......................................................................................... 75
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b. Categorizing Recommendations with an Updated Review of the Evidence........................................... 76

c. Categorizing Recommendations without an Updated Review of the Evidence ..................................... 77

F. Drafting and Submitting the Final Clinical Practice Guideline..........................................................77

Appendix B: Pharmacotherapy for Alcohol Use Disorder and Opioid Use Disorder ............................. 79

Appendix C: Psychosocial Interventions ............................................................................................. 91

A. Behavioral Couples Therapy..............................................................................................................91

B. Cognitive-Behavioral Coping Skills Therapy......................................................................................92

C. Community Reinforcement Approach..............................................................................................92

D. Contingency Management for Substance Use Disorders Treatment..............................................92

E. Individual Drug Counseling................................................................................................................93

F. Motivational Enhancement Therapy ................................................................................................93

G. 12-Step Facilitation............................................................................................................................93

Appendix D: Evidence Table ............................................................................................................... 94

Appendix E: 2009 Recommendation Categorization Table ................................................................ 101

Appendix F: Participant List.............................................................................................................. 129

Appendix G: Conflict of Interest Disclosures Based on Financial Relationships with Industry............. 131

Appendix H: Literature Review Search Terms and Strategy............................................................... 132

A. Topic-specific Search Terms............................................................................................................132

B. Search Strategies .............................................................................................................................138

Appendix I. Acronym List................................................................................................................. 149

References .......................................................................................................................................... 152
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I. Introduction

The Department of Veterans Affairs (VA) and Department of Defense (DoD) Evidence-Based Practice Work

Group (EBPWG) was established and first chartered in 2004, with a mission to advise the “...Health 

Executive Council on the use of clinical and epidemiological evidence to improve the health of the 

population across the Veterans Health Administration and Military Health System,” by facilitating the 

development of clinical practice guidelines (CPGs) for the VA and DoD populations.[1] This CPG is intended 

to provide healthcare providers with a framework by which to evaluate, treat, and manage the individual 

needs and preferences of patients with substance use disorders (SUD), thereby leading to improved clinical 

outcomes.

In 2009, the VA and DoD published a CPG for the Management of Substance Use Disorders (2009 SUD

CPG), which was based on evidence reviewed through 2007. Since the release of that guideline, a growing 

body of research has expanded the general knowledge and understanding of SUD. Improved recognition of 

the complex nature of these conditions has led to the adoption of new strategies to manage and treat 

patients with SUD, including new developments related to pharmacotherapy and other treatment options. 

Consequently, a recommendation to update the 2009 SUD CPG was initiated in 2014. The updated CPG 

includes objective, evidence-based information on the management of SUD. It is intended to assist 

healthcare providers in all aspects of patient care, including, but not limited to, diagnosis, treatment, and 

follow-up. The system-wide goal of evidence-based guidelines is to improve the patient’s health and 

wellbeing by guiding health providers who are taking care of patients with SUD along the management 

pathways that are supported by evidence. The expected outcome of successful implementation of this 

guideline is to:

• Assess the patient’s condition and determine in collaboration with the patient the best

treatment method

• Optimize each individual’s recovery to decrease or eliminate consumption, improve health and

wellness, live a self-directed life, and strive to reach his or her full potential [2]

• Minimize preventable complications and morbidity

• Emphasize the use of patient-centered care

II. Background

A. Description of Substance Use Disorders

SUD can develop in individuals who use alcohol or other addicting drugs in harmful quantities. About 9% of 

Americans over age 18 have a non-tobacco SUD, and about one in every four Americans will develop a 

non-tobacco SUD over the course of a lifetime.[3,4] According to the Centers for Disease Control and 

Prevention (CDC), excessive alcohol use costs the United States (U.S.) over $223.5 billion annually.[5] 

According to the U.S. Department of Justice, the estimated cost of illicit drug use in the U.S. was more than 

$193 billion (in 2007).[6] This reflects direct and indirect public costs related to crime ($61.4 billion), health 

($11.4 billion), and lost productivity ($120.3 billion).[6] Excessive alcohol use itself leads to about 88,000 

premature deaths each year from acute (e.g., alcohol poisoning, motor vehicle accidents) and chronic 

causes (e.g., liver disease, hypertension, heart disease, stroke, pancreatitis). SUDs including tobacco 
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represent the leading actual cause of death in the U.S.[7] While the costs to our nation’s health are high, 

healthcare professionals are in a unique position to positively impact the health and wellbeing of the 

Service Members and Veterans they treat by implementing effective SUD prevention and treatment 

strategies.

As termed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), a “substance 

use disorder describes a problematic pattern of using alcohol or another substance that results in 

impairment in daily life or noticeable distress.”[8] This use can lead to a change in the way the brain 

functions and can cause other long-term health problems such as cardiovascular disease, stroke, and lung 

disease.[9] It can also limit a person’s ability to fulfill roles in his or her professional or personal life and can 

have other legal, social, or physical ramifications.[10,11] 

In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (and in International 

Classification of Diseases, Tenth Revision), SUD consists of two distinct conditions, abuse and dependence, 

as they relate to substances such as tobacco, alcohol, opioids, cannabis, and seven others. Field trials of 

the DSM-IV criteria showed that the substance dependence syndrome was both reliable and valid as a 

definition, but that the abuse syndrome based on a theoretical and hierarchical relationship between 

abuse (less severe) and dependence (more severe) was not valid. Some symptoms of “abuse” (e.g., failure 

to fulfill major role obligations) indicated severe SUD, while about half of the “abuse” definitions were 

based only on a single criterion, most often “hazardous use.”[12] Factor analysis supports a single SUD 

syndrome. Thus, DSM-5 now defines SUD using 11 diagnostic criteria and defines mild, moderate, and 

severe sub-classifications.[8] Presence of at least two symptoms indicates a disorder. Severity is defined as 

mild, moderate, and severe, with the presence of two to three, four to five, and six or more symptoms, 

respectively.[8,12] 

Addictive substances disrupt the functioning of brain circuits that mediate a complex array of functions 

(e.g., motivation, decision making, memory) involved in obtaining the natural rewards such as food and 

water that are essential for survival. Addicting substances act by either mimicking the brain’s natural 

chemicals or by interfering with the brain’s regulation of its chemicals, or both.[13] This activity changes 

the reward system in patients with SUD. When functioning normally, the mesolimbic dopamine pathway 

allows a person to experience pleasure in response to stimuli such as food and social interactions, and 

therefore encourages and motivates an individual to seek out these stimuli. Connections between 

mesolimbic dopamine and memory circuits enable a person to remember the people, places, and things 

associated with the reward. Addicting substances activate mesolimbic dopamine pathways more 

powerfully than natural rewards. With sufficient repeated use of addicting substances, one can develop an 

SUD. In patients with SUD, the mesolimbic pathway responds to cues that addictive substances are 

available, while its response to the drug itself and to natural rewards diminishes. Simultaneously, repeated 

substance use impairs the ability to exert inhibitory control. Over time, substance-related cues become 

more salient, drug craving becomes more compelling, and the individual is less able to inhibit impulses to 

use substances even as the “high” experienced is diminished.[14] This leads to impairment in substancerelated decision making that leads to many of the DSM-5 symptoms of an SUD.
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B. Epidemiology and Impact

In 2014, an estimated 8.1% of the population indicated they were affected by SUD within the past year. An 

estimated 6.4% were affected by alcohol use disorder (AUD), while 2.7% were affected by an illicit drug 

use disorder.[15] The leading causes of death in 2000 were tobacco (435,000 deaths; 18.1% of total U.S.

deaths), poor diet and physical inactivity (365,000 deaths; 15.2%), and alcohol consumption (85,000 

deaths; 3.5%). Other causes of death were microbial agents (75,000), toxic agents (55,000), motor vehicle 

crashes (43,000), incidents involving firearms (29,000), sexual behaviors (20,000), and illicit use of drugs 

(17,000).[7] From 1990-2010, the highest disability-adjusted life years, which accounted for years of life 

lost due to premature mortality as well as years lived with disability, were associated with risk factors 

including dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma 

glucose, physical inactivity, and alcohol use.[16] Since the early 1990s, there has been an increase in 

marijuana and prescription drug use disorders.[17] During a similar time period (1999-2008), overall opioid 

related death rates also increased. [18] Deaths from opioid overdose more than tripled between 1999 and 

2012.[19] Following the rise in prescription opioid use, heroin use increased from 2002 to 2013, and 

deaths resulting from heroin overdose also concurrently increased.[20] 

Despite the increases in both use of many of these substances and associated mortality, alcohol and drug 

use disorders continue to be undertreated.[17,21] From the 2012-2013 National Epidemiologic Survey on 

Alcohol and Related Conditions III (NESARC-III), only 19.8% of respondents with lifetime AUD were ever 

treated for AUD.[21] Many individuals who are untreated identify stigma as a major barrier.[22,23] 

For treatment of alcohol or illicit drug use in 2013, the most common locations of treatment were 

outpatient rehabilitation facilities or mutual help groups.[24,25] Among Gulf War, Afghanistan, and Iraq 

War era Veterans, Veterans who were deployed were found to be at increased risk of AUD compared to 

Veterans who were not deployed.[26] 

C. Factors Affecting Risk of Substance Use Disorders

The risk of a person developing SUD is affected by a number of factors. One factor is biology, including 

genetic make-up, gender, ethnicity, and the presence of other comorbidities. For instance, rates of alcohol 

and drug use disorders in males are nearly double that in females.[27] In 2012-2013, 12-month and 

lifetime prevalence of AUD were higher for people who identified as white and Native American.[21] There 

is an increased risk for developing substance and other mental health disorders if a relative is affected by 

SUD.[27] Other factors that may affect development of the disease are social environment and age or 

stage of development. As adolescents’ brains are still developing, including areas governing decision 

making and self-control, they may be more susceptible to taking risks such as using alcohol or drugs. The 

prevalence of alcohol and drug use disorders peaks in late adolescence and early adulthood, and starts to 

decrease after age 26.[27] In addition, those who were affected by substance use earlier in their lives are 

more likely to be affected by SUD in adulthood.[28] Socioeconomic status, SUD in family and friends, and 

quality of life can also influence risk.[29] 

D. Substance Use Disorders in the Department of Veterans Affairs and the 

Department of Defense

SUD commonly co-occurs with and complicates other conditions or issues. These conditions or issues may 

be health-related, such as other mental health conditions, or may be societal, such as homelessness, 
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criminal justice involvement, or unemployment. For instance, among Veterans with posttraumatic stress 

disorder (PTSD), co-occurring SUD was common and found to be associated with an increase in mortality. 

The association was especially pronounced for young Veterans, including those who served in Iraq and 

Afghanistan.[30] Furthermore, it was found that roughly 33% and 22% of homeless Veterans had spent 

money on alcohol and drugs, respectively, in the past month; however, there was no significant 

association found between the source of income (e.g., VA disability compensation) and the amount spent 

on alcohol and drugs.[31] Among Iraq or Afghanistan Veterans who were first-time users of VA healthcare 

between October 15, 2001 and September 30, 2009 and followed through January 1, 2010, SUD diagnoses 

were associated with being male, less than 25 years of age, and exposed to combat.[32] Of those with an 

SUD diagnosis, 55-75% also received diagnoses for PTSD or depression.[32] 

E. Working Toward Successful Substance Use Disorders Treatment

It is common for a person to relapse, even if his or her condition is being managed, and he or she is 

amenable to treatment. Relapse does not indicate that treatment has failed, but only signals that it needs 

to be adjusted, reinstated, or changed in order to move toward recovery.[33] 

III. About this Clinical Practice Guideline

This guideline represents a significant step toward improving the treatment and management of patients 

with SUD in the VA and DoD. As with other CPGs, however, challenges remain, including evidence gaps, 

the need to develop effective strategies for guideline implementation and to evaluate the effect of 

guideline adherence on clinical outcomes. This guideline is intended for VA and DoD healthcare 

practitioners including physicians, nurse practitioners, physician assistants, psychologists, social workers, 

nurses, pharmacists, chaplains, addiction counselors, and others involved in the care of Service Members 

or Veterans who have a suspected or diagnosed SUD.

As elaborated in the qualifying statement on page one, this CPG is not intended to serve as a standard of 

care. Standards of care are determined on the basis of all clinical data available for an individual patient

and are subject to change as scientific knowledge and technology advance and patterns evolve. This CPG is 

based on information available by January 2015 and is intended to provide a general guide to best 

practices. The guideline can assist care providers, but the use of a CPG must always be considered as a 

recommendation, within the context of a provider’s clinical judgment and patient values and preferences,

for the care of an individual patient.

A. Methods

The current document is an update to the 2009 VA/DoD Clinical Practice Guideline for the Management of 

Substance Use Disorders. The methodology used in developing the 2015 CPG follows the Guideline for 

Guidelines,[1] an internal document of the VA and DoD EBPWG. The Guideline for Guidelines can be 

downloaded from http://www.healthquality.va.gov/policy/index.asp. This document provides information 

regarding the process of developing guidelines, including the identification and assembly of the Guideline 

Champions (Champions) and other subject matter experts from within the VA and DoD, known as the 

Work Group, and ultimately, the development and submission of a new or updated SUD CPG.
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The Champions and Work Group for this CPG were charged with developing evidence-based clinical 

practice recommendations and writing and publishing a guideline document to be used by providers 

within the VA/DoD healthcare systems. Specifically, the Champions and Work Group members for this 

guideline were responsible for identifying the key questions (KQs) of the most clinical relevance, 

importance, and interest for the management of patients with SUD. The Champions and the Work Group 

also provided direction on inclusion and exclusion criteria for the evidence review and assessed the level 

and quality of the evidence. The amount of new scientific evidence that had accumulated since the 

previous version of the CPG was also taken into consideration in the identification of the KQs. In addition, 

the Champions assisted in:

• Identifying appropriate disciplines of individuals to be included as part of the Work Group

• Directing and coordinating the Work Group

• Participating throughout the guideline development and review processes

The VA Office of Quality, Safety and Value, in collaboration with the Office of Evidence Based Practice, U.S.

Army Medical Command, the proponent for CPGs for the DoD, identified three clinical leaders, Karen 

Drexler, MD and Daniel Kivlahan, PhD from the VA and Lieutenant Colonel Christopher Perry, MD from the

DoD, as Champions for the 2015 CPG. 

The Lewin Team, including The Lewin Group, Duty First Consulting, ECRI Institute, and Sigma Health 

Consulting, LLC, was contracted by the VA and DoD to support the development of this CPG and conduct 

the evidence review. The first conference call was held in October 2014, with participation from the 

contracting officer’s representative (COR), leaders from the VA Office of Quality, Safety and Value and the 

DoD Office of Evidence Based Practice, and the Champions. During this call, participants discussed the 

scope of the guideline initiative, the roles and responsibilities of the Champions, the project timeline, and 

the approach for developing and prioritizing specific research questions on which to base a systematic 

review (SR) about the management of SUD. The group also identified a list of clinical specialties and areas 

of expertise that are important and relevant to the management of SUD, from which Work Group 

members were recruited. The specialties and clinical areas of interest included: psychiatry, psychology, 

nursing, pharmacy, social work, primary care, family medicine, religious and spiritual services, bioethics, 

dietetics, pain, addiction psychiatry, addiction medicine, and substance use specialties.

The guideline development process for the 2015 CPG update consisted of the following steps:

1. Formulating and prioritizing evidence questions (KQs)

2. Conducting the SR

3. Convening a face-to-face meeting with the CPG Champions and Work Group members

4. Drafting and submitting a final CPG about the management of SUD to the VA/DoD EBPWG

Appendix A provides a detailed description of each of these tasks.

a. Grading Recommendations

The Champions and Work Group used the Grading of Recommendations Assessment, Development and 

Evaluation (GRADE) system to assess the quality of the evidence base and assign a grade for the strength 
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for each recommendation. The GRADE system uses the following four domains to assess the strength of 

each recommendation:[34] 

• Balance of desirable and undesirable outcomes

• Confidence in the quality of the evidence

• Patient or provider values and preferences

• Other implications, as appropriate, e.g.,:

 Resource use

 Equity

 Acceptability

 Feasibility

 Subgroup considerations

Using this system, the Champions and Work Group determined the relative strength of each 

recommendation (Strong or Weak). A strong recommendation indicates that the Work Group is highly 

confident that desirable outcomes outweigh undesirable outcomes. If the Work Group is less confident of 

the balance between desirable and undesirable outcomes, they give a weak recommendation. 

They also determined the direction of each recommendation (For or Against). Similarly, a recommendation 

for a therapy or preventive measure indicates that the desirable consequences outweigh the undesirable 

consequences. A recommendation against a therapy or preventive measure indicates that the undesirable 

consequences outweigh the desirable consequences.

Using these elements, the grade of each recommendation is presented as part of a continuum:

• Strong For (or “We recommend offering this option ...”)

• Weak For (or “We suggest offering this option ...”)

• Weak Against (or “We suggest not offering this option ...”)

• Strong Against (or “We recommend against offering this option ...”)

The grade of each recommendation made in the 2015 CPG can be found in the section on 

Recommendations. Additional information regarding the use of the GRADE system can be found in 

Appendix A. 

b. Reconciling 2009 Clinical Practice Guideline Recommendations

Evidence-based CPGs should be current, which typically requires revisions of previous guidelines based on 

new evidence, or as scheduled, subject to time-based expirations.[35] For example, the U.S. Preventive 

Services Task Force (USPSTF) has a process for refining or otherwise updating its recommendations 

pertaining to preventive services.[36] Further, the inclusion criteria for the National Guideline 

Clearinghouse specify that a guideline must have been developed, reviewed, or revised within the past five 

years. 
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The SUD Guideline Work Group focused largely on developing new and updated recommendations based 

on the evidence review conducted for the priority areas addressed by the KQs. In addition to those new 

and updated recommendations, the Guideline Work Group considered, without complete review of the 

relevant evidence, the current applicability of other recommendations that were included in the previous 

2009 SUD CPG, subject to evolving practice in today’s environment. 

A set of recommendation categories was adapted from those used by the National Institute for Health and 

Care Excellence (NICE).[37,38] These categories, along with their corresponding definitions, were used to 

account for the various ways in which older recommendations could have been updated. In brief, the 

categories took into account whether or not the evidence that related to a recommendation was 

systematically reviewed, the degree to which the recommendation was modified, and the degree to which 

a recommendation is relevant in the current patient care environment and inside the scope of the CPG. 

Additional information regarding these categories and their definitions can be found in Appendix A. The 

categories for the recommendations included in the 2015 version of the guideline can be found in the 

section on Recommendations. The categories for the recommendations from the 2009 SUD CPG are noted 

in Appendix E. 

The CPG Work Group recognized the need to accommodate the transition in evidence rating systems from 

the 2009 SUD CPG to the current CPG. In order to report the strength of all recommendations using a 

consistent format (i.e., the GRADE system) the CPG Work Group converted the USPSTF strengths of the 

recommendation accompanying the carryover recommendations from the 2009 guideline to the GRADE 

system. As such, the CPG Work Group considered the strength of the evidence cited for each 

recommendation in the 2009 SUD CPG as well as harms and benefits, values and preferences, and other 

implications, where possible. The CPG Work Group referred to the available evidence as summarized in 

the body of the 2009 SUD CPG and did not re-assess the evidence systematically. In some instances, peerreviewed literature published since the 2009 SUD CPG was considered along with the evidence base used 

for that CPG.

Where such newer literature was considered when converting the strength of the recommendation from 

the USPSTF to the GRADE system, it is referenced in the discussion that follows the corresponding 

recommendation, as well as in Appendix D. 

The CPG Work Group recognizes that, while there are practical reasons for incorporating findings from a 

previous SR, previous recommendations,[39] or recent peer-reviewed publications into an updated CPG, 

doing so does not involve an original, comprehensive SR and, therefore, may introduce bias. 

c. Peer Review Process

The CPG was developed through an iterative process in which the Work Group produced multiple drafts of 

the CPG. The process for developing the initial draft is described in more detail in Drafting and Submitting 

the Final Clinical Practice Guideline. 

Once a near-final draft of the guideline was agreed upon by the Champions and Work Group members, the 

draft was sent out for peer review and comment. The draft was posted on a wiki website for a period of 14 

business days. The peer reviewers comprised individuals working within the VA and DoD health systems as 

well as experts from relevant outside organizations designated by the Work Group members.
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Organizations designated by the Work Group who were contacted to participate in the peer review 

included the following: 

• American Psychiatric Nurses Association, Addictions Council

• International Nurses Society on Addictions

• Substance Abuse and Mental Health Services Administration, Center for Substance Abuse

Treatment

The VA and DoD Leadership reached out to both the internal and external peer reviewers to solicit their 

feedback on the CPG. Reviewers were provided a hyperlink to the wiki website where the draft CPG was 

posted. All reviewer feedback was posted in tabular form on the wiki site, along with the name of the 

reviewer, for transparency. All feedback from the peer reviewers was discussed and considered by the 

Work Group. Modifications made throughout the CPG development process were made in accordance 

with the evidence. 

B. Conflict of Interest

At the start of this guideline development process and at other key points throughout, the project team 

was required to submit disclosure statements to reveal any areas of potential conflict of interest (COI) in 

the past 12 months. Verbal affirmations of no COI were used as necessary during meetings throughout the 

guideline development process. The project team was also subject to random web-based surveillance (e.g., 

ProPublica). Disclosed industry related COIs are listed in Appendix G. 

If a project team member reported a COI (actual or potential), then it was reported to the Office of 

Evidence Based Practice. It was also discussed with the SUD CPG Work Group in tandem with their review 

of the evidence and development of recommendations. The Office of Evidence Based Practice and the SUD 

CPG Work Group determined whether or not action, such as restricting participation and/or voting on 

sections related to the conflict or removal from the Work Group, was necessary. If it was deemed 

necessary, action was taken by the co-chairs and Office of Evidence Based Practice, based on the level and 

extent of involvement, to mitigate the COI. 

Several Work Group members disclosed relationships and/or affiliations which had the potential to 

introduce bias into the guideline. Based on the level and extent of involvement, no individuals were 

removed from the Work Group. In order to mitigate the risk of bias while maximizing the contributions of 

those with expertise in a specific area of SUD treatment, co-chairs asked Work Group members to disclose 

relevant relationships during related guideline development discussions. Members with potential COIs

contributed to the discussions related to their particular areas of expertise as well as the overarching 

guideline document in order to ensure differing viewpoints and experiences were adequately represented. 

C. Scope of this Clinical Practice Guideline

Regardless of setting, any patient in the healthcare system should be offered access to the interventions 

that are recommended in this guideline after taking into consideration the patient’s specific circumstances. 

Guideline recommendations are intended to be patient-centered. Thus, treatment and care should take 

into account a patient’s needs and preferences. Good communication between healthcare professionals 

and the patient is essential and should be supported by evidence-based information tailored to the 
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patient’s needs. Use of an empathetic and non-judgmental (versus a confrontational) approach facilitates 

discussions sensitive to gender, culture, and ethnic differences. The information that patients are given

about treatment and care should be culturally appropriate and also available to people with limited 

literacy skills. It should also be accessible to people with additional needs such as physical, sensory, or 

learning disabilities. Family involvement should be considered if appropriate.

This CPG is designed to assist providers in managing or co-managing patients with SUD. Moreover, the 

patient population of interest for this CPG is adults who are eligible for care in the VA and DoD healthcare

delivery systems. It includes Veterans as well as deployed and non-deployed Active Duty Service Members.

This CPG does not provide recommendations for the management of SUD in children or adolescents. 

The literature review encompassed interventional studies (primarily randomized controlled trials [RCTs]) 

published between November 2007 and January 2015, and targeted 12 KQs focusing on the means by 

which the delivery of healthcare could be optimized for patients with SUD. The selected KQs were 

prioritized from many possible KQs. Due to resource constraints, a review of the evidence in all important 

aspects of care for patients with SUD was not feasible for the update to this CPG. 

D. Highlighted Features of this Clinical Practice Guideline

The 2015 edition of the VA/DoD Clinical Practice Guideline for the Management of Substance Use 

Disorders is the second update to the original CPG. It provides practice recommendations for the care of 

populations with SUD with any level of severity. While screening for and addressing co-occurring mental 

disorders is considered good clinical practice, specific guidance on management of co-occurring mental 

health conditions and SUD is beyond the scope of this CPG. Interested readers are referred to related VADoD CPGs (see Substance Use Disorders and Co-occurring Conditions). A particular strength of this CPG is 

the multidisciplinary stakeholder involvement from its inception, ensuring representation from the broad 

spectrum of clinicians engaged in the treatment and management of patients with SUD. 

The framework for recommendations in this CPG considered factors beyond the strength of the evidence, 

including balancing desired outcomes with potential harms of treatment, equity of resource availability, 

and the potential for variation in patient values and preferences. Applicability of the evidence to VA/DoD 

populations was also taken into consideration. A structured algorithm accompanies the guideline to

provide an overview of the recommendations in the context of the flow of patient care and clinician 

decision making and to assist with training providers. The algorithm may be used to help facilitate 

translation of guideline recommendations into effective practice.

E. Patient-centered Care

VA/DoD CPGs encourage clinicians to use a patient-centered care approach that is individualized based on 

patient capabilities, needs, goals, prior treatment experience and preferences. Regardless of setting, all 

patients in the healthcare system should be offered access to evidence-based interventions appropriate to 

that patient. When properly executed, PCC may decrease patient anxiety, increase trust in clinicians,[40] 

and improve treatment adherence.[41] Improved patient-clinician communication through PCC can be 

used to convey openness to discuss any future concerns. 

As part of the PCC approach, clinicians should review the outcomes of previous self-change efforts, past 

treatment experiences, and outcomes (including reasons for treatment drop-out) with the patient. They 
VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders

December 2015 Page 15 of 169

should ask the patient about willingness to accept a referral to an addiction specialist. Lastly, they should 

involve the patient in prioritizing problems to be addressed and in setting specific goals regardless of the 

selected setting or level of care. 

F. Shared Decision Making

Throughout this VA/DoD CPG, the authors encourage clinicians to focus on shared decision making (SDM).

The SDM model was introduced in Crossing the Quality Chasm, an Institute of Medicine report, in 

2001.[42] It is readily apparent that patients with SUD, together with their clinicians, make decisions 

regarding which care they choose to engage in; however, these patients require sufficient information to 

be able to make informed decisions. Clinicians must be adept at presenting information to their patients 

regarding both individual treatments and levels and locations of care. For instance, for a patient who is not 

interested in specialty referral, the clinician should briefly explore the patient’s rationale, present relevant 

and individualized information about how specialty care might better meet the patient’s needs, identify

reasons a specialty referral might be recommended for his or her specific case, and provide information 

regarding the abilities and the limitations of the primary care or general mental health clinic. If the patient 

continues to decline specialty referral despite counseling, the primary care clinician should respect this 

decision by providing as much care as possible for the patient. Unfortunately, SDM can be complicated as 

the patients’ ability to make decisions may be impaired by the SUD itself.[43] 

G. Engagement Strategies

A fundamental goal of this VA/DoD CPG is to promote early engagement and retention of patients with 

substance use conditions who can benefit from addiction-focused treatment. Many patients may initially 

decline voluntary referral,[44] or at least express ambivalence, but provider encouragement and support 

may improve patient willingness to pursue further involvement if they see it as consistent with their other 

priorities. There is considerable evidence from psychotherapy research that general factors such as 

therapist skill, the strength of the therapeutic alliance, and the structure provided by regular clinical 

contact can have as powerful an effect on engagement as the specific content or conceptual approach of 

specialized interventions.[45] Therefore, attention to these general therapeutic factors is at least as 

important as the specific treatment approach selected.

The following principles are fundamental to the engagement/re-engagement process for patients with SUD:

1. Indicate to the patient and significant others that treatment is more effective than no treatment

(i.e., “Treatment works”).

2. Consider the patient’s prior treatment experience and respect patient preference for the initial

intervention approach(es), since no single intervention approach has emerged as the treatment of

choice.

3. Regardless of the particular psychosocial intervention chosen, use motivational interviewing (MI)

style during therapeutic encounters with patients [46-48] and emphasize the common elements of

effective interventions including: improving self-efficacy for change, promoting a therapeutic

relationship, strengthening coping skills, changing reinforcement contingencies for recovery, and

enhancing social support for recovery.
VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders

December 2015 Page 16 of 169

4. Emphasize that the most consistent predictors of successful outcome are retention in formal

treatment and/or active involvement with community support for recovery.

5. Use strategies demonstrated to be efficacious to promote active involvement in available mutual

help programs (e.g., Alcoholics Anonymous [AA], Narcotics Anonymous [NA]).

6. Coordinate addiction-focused psychosocial interventions with evidence-based intervention(s) for

other biopsychosocial problems to address identified concurrent problems consistent with patient

priorities.

7. Provide intervention in the least restrictive setting necessary to promote access to care, safety and

effectiveness.

8. If a patient drops out of treatment, the treatment team should make efforts to contact the patient

and re-engage him/her in treatment.

9. If the patient remains unwilling to engage in any addiction-focused care, maintain MI style of

interactions. Emphasize that options remain available in the future and determine whether

treatment for medical and psychiatric problems can be effectively and safely provided while

looking for windows of opportunity to engage the patient in addiction treatment.

Even when patients refuse referral or are unable to participate in specialized addiction treatment, many 

are accepting of general medical or mental health care. The chronic illness approach is consistent with 

management approaches for many other disorders treated in medical and psychiatric settings.[33,49] 

H. Addiction-focused Medical Management

Addiction-focused Medical Management is a manualized psychosocial intervention designed to be 

delivered by a medical professional (e.g., physician, nurse, physician assistant) in a primary care 

setting.[50] The treatment provides strategies to increase medication adherence and monitoring of 

substance use and consequences, as well as supporting abstinence through education and referral to 

support groups.

While variably defined, addiction-focused Medical Management typically includes:[51-55] 

1. Monitoring self-reported use, laboratory markers, and consequences

2. Monitoring adherence, response to treatment, and adverse effects

3. Education about AUD and/or OUD consequences and treatments

4. Encouragement to abstain from non-prescribed opioids and other addictive substances

5. Encouragement to attend community supports for recovery (e.g., mutual help groups) and to

make lifestyle changes that support recovery

Session structure varies according to the patient’s substance use status and treatment compliance. An 

initial session (40-60 minutes) may involve discussion of the specific findings and diagnosis, negative 

consequences from substance use, a recommendation to abstain, medication information, strategies to 

enhance medication adherence, and referral to support groups. In the subsequent monitoring visits, the 

clinician assesses the patient’s substance use. The assessment includes monitoring lab or physiologic 

measures and assessing overall functioning, medication adherence, and any medication side effects.
VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders

December 2015 Page 17 of 169

Follow-up sessions are typically 15-20 minutes initially twice weekly tapering to weekly then biweekly for 

up to 12 weeks. When the patient does not adhere to the medication regimen, the clinician evaluates the 

reasons and helps the patient devise plans to address the problem(s). Clinicians offer common sense 

recommendations, such as avoiding specific situations like going to bars. If the patient suffers from 

medication side effects, the clinician specifies procedures for using concomitant medication to ameliorate 

them or reduces the dosage of medication, resuming medications if side effects remit. If a patient 

discontinues medication because he or she cannot tolerate it, the clinician schedules a monthly 15- to 25-

minute “medical attention” meeting, during which the clinician employs a similar approach that focuses on 

the patient’s substance use and overall health, omitting the medication adherence component.

I. Accreditation Standards

This VA/DoD CPG was developed with a focus on evidence-based practices to help improve patient 

outcomes. Although they are not explicitly evidence-based, attention should be given to standards 

provided by various accrediting agencies, most notably The Joint Commission (TJC) and the Commission on 

Accreditation of Rehabilitation Facilities (CARF). TJC standards can be found at: 

http://www.jointcommission.org/standards_information/standards.aspx. CARF standards can be found at: 

http://www.carf.org/home/. 

TJC accreditation requirements address important functions relating to the care, treatment, or services of 

individuals and the management of behavioral health care organizations. They provide a framework to 

help manage risk and enhance the quality and safety of care, treatment, and services. For many providers 

and organizations, including VA and DoD, these requirements are considered to be the standard of care.

The mission of CARF is to promote the quality, value, and optimal outcomes of services through a 

consultative accreditation process and continuous improvement services that center on enhancing the 

lives of persons served.

Among the accreditation standards, clinicians are expected to obtain a comprehensive biopsychosocial 

assessment with a diagnostic formulation that synthesizes the various assessments and, using the 

results from the assessment, to develop an individualized treatment plan in accordance with TJC or 

CARF standards.

J. Management of Substance Use Disorders in Department of Defense

Healthcare Settings 

As specified by the DoD, “Substance abuse1 by military personnel is inconsistent with the Department of 

Defense’s Values, the Warrior Ethos, and the standards of performance, discipline, and readiness 

necessary to accomplish the DoD’s mission.”[56] On 28 September 1971, Public Law (PL) 92-129, 

mandated that the Secretary of Defense develop programs for the identification, treatment, and 

1 Although the terminology “substance abuse” is not a diagnostic term and is not used elsewhere in the CPG, it is the language used 

in DoD policy and is thus used in this section.
VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders

December 2015 Page 18 of 169

rehabilitation of alcohol or other substance dependent persons in the Armed Forces.[57] In turn, the 

Secretary of Defense requires each of the Services to develop alcohol and other substance abuse 

prevention and control programs in accordance with Department of Defense Directive (DODD) 1010.4.[58] 

In response to these directives, the DoD conducts a comprehensive program to prevent and control the 

abuse of alcohol and other substances. The service specific programs are designed to strengthen the 

overall fitness and effectiveness of the DoD workforce, conserve manpower, enhance combat readiness, 

and increase individual fitness and overall unit readiness. 

The DoD substance abuse programs are command and medical programs that emphasize readiness and 

personal responsibility. These programs are designed to provide services which are proactive and 

responsive to the needs of the DoD workforce by emphasizing alcohol and other substance abuse 

deterrence, prevention, education, and rehabilitation. The implementation of alcohol and other substance 

risk reduction and prevention strategies are designed to provide effective alcohol and other substance 

abuse prevention and education at all levels of command, and encourage commanders to provide alcohol 

and drug-free leisure activities. The ultimate goal of DoD substance use programs is to improve readiness 

and to restore to duty those substance-impaired Service Members who have the potential for continued 

military service.

In the DoD, Active Duty Service Members who are involved in the abuse of alcohol or use of illicit 

substances are encouraged to voluntarily refer themselves for care and treatment to a substance use 

program. However, if a Service Member screens positive for the use of illicit drugs during a mandatory unit 

urinalysis, regulations require that the Service Member enroll into a substance abuse program and be 

processed for possible separation from the military. The Service Member’s commander intervenes early 

for all personnel assigned to his/her command suspected of being alcohol and/or substance abusers. 

Service Members, who fail to participate adequately in substance use programs or to respond successfully 

to rehabilitation, may be faced with administrative separation from the military. 

After enrollment into substance abuse programs, all Active Duty Service Members will have a treatment 

team convene with the patient, clinician, and command representative to review the treatment plan and 

goals. Recognizing the importance of medical readiness, the Health Insurance Portability and 

Accountability Act (HIPAA) specifically exempts some communication between clinicians and commanders. 

Regulations require that Active Duty personnel enrolled in rehabilitation and referral services have an 

individualized aftercare plan designed to identify the continued support of the patient with monthly 

monitoring (minimally) during the first year after inpatient treatment. The following regulations guide the 

rehabilitation programs in the various services: Army Regulation 600-85, The Army Substance Abuse 

Program dated 28 Dec 2012;[56] OPNAVINST 5350.4D, Navy Alcohol and Drug Abuse Prevention and 

Control dated 04 Jun 2009;[59] Air Force Instruction 44-121, Alcohol and Drug Abuse Prevention and 

Treatment (ADAPT) dated 08 July 2014.[60] 

Care of Veterans and Service Members in transition between facilities, services, or from the DoD 

healthcare system to the VA healthcare system should include a transition plan that ensures continuity of 

care and coordination among providers. Healthcare teams should work jointly to provide assessment and 

services to patients within this transitioning population. Management should be reviewed throughout the 

transition process, and there should be clarity about who is the lead clinician to ensure continuity of care. 
VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders

December 2015 Page 19 of 169

If a clear transition process is lacking, then an effort should be made to construct a functional transition 

process that supports PCC.

K. Substance Use Disorders and Co-occurring Conditions

a. Substance Use Disorder and Tobacco Use

In Combatting Tobacco Use in Military and Veteran Populations, the Institute of Medicine (2009) notes 

that great progress has been made in decreasing the rate of smoking of Active Duty and Veterans from 

51% in 1980 to 32% in 2005, but that about 22% of Veterans enrolled in VA healthcare continue to 

smoke.[61] In its discussion about tobacco use disorder treatment during SUD treatment the Substance 

Abuse and Mental Health Services Administration (SAMHSA) (2011) notes an early study on the morbidity 

and mortality among people seeking treatment for addictions.[62] Among the 845 participants in that 

study, 51% died as a result of tobacco-related causes rather than from other substance-related causes.[63] 

Quitting tobacco use has clear benefits for improving ongoing health and decreasing mortality and is 

strongly encouraged for all patients with SUD. Consistently offering tobacco use disorder treatment 

throughout SUD treatment supports the principles of PCC, shared decision making (SDM), and recovery. 

For management of tobacco use disorder, refer to the CPG: Treating Tobacco Use & Dependence: 2008 

Update from the U.S. Department of Health and Human Services, available at: 

http://bphc.hrsa.gov/buckets/treatingtobacco.pdf; VA/DoD Clinical Practice Guideline for the 

Management of Tobacco Use, available at: http://www.healthquality.va.gov/guidelines/cd/mtu/index.asp; 

and the USPSTF Final Recommendation Statement Behavioral and Pharmacotherapy Interventions for 

Tobacco Smoking Cessation in Adults and Pregnant Women, available at: 

http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/tobacc

o-use-in-adults-and-pregnant-women-counseling-and-interventions1. 

b. Patients with Multiple Substance Use Disorders

Patients with more than one SUD should be managed according to the recommendations made for each of 

those individual disorders. 

c. Substance Use Disorder and Other Co-occurring Conditions

For management of patients presenting with SUD and one or more of the following conditions, refer to the 

appropriate VA/DoD CPG, as available, at http://www.healthquality.va.gov/: 

• Bipolar disorder

• Chronic Kidney Disease (CKD)

• Chronic Multisymptom Illness (CMI)

• Diabetes

• Hypertension

• Low Back Pain

• Major Depressive Disorder (MDD)

• Mild Traumatic Brain Injury (mTBI)
December 2015 Page 20 of 169

• PTSD

• Chronic Opioid Therapy

• Suicide

L. Implementation

This CPG and algorithm are designed to be adapted by individual healthcare providers with consideration 

of local needs and resources. The algorithms serve as a tool to prompt providers to consider key decision 

points in the course of an episode of care. 

Although this CPG represents the recommended practice on the date of its publication, medical practice is 

evolving and this evolution requires continuous updating based on published information. New technology 

and more research will improve patient care in the future. The CPG can assist in identifying priority areas 

for research and to inform optimal allocation of resources. Future studies examining the results of CPG

implementation may lead to the development of new evidence particularly relevant to clinical practice. 
December 2015 Page 21 of 169

IV. Guideline Work Group

Guideline Work Group* 

Department of Veterans Affairs Department of Defense

Karen Drexler, MD (Co-Chair) LTC Christopher Perry, MD (Co-Chair)

Daniel Kivlahan, PhD (Co-Chair) CDR Jennifer Bodart, PsyD

Michael O. Chaffman, PharmD, BCPS LCDR Danyell Brenner, BCD, LCSW, MBA

Carol Essenmacher, PMHCNS-BC, DNP, C-TTS Corinne K. B. Devlin, MSN, RN, FNP-BC

Francine Goodman, PharmD, BCPS Marina Khusid, MD, ND, MSA

Adam Gordon, MD, MPH, FACP, FASAM Timothy Lacy, MD

James R. McKay, PhD CDR Marisol Martinez, PharmD

Renee Redden, MSN, PMHCNS, BC CH (LTC) Robert Miller, DMin, MDiv, MABMH

Marghani Reever, PhD, LCSW CDR Robert M. Selvester, MD

Andrew Saxon, MD Maj Tracy L. Snyder, MS, RD

Christopher Spevak, MD, MPH, JD

Office of Quality, Safety and Value

Veterans Health Administration

Office of Evidence Based Practice

U.S. Army Medical Command

Eric Rodgers, PhD, FNP, BC

Rene Sutton, BS, HCA

Ernest Degenhardt, COL USA (Ret.) RN, MSN, 

ANP/FNP, BC

Corinne K. B. Devlin, MSN, RN, FNP-BC 

James Sall, PhD, FNP-BC

Lewin Group ECRI Institute

Clifford Goodman, PhD

Christine Jones, MS, MPH

Erika Beam, MS

Anjali Jain, MD

James Reston, PhD, MPH

Kristen D’Anci, PhD

Oluwaseun Akinyede, MPH

Joann Fontanarosa, PhD

Sigma Health Consulting, LLC

Frances Murphy, MD, MPH

*Additional contributor contact information is available in Appendix F.
December 2015 Page 22 of 169

V. Algorithm

This CPG includes an algorithm which is designed to facilitate understanding of the clinical pathway and 

decision making process used in management of SUD. The use of the algorithm format as a way to 

represent patient management was chosen based on the understanding that such a format may promote 

more efficient diagnostic and therapeutic decision making and has the potential to change patterns of 

resource use. Recognizing that some clinical care processes are non-linear, the algorithm format allows the 

provider to follow a simplified linear approach in assessing the critical information needed at the major 

decision points in the clinical process, and includes:

• An ordered sequence of steps of care

• Recommended observations and examinations

• Decisions to be considered

• Actions to be taken

A clinical algorithm diagrams a guideline into a step-by-step decision tree. Standardized symbols are used 

to display each step in the algorithm, and arrows connect the numbered boxes indicating the order in 

which the steps should be followed.[64] 

Rounded rectangles represent a clinical state or condition.

Hexagons represent a decision point in the guideline, formulated as a question 

that can be answered Yes or No.

Rectangles represent an action in the process of care.
December 2015 Page 23 of 169

A. Module A: Screening and Treatment 
December 2015 Page 24 of 169

B. Module B: Stabilization
December 2015 Page 25 of 169

VI. Recommendations

# Recommendation Strength* Category† 

A. Screening

1. For patients in general medical and mental healthcare settings, we 

recommend screening for unhealthy alcohol use annually using the 

three-item Alcohol Use Disorders Identification Test-Consumption 

(AUDIT-C) or Single Item Alcohol Screening Questionnaire (SASQ).

Strong For Not reviewed, 

Amended

B. Brief Alcohol Intervention

2. For patients without documented alcohol use disorder who screen 

positive for unhealthy alcohol use, we recommend providing a single 

initial brief intervention regarding alcohol-related risks and advice to 

abstain or drink within nationally established age and gender-specific 

limits for daily and weekly consumption.

Strong For Reviewed, Newreplaced

C. Determination of Treatment Setting

3. For patients with a diagnosis of a substance use disorder, we suggest 

offering referral for specialty substance use disorder care based on 

willingness to engage in specialty treatment.

Weak For Not reviewed, 

Amended

4. For patients with substance use disorders, there is insufficient evidence 

to recommend for or against using a standardized assessment that 

would determine initial intensity and setting of substance use disorder

care rather than the clinical judgment of trained providers.

N/A Reviewed, Newreplaced

D. Treatment

a. Alcohol Use Disorder

i. Pharmacotherapy

5. For patients with moderate-severe alcohol use disorder, we recommend 

offering one of the following medications:

 Acamprosate

 Disulfiram

 Naltrexone- oral or extended release

 Topiramate

Strong For Reviewed, Newreplaced

6. For patients with moderate-severe alcohol use disorder for whom firstline pharmacotherapy is contraindicated or ineffective, we suggest 

offering gabapentin.

Weak For Reviewed, Newreplaced 

ii. Psychosocial Interventions

7. For patients with alcohol use disorder we recommend offering one or 

more of the following interventions considering patient preference and 

provider training/competence: 

 Behavioral Couples Therapy for alcohol use disorder

 Cognitive Behavioral Therapy for substance use disorders

 Community Reinforcement Approach 

 Motivational Enhancement Therapy

 12-Step Facilitation

Strong For Reviewed, Newreplaced
December 2015 Page 26 of 169

# Recommendation Strength* Category† 

b. Opioid Use Disorder

i. Pharmacotherapy

8. For patients with opioid use disorder, we recommend offering one of 

the following medications considering patient preferences: 

 Buprenorphine/naloxone 

 Methadone in an Opioid Treatment Program

Strong For Reviewed, Newreplaced

9. In pregnant women with opioid use disorder for whom buprenorphine is 

selected, we suggest offering buprenorphine alone (i.e., without 

naloxone) considering patient preferences.

Weak For Reviewed, Newadded

10. For patients with opioid use disorder for whom buprenorphine is 

indicated, we recommend individualizing choice of appropriate 

treatment setting (i.e., Opioid Treatment Program or office-based) 

considering patient preferences.

Strong For Reviewed, Newreplaced

11. For patients with opioid use disorder for whom opioid agonist treatment 

is contraindicated, unacceptable, unavailable, or discontinued and who 

have established abstinence for a sufficient period of time (see 

narrative), we recommend offering: 

 Extended-release injectable naltrexone

Strong For Reviewed, Newreplaced

12. There is insufficient evidence to recommend for or against oral 

naltrexone for treatment of opioid use disorder.

N/A Reviewed, Newreplaced

13. At initiation of office-based buprenorphine, we recommend addictionfocused Medical Management (see narrative) alone or in conjunction 

with another psychosocial intervention.

Strong For Reviewed, Newreplaced

ii. Psychosocial Interventions With or Without Pharmacotherapy

14. For patients in office-based buprenorphine treatment, there is 

insufficient evidence to recommend for or against any specific 

psychosocial interventions in addition to addiction-focused Medical 

Management. Choice of psychosocial intervention should be made 

considering patient preferences and provider training/competence. 

N/A Reviewed, Newreplaced

15. In Opioid Treatment Program settings, we suggest offering individual 

counseling and/or Contingency Management, considering patient 

preferences and provider training/competence.

Weak For Reviewed, Newreplaced

16. For patients with opioid use disorder for whom opioid use disorder 

pharmacotherapy is contraindicated, unacceptable or unavailable, there 

is insufficient evidence to recommend for or against any specific 

psychosocial interventions. 

N/A Reviewed, Newreplaced

c. Cannabis Use Disorder

i. Pharmacotherapy

17. There is insufficient evidence to recommend for or against the use of 

pharmacotherapy in the treatment of cannabis use disorder.

N/A Reviewed, Newadded

ii. Psychosocial Interventions

18. For patients with cannabis use disorder, we recommend offering one of 

the following interventions as initial treatment considering patient 

preference and provider training/competence:

 Cognitive Behavioral Therapy

 Motivational Enhancement Therapy

 Combined Cognitive Behavioral Therapy/Motivational 

Enhancement Therapy

Strong For Reviewed, Newreplaced
December 2015 Page 27 of 169

# Recommendation Strength* Category† 

d. Stimulant Use Disorder

i. Pharmacotherapy

19. There is insufficient evidence to recommend for or against the use of 

any pharmacotherapy for the treatment of cocaine use disorder or 

methamphetamine use disorder.

N/A Reviewed, Newadded

ii. Psychosocial Interventions

20. For patients with stimulant use disorder, we recommend offering one or 

more of the following interventions as initial treatment considering 

patient preference and provider training/competence:

 Cognitive Behavioral Therapy

 Recovery-focused behavioral therapy

 General Drug Counseling

 Community Reinforcement Approach

 Contingency Management in combination with one of the 

above 

Strong For Reviewed, Newreplaced

E. Promoting Group Mutual Help Involvement

21. For patients with substance use disorders in early recovery or following 

relapse, we recommend promoting active involvement in group mutual 

help programs using one of the following systematic approaches 

considering patient preference and provider training/competence:

 Peer linkage 

 Network support

 12-Step Facilitation

Strong For Reviewed, Newreplaced

F. Co-occurring Mental Health Conditions and Psychosocial Problems

22. Among patients in early recovery from substance use disorders or 

following relapse, we suggest prioritizing other needs through shared 

decision making (e.g., related to other mental health conditions, 

housing, supportive recovery environment, employment, or related 

recovery-relevant factors) among identified biopsychosocial problems 

and arranging services to address them. 

Weak For Not reviewed, 

Amended

G. Follow-up

23. We suggest assessing response to treatment periodically and 

systematically, using standardized and valid instrument(s) whenever 

possible. Indicators of treatment response include ongoing substance 

use, craving, side effects of medication, emerging symptoms, etc. 

Weak For Reviewed, Newreplaced

24. For patients who have initiated an intensive phase of outpatient or 

residential treatment, we recommend offering and encouraging ongoing 

systematic relapse prevention efforts or recovery support individualized 

on the basis of treatment response.

Strong For Not reviewed, 

Amended

25. For patients in substance use disorders specialty care, we recommend 

against automatic discharge from care for patients who do not respond 

to treatment or who relapse. 

Strong Against Not reviewed, 

Amended

H. Stabilization and Withdrawal

a. Assessment

26. For patients with alcohol or opioid use disorder in early abstinence, we 

suggest using standardized measures to assess the severity of 

withdrawal symptoms such as Clinical Institute Withdrawal Assessment 

for Alcohol (revised version) (CIWA-Ar) for alcohol or Clinical Opiate

Withdrawal Scale (COWS) for opioids.

Weak For Not reviewed, 

Amended
December 2015 Page 28 of 169

# Recommendation Strength* Category† 

27. We recommend inpatient medically supervised alcohol withdrawal 

management for patients with any of the following conditions: 

 History of delirium tremens or withdrawal seizures 

 Inability to tolerate oral medication

 Co-occurring medical conditions that would pose serious risk 

for ambulatory withdrawal management (e.g., severe coronary 

artery disease, congestive heart failure, liver cirrhosis) 

 Severe alcohol withdrawal (i.e., Clinical Institute Withdrawal 

Assessment for Alcohol [revised version] [CIWA-Ar] score ≥20)

 Risk of withdrawal from other substances in addition to alcohol 

(e.g., sedative hypnotics)

Strong For Reviewed, 

Amended

28. We suggest inpatient medically supervised withdrawal for patients with 

symptoms of at least moderate alcohol withdrawal (i.e., Clinical Institute 

Withdrawal Assessment for Alcohol [revised version] [CIWA-Ar] score 

≥10) and any of the following conditions:

 Recurrent unsuccessful attempts at ambulatory withdrawal 

management

 Reasonable likelihood that the patient will not complete 

ambulatory withdrawal management (e.g., due to 

homelessness) 

 Active psychosis or severe cognitive impairment 

 Medical conditions that could make ambulatory withdrawal 

management problematic (e.g., pregnancy, nephrotic 

syndrome, cardiovascular disease, lack of medical support 

system)

Weak For Reviewed, 

Amended

b. Alcohol Use Disorder Stabilization and Withdrawal

29. We recommend using one of the following pharmacotherapy strategies 

for managing alcohol withdrawal symptoms:

 A predetermined fixed medication tapering schedule with 

additional medication as needed 

 Symptom-triggered therapy where patients are given 

medication only when signs or symptoms of withdrawal occur 

(e.g., as needed dosing)

Strong For Not reviewed, 

Amended

30. For treatment of moderate to severe alcohol withdrawal, we 

recommend using benzodiazepines with adequate monitoring because 

of documented efficacy and high margin of safety. 

Strong For Reviewed, 

Amended

31. For managing mild to moderate alcohol withdrawal in patients for whom 

risks of benzodiazepines outweigh benefits (e.g., inadequate monitoring 

available, abuse liability, or allergy/adverse reactions), we suggest 

considering carbamazepine, gabapentin, or valproic acid as an 

alternative.

Weak For Reviewed, Newreplaced

32. We recommend against using alcohol as an agent for medically 

supervised withdrawal.

Strong Against Not reviewed, 

Amended

c. Opioid Use Disorder Stabilization and Withdrawal

33. For patients not yet stabilized from opioid use disorder, we recommend 

against withdrawal management alone due to high risk of relapse and 

overdose (see Recommendations 8 and 11). 

Strong Against Reviewed, Newreplaced
December 2015 Page 29 of 169

# Recommendation Strength* Category† 

34. Among patients with opioid use disorder for whom maintenance agonist 

treatment is contraindicated, unacceptable, or unavailable, we 

recommend using a methadone (in Opioid Treatment Program only) or 

buprenorphine taper for opioid withdrawal management (see 

Recommendation 11).

Strong For Reviewed, Newreplaced

35. For patients with opioid use disorder for whom methadone and 

buprenorphine are contraindicated, unacceptable, or unavailable, we 

recommend offering clonidine as a second-line agent for opioid 

withdrawal management (see Recommendation 11).

Strong For Reviewed, Newreplaced

d. Sedative Hypnotic Use Disorder Stabilization and Withdrawal

36. For patients in need of withdrawal management for sedative hypnotics, 

we suggest one of the following:

 Gradually taper the original benzodiazepine

 Substitute a longer acting benzodiazepine then taper gradually

 Substitute phenobarbital for the addicting agent and taper 

gradually

Weak For Not reviewed, 

Amended

*For additional information, please refer to Grading Recommendations.

†For additional information, please refer to Recommendation Categorization and Appendix E. 

A. Screening

Recommendation

1. For patients in general medical and mental healthcare settings, we recommend screening for

unhealthy alcohol use annually using the three-item Alcohol Use Disorders Identification TestConsumption (AUDIT-C) or Single Item Alcohol Screening Questionnaire (SASQ).

(Strong For | Not reviewed, Amended)

Discussion

Annual Screening for Unhealthy Alcohol Use

Annual screening for unhealthy alcohol use is recommended for all patients based on moderate to high 

confidence in evidence that alcohol screening followed by brief alcohol counseling is efficacious for 

reducing drinking.[65,66] Screening should identify patients along the entire continuum of unhealthy 

alcohol use including those who drink above recommended limits (often called risky or hazardous 

drinking) and those with severe AUD. Most screen-positive patients will not have AUD and will be 

appropriate candidates for brief alcohol counseling as the initial treatment approach for unhealthy 

alcohol use.[66] One of two validated brief screens is recommended to identify past-year unhealthy 

alcohol use: the AUDIT-C [67-70] or a single item alcohol screen for drinking above recommended daily 

limits (SASQ).[71] More information on the AUDIT-C and SASQ can be found in Table 1.

Selection of an Approach to Unhealthy Alcohol Use Screening in a Particular Setting Should

Reflect Local Factors

The AUDIT-C may be preferable in the following situations:

• When the clinician preference is to obtain information regarding:

 Any drinking (for those with contraindications)

 Typical drinking (for medication interactions) 
December 2015 Page 30 of 169

 Episodic heavy drinking

 The severity of unhealthy alcohol use provided by the AUDIT-C [72-74] 

• When there is a specific service requirement (i.e., VA or DoD quality indicators)

• When an electronic medical record can score the AUDIT-C and provide decision support to the

provider

The SASQ screen is easier to integrate into clinician interviews, as primary care clinicians are unlikely to 

recall response options and scoring for the AUDIT-C.

Table 1. Screening Tools for Unhealthy Alcohol Use

Alcohol Use Disorders Identification Test- Consumption 

(AUDIT-C) 

Single-Item Alcohol Screening 

Questionnaire (SASQ)

Items

1. How often did you have a drink containing alcohol in the past

year?

1. Do you sometimes drink beer,

wine, or other alcoholic

beverages?

(Followed by the screening

question)

2. How many times in the past

year have you had...

Men:

5 or more drinks in a day

Women:

4 or more drinks in a day

Never 0 point

Monthly or less 1 point

2-4 times per month 2 points

2-3 times per week 3 points

4 or more times per week 4 points

2. On days in the past year when you drank alcohol how many drinks 

did you typically drink?

0, 1, or 2 0 point

3 or 4 1 point

5 or 6 2 points

7-9 3 points

10 or more 4 points

3. How often did you have 6 or more drinks on an occasion in the

past year?

Never 0 point

Less than monthly 1 point

Monthly 2 points

Weekly 3 points

Daily or almost daily 4 points

Scoring

The minimum score (for non-drinkers) is 0 and the maximum possible 

score is 12.

Consider a screen positive for unhealthy alcohol use if AUDIT-C score 

is ≥4 points for men or ≥3 points for women.

Note: For VA, documentation of brief alcohol counseling is required 

for those with AUDIT-C ≥5 points, for both men and women. This 

higher score for follow-up was selected to minimize the false-positive 

rate and to target implementation efforts. Follow-up of lower 

screening scores <5 is left to provider discretion.

A positive screen is any report of 

drinking 5 or more (men) or 4 or 

more (women) drinks on an 

occasion in the past year.
December 2015 Page 31 of 169

Although qualitative work reflects some reservations among providers about screening for unhealthy 

alcohol use,[75] evidence does not support provider concerns that delivering brief intervention (BI) based 

on alcohol screening results adversely affects patients' perceptions of care.[76,77] 

More research is needed on the optimal frequency of screening for unhealthy alcohol use [78,79] and 

alternative methods to promote more efficient and accurate collection of screening data directly from

patients.[80,81]

B. Brief Alcohol Intervention

Recommendation

2. For patients without documented alcohol use disorder who screen positive for unhealthy alcohol

use, we recommend providing a single initial brief intervention regarding alcohol-related risks and

advice to abstain or drink within nationally established age and gender-specific limits for daily and

weekly consumption.

(Strong For | Reviewed, New-replaced)

Discussion

For adults who screened positive for unhealthy alcohol use (e.g., AUDIT-C score ≥3 for women, >4 for 

men), a single brief intervention (BI) is recommended based on several SRs.[65,66,82] These reviews 

present moderate strength of evidence for efficacy of a BI in reducing consumption outcomes and 

improving certain health outcomes and moderate confidence that benefits outweigh harms among those 

with unhealthy alcohol use who do not meet diagnostic criteria for AUD. At the provider’s discretion, 

individuals who are higher risk for AUD (e.g., AUDIT-C score ≥8 or current alcohol use in the context of 

previously documented AUD treatment or diagnosis) may be further evaluated for AUD diagnosis or 

referred for further evaluation and managed in accordance with the algorithm.

The reviewed evidence is insufficient to recommend for or against multi-contact BIs over a single BI due to 

the lack of direct comparisons within studies.[65] Based on this finding, and to minimize opportunity costs 

resulting from multiple sessions of BI delaying or diverting medical resources that might have been used to 

address other, more pressing concerns, this guideline recommends a single initial BI. Follow-up BIs may be 

offered as clinically indicated, based on additional independent risk factors and co-occurring conditions. 

Similarly, there is no evidence to suggest that there is a difference in efficacy between 5, 10, or 20 minute 

interventions [82,83] or that certain components of BIs are more effective than others.[65,84] Two BI 

elements that are offered consistently in positive randomized clinical trials (RTCs) are: (1) providing 

individualized feedback on patient’s level of alcohol-related risk (i.e., mild, moderate, high) and any 

alcohol-related adverse health effects; and (2) brief advice to abstain or drink within recommended 

limits.[65] Additional topics that can be discussed are the benefits of cutting down and effective strategies 

for reducing alcohol consumption. Motivational interventions focused on supporting the patient in 

choosing a drinking goal, when he/she is ready to make a change, have been shown to be effective as 

well[85-90] and can be offered by providers trained in this approach. 

The efficacy of a BI is specific to the following consumption outcomes: decrease in mean drinks per week, 

decrease in number of heavy drinking episodes, and increase in the percentage of patients whose alcohol 
December 2015 Page 32 of 169

consumption is within recommended drinking limits.[65] Similar decreases in alcohol consumption 

outcomes were shown in women-only trials,[82] in pregnant women,[91,92] and in Veterans,[84] but with 

a lower quality of evidence. The health outcomes improved with BIs were all-cause mortality,[65] 

hospitalization rates,[65] and systolic blood pressure.[93] 

BIs were found to be effective for adults with unhealthy alcohol use who do not have AUD in a variety of 

clinical settings, such as primary care,[65,94] emergency department,[95,96] and hospital settings.[97,98] 

Evidence also shows that BIs are effective when provided by primary care providers,[65] nurses,[65,99] 

psychologists,[88] or health educators.[100,101] Therefore, we recommend that various providers can 

administer BIs consistent with this recommendation, as long as it is within the scope of practice and 

privileges at their facility. 

Additional research is needed on the effectiveness of procedures to screen for and address risks related to 

use of substances other than alcohol and tobacco. According to the USPSTF, the evidence is insufficient to 

assess the balance of benefits and harms of screening for illicit drug use.[102] Several recent trials have 

failed to support effectiveness of BIs in primary care for drug problems,[103,104] but one trial found 

encouraging results of a multi-component intervention.[105] 

C. Determination of Treatment Setting

Recommendation 

3. For patients with a diagnosis of a substance use disorder, we suggest offering referral for specialty

substance use disorder care based on willingness to engage in specialty treatment.

(Weak For | Not reviewed, Amended)

Discussion

Most patients with alcohol and other SUD do not receive adequate treatment,[21] and many patients will 

not accept referrals to a specialty clinic for SUD [21,44,106,107] for reasons including, but not limited to, 

lack of perceived need, fear of stigma, lack of readiness for treatment, lack of resources, time restrictions, 

etc. While there is evidence that selected patients with SUD can be treated in primary care or general 

mental healthcare, there is value in initially offering a referral to an SUD specialty clinic when available. A 

referral to specialty care may help the patient recognize that there is significant concern, which might 

motivate the patient to address the issue(s) more fully. If a patient has stated that he/she does not want 

and will not accept a referral to the specialty clinic, then efforts should be made to engage the patient in 

primary care to include monitoring and treating substance-related problems. 

Thus, a referral to specialty SUD care should be offered if the patient has at least one of the following:

• May benefit from additional evaluation of his/her substance use and related problems

• Has been diagnosed as having an SUD

• Is willing to engage in specialty care

Benefits of offering a referral far outweigh any associated harms, and patients vary widely in their values 

and preferences regarding engaging in specialty care. The offer of a referral expresses care and concern on 

the part of the provider and allows an opportunity for patients to receive sufficient information for 
December 2015 Page 33 of 169

reasoned decision making. Referrals may have implications for resource utilization in both the primary and 

specialty care settings and may not be able to be based on positive screening results alone. 

Recommendation

4. For patients with substance use disorders, there is insufficient evidence to recommend for or

against using a standardized assessment that would determine initial intensity and setting of

substance use disorder care rather than the clinical judgment of trained providers.

(N/A | Reviewed, New-replaced)

Discussion

Identifying the appropriate level of care in SUD treatment is a challenge, and numerous variables, including 

patient preference, patient motivation, patient willingness, and available resources can be taken into 

consideration. However, there is a lack of clear evidence that any specific factor accurately predicts the 

optimal level or intensity of care. The American Society of Addiction Medicine Patient Placement Criteria 

(The ASAM Criteria, 2013) [108] have been widely promulgated as a system to determine level of care

based on assessment of six dimensions (acute intoxication and/or withdrawal potential; biomedical 

conditions and complications; emotional, behavioral or cognitive conditions and complications; readiness 

to change; relapse, continued use, or continued problem potential; and recovery/living environment), but 

controlled trials evaluating placement outcomes based on standardized assessment of these dimensions 

are lacking. Future research is needed to evaluate whether recently developed software to conduct the 

multidimensional assessment and yield an algorithmically derived placement recommendation leads to 

better outcomes than clinical judgment that may rely more generally on the six ASAM assessment 

dimensions and placement principles. 

D. Treatment

a. Alcohol Use Disorder

i. Pharmacotherapy

Recommendations 

5. For patients with moderate-severe alcohol use disorder, we recommend offering one of the

following medications:

 Acamprosate

 Disulfiram

 Naltrexone- oral or extended release

 Topiramate 

(Strong For | Reviewed, New-replaced)

6. For patients with moderate-severe alcohol use disorder for whom first-line pharmacotherapy is

contraindicated or ineffective, we suggest offering gabapentin.

(Weak For | Reviewed, New-replaced)

Discussion

Naltrexone, acamprosate, disulfiram, and topiramate are recommended for the treatment of AUD based 

on RCTs [109] and several SRs/meta-analyses.[110-112] The clinical trials reviewed were based on DSM-IV 
December 2015 Page 34 of 169

criteria for alcohol dependence which is equivalent to DSM-5 criteria for moderate-severe AUD. These 

medications should be offered in conjunction with a psychosocial intervention and considering the 

preferences of appropriately informed patients. Dosing of these pharmacotherapies should be consistent 

with medication trials and published recommendations.

In the absence of contraindications, there is insufficient evidence to recommend for or against the 

routine use of one of these recommended medications over another; therefore, treatment should be 

individualized considering patient preferences. These medications are presented below in alphabetical 

order. Additional information can be found in Appendix B, Table B-1. This information includes 

indications, contraindications, warnings/precautions, baseline evaluation, dosage and administration, 

alternative dosing schedules, dosing in special populations, adverse effects, drug interactions, 

monitoring, and patient education.

Acamprosate

Acamprosate may act by normalizing central glutamatergic dysregulation in AUD, thereby relieving 

symptoms of prolonged alcohol withdrawal.[113] Numerous European trials found acamprosate effective 

in reducing drinking days, increasing complete abstinence, and lengthening time to relapse; however, U.S.

trials failed to show benefit.[112] These discordant results may have been due to methodological 

differences between the U.S. and European studies including: site of pretreatment detoxification, duration 

of pretreatment abstinence, duration of study treatment, concomitant medications, nature and intensity 

of accompanying psychosocial treatment, outcome measures used, and severity of participants’ AUD.[113] 

The three doses per day and large tablet size present a challenge to many patients and can negatively 

affect treatment adherence. Acamprosate should be considered in patients with AUD who are also taking 

prescribed opioids or who have significant hepatic damage/impairment, as it is the only first-line drug 

recommended by the SUD CPG Work Group that is not subject to hepatic clearance. Patients who are wellsuited for acamprosate include those who are highly motivated, abstinent prior to initiation, and not 

discouraged by the three times per day dosing burden. Some patients and providers may opt for other 

agents dosed once daily depending upon patient preferences and values. 

Disulfiram

Patients taking disulfiram should avoid ingestion of alcohol due to the expectation of a toxic reaction if 

alcohol is consumed; thus, it has been suggested that the optimal assessment of disulfiram efficacy has 

resulted from open-label trials where patient awareness of active treatment allowed treatment to have its 

full preventive effect.[111] Disulfiram supports a behavioral treatment paradigm in which alcohol 

consumption is consistently and quickly followed by adverse effects in the form of the alcohol-disulfiram 

reaction. The human tendency to avoid punishment may affect not only alcohol consumption but also 

adherence to disulfiram, thus reducing its effectiveness when administration is unsupervised. A metaanalysis of 22 RCTs of disulfiram, showed no advantage to disulfiram compared to control conditions in 

blinded trials, modest advantage in open-label unsupervised trials, and a moderately large effect size in 

supervised versus unsupervised open-label trials.[111] Because the action of disulfiram depends on the

expectation of adverse effects, the drug should not be given to patients who are unable to consider the 

consequences of alcohol consumption while taking disulfiram. Disulfiram is thus best suited to patients 

who have made an informed choice of this type of treatment, are highly compliant, and are under close 

medical supervision. Because of the risk of significant toxicity, the risks and benefits of disulfiram should be 
December 2015 Page 35 of 169

carefully considered. Disulfiram should only be used when abstinence is the goal and when initiated with 

addiction-focused counseling. Verification of abstinence and the informed consent discussion with the 

patient should be documented. 

Naltrexone

Naltrexone is an opioid antagonist available for once-daily oral administration and in an extended-release 

suspension for once-monthly intramuscular injection. The two formulations have not been directly 

compared to evaluate whether the long-acting injectable formulation improves treatment adherence and 

clinical outcomes;[112] however, injectable naltrexone should be considered when medication adherence 

is a significant concern, and the patient is accepting of treatment that requires monthly injections by a 

provider. Naltrexone injection must be stored under refrigeration, and provision to Service Members 

deployed to remote locations may be problematic. In a multicenter trial (Combining Medications and 

Behavioral Interventions [COMBINE]) comparing oral naltrexone and/or acamprosate to double placebo 

with addiction-focused Medical Management (see Addiction-focused Medical Management for additional 

information) and/or Combined Behavioral Intervention (CBI), patients receiving addiction-focused Medical 

Management with naltrexone, CBI, or both, fared better on drinking outcomes than those receiving 

acamprosate or double placebo.[114] 

Topiramate

Topiramate is believed to decrease alcohol reinforcement and the propensity to drink by reducing craving 

for alcohol through antagonism of glutamate receptors and inhibition of dopamine release.[110] 

Topiramate is not Food and Drug Administration (FDA) approved for AUD but is recommended here 

because there is moderate quality evidence which favors significant reduction in heavy drinking and 

promotion of abstinence with its use [110,112,115] as well as one recent pilot trial showing benefit with 

Veterans who had AUD and co-occurring PTSD.[109] These benefits may be accompanied by welldocumented side effects which include paresthesia/numbness, anorexia, taste abnormalities, cognitive 

impairment, and rash. Fortunately, some common side effects can usually be managed by lowering the 

topiramate dose. A lower dose of 200 mg daily has been shown to be effective [110] and is less prone to 

causing side effects than higher doses; thus, the 200 mg daily dose is the recommended regimen. 

Gabapentin

Gabapentin is suggested as an option for patients with AUD for whom first-line pharmacotherapy is 

contraindicated or ineffective. The effects of gabapentin likely occur through modulation of γaminobutyric acid (GABA) activity in the amygdala associated with AUD. One RCT in 150 patients indicated 

gabapentin significantly improved the rates of abstinence and heavy drinking; however, the single-site 

setting and high dropout rate in this study raise concerns regarding its generalizability and potential for 

bias.[116] Another trial indicated that the addition of gabapentin to oral naltrexone improved drinking 

outcomes over those obtained with naltrexone alone.[112] The need for more than once-daily dosing may 

make treatment adherence difficult for some patients. Also, there are increasing concerns regarding the 

abuse potential of gabapentin if taken at doses far exceeding therapeutic recommendations.[117] 

However, when taken as directed, gabapentin has a high margin of safety, and many primary care 

providers have experience prescribing the drug for non-AUD indications. Gabapentin may be a treatment 

consideration for patients with co-occurring neuropathic pain or in patients with hepatic disease who 

cannot take acamprosate. 
December 2015 Page 36 of 169

Other medications, not recommended

Two RCTs of baclofen provided low quality evidence for the drug’s efficacy but had inconsistent findings

regarding consumption outcomes.[112] Additional studies of better overall quality are needed to make a 

recommendation for or against the use of baclofen for AUD. Abrupt withdrawal of baclofen can be 

associated with hallucinations and seizures. 

There are no large, randomized, double-blind studies of valproic acid; however, two very small trials 

provided low to moderate quality evidence for a positive effect on alcohol consumption.[112] 

The use of buspirone, citalopram, fluoxetine, and quetiapine in patients with AUD showed either no 

benefit or an inconsistent benefit in studies typically providing a very low or low overall quality of 

evidence.[112,118] 

ii. Psychosocial Interventions

Recommendation

7. For patients with alcohol use disorder we recommend offering one or more of the following

interventions considering patient preference and provider training/competence:

 Behavioral Couples Therapy for alcohol use disorder

 Cognitive Behavioral Therapy for substance use disorders 

 Community Reinforcement Approach 

 Motivational Enhancement Therapy

 12-Step Facilitation 

(Strong For | Reviewed, New-replaced) 

Discussion

A brief description of these psychosocial interventions and evidence for their use for patients with AUD 

can be found below. Additional information about these interventions, as well as the appropriateness of 

their use for patients with specific types of SUD, can be found in Appendix C. 

Most versions of Behavioral Couples Therapy (BCT) are focused both on reducing alcohol use in the 

identified patient and on improving overall marital satisfaction for both partners. To improve relationship 

functioning, BCT uses a series of behavioral assignments to increase positive feelings, shared activities, and 

constructive communication because improving these relationship factors is also conducive to sobriety.

Cognitive Behavioral Therapy (CBT) for AUD focuses on teaching patients to modify both thinking and 

behavior related to alcohol use, as well as to change other areas of life functionally related to alcohol use. 

Patients learn to track their thinking and activities and identify the affective and behavioral consequences 

of those thoughts and activities, including increases in craving and episodes of alcohol use. Patients then 

learn techniques to change thinking and behaviors that contribute to alcohol use, and to strengthen coping 

skills, improve mood and interpersonal functioning, and enhance social support. Treatment incorporates 

structured practice outside of session, including scheduled activities, self-monitoring, thought recording 

and challenging, and interpersonal skills practice.

Community Reinforcement Approach (CRA) is a comprehensive cognitive-behavioral intervention for the 

treatment of AUD that focuses on environmental contingencies that impact and influence the patient’s 
December 2015 Page 37 of 169

behavior. Given that environmental contingencies play a crucial role in an individual’s addictive behavior 

and recovery, CRA utilizes familial, social, recreational, and occupational events to support the individual in 

changing his or her drinking behaviors so that a sober lifestyle is more rewarding than one that is 

dominated by alcohol. CRA integrates several treatment components, including increasing positive 

reinforcement, learning new coping behaviors, and involving significant others in the recovery process. In 

some versions of CRA, incentives are also provided for positive behaviors, such as attending treatment, 

taking medication, or being abstinent.

Motivational Enhancement Therapy (MET) is a less intensive psychosocial intervention for patients with 

AUD. MET uses principles of motivational interviewing (MI) to heighten awareness of ambivalence about 

change, promote commitment to change, and enhance self-efficacy. MET differs from MI in that it is a 

more structured intervention that is based to a greater degree on systematic assessment with 

personalized feedback. The therapeutic style uses MI to elicit patient reactions to assessment feedback, 

commitment to change, and collaboration on development of an individualized change plan. Involvement 

of a significant other is encouraged in at least one of the MET sessions.

12-Step Facilitation (TSF) therapy aims to increase the patient’s active involvement in Alcoholics 

Anonymous (AA) or other 12-step-based group mutual help resources. This approach is systematized in 

a manual and is delivered as 12 sessions of individual therapy in which the therapist actively encourages 

engagement in AA and walks the patient through the first four steps of the AA program. The first part of 

each session includes reviewing relevant events of the last week (including urges to use, drinking 

behavior, and recovery-oriented activities) and a homework assignment. The middle portion introduces 

new material related to the 12-steps. The conclusion of the session includes a homework assignment 

and development of a plan for recovery-oriented activities (meeting attendance, sponsor contact).

Other interventions based on TSF have also focused on increasing positive social support outside of 12-

step programs.

Three SRs have indicated that CBT is generally more effective than minimal or control comparators for 

individuals with AUD, but not superior to other active treatments.[119-121] Other individual studies of CBT 

in patients with AUD and mental health comorbidities generated mixed results, with one study finding 

positive effects [122] and two finding positive effects at some, but not all, follow-up points.[123,124] 

The combination of CBT plus MI appears to be more effective than comparison conditions for individuals 

with AUD and co-occurring anxiety or depression disorders.[125] Studies have consistently found that BCT 

and CRA produce improved alcohol use outcomes during treatment and/or follow-up, relative to various 

active comparison conditions.[126-129] BCT generally has positive effects on measures of marital 

satisfaction as well.

As a stand-alone treatment, MET provided over 3-4 sessions yielded comparable benefits to more 

intensive manualized interventions (CBT or TSF) involving 8-12 sessions.[130,131] TSF and other

treatments designed to increase participation in self/mutual help programs and other sources of social 

support in the community (See Promoting Group Mutual Help Involvement for additional information) 

have consistently increased participation in these programs and produced greater improvements in some

drinking outcomes compared to CBT or MET.[130] 
December 2015 Page 38 of 169

Confidence in the quality of the evidence regarding the effectiveness of these interventions for the 

treatment of AUD is moderate, with benefits outweighing harms. Because of variations in patient values 

and preferences for psychosocial intervention approaches, we recommend offering a menu of options 

using a shared decision making (SDM) approach. The primary concerns regarding the use of these 

interventions are that they require considerable training to implement with fidelity and are resourceintensive to deliver. The research evidence is based almost entirely on studies in which these interventions 

were delivered individually to patients, whereas most AUD treatment in the VA and DoD is delivered in 

groups. Finally, little is known about the effectiveness of some of these interventions within specific 

subgroups, most notably the effectiveness of BCT in women and lesbian, gay, bisexual, and transgender

individuals.

b. Opioid Use Disorder

i. Pharmacotherapy

Recommendation

8. For patients with opioid use disorder, we recommend offering one of the following medications

considering patient preferences:

 Buprenorphine/naloxone

 Methadone in an Opioid Treatment Program

(Strong For | Reviewed, New-replaced)

9. In pregnant women with opioid use disorder for whom buprenorphine is selected, we suggest

offering buprenorphine alone (i.e., without naloxone) considering patient preferences.

(Weak For | Reviewed, New-added)

10. For patients with opioid use disorder for whom buprenorphine is indicated, we recommend

individualizing choice of appropriate treatment setting (i.e., Opioid Treatment Program or officebased) considering patient preferences.

(Strong For | Reviewed, New-replaced)

11. For patients with opioid use disorder for whom opioid agonist treatment is contraindicated,

unacceptable, unavailable, or discontinued and who have established abstinence for a sufficient

period of time (see narrative), we recommend offering:

 Extended-release injectable naltrexone

(Strong For | Reviewed, New-replaced)

12. There is insufficient evidence to recommend for or against oral naltrexone for treatment of opioid

use disorder.

(N/A | Reviewed, New-replaced)

13. At initiation of office-based buprenorphine, we recommend addiction-focused Medical

Management (see narrative) alone or in conjunction with another psychosocial intervention.

(Strong For | Reviewed, New-replaced)
December 2015 Page 39 of 169

Discussion

Medications in General—Opioid Agonists and Antagonists

Buprenorphine and methadone are recommended for the treatment of opioid use disorder (OUD) based 

on high quality evidence from multiple RCTs and meta-analyses. High quality evidence supports the use of 

medication-assisted treatment using methadone or buprenorphine over psychosocial treatment alone to 

improve outcomes for OUD.[132-147] Extended-release injectable naltrexone is also recommended for 

maintenance treatment of OUD based on moderate quality evidence. In addition to the quality of evidence 

(listed below under each medication), our recommendations are based on decisions regarding three other 

domains: the balance of desirable and undesirable medication effects, values and preferences of patients, 

and other associated implications, such as DoD mission-readiness. If a patient refuses or defers 

medication-assisted treatment, we suggest using a motivational approach to encourage reconsideration. 

One motivational strategy is to provide treatment options, as there may be variations in values and 

preferences among patients with OUD.

Opioid Agonists

Opioid agonist therapy (OAT) for OUD consists of administering a medication, such as methadone or 

sublingual or buccal buprenorphine, in combination with a comprehensive range of medical, counseling,

and rehabilitative services, as indicated. By administering an opioid to prevent withdrawal, to reduce 

craving, and to reduce the effects of illicit opioids, the patient with OUD is able to focus more readily on 

recovery activities. In addition, OAT has been associated with a reduction in human immunodeficiency 

virus (HIV) risk behavior and drug-related criminal behavior. When compared to medically supervised 

withdrawal attempts, OAT is more successful in achieving the long-term goal of reducing opioid use and 

the associated negative medical, legal, and social consequences, including death from overdose.

Five SRs showed that using opioid agonists for the treatment of OUD was effective in both licensed Opioid 

Treatment Programs (OTPs) as well as within general medical settings.[133,135,143,144,148] OTPs are 

structured, licensed facilities that are not available within the DoD, nor in many VA facilities or 

communities. Some OTPs provide comprehensive services including individual counseling, group therapy, 

and family counseling.[149] OTPs can provide opioid maintenance and withdrawal management using 

methadone or buprenorphine, although most OTPs predominately provide methadone. In the U.S.,

methadone can be dispensed within OTPs only, whereas buprenorphine can also be prescribed by 

physicians in office-based settings, including primary care, outpatient specialty SUD treatment, and mental 

health clinics. Provision of care at OTPs is highly regulated with provider- and patient-level requirements 

including limitations on the number of take-home medication doses, drug screens required at least eight 

times annually, and implementation of appropriate psychosocial interventions. For some patients with 

OUD, OTPs may not be feasible due to their distance from home or the impact on mission-readiness in the 

DoD.

Overall, the benefits of the recommended treatments outweigh their potential harms. While offering 

methadone or buprenorphine is recommended, patients’ values and preferences for treatments may vary, 

particularly for Active Duty military and those in safety-sensitive positions. Some patients may want officebased care using buprenorphine, some may want methadone or buprenorphine treatment in OTPs, while 

others may refuse agonist medication altogether. 
December 2015 Page 40 of 169

Buprenorphine

Buprenorphine treatment includes both the buccal and sublingual forms of the mono-product 

buprenorphine or combination-product buprenorphine/naloxone. In contrast to the more highly 

controlled methadone, treatment with buprenorphine can be provided by physicians who have received a 

waiver from the SAMHSA and have a special Drug Enforcement Administration (DEA) number. To qualify 

for a waiver under the Drug Addiction Treatment Act of 2000 (DATA 2000), a licensed physician (MD or 

DO) must complete an approved eight-hour training course or meet other specific criteria.[150] For the 

first year a physician has her or his waiver, the physician may only dispense or prescribe buprenorphine for 

up to 30 patients at a time under the provisions of DATA 2000. After the first year the qualified physician 

can apply to SAMHSA to raise her or his treatment limit to 100 patients. Given active discussion of changes 

to regulations related to the use of buprenorphine, providers can find updates at 

http://www.samhsa.gov/medication-assisted-treatment. 

RCTs have demonstrated the effectiveness of buprenorphine treatment.[136,137,151] In addition, 

buprenorphine has been shown to be effective in a variety of real-world settings for different patient 

populations, including those who are homeless or infected with HIV.[152-157] Meta-analyses of studies 

comparing buprenorphine treatment to methadone treatment indicate that, overall, both are equivalent 

in terms of suppressing illicit opioid use, but that methadone has slightly better treatment retention.[134] 

We found high quality evidence that buprenorphine is more effective than oral naltrexone or placebo 

therapy in improving opioid consumption and time to relapse.[136] Moderate evidence also supports 

higher versus lower dosing of buprenorphine for improving treatment retention.[133] Low quality 

evidence supports higher versus lower dosing of buprenorphine or methadone for improving opioid 

consumption outcomes. We found low quality evidence favoring flexible versus fixed buprenorphine 

dosage regimens.[135] Because of significantly higher attrition in the lower dose and fixed dose groups, 

the confidence in the final opioid consumption estimates was reduced.

Buprenorphine for Maintenance versus Taper

We found high quality evidence supporting buprenorphine for maintenance (14 weeks) over taper (four 

weeks) for improving treatment retention and moderate quality evidence supporting buprenorphine for 

improving opioid consumption outcomes. The high loss to follow-up in the group receiving the four-week 

taper compromised the confidence in the average rates of opioid use between the two conditions. Other 

considerations, such as resource use, also favor maintenance because of human capital and financial costs 

of relapse including opioid overdose death after taper. If taper is chosen, then we recommend extendedrelease injectable naltrexone upon completion of taper. Moderate quality evidence indicates that a slower 

taper is better than a faster taper with benefits outweighing risks. There is some variation in preferences, 

particularly for those in safety-sensitive positions.[158] 

Buprenorphine- Use in Pregnancy

Women who have OUD may consider becoming pregnant or may be pregnant. With the rise in prescribed 

and illicitly used opioids, it was reported in 2012 that the incidence of identification of maternal opioids at 

delivery increased more than four-fold in the past decade. It was also reported that the incidence of 

neonatal opioid withdrawal identified at delivery increased almost three-fold in the past decade.[159,160] 

Since the 1960s, methadone has been the most prominent medication to treat pregnant women with OUD 
December 2015 Page 41 of 169

and has been associated with good maternal and neonatal outcomes.[161,162] Since the advent of 

buprenorphine to treat OUD in 2002, there has been increased interest in using this medication to treat 

OUD in pregnancy. 

Several studies have shown that buprenorphine can be used successfully in pregnancy.[139,163-165] In a 

double-blind, double-dummy, flexible-dosing RCT comparing buprenorphine treatment to methadone 

treatment for pregnant women with OUD, Jones et al. (2010) found that infants born to mothers treated 

with buprenorphine compared to infants born to mothers treated with methadone required significantly 

lower amounts of morphine to treat neonatal abstinence syndrome. Neonates born to mothers treated 

with buprenorphine had shorter hospital stays and significantly shorter duration of treatment for neonatal 

abstinence syndromes.[166] In terms of pregnancy-related complications, there was no difference 

between methadone and buprenorphine for maternal adverse events. There was also no difference in 

maternal serious adverse events between methadone and buprenorphine.[166] If treatment retention is 

the main priority, women on OAT should likely be on methadone as methadone treatment programs are 

likely to offer more structure to non-pharmacotherapy and pharmacotherapy treatment than office-based 

treatment with buprenorphine. If having fewer neonatal complications or serious maternal complications 

during delivery is a priority, we recommend using buprenorphine. Furthermore, patient choice is an 

important factor in deciding between methadone and buprenorphine in pregnancy. However, availability 

of medication should be taken into consideration, as buprenorphine is more widely available in some 

settings than methadone.

For stabilization in pregnant women, patients could be administered immediate maintenance therapy with 

no taper. If the patient chooses to taper, then taper should be used the same as in other patients. See 

Stabilization and Withdrawal for specific recommendations to minimize withdrawal symptoms. 

It is important to note that the mono-product of buprenorphine (not buprenorphine/naloxone) was used 

in the four previously cited clinical trials in order to minimize risks to the fetus. Both buprenorphine and 

naloxone are FDA-labeled as Pregnancy Category C, that is, “animal reproduction studies have shown an 

adverse effect on the fetus, and there are no adequate and well-controlled studies in humans, but 

potential benefits may warrant use of the drug in pregnant women despite potential risks.”[167] FDA 

labeling for Suboxone (buprenorphine/naloxone) states “SUBOXONE sublingual tablets should be used 

during pregnancy only if the potential benefit justifies the potential risk to the fetus.” Two small pilot

studies have found similar outcomes for pregnant women with OUD and their neonatal offspring who 

were treated with buprenorphine-naloxone combination product compared to published outcomes for 

methadone or buprenorphine mono-product [168] or compared to matched controls receiving 

methadone.[169] Clinicians should weigh the unknown risks of long-term harm to the fetus from limited 

exposure to naloxone in the combination product versus the risks of misuse or diversion posed by 

prescribing the mono-product to the mother during pregnancy.

Buprenorphine- Determining Appropriate Setting

First-line treatment for OUD is OAT which can be provided in federally regulated Opioid Treatment 

Programs (OTPs) or through Office-based Opioid Therapy (OBOT). Buprenorphine and long-acting 

injectable naltrexone can be provided in a variety of settings, whereas methadone for the treatment of 

OUD can only be provided in federally regulated OTPs.[170] 
December 2015 Page 42 of 169

OBOT using buprenorphine can be provided in both general healthcare and specialty SUD treatment 

settings by appropriately credentialed physicians in accordance with DATA 2000.[170] Buprenorphine is 

the only opioid agonist medication approved for OBOT. For OBOT using buprenorphine history and 

physical exam are recommended as are capacity to obtain laboratory tests including urine drug testing. 

Capacity to provide or refer to counseling and treatment services if indicated is required. 

Clinical judgment suggests that some patients will respond better in an OTP versus OBOT (Table 2). 

Table 2: Patient Characteristics Suggestive of Suitability for OBOT versus OTP

Criteria OBOT OTP

Can an office-based setting provide needed resources 

for the patient? Yes No

Patient’s psychosocial supports Good Poor

Previous failed treatment attempts with opioid 

maintenance None/few Many

Difficulty accessing OTP (geographic distance, DoD 

mobility requirements, etc.) Yes No

Pain condition that requires ongoing or recurrent 

treatment with short-acting opioids No Yes

Abbreviations: DoD: Department of Defense; OBOT: Office-based Opioid Therapy; OTP: Opioid Treatment Programs

Methadone and Methadone Maintenance Therapy

High quality evidence favors methadone over placebo or non-pharmacologic intervention for opioid use 

and treatment retention.[148] The benefits of methadone maintenance therapy (MMT) outweigh harms 

for a wide variety of secondary outcome measures as well. Methadone has been shown to reduce the 

morbidity and criminality associated with heroin use, improve social engagement and vocational 

productivity, and prevent the spread of blood borne diseases associated with sharing needles.[135] 

Despite strong evidence of benefit, both clinicians and patients have varying preferences regarding MMT. 

Some clinicians, for example, are concerned about methadone’s adverse effects including prolonged time 

from the start of the Q wave to the end of the T wave (QT interval) and respiratory depression. Methadone 

is less widely available due to the regulatory framework which restricts methadone treatment to OTPs 

with strict guidelines for dosing, supervised treatment, and associated services. In addition, MMT has 

mission-readiness implications for Active Duty personnel. Military personnel are not deployed if they are 

on MMT. 

Decades of experience with MMT have yielded additional evidence to enhance treatment outcomes. The 

optimal dosage of methadone for retention in treatment is ≥60 mg/day. In addition, flexible dosage 

strategies are better than fixed dosage strategies in improving retention.[135] Under usual practices, a 

stable target dose is ˃60 mg/day, and many patients will require considerably higher doses in order to 

achieve a pharmacologic blockade of reinforcing effects of illicit opioids. Risk of relapse to opioid use from 

lower doses must be weighed against risks of adverse events such as sedation, constipation, hyperalgesia, 

prolongation of cardiac conduction, and torsade de pointes. Torsade de pointes is an often fatal, but 

extremely rare, adverse event. Two recent studies found no correlation between methadone daily dose 

and QTc (the heart rate corrected time from the start of the Q wave to the end of the T wave).[171,172] 
December 2015 Page 43 of 169

Other risk factors must be considered such as history of heart disease and concurrent medications that 

also prolong QTc.

Opioid Antagonists

Naltrexone Therapy

Moderate quality evidence supports the use of long-acting injectable naltrexone for OUD.[173] The opioid 

antagonist naltrexone may be prescribed in either an oral or extended release injectable form. Long-acting 

injectable naltrexone can also be provided in both general healthcare and specialty SUD treatment 

settings. An RCT demonstrated that extended-release injectable naltrexone reduced opioid consumption

and improved retention in treatment for patients with OUD.[173] While documented abstinence from 

alcohol is not required for therapeutic benefit with injectable naltrexone, even greater benefit may be 

seen in patients who achieve some duration of alcohol abstinence (e.g., two to four days) prior to the 

initial injection of naltrexone.[174] 

While oral naltrexone was originally developed for treatment of OUD, a meta-analysis of 13 studies 

comparing oral naltrexone to placebo, another medication, or non-pharmacologic treatment found no 

difference between naltrexone and the control conditions in treatment retention or opioid use. A major 

barrier to treating OUD with oral naltrexone was treatment retention, which averaged 28%.[175] Three 

additional clinical trials addressed concerns about medication adherence (using a riboflavin marker or 

observed dosing) but found inconsistent results with regard to treatment retention and opioid 

consumption outcomes. For treatment retention, one trial favored naltrexone over placebo [176] while 

another found no difference between naltrexone and treatment as usual (TAU).[177] For opioid 

consumption, one trial favored naltrexone [176] while two found no difference between oral naltrexone 

and placebo [136] or TAU.[177] Further research is needed to determine whether additional measures to 

improve treatment retention (e.g., Contingency Management [CM]) together with measures to improve 

medication adherence would reduce opioid consumption. Based on the available evidence, oral naltrexone 

cannot be recommended for treatment of OUD.[175-177] There is insufficient evidence of efficacy of oral 

naltrexone, and the staff time that is associated with observing and monitoring medication adherence

must be taken into consideration when making the decision to use oral naltrexone. 

Buprenorphine and Addiction-focused Medical Management

Buprenorphine should be initiated along with a psychosocial intervention ranging from addiction-focused 

Medical Management (see Addiction-focused Medical Management for additional information) to more 

intensive psychosocial interventions. Available evidence has examined use of buprenorphine provided 

with psychosocial interventions. Addiction-focused Medical Management is an important adjunct for 

buprenorphine treatment in office-based settings. 

Several studies have shown that adding more addiction-specific counseling provides no added benefit 

when compared with addiction-focused Medical Management alone.[51,53,54] 

Weiss et al. (2011) conducted a multisite randomized controlled clinical trial of medically and 

psychiatrically stable patients with prescription OUD, 42% of whom reported concurrent chronic pain.[53] 

All participants received buprenorphine and addiction-focused Medical Management. After an initial 30-60 

minute evaluation and feedback session, addiction-focused Medical Management consisted of 15-20-
December 2015 Page 44 of 169

minute twice weekly tapering to biweekly individual sessions with the physician, as described in the 

introductory addiction-focused Medical Management section. The study found no added benefit of 

additional twice weekly tapering to biweekly 45-60 minute individual counseling sessions with a counselor.

Similarly, Fiellin et al. (2013) examined a sample of patients with OUD receiving buprenorphine in primary 

care. [54] Patients with concurrent alcohol, benzodiazepine or cocaine use disorder or those who were 

psychiatrically unstable were referred to specialty SUD care. All patients received a 45-60 minute initial 

evaluation and feedback session with the prescribing physician and eight 15-20 minute addiction-focused 

Medical Management sessions over 12 weeks. For these psychiatrically stable patients with OUD, there 

was no evidence of added benefit for the addition of 12 weekly individual Cognitive Behavioral Therapy 

(CBT) sessions. A study by Ling et al. (2013) evaluated four different behavioral interventions in 

combination with pharmacotherapy and addiction-focused Medical Management.[51] Among outpatients 

selected for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IVTR) diagnosis of opioid dependence, lack of co-occurring alcohol or benzodiazepine misuse, and good 

general mental and physical health, little benefit was obtained when adding behavioral treatment to OBOT 

and manually-driven addiction-focused Medical Management. 

Because OBOT patients who received addiction-focused Medical Management alone received a standard 

set of psychosocial interventions that may not be routinely provided in many clinics, one must be cautious 

in overgeneralizing the results described above to all populations and treatment settings. Addictionfocused Medical Management should include drug use monitoring and psychosocial support including 

motivational interviewing (MI) or a shared decision-making (SDM) approach and encourage participation

in mutual help programs, even if no specific, manualized treatment is provided. One suggested approach is 

to consider addiction-focused Medical Management alone for less complicated patients and to reserve 

adding ancillary counseling services for those patients who have suboptimal outcomes or who have more 

complex psychosocial needs. 

Research into the minimum components of physician management that provide beneficial outcomes for 

particular patients is needed. In addition, patients who have OUD with primarily prescription drug use 

versus heroin drug use, and who seek care in primary care may be different in treatment needs and 

response to treatment.[178] Thus research is needed to understand how to “match” appropriate 

treatments to patients who seek OUD treatment in primary care settings.

In both the Weiss et al. (2011) and Fiellin et al. (2006) studies, outcomes reported were addiction-related. 

It is not known whether other patient or provider outcomes are improved by the addition of CBT or 

additional OUD counseling beyond addiction-focused Medical Management.[52,53] Further research 

should examine the non-addiction related benefits of providing additional psychotherapy to patients in 

primary care settings on buprenorphine or when the physician is not well versed in addiction-focused 

Medical Management. Patients may also refuse non-medical, ancillary treatments, and it is unclear how 

best to help such patients.
December 2015 Page 45 of 169

ii. Psychosocial Interventions

Recommendation

14. For patients in office-based buprenorphine treatment, there is insufficient evidence to

recommend for or against any specific psychosocial interventions in addition to addiction-focused

Medical Management. Choice of psychosocial intervention should be made considering patient

preferences and provider training/competence.

(N/A | Reviewed, New-replaced)

Discussion

A brief description of these psychosocial interventions and evidence for their use for patients with OUD 

can be found below. Additional information on these interventions, as well as the appropriateness of their 

use for patients with specific types of SUD, can be found in Appendix C. 

OBOT using buprenorphine has increased availability of OAT to a wider variety of persons with OUDs. 

According to the federal regulation, a physician must have “the capacity to refer the patients for 

appropriate counseling and other appropriate ancillary services.”[179,180] Addiction-focused Medical 

Management (see Addiction-focused Medical Management for more information) in OBOT typically 

combines monitoring of medication adherence and drug use through urine drug testing with brief 

counseling by the physician using MI and encouraging participation in mutual help programs (e.g., 

Alcoholics Anonymous [AA], Narcotics Anonymous [NA]) participation. 

CM is a motivational intervention that uses behavioral reinforcement principles (such as providing 

vouchers, money, or other rewards) to encourage behavior change. Ling et al. found no positive effects for 

contingencies on the proportion of opioid negative urine test results over the number of tests possible, in 

a sample of patients receiving buprenorphine and medical management.[51] Conversely, two studies 

demonstrated that adding a computerized version of a behavior therapy approach known as Community 

Reinforcement Approach (CRA) may improve OBOT outcomes compared to providing CM alone [181] or 

standard care alone.[182] So-called “standard care” usually consists initially of medication treatment plus 

weekly, individualized, supportive counseling sessions that address psychosocial issues as experienced by 

each patient. In contrast, CRA is a cognitive behavioral approach that includes counseling in specific life 

skills (e.g., affect and behavioral regulation, psychosocial skills, drug-refusal) and practice exercises via 

standardized training modules. CRA has a solid base in evidence as reviewed by Bickel et al. (2008).[182] 

These modules, when used, are usually applied by therapists via live/in-person sessions. Computerized 

versions of CRA allow patients to work through the modules in an interactive fashion (i.e., they are not 

static “lessons”). There is evidence that adding either of these two approaches (in-person or computerdelivered) yields equivalent outcomes that are superior to treatment without CRA.[181,182] Importantly, 

the use of a computerized treatment program had no negative impact on therapeutic alliance (see section 

on Engagement Strategies). 

Recommendation

15. In Opioid Treatment Program settings, we suggest offering individual counseling and/or

Contingency Management, considering patient preferences and provider training/competence.

(Weak For| Reviewed, New-replaced)
December 2015 Page 46 of 169

Discussion

OTPs provide OAT, most commonly methadone, according to the Code of Federal Regulations.[170] 

Research supports offering a variety of psychosocial interventions in combination with OAT.[183-185] 

Psychosocial interventions are typically introduced early and sustained throughout the course of OAT

based on patient needs and preferences. 

While methadone medication alone is effective in reducing illicit opioid use,[186] recovery is enhanced 

by providing standard methadone maintenance that includes individual counseling.[184,185] Enhanced 

methadone maintenance addresses additional psychosocial needs (i.e., vocational counseling, legal 

assistance) and provides psychotherapy to address co-occurring disorders. One small study suggests it 

may improve recovery outcomes when the services provided are directed specifically at the problem 

areas pertinent to each individual patient.[184] The Code of Federal Regulations requires that OTPs 

conduct a comprehensive biopsychosocial assessment and treatment plan that addresses each 

identified need. Subsequent clarification [170] and TJC standards require that OTPs provide psychosocial 

interventions similar to standard methadone maintenance as described by McLellan et al.[184] 

A SR [187] and a clinical trial [188] found no significant difference in treatment retention for patients 

receiving standard methadone maintenance [184] versus the addition of another specific psychosocial 

intervention. Other opioid outcomes were not included. The authors noted that standard methadone 

maintenance provided substantial psychosocial interventions and cautioned that their results should not 

be interpreted to mean psychosocial interventions were not necessary. At least three well-designed, RCTs

have studied this topic with clear and consistent findings.[184,189,190] Two of the studies compared 

medication only to medication with standard counseling and to enhanced services added to the standard 

condition.[184,189] One study compared standard counseling to a day treatment program.[190] The two 

studies that included medication only showed that adding standard counseling improved outcomes. Two 

of the studies found no differences in outcomes between standard counseling and enhanced services. One 

study found a benefit of enhanced services if those services were specifically directed to areas of identified 

need, but subsequently found that these additional services were not cost effective.[191] More recently, 

Kidorf et al. (2013) conducted a randomized trial evaluating the efficacy of CM to encourage attendance at 

psychiatric sessions. The intervention was aimed at improving the delivery of onsite and integrated 

psychiatric services in a sample of opioid-dependent outpatients with co-occurring psychiatric disorder 

receiving methadone in an OTP.[192] Although CM improved the utilization of psychiatric services within 

an OTP, there was no difference in psychiatric symptoms or percentage of opioid or cocaine positive urine 

tests obtained during the 12 week study or on self-reports of substance use between groups.[192] 

Similarly, Tuten et al. (2012) found no differences between escalating incentives, fixed incentives, or a 

control group where incentives were not tied to abstinence on opioid- or cocaine-positive urine test 

results.[188] 

Recommendation

16. For patients with opioid use disorder for whom opioid use disorder pharmacotherapy is

contraindicated, unacceptable or unavailable, there is insufficient evidence to recommend for or

against any specific psychosocial interventions.

(N/A | Reviewed, New-replaced)
December 2015 Page 47 of 169

Discussion

The evidence identified in the SR for this CPG primarily comprised studies in which patients received 

psychosocial intervention in conjunction with, or as an adjunct to, medication-assisted therapy.

Epidemiologic data indicates a high mortality associated with OUD [193] and clinical trials indicate a high 

risk of relapse after opioid detoxification.[53] Therefore, there was insufficient evidence on the 

effectiveness of psychosocial interventions in the patient population who were not on medication-assisted 

therapy.

c. Cannabis Use Disorder

i. Pharmacotherapy

Recommendation

17. There is insufficient evidence to recommend for or against the use of pharmacotherapy in the

treatment of cannabis use disorder.

(N/A | Reviewed, New-added)

Discussion

Some patients seek pharmacologic assistance in cutting down or abstaining from marijuana use. However, 

no medication has been shown to be effective. Drug trials examining candidate therapies in the marijuana 

literature are characterized by small sample sizes (n=20-100), short duration (on the order of 12 weeks), 

high dropout rates (typically 50-70% by study end), and absence of treatment effect attributable to the 

intervention drug. Some form of psychotherapy was provided to both treatment and control groups, and 

intensity of marijuana usage declined in both groups at similar rates over the duration of the studies. 

Four of five RCTs failed to show a primary treatment effect in the experimental drug group. This includes 

one study each for bupropion sustained-release,[194] nefazodone,[194] fluoxetine,[195] buspirone,[196] 

and atomoxetine.[197] Only a single gabapentin study demonstrated meaningful improvements in 

marijuana use and withdrawal symptoms, but the sample size was small (n=50);[198] additional 

corroborating studies are needed. Fluoxetine showed efficacy for depressive symptoms, but did not

improve marijuana use measures.[195] 

ii. Psychosocial Interventions

Recommendation

18. For patients with cannabis use disorder, we recommend offering one of the following

interventions as initial treatment considering patient preference and provider

training/competence:

 Cognitive Behavioral Therapy

 Motivational Enhancement Therapy

 Combined Cognitive Behavioral Therapy/Motivational Enhancement Therapy

(Strong For | Reviewed, New-replaced) 
December 2015 Page 48 of 169

Discussion

A brief description of the evidence for the use of these interventions for patients with cannabis use 

disorder can be found below. Additional information about these interventions, as well as the 

appropriateness of their use for patients with specific types of SUD, can be found in Appendix C. 

A SR of fair quality by Davis et al. (2015) assessed the efficacy of behavioral therapy (BT) in cannabis 

users.[199] Each study included Cognitive Behavioral Therapy (CBT) as one of the intervention groups. The 

BT intervention significantly outperformed the control group by 66% in pooled outcomes including 

frequency and severity of use and measures of psychosocial functioning. The effect sizes of BT were 

greater compared to waitlist controls and active controls (e.g., those who received case management 

alone). BT alone did not significantly outperform active controls, and abstinence rates were low in both 

groups. The quality of evidence was rated moderate compared to waitlist. An earlier multisite trial found 

that among patients with cannabis dependence, two sessions of Motivational Enhancement Therapy 

(MET), did not reduce marijuana use over 15-month follow-up as much as a nine-session multicomponent 

intervention that also included CBT and case management.[200] 

There is insufficient evidence for or against recommending any other specific psychosocial interventions 

for cannabis use disorder; however there is preliminary work on patients with cannabis use disorder and 

co-occurring mental health conditions. A fair quality SR by Hjorthoj et al. (2014) studied interventions 

targeting cannabis use disorder in patients with schizophrenia spectrum disorders.[201] They evaluated 

the effect of motivational interviewing (MI) with or without CBT versus control (TAU), routine family 

support, or psychoeducation). In terms of consumption, MI, when compared to control, significantly 

reduced the amount of cannabis used but not the frequency of use. 

Brief MI/CBT in patients with a DSM-IV diagnosis of cannabis use dependence or abuse and non-affective 

psychotic disorder was studied in comparison to long MI/CBT versus standard of care.[202] Low quality 

evidence found no significant differences between MI/CBT and TAU in abstinence, relapse of psychotic 

symptoms, days to relapse, or hospitalization outcomes at various time points. In a study by Kay-Lambkin 

et al. (2011) participants with cannabis use disorder and depression received either therapist or 

computerized-delivered CBT/MI or person-centered therapy (PCT).[203] The analysis found no difference 

by treatment groups in change in cannabis use, abstinence, or percent of patients achieving a ≥50% 

reduction in use. 

d. Stimulant Use Disorder

i. Pharmacotherapy

Recommendation

19. There is insufficient evidence to recommend for or against the use of any pharmacotherapy for

the treatment of cocaine use disorder or methamphetamine use disorder.

(N/A | Reviewed, New-added)

Discussion

Evidence does not support the use of indirect dopamine agonist therapy (e.g., disulfiram, modafinil, 

bupropion, methylphenidate, dexamphetamine, mixed amphetamine salts), doxazosin, or topiramate for the 

treatment of cocaine use disorder or methamphetamine use disorder. A number of small studies have shown 
December 2015 Page 49 of 169

mixed results with some studies showing modest benefits, while a number have shown no benefit.[204,205] 

Further complicating the situation, there is evidence that disulfiram at some doses worsens cocaine use 

disorder while at a dose of 250 mg/day, cocaine use decreases.[205-207] Further research into the use of 

dexamphetamine to treat methamphetamine use disorder is needed, as an initial study showed that its use 

increased participation in treatment while not decreasing use.[208] Given the potential misuse of 

dexamphetamine, the authors cannot recommend its use without further evidence.

Given the wide variation in the results of the studies, we have little confidence in the evidence to guide 

treatment either for or against the use of indirect dopamine agonist therapy for either cocaine or 

stimulant use disorder. Given the absence of clear evidence of benefit, clinicians must consider other 

implications specific to the medication. For instance, the likelihood of misuse and diversion in patients 

receiving methylphenidate, dexamphetamine, and mixed amphetamine salts should be considered. 

A small number of RCTs have explored the use of topiramate to decrease cocaine use. One study showed a 

decrease in use,[209] while two other studies showed no difference in cocaine use.[210,211] One study 

showed that there were no significant differences in rate of abstinence in methamphetamine use disorder 

with use of topiramate compared to placebo.[212] 

ii. Psychosocial Interventions

Recommendation

20. For patients with stimulant use disorder, we recommend offering one or more of the following

interventions as initial treatment considering patient preference and provider

training/competence:

 Cognitive Behavioral Therapy

 Recovery-focused behavioral therapy

 General Drug Counseling

 Community Reinforcement Approach

 Contingency Management in combination with one of the above

(Strong For| Reviewed, New-replaced) 

Discussion

A brief description of the evidence for the use of these interventions for patients with stimulant use 

disorder can be found below. Additional information about these interventions, as well as the 

appropriateness of their use for patients with specific types of SUD, can be found in Appendix C. 

Cognitive Behavioral Therapy (CBT) has been found to be effective for the treatment of cocaine use 

disorder.[213-215] In addition, individual drug counseling, which is based on a 12-step addiction treatment 

model, improved outcomes over group drug counseling only and was also superior to cognitive therapy 

and a psychodynamic approach in one large, multi-site study.[216] 

Contingency Management (CM) has the strongest evidence of effectiveness for cocaine use disorder, when 

used adjunctive to another psychosocial intervention.[213,217,218] Another recent SR found CM to be 

consistently more effective than CBT during treatment, with less evidence of superiority during posttreatment follow-ups.[219] Extending the duration in which reinforcement for abstinence is provided 

extends the positive effects of CM,[220] but positive effects generally deteriorate fairly rapidly after the 
December 2015 Page 50 of 169

intervention has ended in most, but not all, studies. For example, Higgins et al. (2000) found evidence of 

sustained positive effects for 12 months after the end of CM.[221] Treatment effects are generally much 

larger when abstinence, as opposed to attendance, is reinforced, although this may not be the case with 

better-prognosis patients who are cocaine abstinent when they enter treatment.[222] Higher monetary 

value reinforcers produce higher rates of cocaine abstinence,[223] particularly in those with more severe 

cocaine problems.[222] Prize-based CM interventions, in which the amount of the reinforcement varies by 

chance, may be more cost-effective than fixed-value reinforcement.[224,225] 

The Community Reinforcement Approach (CRA), a comprehensive intervention that combines CBT, 

couples counseling, and other recovery focused components, as well as CM in some cases, has 

outperformed comparison conditions (e.g., 12-step counseling, drug counseling, and CRA without voucher 

incentives), in several studies.[226-228] In some studies the combination of CM and other behavioral 

interventions, such as CRA or CBT, has been more effective than comparison conditions.[213,229] For 

example, Higgins et al. (2003) found that the combination of CRA and CM produced better withintreatment cocaine use outcomes than CM only, as well as fewer days of heavy drinking, better 

employment outcomes, lower depression, and fewer medical hospitalizations during treatment and a post 

treatment follow-up.[226] 

There is considerably less evidence concerning effective treatments for other stimulant disorders. One SR

found that behavioral interventions, including CBT, CBT plus motivational interviewing (MI), and MI, were 

not more effective than passive or minimal interventions with regard to non-cocaine stimulant 

consumption outcomes. However, high intensity or adjunctive treatments, such as gay-specific CBT, CM

plus CBT, CM plus TAU, and CM plus placebo, did produce better stimulant use outcomes than single 

active treatments (CBT or TAU).[230] It should be noted that most of these high intensity interventions 

included CM, so the positive effect identified may really be for CM over other active behavioral 

interventions. 

Confidence in the quality of the evidence regarding the effectiveness of these interventions for the 

treatment of cocaine and other stimulant use disorders is moderate for CM interventions, and low-tomoderate for other behavioral interventions, with benefits outweighing harms and burdens and some 

variations in patient values and preferences. Primary concerns regarding use of these interventions include 

the considerable training to implement with fidelity (CBT and CRA) and the resource intensive delivery 

(CM, CBT, and CRA). CM, for example, requires the collection and rapid analysis of 2-3 urine samples per 

week, plus timely feedback on the results. However, a recent large-scale demonstration project has 

indicated that CM is feasible to deliver within VA SUD treatment programs.[231] Finally, the research 

evidence is based almost entirely on studies in which these interventions were delivered individually to 

patients, whereas most SUD treatment in the VA and DoD is delivered in groups.

E. Promoting Group Mutual Help Involvement

Recommendation

21. For patients with substance use disorders in early recovery or following relapse, we recommend

promoting active involvement in group mutual help programs using one of the following

systematic approaches considering patient preference and provider training/competence:

 Peer linkage 
December 2015 Page 51 of 169

 Network support

 12-Step Facilitation 

(Strong For | Reviewed, New-replaced)

Discussion

Several effective interventions have been developed to increase attendance at and participation in mutual 

help programs and other recovery oriented social support programs. The first of these is 12-Step 

Facilitation (TSF) which is delivered over 12 sessions and is focused on helping participants complete the 

first five steps of the Alcoholics Anonymous (AA) program. TSF fosters regular attendance at mutual help 

meetings and active participation in the programs, including speaking at meetings, obtaining a sponsor, 

using the telephone to get support, and participating in social activities outside of the meetings.[232] In a 

sample of individuals with co-occurring SUD and major depression, TSF led to higher attendance at and 

participation in mutual help programs than Cognitive Behavioral Therapy (CBT) during the 24-week 

treatment phase.[233,234] However, there were no differences between the two interventions on group 

mutual help variables in the year following treatment.

A three-session peer linkage intervention focused on increasing attendance at mutual help meetings.[235] 

This intervention consisted of information about the 12-step approach to recovery, contracting to attend 

mutual help meetings, linkage with a peer in a 12-step program with whom the participant could attend 

meetings, monitoring of 12-step meeting attendance, and help in obtaining a temporary sponsor. Results 

indicated that patients randomized to this enhanced referral condition had higher rates of 12-step meeting 

attendance and program involvement over the 12-month follow-up than those randomized to standard 

referral.[235,236] Moreover, the peer linkage referral condition also produced higher abstinence rates 

over the follow-up than standard referral.[236] 

Litt et al. (2007) adapted the TSF intervention to develop Network Support (NS), which stresses changing 

one’s broader social network to be more supportive of abstinence, as well as advocates involvement in 12-

step programs.[237] AA philosophy and focus on a higher power are de-emphasized in this 12-session 

intervention, in favor of AA as a means to make new friends and increase involvement in enjoyable social 

activities that would make abstinence more reinforcing. Other social network programs were explored, 

particularly for patients who will not attend mutual help programs. Results of an RCT comparing NS to case 

management found increased social support for abstinence, through an increase in abstinent friends, 

relative to case management.[237] With regard to mutual help attendance, those in NS were over seven

times more likely to attend AA over the 15-month follow-up than those in case management. Analyses of 

24-month outcomes confirmed that the positive effect of NS on AA attendance, relative to case 

management, was sustained.[238] 

Confidence in the quality of the evidence regarding the effectiveness of interventions to increase 

participation in mutual help organizations and other recovery oriented social supports is moderate, with 

benefits outweighing harms and burdens, and variations in patient values and preferences. Evidence has 

primarily focused on use of these interventions in the short-term. Counter-therapeutic advice from peerled resources is a potential harm in using systematic interventions to increase the participation of patients 

and their families to mutual help programs. Potential burdens include difficulty for some patients in 

tolerating group meetings (e.g., those with PTSD or social anxiety disorder), potential travel costs and 
December 2015 Page 52 of 169

accessibility issues. Patient values and preferences should always be considered in developing treatment 

options and in referring to mutual help programs. 

In order for providers to discuss the potential benefits of mutual help groups and other recovery oriented 

social supports with their patients, providers need to know about these programs and the differences 

between them. Moreover, it is advisable to have information on location and scheduling of local meetings 

available.[239] 

F. Co-occurring Mental Health Conditions and Psychosocial Problems

Recommendation

22. Among patients in early recovery from substance use disorders or following relapse, we suggest

prioritizing other needs through shared decision making (e.g., related to other mental health

conditions, housing, supportive recovery environment, employment, or related recovery-relevant

factors) among identified biopsychosocial problems and arranging services to address them.

(Weak For | Not reviewed, Amended)

Discussion

Many patients with SUD have co-occurring psychosocial problems that affect their likelihood of 

establishing and maintaining good clinical outcomes and improved functional status. Some of these 

problems are consequences of SUD that persist even after early recovery is established. Others occur 

independently of SUD, but can complicate access to care or present relapse risk. These problems include 

co-occurring mental health conditions, access to a supportive recovery environment (housing and social 

support for sobriety), difficulties with family and social relationships, 

unemployment/underemployment, and/or unresolved legal issues. Patients are likely to have individual 

priorities for when and how these needs are addressed. However, these issues are often related and 

interact with one another, and they can be difficult to prioritize. Although it may be optimal to have 

services coordinated by a single treatment team, there is likely to be variability in the extent of 

comprehensive services available in different clinical settings.

Fair quality evidence reviewed in the prior version of the guideline indicates targeting individualized 

services for identified problem areas is more effective than routinely increasing the intensity of addictionfocused psychosocial treatment alone.[240-242] An important consideration is providing adjunctive 

recovery services in the least restrictive setting that promotes engagement in continuing addiction care 

(e.g., via transitional housing that improves access to treatment, accommodating employment schedules 

and other service appointments). For practical purposes, it is common to defer attention to some initially 

identified problems and monitor for emerging clinical needs until early recovery has stabilized. 

G. Follow-up

Recommendation

23. We suggest assessing response to treatment periodically and systematically, using standardized

and valid instrument(s) whenever possible. Indicators of treatment response include ongoing

substance use, craving, side effects of medication, emerging symptoms, etc.

(Weak For | Reviewed, New-replaced)
December 2015 Page 53 of 169

Discussion

Measurement-based care is the periodic and systematic assessment of response to treatment, using 

standardized and valid instrument(s) whenever possible.[243,244] Periodic monitoring of patients’ 

progress offers patients and providers the opportunity to identify barriers to adequate progress on 

problems identified at intake and any new problems that emerge, thereby facilitating needed changes in

treatment strategies. Periodic intervals for follow-up or monitoring may include, but are not limited to:

• At agreed upon milestones during treatment

• At discontinuation or change in intensity of specialty care

• Based on laboratory or other monitoring

• If patient is non-adherent

Although there was insufficient evidence to make a recommendation for or against measurement-based 

care in either primary or specialty care settings for improving consumption and health outcomes, there are 

a number of benefits to consider which include:

• Patient accountability (“No one will know” is a common trigger for relapse)

• Continual feedback and monitoring of treatment response

• Compliance with accrediting expectations of outcome evaluation

When indicated, management should be adjusted to optimize treatment outcomes. There is large 

variation in patient and provider preferences that should be taken into consideration when planning which 

outcomes to measure with what methods and how frequently. Other implications to consider when 

customizing care may include patient acceptability, resource use, feasibility, and administrative workload. 

Recommendation

24. For patients who have initiated an intensive phase of outpatient or residential treatment, we

recommend offering and encouraging ongoing systematic relapse prevention efforts or recovery

support individualized on the basis of treatment response.

(Strong For | Not reviewed, Amended)

Discussion

Clinicians commonly emphasize that many or most patients in SUD treatment will benefit from continuing 

care (“aftercare”) after participating in a more intensive, initial phase of treatment. The National Institute 

on Drug Abuse (NIDA) has also stressed that retaining patients for longer treatment durations, in particular 

90 days or more, is more likely to lead to successful outcomes.[245] A meta-analysis of 19 controlled 

studies found that continuing care had a small but significant positive effect on substance use outcomes 

over no/minimal continuing care at the end of the intervention and at follow-up.[246] 

Although there had been some evidence in prior narrative reviews that continuing care interventions were 

more likely to be effective when they were at least 12 months in duration and included more active efforts 

to deliver the intervention to patients,[247] the Blodgett et al. (2014) meta-analysis did not find that 

continuing care effects varied by intervention duration, intensity, modality, or setting.[246] Therefore, the 

selection of appropriate continuing care should be made on the basis of patient preference and the 
December 2015 Page 54 of 169

availability of treatment options, using evidence-based SUD interventions whenever possible. Continuing 

care efforts should be directed at preventing relapse and limiting the severity of relapses that do occur, 

and should address other issues that can interfere with recovery, as needed. Services can be provided via 

individual or group sessions in the clinic, with some evidence that effective continuing care can also be 

provided over the telephone.[248-250] 

Given the findings of the Blodgett et al. (2014) review,[246] confidence in the quality of the evidence for 

this recommendation is moderate to high. Because extended participation in treatment does confer some 

burden to patients, and the positive effects appear to be small overall, the benefits are seen as slightly 

outweighing the harms or burdens. There is large variation in patient willingness to engage in continuing 

care. Moreover, accessibility can be an issue in more rural areas and for Veterans with disabilities or other 

issues that make travel to a treatment program more difficult. For such patients, telephone continuing 

care may be considered.

Recommendation

25. For patients in substance use disorders specialty care, we recommend against automatic discharge

from care for patients who do not respond to treatment or who relapse.

(Strong Against | Not reviewed, Amended)

Discussion

Relapse during the course of SUD treatment is common, even for patients who are receiving effective, 

evidence-based interventions. Moreover, some patients who eventually abstain do not achieve abstinence 

early in treatment. At one point, it was common practice in SUD treatment programs to continue to 

provide standard, unmodified care to such patients or to discharge them. However, it may be possible to 

improve the outcomes of treatment non-responders by retaining them in care and modifying their 

treatment in some way. For example, there is some evidence that patients who make poor progress 

toward achieving their goals with intensive outpatient treatment, particularly those who fail to stop using 

alcohol or cocaine, will have better substance use outcomes if they receive either more intensive, face-toface [249] or extended [250,251] continuing care. On the other hand, some patients who are not 

responding may benefit from a lower intensity treatment approach, if they find the current level of care 

too burdensome. Lower intensity engagement strategies also provide the opportunity to monitor patient 

readiness for involvement in more intensive or other treatment interventions to promote recovery.

It has become standard practice in most areas of medicine to regularly and systematically monitor 

response to treatment and, on the basis of patient response, make modifications to care as needed over 

time. Although there is not a strong empirical base for this approach in SUD treatment at this point, there 

is expert consensus to support it.[252,253] Therefore, rather than discharge patients who have not 

responded to treatment, or who responded initially but subsequently resumed problematic substance use, 

we suggest providers consider modifying treatment in one of the following ways: 

• Add or substitute another medication or psychosocial intervention, and/or

• Change treatment intensity by:

 Increasing the intensity of care, or

 Adjusting the dose of the medication, or
December 2015 Page 55 of 169

 Decreasing the intensity to a minimum level of care that is agreeable to the patient, 

such as monitoring in general healthcare.

Given the lack of a strong empirical base demonstrating the efficacy of this approach over more traditional 

treatment models, confidence in the quality of the evidence is very low. Further research is needed to 

compare the risks and benefits of administrative discharge from care and of various models of adjusting 

care based on response to treatment. However, the benefits of retaining patients in treatment and 

modifying their care in an effort to improve response or acceptability clearly outweigh harms or burdens 

to the patient. One important consideration is that retaining non-responding patients and modifying their 

treatment as needed can require additional staff time and effort. Clinics may have limited resources to 

support the availability of a menu of other interventions for non-responders. Finally, some non-responders 

are simply not interested in further addiction-focused treatment of any kind at that point in time, 

regardless of efforts made to retain them or treatment options made available. 

H. Stabilization and Withdrawal

a. Assessment

Recommendation

26. For patients with alcohol or opioid use disorder in early abstinence, we suggest using standardized

measures to assess the severity of withdrawal symptoms such as Clinical Institute Withdrawal

Assessment for Alcohol (revised version) (CIWA-Ar) for alcohol or Clinical Opiate Withdrawal Scale

(COWS) for opioids.

(Weak For | Not reviewed, Amended)

Discussion

Standardized scales to quantify the severity of alcohol and opioid withdrawal have been developed for 

clinical and research purposes to aid in the diagnosis of withdrawal, to indicate the need for medications, 

and to predict severity of alcohol withdrawal and need for intensive care.[254] In research settings, such 

scales aid in comparing clinical trial outcomes; in clinical settings, they may improve patient safety through 

assuring systematic assessment and symptom-guided administration of medication.[254-257] 

For assessing alcohol withdrawal, the CIWA-Ar is perhaps the most widely adopted standardized 

scale.[254,256,258] This is due in part to its ability to meet all three purposes for standardized withdrawal 

assessment. It has validity and interrater reliability in assessing the severity of alcohol withdrawal, is 

relatively quick to administer (about one minute for trained administrators), and is able to distinguish 

alcohol withdrawal symptoms in patients whose vital signs are elevated due to concurrent medical 

illnesses, such as infections and cardiovascular disease, rather than due to withdrawal itself.[259,260] It 

can help predict those patients at risk for more complicated alcohol withdrawal.[254,255,261] Its use in 

determining need for medication in symptom-triggered protocols is associated with lower total dose of 

benzodiazepines and shorter lengths of hospital stay.[257,262] Its incorporation as part of an emergency 

department protocol for assessment of alcohol withdrawal risk was associated with fewer inpatient 

admissions for management of alcohol withdrawal.[263] 

While the CIWA-Ar has been widely adopted, several investigators have sought modifications or 

alternative scales to address several specific shortcomings. While the CIWA-Ar is quicker to administer 
December 2015 Page 56 of 169

than many of its predecessors, some investigators have cited the need for staff training and time for 

administration as barriers to its use in many clinical settings.[254] Gossop et al. (2002) developed the 10-

item Short Alcohol Withdrawal Scale (SAWS) which demonstrates good interrater reliability and correlation 

with CIWA-Ar.[264] Reoux and Oreskovich (2006) modified the CIWA-Ar to include additional alcohol 

withdrawal symptoms from the DSM-IV-TR that are not covered in the CIWA-Ar and to eliminate items 

that were not in the DSM-IV diagnostic criteria for alcohol withdrawal.[258] The resulting seven-item 

CIWA-AD agrees closely with the CIWA-Ar.[258] 

CIWA-Ar does not predict risk of complicated alcohol withdrawal in patients before the onset of alcohol 

withdrawal syndrome (AWS). In a case-control retrospective chart review of general medical inpatients, 

Pecoraro et al. (2014) used the routinely administered Alcohol Use Disorders Identification Test-Primary 

Care (AUDIT-PC), a screening tool for alcohol misuse, to determine a score that predicted alcohol 

withdrawal or alcohol withdrawal delirium by International Classification of Diseases, Ninth Revision 

discharge diagnosis. An AUDIT-PC score of four or more was associated with predicted AWS with 91.0% 

sensitivity and 89.7% specificity, identifying 17 false positives for every true positive.[265] Wetterling et al.

(2006) developed the Luebeck Alcohol Withdrawal Risk Scale-11 (LARS-11), on which a score of 10 or 

higher can be used to predict at hospital admission which patients would require close medical 

attention.[266] The positive predictive value for severe AWS was 76%, while the negative predictive value 

was 98.7%. The sensitivity and specificity for LARS-11 were high at 95% and 92.5%, respectively.[266] 

Stephens et al. (2014) developed an emergency department protocol for assessment of alcohol withdrawal 

risk that included the CIWA-Ar, blood alcohol level (BAL), vital signs, assessment of concurrent medical 

conditions, and history of withdrawal seizures and delirium tremens. By systematically applying the 

resulting algorithm, they decreased the number of inpatient admissions for alcohol withdrawal without 

increasing patient returns to the emergency department for treatment of alcohol withdrawal.[263] In a SR

of the literature, Goodson, Clark, and Douglas (2014) identified a previous history of delirium tremens or 

alcohol withdrawal seizures as the strongest predictors of subsequent complications.[267] Maldonado et 

al. incorporated history of delirium tremens and alcohol withdrawal seizures into a 10-item screening 

questionnaire, the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), to predict moderate to severe 

alcohol withdrawal. A PAWSS score ≥4 demonstrated 93.1% sensitivity and 99.5% specificity with a positive 

predictive value of 93.1% and a negative predictive value of 99.5% in a prospective validation study of 409 

medical inpatients.[268] While the PAWSS demonstrated excellent predictive value for medical inpatients, 

more research is needed to determine its predictive value in other populations such as psychiatric 

inpatients and those seeking outpatient or residential treatment of SUD. 

Similarly, investigators have sought reliable, valid, and practical systematic assessment tools for opioid 

withdrawal. Handelsman et al. (1987) developed the 16-item Subjective Opiate Withdrawal Scale (SOWS) 

and the 13-item Objective Opiate Withdrawal Scale (OOWS) as brief and practical alternatives to the 73-

item Addiction Research Center Inventory-Weak Opiate Withdrawal Scale.[269] Wesson and Ling (2003)

developed the 11-item clinician-administered COWS to assess for precipitated opioid withdrawal in 

patients starting treatment with buprenorphine.[270] The COWS was subsequently validated against a 

longer, but validated, research scale, the Clinical Institute Narcotic Assessment Scale.[271] 

While many scales have been developed to assist in systematic assessment of alcohol and opioid 

withdrawal, and there is evidence for benefit in terms of shortening length of hospital stay, reducing 
December 2015 Page 57 of 169

amount of sedative medications, and averting unnecessary hospitalization, there have been no 

randomized, controlled comparisons of the outcome of alcohol or opioid withdrawal treatment with and 

without systematic assessments. Further research is needed to define the risks and benefits of systematic 

assessment scales and decision support tools for withdrawal treatment in common treatment settings 

such as inpatient psychiatry units, residential SUD treatment programs and outpatient general mental 

health, general medicine, and specialty SUD treatment clinics.

Recommendations

27. We recommend inpatient medically supervised alcohol withdrawal management for patients with

any of the following conditions:

 History of delirium tremens or withdrawal seizures 

 Inability to tolerate oral medication

 Co-occurring medical conditions that would pose serious risk for ambulatory withdrawal 

management (e.g., severe coronary artery disease, congestive heart failure, liver 

cirrhosis) 

 Severe alcohol withdrawal (i.e., Clinical Institute Withdrawal Assessment for Alcohol 

[revised version] [CIWA-Ar] score ≥20)

 Risk of withdrawal from other substances in addition to alcohol (e.g., sedative 

hypnotics) 

(Strong For | Reviewed, Amended)

28. We suggest inpatient medically supervised withdrawal for patients with symptoms of at least

moderate alcohol withdrawal (i.e., Clinical Institute Withdrawal Assessment for Alcohol [revised

version] [CIWA-Ar] score ≥10) and any of the following conditions:

 Recurrent unsuccessful attempts at ambulatory withdrawal management

 Reasonable likelihood that the patient will not complete ambulatory withdrawal 

management (e.g., due to homelessness) 

 Active psychosis or severe cognitive impairment 

 Medical conditions that could make ambulatory withdrawal management problematic 

(e.g., pregnancy, nephrotic syndrome, cardiovascular disease, lack of medical support 

system)

(Weak For | Reviewed, Amended)

Discussion

AWS includes: insomnia, autonomic symptoms, increased hand tremors, nausea and/or vomiting, 

psychomotor agitation, anxiety, seizures, and hallucinations. There are also specific potential harms 

(including death) associated with severe AWS and, in the presence of other risk factors, moderate AWS. A 

patient’s history of delirium tremens, previous episodes of AWS, and co-occurring medical conditions are 

all commonly accepted as indications for inpatient medically supervised alcohol withdrawal.

Moreover, while patients are more likely to successfully complete an inpatient medically supervised 

alcohol withdrawal protocol, long-term alcohol withdrawal outcomes do not differ between those in

inpatient or outpatient programs.[272,273] Other factors to consider when determining inpatient or 

outpatient medically supervised alcohol withdrawal include:[274] 
December 2015 Page 58 of 169

Ambulatory withdrawal management has the potential advantages of: 

• Facilitating continuity of care in the outpatient setting

• Reducing disruption to the patient’s life

• Lowering costs

Inpatient withdrawal management has the advantages of: 

• Having fewer medical and legal logistical concerns (e.g., arranging for patient transportation,

driving during the course of medically supervised withdrawal)

• Allowing closer monitoring of AWS

• Providing complex addiction-focused Medical Management (see Addiction-focused Medical

Management for additional information) of AWS and co-occurring medical conditions (e.g.,

cardiac monitoring, intravenous hydration, medications)

• Having higher likelihood of completing the AWS management protocol

b. Alcohol Use Disorder Stabilization and Withdrawal

Recommendation

29. We recommend using one of the following pharmacotherapy strategies for managing alcohol

withdrawal symptoms:

 A predetermined fixed medication tapering schedule with additional medication as 

needed 

 Symptom-triggered therapy where patients are given medication only when signs or 

symptoms of withdrawal occur (e.g., as needed dosing)

(Strong For | Not reviewed, Amended)

Discussion

Strong evidence supports both of the above approaches to the management of acute alcohol withdrawal.

In the fixed dose approach, medication is given in advance of the emergence of anticipated withdrawal 

signs and symptoms. The advantages of a fixed-dose approach with additional medication as needed are 

that the patient will likely receive sufficient medication to prevent the emergence of alcohol withdrawal 

signs and symptoms and that the level of clinical monitoring needed may be somewhat less than with the 

symptom-triggered approach. The disadvantage of the fixed-dose approach is that, since it is challenging 

to predict the severity of alcohol withdrawal for any given patient, the patient may receive more 

medication than is actually needed and could incur side effects from the medications used to treat 

withdrawal.

The advantage of the symptom-triggered approach is that the patient only receives the amount of 

medication needed to manage alcohol withdrawal during that specific episode of care. However, the 

symptom-triggered approach does require skilled staff to assess severity of alcohol withdrawal frequently 

using a validated measure (typically the CIWA-Ar).
December 2015 Page 59 of 169

One randomized, double-blind trial of fixed-dose versus symptom-triggered treatment was completed 

with Veterans on an inpatient unit.[275] The symptom-triggered group had a significantly shorter duration 

of treatment and used significantly less chlordiazepoxide during withdrawal. Another double-blind 

randomized trial comparing these two approaches conducted in Switzerland and using oxazepam had 

similar findings with the exception that one patient in the symptom-triggered condition had a withdrawalrelated seizure.[276] Other observational studies generally support these findings.[262,277] Clinicians 

need to consider staffing and patient characteristics when weighing risks of complicated withdrawal versus 

benefits of shorter length of hospital stay associated with symptom-triggered withdrawal.

Recommendation

30. For treatment of moderate to severe alcohol withdrawal, we recommend using benzodiazepines

with adequate monitoring because of documented efficacy and high margin of safety.

(Strong For | Reviewed, Amended)

Discussion

Strong evidence involving numerous controlled trials supports the use of benzodiazepines in the treatment 

of Alcohol Withdrawal Syndrome (AWS).[278,279] Compared to placebo, benzodiazepines reduce 

withdrawal severity, incidence of delirium, and withdrawal seizures. Benzodiazepines are the drug of 

choice, given adequate monitoring, because they reduce withdrawal severity, incidence of delirium, and 

seizures. Benzodiazepines are generally well tolerated, although some sedation can occur. 

Although a few small RCTs also support the efficacy of anticonvulsants (e.g., gabapentin, carbamazepine, 

valproic acid) in the treatment of alcohol withdrawal,[278,280-282] the body of evidence at this time is 

not sufficient to recommend these agents as first-line treatments. In particular, it is not clear that these 

agents are as efficacious in preventing alcohol withdrawal seizures as are benzodiazepines.

Recommendation

31. For managing mild to moderate alcohol withdrawal in patients for whom risks of benzodiazepines

outweigh benefits (e.g., inadequate monitoring available, abuse liability, or allergy/adverse

reactions), we suggest considering carbamazepine, gabapentin, or valproic acid as an alternative.

(Weak For | Reviewed, New-replaced)

Discussion

In cases for which risks of benzodiazepines outweigh benefits, the anticonvulsants gabapentin, 

carbamazepine, and valproic acid appear to be reasonable alternative agents for management of alcohol 

withdrawal.[278,280-282] Although the studies to date examining these medications have been primarily 

small single site randomized trials, the evidence available suggests that outcomes, such as reduction of 

withdrawal symptoms, time to withdrawal completion, and adverse events, are generally equivalent with 

these anticonvulsants and benzodiazepines. However, it is not entirely clear if these medications are 

equivalent to benzodiazepines for preventing withdrawal delirium or withdrawal seizures where there is 

elevated risk. 
December 2015 Page 60 of 169

These agents may have particular utility for ambulatory medically supervised withdrawal when concerns 

exist about the prescribing of a controlled substance such as a benzodiazepine. Furthermore, valproic acid 

can also be used as an effective supplement to benzodiazepines. 

Recommendation

32. We recommend against using alcohol as an agent for medically supervised withdrawal.

(Strong Against | Not reviewed, Amended)

Discussion

Alcohol itself is still used by some practitioners to treat AWS.[283,284] No solid evidence exists, other than 

clinical experience, to support this practice. One small RCT conducted in an intensive care unit compared 

prophylactic treatment with an intravenous alcohol infusion to prophylactic treatment with 

diazepam.[285] No advantages were found with alcohol compared to diazepam. More patients treated 

with alcohol exhibited inadequate sedation. One patient on the ethanol regimen failed treatment and had 

to be protectively transferred to a diazepam regimen.

Since alcohol has a very short duration of action, it is more likely to cause respiratory depression than are 

benzodiazepines. It can have proconvulsant effects and is damaging to many organ systems. Furthermore, 

no convincing rationale supports the use of alcohol to treat alcohol withdrawal when a safer and more 

effective alternative, benzodiazepines, is available.[286] 

c. Opioid Use Disorder Stabilization and Withdrawal

Recommendation

33. For patients not yet stabilized from opioid use disorder, we recommend against withdrawal

management alone due to high risk of relapse and overdose (see Recommendations 8 and 11).

(Strong Against | Reviewed, New-replaced)

Discussion

For the treatment of opioid use disorder (OUD), for patients who are not stabilized, administration of longterm opioid agonists are generally preferred over short tapers of opioid agonists in “detoxification” 

protocols. Most patients who are provided detoxification, particularly those who do not receive formal, 

structured non-pharmacotherapy treatment, relapse with resultant morbidity and mortality.[287,288] 

Furthermore, opioid agonist therapies have been shown to be more effective than other 

pharmacotherapies over time and are likely safer.[289,290] Methadone has been used effectively over 

long periods of time for decades. Studies have also shown buprenorphine to be used successfully in officebased settings over long periods (years).[152-154,291] In addition, recent studies have shown that long 

term treatment, versus a quick taper, of patients with buprenorphine are more effective in achieving 

positive patient outcomes.[137] 

There are certain situations where medically supervised withdrawal from opioids is preferred over longterm opioid agonist therapy (OAT). For instance, short taper of opioids using methadone, buprenorphine, 

or other symptom-treatment medications can be used if patients are (1) entering an environment which 

requires abstinence from any opioids (e.g., prison, some addiction treatment programs), (2) wish to 

receive non-opioid agonist treatment (e.g., treatment with injectable naltrexone), (3) have minimal 
December 2015 Page 61 of 169

symptoms of physical opioid dependency, and (4) are in a profession that requires no opioid agonist 

treatments (e.g., military, healthcare provider, air traffic controller). Buprenorphine can be used to provide 

relatively short, safe, medically supervised withdrawal treatment.[292-298] There is no consensus on the

treatment duration (e.g., 7- versus 28-day or 5- versus 30-day) for short term medically supervised 

withdrawal from opioids.[299,300] Recently, one randomized, double blind study found that a four-week 

buprenorphine taper was superior to a one-week or two-week taper for the outcome measure of opioidnegative urine drug screens.[151] 

Recommendation

34. Among patients with opioid use disorder for whom maintenance agonist treatment is

contraindicated, unacceptable, or unavailable, we recommend using a methadone (in Opioid

Treatment Program only) or buprenorphine taper for opioid withdrawal management (see

Recommendation 11).

(Strong For | Reviewed, New-replaced)

35. For patients with opioid use disorder for whom methadone and buprenorphine are

contraindicated, unacceptable, or unavailable, we recommend offering clonidine as a second-line

agent for opioid withdrawal management (see Recommendation 11).

(Strong For | Reviewed, New-replaced)

Discussion

The preferred approaches for medically supervised opioid withdrawal are initial stabilization with 

methadone or buprenorphine followed by a short or extended taper. Patient preferences play an 

important role in medication selection. The stigma of Opioid Treatment Programs (OTPs) may prevent a 

patient from choosing this option. In addition, access to care in OTPs and/or buprenorphine (from a 

provider with the appropriate DEA authorization) should be considered. According to the federal 

regulation, a physician must have “the capacity to refer the patients for appropriate counseling and other 

appropriate ancillary services.”[179,180] 

Treatment completion is one metric of success and has been evaluated by a number of RCTs. One study 

concluded that there are no significant differences in treatment completion with methadone versus 

buprenorphine; however, methadone was found to be superior to placebo in one study.[287] Three RCTs 

concluded that buprenorphine may be more effective than methadone.[296] In addition, buprenorphine 

and methadone were found to be more effective than clonidine.[296] Finally, one study was suggestive of 

no significant difference between methadone over clonidine in terms of treatment completion.[287] We 

found no evidence to support addition of clonidine to a regimen of buprenorphine or methadone. 

Clonidine may be considered as a second line agent for symptom relief during inpatient medically 

supervised opioid withdrawal. Outpatient success is lower. If using clonidine, adjuvant medications for 

anxiety, restlessness, insomnia, muscle aches, nausea, and diarrhea may also be prescribed. Caution 

should be exercised when using clonidine as a second line agent, as it is associated with a decrease in 

systolic and diastolic blood pressure with resultant dizziness on standing compared to methadone.[301] 

Extra caution should be exercised in patients older than 50 due to the risk of dizziness and falling as well as 
December 2015 Page 62 of 169

in those patients who are prone to hypotension. In addition to decreased blood pressure, clonidine is 

associated with dysphoria.[302,303] 

d. Sedative Hypnotic Use Disorder Stabilization and Withdrawal

Recommendation

36. For patients in need of withdrawal management for sedative hypnotics, we suggest one of the

following:

 Gradually taper the original benzodiazepine

 Substitute a longer acting benzodiazepine then taper gradually

 Substitute phenobarbital for the addicting agent and taper gradually

(Strong For | Reviewed, New-replaced)

Discussion

Benzodiazepine discontinuation is associated with a characteristic triad of symptoms: recurrence, rebound, 

and withdrawal. While the pattern and intensity of recurrent symptoms often resemble those of the 

original illness, rebound symptoms may be more intense and withdrawal symptoms may be severe and 

debilitating. Optimal clinical management of benzodiazepine discontinuation, including avoidance of 

abrupt drug discontinuation, can lessen withdrawal symptoms and promote successful drug 

discontinuation or dose reduction.[304] 

The recommended clinical approach to benzodiazepine discontinuation is gradual dose tapering. Little 

data exists on the optimal rate of withdrawal; optimal duration of withdrawal may vary from patient to 

patient. The early stages of withdrawal are easier to tolerate than later stages so tapering schemes usually 

start with early rapid step-down in dose followed by a slower rate of reduction.[304] Low dose use of 

benzodiazepines can be tapered by 20% per week; however, higher dose benzodiazepine withdrawal 

should be conducted over an 8 to 12 week period, and up to six months should be allowed in exceptional 

cases.[304] A commonly used slow tapering strategy in a higher dose patient: weekly 25% dose reduction 

until 50% of the dose remains, followed by a one-eighth dose reduction every four to seven days.[305] 

Slow tapering schedules are associated with total cessation of benzodiazepine use in about two-thirds of 

patients.[304] 

Substitution of a short-acting benzodiazepine with a longer acting agent such as diazepam or 

chlordiazepoxide is a common strategy designed to promote a smoother reduction of drug levels over 

time. A conversion chart (Table B-3) is used to determine the equivalent dose of the long-acting agent 

(which may be significantly higher than anticipated) and the slow taper is conducted as described above.

Phenobarbital can also be substituted for the dependent substance and gradually tapered. The average 

daily sedative-hypnotic dose is converted to a phenobarbital equivalent and divided into three doses per 

day for two days; beginning on day three, the phenobarbital dose should be reduced by 30 mg/day. 

Management of benzodiazepine withdrawal and patient outcomes can be improved when extended 

tapering interventions take place in a structured clinical environment which includes close monitoring, 

optimized patient instruction/education, and Cognitive Behavioral Therapy (CBT).[306,307] Patients should 
December 2015 Page 63 of 169

be monitored throughout the tapering period for withdrawal symptoms as well as for the disorder being 

treated; emergence of severe withdrawal symptoms signals a need to slow the tapering process. 

VII. Knowledge Gaps and Recommended Research

As indicated throughout the CPG and in the sections below, further evidence is needed in particular areas 

of management for SUD. The items listed below are selected examples of gaps in knowledge.

Organizations such as the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National 

Institute on Drug Abuse (NIDA) put forth strategic plans which also can be used as resources on the current 

gaps and areas of focus for research in the future. 

A. Determination of Treatment Setting

Future research is needed to evaluate whether recently developed software to conduct the 

multidimensional assessment and yield an algorithmically derived placement recommendation leads to 

better outcomes than clinical judgment that may rely more generally on the six ASAM assessment 

dimensions and placement principles. 

B. Pharmacotherapy

There are many unanswered questions regarding use of pharmacotherapy in SUD. The following are select 

examples of these questions. More research is needed to identify medications for the majority of the 

categories of SUD, including cannabis use disorder.

a. Opioid Use Disorder

While strong evidence supports opioid agonist therapy (OAT) and moderate evidence supports extendedrelease injectable naltrexone, some patients may prefer oral naltrexone despite its lack of demonstrated 

effectiveness. Further research is needed to determine whether additional measures to improve 

treatment retention and medication adherence (e.g., Contingency Management [CM]) would reduce 

opioid consumption in patients taking oral naltrexone. 

Further research is needed to determine risks and benefits of buprenorphine/naloxone versus 

buprenorphine mono-product versus methadone for long-term outcome for children born to women 

with OUD. 

b. Stimulant Use Disorder

Further research into the use of dexamphetamine to treat methamphetamine use disorder is indicated, as 

an initial study showed that its use increased participation in treatment while not decreasing use.[208] 

Given the potential misuse of dexamphetamine, the authors cannot recommend for its use without 

further evidence. A small RCT including only men who have sex with men with methamphetamine use 

disorder showed a benefit of the antidepressant mirtazapine compared to placebo in reducing 

methamphetamine use.[308] Further research is indicated into the use of mirtazapine to treat 

methamphetamine use disorder. Additional research should be conducted on pharmacotherapy for 

stimulant use disorders. 
December 2015 Page 64 of 169

C. Psychosocial Interventions

a. Substance Use Disorders

Further research is needed regarding appropriate additional non-pharmacological therapy specific to the 

individual and to the setting of care. Additionally, research is needed regarding the comparative 

effectiveness of interventions when delivered to patients in groups. Current staffing models are based on 

care being delivered in a group format for all SUDs. More research is needed to determine specific 

protocols, efficacy and effectiveness of the group approach. 

b. Opioid Use Disorder

Given patients’ reluctance to accept referrals to SUD specialty care, clinical trials supporting delivery of 

AUD and OUD pharmacotherapy in general care settings using addiction-focused Medical Management

offer promise of increasing rates of treatment for those with AUD and OUD. The provider time required by 

these protocols limits the generalizability of the findings based on current staffing models. Further 

research is needed to determine whether more cost-effective models could be developed for delivering 

addiction-focused Medical Management for OUD and AUD. For example, research is needed on the 

effectiveness of sharing various components of addiction-focused Medical Management effectively among 

members of a Patient-aligned Care Team and co-located Primary Care-Mental Health Integration 

therapists and prescribers, whether the initial session (40-60 minutes) could be shortened and whether 

telehealth could be utilized to deliver addiction-focused medical management. Further research is also 

needed to determine the benefits of additional psychosocial interventions to address co-occurring 

conditions in this setting versus referral to specialty SUD care. 

D. Follow-up

Further research is needed to determine models for effective and cost-effective continuing care. While 

there is expert consensus based on observational studies that the benefits of engagement in continuing 

SUD care outweigh risks when patients relapse or continue to use substances, we have found no RCTs,

automatic “disciplinary” discharge from treatment continues in practice. Further research may be needed 

to compare the risks and benefits of automatic discharge from care and of various models of adjusting care 

based on response to treatment. 

E. Stabilization and Withdrawal

Further research is needed to define the risks and benefits of systematic assessment scales and decision 

support tools for withdrawal treatment in common treatment settings such as inpatient psychiatry units, 

residential SUD treatment programs and outpatient general mental health, general medicine, and specialty 

SUD treatment clinics. 

F. Telehealth

Additional research on the use of telehealth in SUD may be beneficial, as evidence-based psychosocial 

interventions are not currently offered in all locations. Telehealth may help address barriers to care that 

contribute to low engagement in treatment in the SUD patient population. 
December 2015 Page 65 of 169

Appendix A: Evidence Review Methodology

A. Developing the Scope and Key Questions

The CPG Champions, along with the Work Group, were tasked with identifying KQs to guide the SR of the 

literature on SUD. These questions, which were developed in consultation with the Lewin team, addressed 

clinical topics of the highest priority for the VA and DoD populations. The KQs follow the population, 

intervention, comparison, outcome, timing and setting (PICOTS) framework for evidence questions, as 

established by the Agency for Healthcare Research and Quality (AHRQ). Table A-1 provides a brief 

overview of the PICOTS typology.

Table A-1. PICOTS [309] 

P 

Patients, 

Population, or 

Problem

A description of the patients of interest. It includes the condition(s), populations or subpopulations, disease severity or stage, co-occurring conditions, and other patient 

characteristics or demographics.

I Intervention or 

Exposure

Refers to the specific treatments or approaches used with the patient or population. It 

includes doses, frequency, methods of administering treatments, etc.

C Comparison

Describes the interventions or care that is being compared with the intervention(s) of 

interest described above. It includes alternatives such as placebo, drugs, surgery, lifestyle 

changes, standard of care, etc.

O Outcome

Describes the specific results of interest. Outcomes can include short, intermediate, and 

long-term outcomes, or specific results such as quality of life, complications, mortality, 

morbidity, etc.

(T) Timing, if 

applicable

Describes the duration of time that is of interest for the particular patient intervention and 

outcome, benefit, or harm to occur (or not occur).

(S) Setting, if

applicable

Describes the setting or context of interest. Setting can be a location (such as primary, 

specialty, or inpatient care).

The Champions and evidence review team carried out several iterations of this process, each time 

narrowing the scope of the CPG and the literature review by prioritizing the topics of interest. Due to 

resource constraints, all developed KQs were not able to be included in the systematic evidence review.

Thus, the Champions and Work Group determined which questions were of highest priority, and those 

were included in the review. Table A-2 contains the final set of KQs used to guide the SR for this CPG. 

a. Population(s)

The KQs are specific to adults 18 years or older who have a DSM diagnosis of SUD with or without other 

health conditions. The exception is KQ 4, which specifies patients who screened positive for unhealthy 

alcohol use based on Alcohol Use Disorders Identification Test- Consumption (AUDIT-C) criteria. 

b. Interventions

Pharmacotherapies for AUD included: acamprosate, disulfiram, and naltrexone (either oral or depot 

extended-release injectable formulation). Off label medications for AUD were also considered. These 

included: aripiprazole, atomoxetine, baclofen, benzodiazepines, buspirone, citalopram, desipramine, 

fluoxetine, fluvoxamine, gabapentin, imipramine, olanzapine, ondansetron, paroxetine, quetiapine, 

sertraline, topiramate, valproic acid, and varenicline. For KQ 11, other anticonvulsants, gamma 

hydroxybutyrate, and clonidine were also considered. Pharmacotherapies for OUD included: 
December 2015 Page 66 of 169

buprenorphine, buprenorphine/naloxone, methadone, oral naltrexone, and extended-release injectable 

naltrexone. For KQ 12, clonidine was also considered. Pharmacotherapies for cannabis use disorder 

included: bupropion, divalproex, gabapentin, nabilone, N-acetylcysteine, nefazodone, and dronabinol. 

Pharmacotherapies for cocaine/stimulant use disorder included: disulfiram, doxazosin, topiramate, 

modafinil, agonist replacement therapy, and baclofen. 

A brief intervention (BI), which is defined as an intervention typically lasting from several minutes up to an 

entire visit and which is a patient-centered, empathetic brief counseling intervention that can be offered 

by a clinician who is not a specialist addictions provider or counselor, was also considered. A BI for 

unhealthy alcohol use is a single session or multiple sessions that include motivational discussion focused 

on increasing insight and awareness regarding alcohol use and motivation toward behavioral change. BIs 

can be tailored for variance in population or setting and can be used as a stand-alone treatment for those 

at-risk as well as a vehicle for engaging those in need of more extensive levels of care. Telephone or webbased BIs as sole treatment are beyond the scope of this guideline. However, their use as adjuncts to other 

treatment is within the scope of this guideline.

Criteria to determine initial treatment intensity and setting including disorder severity and psychosocial 

stability were included in the review. 

Strategies for promoting active involvement in mutual help programs include branded 12-Step Facilitation 

(TSF) and other branded strategies (e.g., making Alcoholics Anonymous [AA] easier). 

Psychotherapy and psychosocial interventions included: Behavioral Couples Counseling (BCC); Cognitive 

Behavioral Therapy (CBT); Community Reinforcement Approach (CRA); Contingency Management 

(CM)/motivational incentives; Motivational Enhancement Therapy (MET); twelve-step recovery; 

motivational interviewing (MI); individual social skills training; family psycho-education that aim to 

increase coping strategies, awareness, and self-monitoring behavior; and mindfulness (e.g., mindfulnessbased recovery programs, meditation). 

Possible components of addiction-focused Medical Management included: monitoring of self-reported 

use, laboratory markers, and consequences of substance use; monitoring of medication adherence, 

response to treatment, and adverse effects; integrated or non-integrated treatment of co-occurring 

mental health conditions; and education and referral to community support for recovery (e.g., AA). 

Possible components of measurement-based care included biomarkers and patient reports. Measurement 

instruments included the Brief Addiction Monitor (BAM) and measure of patient health (e.g., Patient 

Health Questionnaire [PHQ-9]).

c. Outcomes

Consumption outcomes included alcohol consumption (drinks per day), opioid consumption, return to any 

drinking, return to heavy drinking, drinking days, heavy drinking days (defined as four or more drinks per 

day for women and five or more drinks per day for men), drinks per drinking day, time to relapse, relapse, 

percent of heavy drinking days, adherence with treatment or abstinence, retention/engagement in the 

treatment program, number lost to treatment (stability and engagement), duration of involvement in 

treatment, adverse events, morbidity, mortality, overdoses, hospitalization or readmission, and emergency 

department utilization. 
December 2015 Page 67 of 169

Side effects of medication included: withdrawals due to adverse events, nausea/vomiting, diarrhea, 

anorexia, palpitations, headache, dizziness, cognitive dysfunction, taste abnormalities, paresthesia

(numbness, tingling), metabolic acidosis, glaucoma, vision changes, suicidal ideation, insomnia, anxiety, 

and rash.

Recovery outcomes included: days in the community, reduction in homelessness, decrease in encounters 

with criminal justice system, and increase in employment. Functional status and quality of life outcomes 

included: mental state, global functioning, social functioning, and quality of life and life satisfaction.

Engagement outcomes included: minimum number of outpatient visits and minimal length of stay in an 

inpatient setting. Health outcomes included: accidents, injuries, mortality, healthcare utilization, functional 

status, and quality of life.

B. Conducting the Systematic Review

Extensive literature searches using the search terms and strategy included in Appendix H identified 4,708 

citations potentially addressing the KQs of interest to this evidence review. Of those, 2,100 were excluded 

upon title review for clearly not meeting inclusion criteria (e.g., not pertinent to the topic, not published in 

English, published prior to study inclusion publication date, not a full-length article). Overall, 2,608 

abstracts were reviewed with 1,621 of those being excluded for the following reasons: not a SR or clinical 

study, did not address a KQ of interest to this review, did not enroll a population of interest, or published 

prior to November 2007. A total of 987 full-length articles were reviewed. Of those, 682 were excluded at 

a first pass review for the following: not addressing a KQ of interest, not enrolling the population of 

interest, not meeting inclusion criteria for clinical study or SR, not meeting inclusion criteria for any KQ, or 

being a duplicate. A total of 305 full-length articles were thought to address one or more KQs and were 

further reviewed. Of these, 184 were ultimately excluded. Reasons for their exclusion are presented in 

Figure A-1 below. 

Overall, 135 studies (in 136 articles) addressed one or more of the KQs and were considered as evidence in 

this review. Table A-2 indicates the number of studies that addressed each of the questions. 
December 2015 Page 68 of 169

Figure A-1. Study Flow Diagram

, 

 184 Citations Excluded at 2nd Pass Full Article 

Level

45 Wrong study population or did not use DSM 

criteria for diagnosing SUDs

44 SR superseded by more comprehensive 

review or study covered in an included SR

15 Wrong study design or does not address a KQ

28 No treatment or comparison of interest

38 Other 

2,100 Citations Excluded at the Title Level

Citations excluded at this level were off-topic, not 

published in English, or published prior to

inclusion date

4,708 Citations Identified by Searches

2,608 Abstracts 

Reviewed

1,621 Citations Excluded at the Abstract Level

Citations excluded at this level were not SR or 

CS, clearly did not address a KQ, did not report 

on an outcome of interest, or were outside cutoff 

publication dates

305 Articles 

Reviewed

135 Included Studies (in 136 publications)

 682 Citations Excluded at 1st Pass Full Article 

Level

Articles excluded at this level did not: address a 

key question of interest, enroll the population of 

interest, meet inclusion criteria for clinical study or 

systematic review, meet inclusion criteria for any 

key question, or were a duplicate.

987 Full-length Articles Reviewed
December 2015 Page 69 of 169

Table A-2. Evidence Base for Key Questions 

Question 

Number Question

Number of Studies 

and Type of 

Studies

Relevant 

Recommendations

1 

In adults with a DSM diagnosis of AUD, what is the 

comparative effectiveness of different medications for 

improving consumption outcomes, adherence outcomes, 

and adverse events in the following? a) Primary care b) 

Specialty care

3 SRs and 6 RCTs 5,6

2 

In adults with a DSM diagnosis of OUD what is the 

comparative effectiveness of different management 

approaches, including different intensity and lengths of 

stay in treatment, for improving consumption outcomes, 

adherence outcomes, and adverse events in the 

following? a) Primary care b) Specialty care

3 SRs and 8 RCTs 8, 9, 10, 11, 12, 33

3 

In adults with a DSM diagnosis of OUD in the primary care

setting, what is the comparative effectiveness of 

pharmacologic-assisted therapy with or without nonpharmacologic therapy for improving consumption 

outcomes, adherence outcomes, and adverse events?

2 SRs and 2 RCTs 13

4 

In adults who screened positive using the AUDIT-C for 

unhealthy alcohol use, what is the comparative 

effectiveness of the following for improving consumption 

and health outcomes? a) Components of brief 

interventions b) Single compared to multiple brief 

interventions

4 SRs and 17 RCTs 2 

5 

In adults with a DSM diagnosis of AUD, what criteria can 

be used to determine the appropriate initial intensity and 

setting of specialty substance use care for improving 

consumption, health, and engagement outcomes?

No studies identified 

by our searches 4 

6 

In adults with a DSM diagnosis of an SUD, what is the 

comparative effectiveness of strategies used for 

promoting active involvement in available mutual help 

programs (e.g., TSF) for improving consumption, health, 

and engagement outcomes?

2 SRs and 8 RCTs 21

7a AUD

In adults with a DSM diagnosis of an SUD, what is the 

comparative effectiveness of addiction-focused 

psychotherapies or psychosocial interventions for 

improving consumption outcomes, adherence outcomes, 

and recovery outcomes?

4 SRs and 13 RCTs 7 

7b OUD 7 RCTs 14, 15, 16

7c 

cannabis 

use 

disorder

2 SRs and 3 RCTs 18

7d 

cocaine/ 

stimulant 

use 

disorder

2 SRs and 14 RCTs 20

8 

In adults with a DSM diagnosis of an SUD, what is the 

comparative effectiveness of the following aspects of 

measurement-based care in primary care and specialty 

care settings for improving consumption and health 

outcomes? a) Components of measurement-based care b) 

Frequency of measurement

2 RCTs 23
December 2015 Page 70 of 169

Question 

Number Question

Number of Studies 

and Type of 

Studies

Relevant 

Recommendations

9 

In adults with a DSM diagnosis of a cannabis use disorder, 

what is the comparative effectiveness of different 

management approaches for improving consumption 

outcomes, adherence outcomes, and adverse events in 

the following? a) Primary or general mental health care b) 

Specialty SUD care

5 RCTs 17

10

In adults with a DSM diagnosis of stimulant/cocaine use 

disorder, what is the comparative effectiveness of 

disulfiram, topiramate and other off-label medications for 

improving consumption outcomes, adherence outcomes, 

and adverse events?

2 SRs and 14 RCTs 19

11

For patients with moderate to severe risk of alcohol 

withdrawal, what is the comparative effectiveness of 

medication for stabilization?

2 SRs and 6 RCTs 27, 28, 30, 31

12

For patients with moderate to severe risk of opioid 

withdrawal, what is the comparative effectiveness of 

medication for stabilization? Does comparative 

effectiveness vary based on dosing and time course used 

with these medications?

3 SRs and 3 RCTs 34, 35

Total Evidence Base 135 studies

Abbreviations: AUD: alcohol use disorder; DSM: Diagnostic and Statistical Manual of Mental Disorders; OUD: opioid use disorder; 

RCT: randomized controlled trial; SR: systematic review; SUD: substance use disorders; TSF: 12-Step Facilitation

a. Criteria for Study Inclusion/Exclusion

i.General Criteria

 Clinical studies or SRs published on or after November 1, 2007

 Studies must be published in English

 Publication must be a full clinical study or SR; abstracts alone were not included. 

Similarly, letters, editorials, and other publications that are not full-length, clinical 

studies were not accepted as evidence. 

 Studies enrolled adults 18 years or older. In studies that mixed adults and children, at 

least 80% of the enrolled patients had to be 18 years or older. 

 Studies must have enrolled a patient population where at least 80% of patients met the 

required diagnostic criteria. 

 Studies of intervention outcomes must have followed patients for at least 12 weeks 

post-randomization unless otherwise noted (KQ 5, 6, 11, and 12 are exempt from this 

requirement). 

 Studies that specifically focus on incarcerated substance use offenders or driving while 

intoxicated/driving under the influence offenders were excluded.
December 2015 Page 71 of 169

ii. Pharmacotherapy/Non-pharmacologic Therapy for SUD (KQ 1-4, 6-10)

 Studies must have been RCTs or SRs of RCTs. In the absence of such evidence, 

prospective comparative studies will be reviewed.

 Randomized crossover trials were considered only if data from the first treatment 

period were reported separately.

 Studies must have enrolled ≥10 patients per treatment arm. 

iii. Criteria for Determining Appropriate Initial Intensity and Setting of Specialty

Substance Use Care (KQ 5)

 Studies must have compared different criteria and enrolled ≥ 10 patients per treatment 

arm. 

b. Literature Search Strategy

Information regarding the bibliographic databases, date limits, and platform/provider can be found in 

Table A-3, below. Additional information on the search strategies, including topic-specific search terms and 

search strategies can be found in Appendix H. 

Table A-3. Bibliographic Database Information

Name Date Limits Platform/Provider

Bibliographic Databases 

The Cochrane Central Register of Controlled Trials 

(CENTRAL) 2007 through January 2015 Wiley

The Cochrane Database of Methodology Reviews 

(Methodology Reviews) 2007 through January 2015 Wiley

The Cochrane Database of Systematic Reviews 

(Cochrane Reviews) 2007 through January 2015 Wiley

Database of Abstracts of Reviews of Effects 2007 through January 2015 Wiley

EMBASE (Excerpta Medica) 2007 through January 2015 Elsevier

Health Technology Assessment Database (HTA) 2007 through January 2015 Wiley

MEDLINE/PreMEDLINE 2007 through January 2015 OVIDSP

PsycINFO 2007 through January 2015 OVIDSP

PubMed (In-process and Publisher records) 2007 through January 2015 NLM

Gray Literature Resources 

AHRQ 2007 through January 2015 AHRQ

Healthcare Standards database 2007 through January 2015 ECRI Institute

National Guideline ClearinghouseTM 2007 through January 2015 AHRQ

National Institute of Health and Clinical Excellence 2007 through January 2015 NHS

TRIP database 2007 through January 2015 TRIP

C. Convening the Face-to-face Meeting

In consultation with the contracting officer's representative (COR), the Champions, and the Work Group, 

the Lewin Team convened a three and a half day face-to-face meeting of the CPG Champions and Work 

Group members on April 14-17, 2015. These experts were gathered to develop and draft the clinical 
December 2015 Page 72 of 169

recommendations for an update to the 2009 SUD CPG. Lewin presented findings from the evidence review 

of KQs 1-10 in order to facilitate and inform the process. 

Under the direction of the Champions, the Work Group members were charged with interpreting the 

results of the evidence review, and asked to categorize and carry forward recommendations from the 

2009 SUD CPG, modifying the recommendations as necessary. The members also developed new clinical 

practice recommendations not presented in the 2009 SUD CPG, based on the 2015 evidence review. The 

subject matter experts were divided into three smaller subgroups at this meeting. 

As the Work Group members drafted clinical practice recommendations, they also assigned a grade for 

each recommendation based on a modified GRADE and USPSTF methodology. Each recommendation was 

graded by assessing the quality of the overall evidence base, the associated benefits and harms, the 

variation in values and preferences, and other implications of the recommendation. 

In addition to developing recommendations during the face-to-face meeting, the Work Group members 

also revised the 2009 SUD CPG algorithms to reflect the new and amended recommendations. They 

discussed the available evidence as well as changes in clinical practice since 2009, as necessary, to update 

the algorithms.

KQs 11 and 12 were developed following the face-to-face meeting, after the need to systematically review 

the evidence related to stabilization for withdrawal from alcohol and opioids was identified. For KQs 11 

and 12, the process for developing and categorizing recommendations was adapted to be used in a 

teleconference format following the face-to-face meeting.

D. Grading Recommendations

This CPG uses the GRADE methodology to assess the quality of the evidence base and assign a grade for 

the strength for each recommendation. The GRADE system uses the following four domains to assess the 

strength of each recommendation:[34] 

• Balance of desirable and undesirable outcomes

• Confidence in the quality of the evidence

• Values and preferences

• Other implications, as appropriate, e.g.,:

 Resource Use

 Equity

 Acceptability

 Feasibility

 Subgroup considerations

The following sections further describe each domain. 

Balance of desirable and undesirable outcomes refers to the size of anticipated benefits (e.g., increased 

longevity, reduction in morbid event, resolution of symptoms, improved quality of life (QoL), decreased 
December 2015 Page 73 of 169

resource use) and harms (e.g., decreased longevity, immediate serious complications, adverse event, 

impaired quality of life, increased resource use, inconvenience/hassle) relative to each other. This 

domain is based on the understanding that the majority of clinicians will offer patients therapeutic or 

preventive measures as long as the advantages of the intervention exceed the risks and adverse effects. 

The certainty or uncertainty of the clinician about the risk-benefit balance will greatly influence the 

strength of the recommendation.

Some of the discussion questions that fall under this domain include:

• Given the best estimate of typical values and preferences, are you confident that the benefits

outweigh the harms and burden or vice versa?

• Are the desirable anticipated effects large?

• Are the undesirable anticipated effects small?

• Are the desirable effects large relative to undesirable effects?

Confidence in the quality of the evidence reflects the quality of the evidence base and the certainty in 

that evidence. This second domain reflects the methodological quality of the studies for each outcome 

variable. In general, the strength of recommendation follows the level of evidence, but not always, as 

other domains may increase or decrease the strength. The evidence review used for the development of 

recommendations for SUD, conducted by ECRI, assessed the confidence in the quality of the evidence base 

and assigned a rate of “High,” “Moderate,” “Low,” or “Very Low.” 

The elements that go into the confidence in the quality of the evidence include: 

• Is there high or moderate quality evidence that answers this question?

• What is the overall certainty of this evidence?

Values and preferences is an overarching term that includes patients’ perspectives, beliefs, expectations, 

and goals for health and life. More precisely, it refers to the processes that individuals use in considering 

the potential benefits, harms, costs, limitations, and inconvenience of the therapeutic or preventive 

measures in relation to one another. For some, the term “values” has the closest connotation to these 

processes. For others, the connotation of “preferences” best captures the notion of choice. In general, 

values and preferences increase the strength of the recommendation when there is high concordance and 

decrease it when there is great variability. In a situation in which the balance of benefits and risks are 

uncertain, eliciting the values and preferences of patients and empowering them and their surrogates to 

make decisions consistent with their goals of care becomes even more important. A recommendation can 

be described as having “similar values,” “some variation,” or “large variation” in typical values and 

preferences between patients and the larger populations of interest.

Some of the discussion questions that fall under the purview of values and preferences include:

• Are you confident about the typical values and preferences and are they similar across the

target population?

• What are the patient’s values and preferences?

• Are the assumed or identified relative values similar across the target population?
December 2015 Page 74 of 169

Other implications consider the practicality of the recommendation, including resources use, equity, 

acceptability, feasibility and subgroup considerations. Resource use is related to the uncertainty around 

the cost-effectiveness of a therapeutic or preventive measure. For example statin use in the frail elderly 

and others with multiple co-occurring conditions may not be effective and depending on the societal 

benchmark for willingness to pay, may not be a good use of resources. Equity, acceptability, feasibility, and 

subgroup considerations require similar judgments around the practically of the recommendation.

The framework below was used by the Work Group to guide discussions on each domain.

Table A-3. Evidence to Recommendation Framework

Decision Domain Judgment

Balance of desirable and undesirable outcomes

 Given the best estimate of typical values and preferences, are you 

confident that the benefits outweigh the harms and burden or vice 

versa?

 Are the desirable anticipated effects large?

 Are the undesirable anticipated effects small?

 Are the desirable effects large relative to undesirable effects?

Benefits outweigh harms/burden

Benefits slightly outweigh harms/burden

Benefits and harms/burden are balanced

Harms/burden slightly outweigh benefits

Harms/burden outweigh benefits

Confidence in the quality of the evidence

 Is there high or moderate quality evidence that answers this 

question?

 What is the overall certainty of this evidence?

High

Moderate

Low

Very low 

Values and preferences

 Are you confident about the typical values and preferences and are 

they similar across the target population?

 What are the patient’s values and preferences? 

 Are the assumed or identified relative values similar across the target

population?

Similar values

Some variation

Large variation

Other implications (e.g., resource use, equity, acceptability, feasibility, subgroup considerations)

 Are the resources worth the expected net benefit from the 

recommendation?

 What are the costs per resource unit?

 Is this intervention generally available?

 Is this intervention and its effects worth withdrawing or not allocating 

resources from other interventions? 

 Is there lots of variability in resource requirements across settings?

Various considerations

The strength of a recommendation is defined as the extent to which one can be confident that the 

desirable effects of an intervention outweigh its undesirable effects and is based on the framework above, 

which combines the four domains.[34] GRADE methodology does not allow for recommendations to be 

made based on expert opinion alone. While strong recommendations are usually based on high or 

moderate confidence in the estimates of effect (quality of the evidence) there may be instances where 

strong recommendations are warranted even when the quality of evidence is low.[310] In these types of 

instances where the balance of desirable and undesirable outcomes and values and preferences played 
December 2015 Page 75 of 169

large roles in determining the strength of a recommendation, this is explained in the discussion section for 

the recommendation.

The GRADE of a recommendation is based on the following elements:

• Four decision domains used to determine the strength and direction (described above)

• Relative strength (Strong or Weak)

• Direction (For or Against)

The relative strength of the recommendation is based on a binary scale, “Strong” or “Weak.” A strong 

recommendation indicates that the Work Group is highly confident that desirable outcomes outweigh 

undesirable outcomes. If the Work Group is less confident of the balance between desirable and 

undesirable outcomes, they present a weak recommendation.

Similarly, a recommendation for a therapy or preventive measure indicates that the desirable 

consequences outweigh the undesirable consequences. A recommendation against a therapy or 

preventive measure indicates that the undesirable consequences outweigh the desirable consequences.

Using these elements, the grade of each recommendation is presented as part of a continuum:

• Strong For (or “We recommend offering this option ...”)

• Weak For (or “We suggest offering this option ...”)

• Weak Against (or “We suggest not offering this option ...”)

• Strong Against (or “We recommend against offering this option ...”)

Note that weak (For or Against) recommendations may also be termed “Conditional,” “Discretionary,” or 

“Qualified.” Recommendations may be conditional based upon patient values and preferences, the 

resources available, or the setting in which the intervention will be implemented. Recommendations may 

be at the discretion of the patient and clinician or they may be qualified with an explanation about the 

issues that would lead decisions to vary.

E. Recommendation Categorization

a. Recommendation Categories and Definitions

For use in the 2015 SUD CPG, a set of recommendation categories was adapted from those used by the 

United Kingdom National Institute for Health and Clinical Excellence (NICE). [37,38] These categories, along 

with their corresponding definitions, were used to account for the various ways in which 

recommendations could have been updated from the 2009 SUD CPG. The categories and definitions can 

be found in Table A-4. 
December 2015 Page 76 of 169

Table A-4. Recommendation Categories and Definitions 

Evidence

Reviewed*

Recommendation

Category* Definition*

Reviewed

New-added New recommendation following review of the evidence

New-replaced Recommendation from previous CPG that has been carried over to the 

updated CPG that has been changed following review of the evidence

Not changed

Recommendation from previous CPG that has been carried forward to the 

updated CPG where the evidence has been reviewed but the recommendation 

is not changed

Amended

Recommendation from the previous CPG that has been carried forward to the 

updated CPG where the evidence has been reviewed and a minor amendment 

has been made

Deleted Recommendation from the previous CPG that has been removed based on 

review of the evidence

Not reviewed

Not changed Recommendation from previous CPG that has been carried forward to the 

updated CPG, but for which the evidence has not been reviewed

Amended

Recommendation from the previous CPG that has been carried forward to the 

updated CPG where the evidence has not been reviewed and a minor 

amendment has been made

Deleted Recommendation from the previous CPG that has been removed because it 

was deemed out of scope for the updated CPG

*Adapted from the NICE guideline manual (2012) [37] and Garcia et al. (2014) [38]

Abbreviation: CPG: clinical practice guideline

b. Categorizing Recommendations with an Updated Review of the Evidence

Recommendations were first categorized by whether or not they were based on an updated review of the 

evidence. If evidence had been reviewed, recommendations were categorized as “New-added,” “Newreplaced,” “Not changed,” “Amended,” or “Deleted.” 

“Reviewed, New-added” recommendations were original, new recommendations that were not in the 

2009 SUD CPG. “Reviewed, New-replaced” recommendations were in the previous version of the 

guideline, but were modified to align with the updated review of the evidence. These recommendations 

could have also included clinically significant changes to the previous version. Recommendations 

categorized as “Reviewed, Not changed” were carried forward from the previous version of the CPG 

unchanged. 

To maintain consistency between 2009 recommendations, which were developed using the USPSTF 

methodology, and 2015 recommendations, which were developed using the GRADE methodology, it was 

necessary to modify the 2009 recommendations to include verbiage to signify the strength of the 

recommendation (e.g., “We recommend,” “We suggest”). Because the 2009 recommendations inherently 

needed to be modified at least slightly to include this language, the “Not changed” category was not used. 

For recommendations carried forward to the updated CPG with review of the evidence and slightly 

modified wording, the “Reviewed, Amended” recommendation category was used. This allowed for the 

wording of the recommendation to reflect GRADE methodology as well as for any other non-substantive 

(i.e., not clinically meaningful) language changes deemed necessary. The evidence used to support these 
December 2015 Page 77 of 169

recommendations was carried forward from the previous version of the CPG and/or was identified in the 

evidence review for the update. 

Recommendations could have also been designated “Reviewed, Deleted.” These were recommendations 

from the previous version of the CPG that were not brought forward to the updated guideline after review 

of the evidence. This occurred if the evidence supporting the recommendations was out of date, to the 

extent that there was no longer any basis to recommend a particular course of care and/or new evidence 

suggests a shift in care, rendering recommendations in the previous version of the guideline obsolete.

c. Categorizing Recommendations without an Updated Review of the Evidence

There were also cases in which it was necessary to carry forward recommendations from the previous 

version of the CPG without a SR of the evidence. Due to time and budget constraints, the update of the 

SUD CPG could not review all available evidence on management of SUD, but instead focused its KQs on 

areas of new or updated scientific research or areas that were not previously covered in the CPG. 

For areas of research that have not changed, and for which recommendations made in the previous 

version of the guideline were still relevant, recommendations could have been carried forward to the 

updated guideline without an updated SR of the evidence. The support for these recommendations in the 

updated CPG was thus also carried forward from the previous version of the CPG. These recommendations 

were categorized as “Not reviewed.” If evidence had not been reviewed, recommendations could have 

been categorized as “Not changed,” Amended,” or “Deleted.” 

“Not reviewed, Not changed” recommendations refer to recommendations from the previous version of 

the SUD CPG that were carried forward unchanged to the updated version. The category of “Not reviewed, 

Amended” was used to designate recommendations which were modified from the 2009 CPG with the 

updated GRADE language, as explained above. 

Recommendations could also have been categorized as “Not reviewed, Deleted” if they were determined 

to be out of scope. A recommendation was out of scope if it pertained to a topic (e.g., population, care 

setting, treatment, condition) outside of the scope for the updated CPG as defined by the Work Group. 

The categories for the recommendations included in the 2015 version of the guideline are noted in the 

Recommendations. Recommendations 1, 22, 24, 25, 26, 29, and 32 were carried forward from the 2009 

SUD CPG using this method. The categories for the recommendations from the 2009 SUD CPG are noted in 

Appendix E. 

F. Drafting and Submitting the Final Clinical Practice Guideline

Following the face-to-face meeting, the Champions and Work Group members were given writing 

assignments to craft discussion sections to support each of the new recommendations and/or to update

discussion sections from the 2009 SUD CPG to support the amended “carried forward” recommendations.

The Work Group also considered tables, appendices, and other sections from the 2009 SUD CPG for 

inclusion in the update. During this time, the Champions and Work Group also made additional revisions to

the algorithms, as necessary. 
December 2015 Page 78 of 169

After developing the initial draft of the updated CPG, an iterative review process was used to solicit 

feedback on and make revisions to the CPG. Once they were developed, the first two drafts of the CPG 

were posted on a wiki website for a period of 14-20 business days for internal review and comment by the 

Work Group. All feedback submitted during each review period was reviewed and discussed by the Work 

Group and appropriate revisions were made to the CPG. 

Draft 3 of the CPG was made available for peer review and comment. This process is described in Peer 

Review Process. After revisions were made based on the feedback received during the peer review and 

comment period, the Champions presented the CPG to the EBPWG for their approval. Changes were made 

based on feedback from the EBPWG and the guideline was finalized. 

The Work Group also produced a set of guideline toolkit materials which included a provider summary, 

pocket cards, and a patient summary. The final 2015 SUD CPG was submitted to the EBPWG in December 

2015.
December 2015 Page 79 of 169

Appendix B: Pharmacotherapy for Alcohol Use Disorder and Opioid Use Disorder

Table B-1. Pharmacotherapy for Alcohol Use Disorder

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Indications

AUD (DSM diagnosis) 

with:

1. At least 3-5 days of

pretreatment

abstinence not

required but may

improve response

2. Initial engagement in

addiction-focused

Medial Management

and/or other

recommended

psychosocial

intervention

AUD (DSM diagnosis) 

with:

1. Pretreatment

abstinence not

required but may

improve response

2. Willingness to

receive monthly

injections

3. Difficulty adhering to

an oral regimen

4. Initial engagement in

addiction-focused

Medial Management

and/or other

recommended

psychosocial

intervention

AUD (DSM diagnosis) 

with:

1. Abstinence at

treatment initiation

2. Initial engagement in

addiction-focused

Medial Management

and/or other

recommended

psychosocial

intervention

AUD (DSM diagnosis) 

with:

1. Abstinence >12 hours 

and BAL=0

2. Combined cocaine

dependence

3. Previous response to

disulfiram

4. Capacity to

appreciate risks and

benefits and to

consent to treatment

5. Initial engagement in

addiction-focused

Medial Management

and/or other

recommended

psychosocial

intervention

6. Note: More effective

with monitored

administration (e.g.,

in clinic, with spouse,

with probation

officer)

AUD (DSM diagnosis) (off 

label) with:

1. Pretreatment

abstinence not

required but may

improve response

2. Initial engagement in

addiction-focused

Medial Management

and/or other

recommended

psychosocial

intervention

AUD (DSM diagnosis) (off 

label) with:

1. Pretreatment

abstinence not

required but may

improve response

2. Initial engagement in

addiction-focused

Medial Management

and/or other

recommended

psychosocial

intervention

1 Not FDA labeled for treatment of AUD
December 2015 Page 80 of 169

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Contraindications

 Receiving opioid 

agonists

 Physiologic opioid 

dependence with 

use within past 7 

days 

 Acute opioid 

withdrawal

 Failed naloxone 

challenge test

 Positive urine opioid 

screen

 Acute hepatitis or 

liver failure

 Hypersensitivity

 Receiving opioid 

agonists

 Physiologic opioid 

dependence with 

use within past 7 

days

 Acute opioid 

withdrawal 

 Failed naloxone

challenge test

 Positive urine opioid 

screen

 Acute hepatitis or 

liver failure

 Hypersensitivity

 Inadequate muscle 

mass

 Hypersensitivity

 Severe renal 

insufficiency (CrCl

≤30 mL/min)

 Severe 

cardiovascular, 

respiratory, or renal 

disease

 Severe hepatic 

dysfunction (i.e., 

transaminase levels 

>3 times upper limit 

of normal or 

abnormal bilirubin)

 Severe psychiatric 

disorders, especially 

psychotic and 

cognitive disorders 

and suicidal ideation

 Poor impulse control 

 Metronidazole or 

ketoconazole 

therapy which 

already induce a 

similar reaction to 

alcohol

 Hypersensitivity

 No contraindications 

in manufacturer’s 

labeling

 Hypersensitivity 
December 2015 Page 81 of 169

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Warnings/Precautions

 Active liver disease

 Severe renal failure

 Active liver disease

 Uncertain effects (no 

data) in moderate to 

severe renal 

insufficiency

 Injection site 

reactions

 Use intramuscular 

injections with 

caution in patients 

with thrombocytopenia or coagulation 

disorders

 Monitor for 

emergence of 

depression or 

suicidality

 Reduce dose in 

patients with renal 

insufficiency, 

including elderly

 Alcohol-disulfiram 

reaction; patients 

must be vigilant to 

avoid alcohol in all 

forms including 

mouthwash, over 

the counter 

medications, etc.

 Do not abruptly 

discontinue therapy; 

taper dosage 

gradually

 Cognitive 

dysfunction, 

psychiatric 

disturbances, and 

sedation may occur 

with use

 Increased risk of 

suicidal ideation 

with antiepileptic 

agents, including 

topiramate

 Do not abruptly 

discontinue therapy; 

taper dosage 

gradually

 May cause CNS 

depression including 

somnolence/ 

dizziness 

 Increased risk of 

suicidal ideation 

with antiepileptic 

agents, including 

gabapentin

 Pregnancy Category 

C 

 Pregnancy Category 

C 

 Pregnancy Category 

C 

 Pregnancy Category 

C 

 Pregnancy Category 

C 

 Pregnancy Category 

C 

Baseline Evaluation

 Liver transaminase 

levels

 Bilirubin within 

normal limits

 Urine beta-HCG for 

females

 Liver transaminase 

levels

 Bilirubin within 

normal limits

 CrCl (estimated or 

measured) 50 

mL/min or greater

 Ensure patient has 

adequate muscle 

mass for injection

 Urine beta-HCG for 

females

 CrCl (estimated or 

measured)

 Urine beta-HCG for 

females

 Liver transaminase 

levels

 Physical assessment

 Psychiatric 

assessment

 Electrocardiogram if 

indicated by history 

of cardiac disease

 Verify abstinence 

with breath or BAL

 Urine beta-HCG for 

females

 Assess renal function

 Urine beta-HCG for 

females

 Assess renal function

 Urine beta-HCG for 

females
December 2015 Page 82 of 169

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Dosage and Administration

 50-100 mg orally 1 

time daily

 380 mg 1 time

monthly by deep 

intramuscular 

injection

 666 mg orally 3 times 

daily, preferably 

with meals

 250 mg orally 1 time

daily (range, 125-

500 mg daily)

 Titrate up gradually 

over several weeks 

to minimize side 

effects

 Initiate at 50 mg/day; 

increase to a 

maximum dose of 

100 mg 2 times daily

 Titrate up gradually 

to minimize side 

effects 

 Initiate at 300 mg on 

day 1 and increase 

by 300 mg daily as 

tolerated to target 

of 1800 mg daily, 

administered in 3 

divided doses

Alternative Dosing Schedules

 25 mg 1- or 2-time(s) 

daily with meals to 

reduce nausea, 

especially during the 

first week 

 100 mg on Monday 

and Wednesday and 

150 mg on Friday

 Reduce dose to 125 

mg to reduce side 

effects 

 For monitored 

administration, 

consider giving 500 

mg on Monday, 

Wednesday, and 

Friday

 Geriatric patients 

with CrCl <70

mL/min/1.73m2 give 

initial dose of 25 

mg/day followed by 

incremental 

increases of 25 mg 

at weekly intervals 

until an effective 

dose is reached

Dosing in Special Populations

 Hepatic or renal 

insufficiency: Use 

caution

 Mild renal 

insufficiency (CrCl 

50-80 mL/min): No 

dosage adjustment 

necessary

 Uncertain effects (no 

data) in moderate to 

severe renal 

insufficiency

 Moderate renal 

insufficiency (CrCl 

30-50 mL/min): 333 

mg 3 times daily

 Do not administer to 

patients with severe 

renal insufficiency

(CrCl ≤30 mL/min)

 CrCl <70 

mL/minute/1.73m2

: 

Administer 50% 

dose and titrate 

more slowly

 Dosage adjustment 

may be required in 

hepatic impairment

 Dosage must be 

adjusted for renal 

function, consider 

target dose <1800 

mg daily when CrCl 

<60 mL/min
December 2015 Page 83 of 169

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Adverse Effects

 Common: Nausea

 Other: Headache, 

dizziness, 

nervousness, 

fatigue, insomnia, 

vomiting, anxiety, 

somnolence

 Major: Eosinophilic 

pneumonia, 

depression, 

suicidality

 Common: Injectionsite reactions, 

injection site 

tenderness, 

injection site 

induration, nausea, 

headache, asthenia 

 Major: Suicidality 

2.4% (vs. 0.8% on 

placebo during the 

first year in clinical 

trials)

 Common: Diarrhea 

(16%)

 Other: Anxiety, 

asthenia, 

depression, 

insomnia

 Major: 

Hepatotoxicity, 

peripheral 

neuropathy, 

psychosis, delirium, 

severe disulfiramethanol reaction

 Common: 

Somnolence, 

metallic taste, 

headache

 CNS: Paresthesia, 

nervousness, 

fatigue, ataxia, 

drowsiness, lack of 

concentration, 

memory 

impairment, 

confusion 

 Gastrointestinal: 

Abdominal pain, 

anorexia 

 CNS: Dizziness, 

drowsiness, ataxia, 

fatigue 

 Gastrointestinal: 

Diarrhea, 

nausea/vomiting, 

abdominal pain

Drug Interactions

 Opioid-containing 

medications, 

including over the 

counter

preparations

 Thioridazine 

(increased lethargy 

and somnolence)

 Opioid-containing 

medications, 

including over the 

counter

preparations

 Thioridazine 

(increased lethargy 

and somnolence)

 Naltrexone: 33% 

increase in Cmax of 

acamprosate (no 

dosage adjustment 

is recommended)

 Antidepressants: 

Weight gain and 

weight loss more 

common than with 

either medication 

alone

 Alcohol containing 

medications, 

including over the 

counter

preparations

 Drug-drug 

interactions may 

occur with 

phenytoin, warfarin, 

isoniazid, rifampin, 

diazepam, 

chlordiazepoxide, 

imipramine, 

desipramine, and 

oral hypoglycemic 

agents

 Use extreme caution 

if used concurrently 

with alcohol or 

other CNS 

depressants

 Topiramate may 

decrease the serum 

concentrations of 

contraceptives and 

decrease their 

effectiveness

 Use extreme caution 

if used concurrently 

with alcohol or 

other CNS 

depressants

 Antacids may 

decrease levels of 

gabapentin
December 2015 Page 84 of 169

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Monitoring

 Repeat liver 

transaminase levels 

at 6 and 12 months 

and then every 12 

months thereafter

 Discontinue 

medication and 

consider 

alternatives if no 

detectable benefit 

after an adequate 

trial (50 mg daily for 

3 months)

 Repeat liver 

transaminase levels 

at 6 and 12 months 

and then every 12 

months thereafter

 Discontinue if there is 

no detectable 

benefit within 3 

months

 Monitor serum 

creatinine/CrCl, 

particularly in the 

elderly and in 

patients with renal 

insufficiency 

 Maintain therapy if 

relapse occurs 

 Repeat liver 

transaminase levels 

within the first 

month, then 

monthly for first 3 

months, and 

periodically 

thereafter as 

indicated

 Consider 

discontinuation in 

event of relapse or 

when patient is not 

available for 

supervision and 

counseling

 Monitor serum 

creatinine/CrCl 

periodically, 

particularly in 

patients with renal 

insufficiency and in 

geriatric patients

 Monitor for change 

in behavior which 

might indicate 

suicidal thoughts or 

depression

 Discontinue 

medication and 

consider alternatives 

if no detectable 

benefit after an 

adequate trial

(300 mg daily for 3 

months)

 Monitor serum 

creatinine/CrCl 

periodically, 

particularly in 

patients with renal 

insufficiency and in 

geriatric patients

 Monitor for change 

in behavior which 

might indicate 

suicidal thoughts or 

depression

 Gabapentin has 

abuse potential 

when taken in 

supratherapeutic 

dosages; monitor 

quantities 

prescribed and 

usage patterns

 Discontinue 

medication and 

consider alternatives 

if no detectable 

benefit from at least 

900 mg daily for 2-3 

months 
December 2015 Page 85 of 169

Naltrexone Oral Naltrexone Injectable Acamprosate Disulfiram Topiramate1 Gabapentin1

Patient Education

 Discuss compliance 

enhancing methods

 Negotiate 

commitment from 

the patient 

regarding monitored 

ingestion

 Side effects, if any, 

tend to occur early 

in treatment and 

can typically resolve 

within 1-2 weeks 

after dosage 

adjustment 

 Report any 

concerning injection 

site reactions

 Report any new or 

worsening 

depression or 

suicidal thinking

 May cause allergic 

pneumonia; contact 

provider if patient

develops signs and

symptoms of 

pneumonia

 Report any new or 

worsening 

depression or 

suicidal thinking

 Avoid alcohol in food 

and beverages, 

including 

medications

 Avoid disulfiram if 

alcohol intoxicated

 May cause sedation; 

caution operating 

vehicles and 

hazardous 

machinery

 Discuss compliance 

enhancing methods

 Family members 

should not 

administer 

disulfiram without 

informing patient

 Provide patients with 

wallet cards that 

indicate the use of 

disulfiram

 Administer without 

regard to meals

 It is not 

recommended to 

crush, break, or 

chew immediate 

release tablets due 

to bitter taste

 Caution patients 

about performing 

tasks requiring 

mental alertness

 Take first dose on 

first day at bedtime 

to minimize 

somnolence and 

dizziness

 Caution patients 

about performing 

tasks requiring 

mental alertness

 If signs and symptoms of acute hepatitis occur, 

discontinue naltrexone and contact provider 

immediately

 Very large doses of opioids may overcome the 

effects of naltrexone and lead to serious injury, 

coma, or death

 Small doses of opioids, such as in analgesic, 

antidiarrheal, or antitussive drugs, may be 

blocked by naltrexone and fail to produce a 

therapeutic effect

 Patients who have previously used opioids may 

be more sensitive to toxic effects of opioids 

after discontinuation of naltrexone

Abbreviations: AUD: alcohol use disorder; BAL: blood alcohol level; Cmax: maximum concentration; CNS: central nervous system; CrCl: creatinine clearance; DSM: Diagnostic and 

Statistical Manual of Mental Disorders; HCG: human chorionic gonadotropin; m: meter(s); mg: milligram(s); min: minute(s); mL: milliliter(s)
December 2015 Page 86 of 169

Table B-2. Pharmacotherapy for Opioid Use Disorder

Methadone 

Buprenorphine/Naloxone or 

Buprenorphine Naltrexone Injectable

Indications

 OUD (DSM diagnosis) and patient 

meets Federal OTP Standards (42 

C.F.R. §8.12)

 OUD (DSM diagnosis)  OUD (DSM diagnosis) with:

1. Pretreatment abstinence from

opioids and no signs of opioid

withdrawal

2. Willingness to receive

monthly injections

Contraindications

 Hypersensitivity  Hypersensitivity  Receiving opioid agonists

 Physiologic opioid dependence 

with use within past 7 days

 Acute opioid withdrawal 

 Failed naloxone challenge test

 Positive urine opioid screen

 Acute hepatitis or liver failure

 Hypersensitivity

 Inadequate muscle mass

Warnings/Precautions

 Concurrent enrollment in another 

OTP 

 Prolonged QTc interval 

 Use caution in patients with 

respiratory, liver, or renal 

insufficiency

 Concurrent benzodiazepines or 

other CNS depressants including 

active AUD (potential respiratory 

depression) and other opioid 

agonists (check PDMP) 

 Use of opioid antagonists (e.g., 

parenteral naloxone, oral or 

parenteral nalmefene, 

naltrexone)

 Buprenorphine/naloxone may 

precipitate withdrawal in 

patients on full agonist opioids

 Use caution in patients with 

respiratory, liver, or renal 

insufficiency

 Concurrent benzodiazepines or 

other CNS depressants, including 

active AUD (potential respiratory 

depression)

 Use of opioid antagonists (e.g., 

parenteral naloxone, oral or 

parenteral nalmefene, 

naltrexone)

 Active liver disease

 Uncertain effects (no data) in 

moderate to severe renal 

insufficiency

 Injection site reactions

 Use intramuscular injections with 

caution in patients with 

thrombocytopenia or

coagulation disorders

 Pregnancy Category C

Baseline Evaluation

 Consider baseline 

electrocardiogram and physical 

examination for patients at risk 

for QT prolongation or 

arrhythmias 

 Liver transaminases  Liver transaminase levels

 Bilirubin within normal limits

 CrCl (estimated or measured) 50 

mL/min or greater

 Ensure patient has adequate 

muscle mass for injection

 Urine beta-HCG for females
December 2015 Page 87 of 169

Methadone 

Buprenorphine/Naloxone or 

Buprenorphine Naltrexone Injectable

Dosage and Administration

 Initial dose: 15-20 mg single dose, 

maximum 30 mg

 Daily dose: Maximum 40 mg/day

on first day

 Usual dosage range for optimal 

effects: 60-120 mg/day

 Titrate carefully, consider 

methadone’s delayed cumulative 

effects

 Give orally in single dose

 Individualize dosing regimens 

(avoid same fixed dose for all 

patients)

Sublingual dosing: 

 Induction dose: 2-8 mg 1 time

daily

 Day 2 and onward: Increase dose 

by 2-4 mg/day until withdrawal 

symptoms and craving are 

relieved

 Stabilization/maintenance: Titrate 

by 2-4 mg/day targeting craving 

and illicit opioid use; usual dose 

12-16 mg/day (up to 32 mg/day) 

 Individualize dosing regimens 

 For any formulation: Do not 

chew, swallow, or move after 

placement

 380 mg 1 time monthly by deep 

intramuscular injection

Alternative Dosing Schedules

 Give in divided daily doses based 

on peak and low levels that 

document rapid metabolism that 

justifies divided doses

 Give equivalent weekly 

maintenance dose divided over 

extended dosing intervals (2 or 3 

times weekly or every 2, 3, or 4 

days)

Dosing in Special Populations

 Renal or hepatic impairment: 

Reduce dose

 Elderly or debilitated: Reduce 

dose

 Hepatic impairment: Reduce dose

 For concurrent chronic pain, 

consider dividing total daily dose 

into 2- or 3-time daily 

administration

 Mild renal insufficiency (CrCl 50-

80 mL/min): No dosage 

adjustment necessary

 Uncertain effects (no data) in 

moderate to severe renal 

insufficiency

Adverse Effects

 Major: Respiratory depression, 

shock, cardiac arrest, 

prolongation of QTc interval on 

electrocardiogram and torsades 

de pointes ventricular 

tachycardia

 Common: Lightheadedness, 

dizziness, sedation, nausea, 

vomiting, sweating, constipation, 

edema

 Less common: Sexual dysfunction

 Major: Hepatitis, hepatic failure, 

respiratory depression (usually 

when misused intravenously or if 

combined with other CNS 

depressants)

 Common: Headache, pain, 

abdominal pain, insomnia, 

nausea, vomiting, sweating, 

constipation

 Sublingual buprenorphine/ 

naloxone: Oral hypoesthesia, 

glossodynia, oral mucosal 

erythema

 Major: Eosinophilic pneumonia, 

depression, suicidality

 Common: Injection-site reaction, 

injection site tenderness, 

injection site induration, nausea, 

headache, asthenia 
December 2015 Page 88 of 169

Methadone 

Buprenorphine/Naloxone or 

Buprenorphine Naltrexone Injectable

Drug Interactions

 Drugs that reduce serum 

methadone levels: Ascorbic acid, 

barbiturates, carbamazepine, 

ethanol (chronic use), interferon, 

phenytoin, rifampin, efavirenz, 

nevirapine, other antiretrovirals 

with CYP3A4 activity

 Drugs that increase serum 

methadone level: Amitriptyline, 

atazanavir, atazanavir/ritonavir, 

cimetidine, delavirdine, 

diazepam, fluconazole, 

fluvoxamine, ketoconazole, 

voriconazole

 Opioid antagonists may 

precipitate withdrawal

 Drugs that reduce serum 

buprenorphine level: Ascorbic 

acid, barbiturates, 

carbamazepine, ethanol (chronic 

use), interferon, phenytoin, 

rifampin, efavirenz, nevirapine, 

other antiretrovirals with CYP3A4 

activity

 Drugs that increase serum 

buprenorphine level: 

Amitriptyline, atazanavir, 

atazanavir/ritonavir, cimetidine, 

delavirdine, diazepam, 

fluconazole, fluvoxamine, 

ketoconazole, voriconazole

 Opioid agonist: 

Buprenorphine/naloxone or 

buprenorphine may precipitate 

withdrawal

 Opioid antagonists may 

precipitate withdrawal

 Opioid-containing medications, 

including over the counter

preparations

 Thioridazine (increased lethargy 

and somnolence)

Monitoring

 Signs of respiratory and CNS 

depression

 Liver function tests prior to 

initiation and during therapy

 Repeat liver transaminase levels 

at 6 and 12 months and then 

every 12 months thereafter
December 2015 Page 89 of 169

Methadone 

Buprenorphine/Naloxone or 

Buprenorphine Naltrexone Injectable

Patient Education

 Strongly advise patient against 

self-medicating with CNS 

depressants during methadone 

therapy

 Serious overdose and death may 

occur if benzodiazepines, 

sedatives, tranquilizers, 

antidepressants, or alcohol are 

taken with methadone

 Store in a secure place out of the 

reach of children

 Strongly advise patient to 

continue in long-term 

methadone maintenance

 If discontinuing methadone, 

recommend transition to 

extended-release injectable 

naltrexone 

 Serious overdose and death may 

occur if patient relapses to 

opioid use after withdrawal from 

methadone

 Strongly advise patient against 

self-medicating with CNS 

depressants during 

buprenorphine therapy

 Serious overdose and death may 

occur if benzodiazepines, 

sedatives, tranquilizers, 

antidepressants, or alcohol are 

taken with buprenorphine

 Store in a secure place out of the 

reach of children

 Strongly advise patient to 

continue in long-term 

buprenorphine maintenance

 If discontinuing buprenorphine, 

recommend transition to 

extended-release injectable 

naltrexone

 Serious overdose and death may 

occur if patient relapses to 

opioid use after withdrawal from 

buprenorphine

 Report any concerning injection 

site reactions

 Report any new or worsening 

depression or suicidal thinking

 May cause allergic pneumonia; 

contact provider if patient 

develops signs and symptoms of 

pneumonia

 If signs and symptoms of acute 

hepatitis occur, discontinue 

naltrexone and contact provider 

immediately

 Very large doses of opioids may 

overcome the effects of 

naltrexone and lead to serious 

injury, coma, or death

 Small doses of opioids, such as in 

analgesic, antidiarrheal, or 

antitussive drugs, may be 

blocked by naltrexone and fail to 

produce a therapeutic effect

 Patients who have previously 

used opioids may be more 

sensitive to toxic effects of 

opioids after discontinuation of 

naltrexone

Abbreviations: AUD: alcohol use disorder; CNS: central nervous system; CrCl: creatinine clearance; DSM: Diagnostic and Statistical 

Manual of Mental Disorders; mg: milligram(s); min: minute(s); mL: milliliter(s); OTP: Opioid Treatment Program; OUD: opioid use 

disorder; PDMP: prescription drug monitoring program; QTc: the heart rate corrected time from the start of the Q wave to the end 

of the T wave; HCG: human chorionic gonadotropin
December 2015 Page 90 of 169

Table B-3. Sedative-hypnotic Conversion [311-316] 

Generic Name 

Approximate 

Equivalents to 

Diazepam 10 mg or

Phenobarbital 30 mg1

Time to Peak 

Plasma level

(in Hours)

Half-life

Parent Drug 

(in Hours)

2

Metabolite 

Activity

(Maximal Half-life 

in Hours)3

Alprazolam 1 mg 1-2 12 ± 2 Inactive

Chlordiazepoxide 25 mg 1-4 10 ± 3.4 Active (up to 120)

Clonazepam 1 mg 1-4 23 ± 5 Inactive

Clorazepate 15 mg Variable 2 ± 0.9 Active (up to 120)

Diazepam 10 mg 1-2 43 ± 13 Active (up to 120)

Estazolam 1 mg 0.5-0.6 10-24 Inactive

Flurazepam 15 mg 0.5-1.0 74 ± 24 Active (up to 100)

Lorazepam 2 mg 2-4 14 ± 5 Inactive

Oxazepam 30 mg 2-3 8.0 ± 2 Inactive

Quazepam 10 mg 1.5 39 Active (up to 75)

Temazepam 15 mg 2.5 11 ± 6 Inactive

Triazolam 0.25 mg 1-2 2.9 ± 1.0 Inactive

Eszopiclone 15 mg 1 6 Active (<parent)

Zaleplon 20 mg 1 1 Inactive

Zolpidem 20 mg 1.6 2 Inactive

Butalbital 50 mg 1-2 35 Inactive

Pentobarbital 100 mg 0.5-1 15-50 Inactive

Phenobarbital 30 mg 1+ 53-140 Inactive

Meprobamate 400 mg 2-3 10 Inactive

Carisoprodol 350 mg 1-3 2 Active (see 

Meprobamate)

Choral hydrate 250 mg 0.5 <1 Active (up to 94)

Abbreviation: mg: milligrams

1 Withdrawal doses of diazepam or phenobarbital are those sufficient to suppress most withdrawal symptoms and may not reflect 

therapeutic dose equivalency. 2 Half-life of active metabolite(s) may differ. 3 Primary route of barbiturate elimination is renal excretion.
December 2015 Page 91 of 169

Appendix C: Psychosocial Interventions

Table C-1. Summary of Effectiveness of Psychosocial Interventions During Early Recovery 

(First 90 Days) on Condition Specific Outcomes of Substance Use Disorders (Use or 

Consequences) or General Psychosocial Functioning

Interventions 

(Alphabetical)

First-line Alternatives at 

Least as Effective as 

Other Bona Fide Active 

Interventions or 

Treatment as Usual

Added Effectiveness as 

Adjunctive 

Interventions in 

Combination with 

Pharmacotherapy 

and/or Other First-line 

Psychosocial 

Interventions

AlcoholOpioidsSt

Comments

imulants/ 

MixedCannabisAlcoholOpioidsStimulants/ MixedCannabis

Behavioral Couples 

Therapy (BCT) √ N/A N/A N/A ? N/A N/A N/A

Effective for male or female 

SUD patients and partners; 

improves marital satisfaction

Cognitive 

Behavioral Coping 

Skills Training

√ N/A √ √ √ √/? N/A √

Added benefit in methadone 

treatment; Unclear added 

benefit of CBT in some studies 

of office-based buprenorphine

Contingency 

Management (CM)/ 

Motivational 

Incentives

N/A N/A N/A N/A ? √ √ √

CM is recommended only as an 

adjunctive treatment. CM for 

cannabis may be problematic 

given slow clearance in urine 

Community 

Reinforcement 

Approach (CRA)

√ N/A √ N/A N/A N/A N/A N/A Complex intervention best 

when including CM

Individual Drug 

Counseling N/A N/A N/A N/A N/A N/A √ N/A

One study found benefit when 

combined with group drug 

counseling

Motivational 

Enhancement 

Therapy (MET)

√ N/A N/A √ √ N/A ? ? 

Some evidence for those with 

AUD and low readiness or high 

anger

12-Step Facilitation 

(TSF) √ N/A N/A N/A √ N/A N/A N/A

12-step involvement is 

instrumental in explaining TSF 

benefits

Symbols: √: Good confidence in effectiveness; ?: Questionable confidence in effectiveness; N/A: Insufficient evidence 

Abbreviations: AUD: alcohol use disorder

A. Behavioral Couples Therapy

Most versions of BCT are focused both on reducing alcohol or drug use in the identified patient and on 

improving overall marital satisfaction for both partners. In BCT sessions, the therapist arranges a daily 

sobriety contract in which the patient states his or her intent not to drink or use drugs that day, and the 

partner expresses support for the patient’s efforts to stay abstinent. The Sobriety Contract can also include 
December 2015 Page 92 of 169

urine drug screens for the patient, attendance at other agreed-to counseling sessions, or 12-step meetings 

by the patient and partner. To improve relationship functioning, BCT uses a series of behavioral 

assignments to increase positive feelings, shared activities, and constructive communication because these 

relationship factors are conducive to sobriety.[317,318] 

B. Cognitive-Behavioral Coping Skills Therapy

Cognitive-behavioral coping skills therapy consists of related treatment approaches for SUD that focus on 

teaching patients to modify both thinking and behavior related not only to substance use, but to other 

areas of life functionally related to substance use. Patients learn to track their thinking and activities and 

identify the affective and behavioral consequences of those thoughts and activities. Patients then learn 

techniques to change thinking and behaviors that contribute to substance use, and to strengthen coping 

skills, improve mood, interpersonal functioning and enhance social support. Primary therapeutic 

techniques include education of the patient about the treatment model, collaboration between the 

patient and therapist to choose goals, identifying unhelpful thoughts and developing experiments to test 

the accuracy of such thoughts, guided discovery (facilitating the patient in identifying alternative beliefs 

through the use of questions designed to explore current beliefs), interpersonal skill building through 

communication and assertiveness training, behavioral rehearsal, and role-play. In addition, treatment 

incorporates structured practice outside of session, including scheduled activities, self-monitoring, thought 

recording and challenging, and interpersonal skills practice.[121,319-321] 

C. Community Reinforcement Approach

CRA is a comprehensive cognitive-behavioral intervention for the treatment of SUD by focusing on 

environmental contingencies that impact and influence the patient’s behavior. Developed in accordance

with the belief that these environmental contingencies play a crucial role in an individual’s addictive 

behavior and recovery, CRA utilizes familial, social, recreational, and occupational events to support the 

individual in changing his or her drinking/using behaviors and in creating a successful sobriety. The goal is 

to rearrange multiple aspects of an individual’s life so that a sober lifestyle is more rewarding than one 

that is dominated by alcohol and/or drugs. CRA integrates several treatment components, including 

building the patient’s motivation to quit drinking/using, helping the patient initiate sobriety, analyzing the 

patient’s drinking/using pattern, increasing positive reinforcement, learning new coping behaviors, and 

involving significant others in the recovery process.[322,323] 

D. Contingency Management for Substance Use Disorders Treatment

CM approaches are based on behavioral principles of reinforcement that reward specific behavioral goals 

related to recovery. Either monetary or nonmonetary rewards are made contingent on objective evidence 

such as negative toxicology results (e.g., biological tests for recent drug or alcohol use), treatment 

adherence, or progress toward treatment goals. The most common form of contingencies provided to 

reinforce desired behaviors are vouchers with monetary value that can be redeemed for goods and 

services, specific material prizes, or draws from a “fishbowl” that contains cards which vary in their 

reinforcing value from simple praise to vouchers worth $1 to $100. Schedules (fixed or intermittent) and 

magnitude of reinforcement have varied and have implications for overall cost of clinical 

implementation.[324] 
December 2015 Page 93 of 169

E. Individual Drug Counseling

The approach to individual drug counseling is manualized [325] and includes patient education about a 

biopsychosocial and spiritual approach to recovery, attention to building a therapeutic alliance, monitored 

urine drug testing and encouragement of 12-step (e.g., Alcoholics Anonymous [AA], Narcotics Anonymous 

[NA]) participation.

F. Motivational Enhancement Therapy

MET is a less intensive form of specialized psychosocial intervention for patients with SUD. MET uses 

principles of motivational interviewing (MI) including an empathic, client-centered, but directive, approach 

intended to heighten awareness of ambivalence about change, promote commitment to change, and 

enhance self-efficacy. MET differs from MI in that it is a more structured intervention that is based to a 

greater degree on systematic assessment with personalized feedback. The therapeutic style using MI elicits 

client reactions to assessment feedback, commitment to change, and collaboration on development of an 

individualized change plan. Involvement of a significant other is encouraged in at least one of the MET 

sessions.[326] 

G. 12-Step Facilitation

TSF therapy aims to increase the patient’s active involvement in AA or other 12-step based mutual help 

groups. This approach was systematized in a manual for National Institute on Alcohol Abuse and 

Alcoholism’s (NIAAA’s) Project MATCH and delivered as 12-sessions of individual therapy in which the 

therapist actively encourages engagement in AA, and walks the patient through the first four steps of the 

AA program. The therapist conveys the concept that addiction is a chronic, progressive, and potentially 

fatal illness for which the only successful strategy is abstinence achieved one day at a time by following a 

12-step program of recovery. Each therapy session is divided into three parts. The first part reviews 

relevant events of the last week (including urges to use, drinking behavior and recovery-oriented activities) 

and a homework assignment. The middle portion introduces new material related to the 12-steps. The 

conclusion of the session includes a homework assignment and development of a plan for recoveryoriented activities (meeting attendance, sponsor contact).[327]
December 2015 Page 94 of 169

Appendix D: Evidence Table

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

1. For patients in general medical and mental healthcare settings,

we recommend screening for unhealthy alcohol use annually

using the three-item Alcohol Use Disorders Identification TestConsumption (AUDIT-C) or Single Item Alcohol Screening

Questionnaire (SASQ).

A, A, A, B, 

None, A

[65-70,72,73] 

Additional References:

[71,74-81] 

Strong For Not reviewed, 

Amended

2. For patients without documented alcohol use disorder who

screen positive for unhealthy alcohol use, we recommend

providing a single initial brief intervention regarding alcoholrelated risks and advice to abstain or drink within nationally

established age and gender-specific limits for daily and weekly

consumption.

A [65,66,82-84,91-99] 

Additional References:

[85-90,100,101] 

Strong For Reviewed, Newreplaced

3. For patients with a diagnosis of a substance use disorder, we

suggest offering referral for specialty substance use disorder care

based on willingness to engage in specialty treatment.

None, B, 

None, None, 

A, None, 

None, None

[44] 

Additional References:

[21,106,107] 

Weak For Not reviewed, 

Amended

1 The 2009 VA/DoD SUD CPG used the USPSTF evidence grading system (http://www.uspreventiveservicestaskforce.org). Inclusion of more than one 2009 Grade indicates that more 

than one 2009 CPG recommendation is covered under the 2015 recommendation. The strength of recommendations were rated as follows: A- a strong recommendation that the 

clinicians provide the intervention to eligible patients; B- a recommendation that clinicians provide (the service) to eligible patients; C- no recommendation for or against the 

routine provision of the intervention is made; D- recommendation is made against routinely providing the intervention; I- the conclusion is that the evidence is insufficient to 

recommend for or against routinely providing the intervention. 2 The evidence column indicates studies that support each recommendation. For new recommendations, developed by the 2015 guideline Work Group, the literature cited 

corresponds directly to the 2015 evidence review. For recommendations that have been carried over from the 2009 VA/DoD SUD CPG, slight modifications were made to the 

language in order to better reflect the current evidence and/or the change in grading system used for assigning the strength of each recommendation (USPSTF to GRADE). For 

these “modified” recommendations, the evidence column indicates “additional evidence,” which can refer to either 1) studies that support the recommendation and which were 

identified through the 2015 evidence review, or 2) relevant studies that support the recommendation, but which were not systematically identified through a literature review. 3 Refer to the Grading Recommendations section for more information on how the strength of the recommendation was determined using GRADE methodology. 4 Refer to the Recommendation Categorization section for more information on the description of the categorization process and the definition of each category.
December 2015 Page 95 of 169

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

4. For patients with substance use disorders, there is insufficient

evidence to recommend for or against using a standardized

assessment that would determine initial intensity and setting of

substance use disorder care rather than the clinical judgment of

trained providers.

B Additional References:

[108] 

N/A Reviewed, Newreplaced

5. For patients with moderate-severe alcohol use disorder, we

recommend offering one of the following medications:

• Acamprosate

• Disulfiram

• Naltrexone- oral or extended release

• Topiramate

None, None, 

None, None, 

A, A, A

[109-112,114] 

Additional References:

[113,115] 

Strong For Reviewed, Newreplaced

6. For patients with moderate-severe alcohol use disorder for whom

first-line pharmacotherapy is contraindicated or ineffective, we 

suggest offering gabapentin.

None, None, 

None, None, 

A, A, A

[112,116,118] 

Additional References:

[117] 

Weak For Reviewed, Newreplaced

7. For patients with alcohol use disorder we recommend offering

one or more of the following interventions considering patient

preference and provider training/competence:

• Behavioral Couples Therapy for alcohol use disorder

• Cognitive Behavioral Therapy for substance use

disorders

• Community Reinforcement Approach

• Motivational Enhancement Therapy

• 12-Step Facilitation

None, A [119-131] Strong For Reviewed, Newreplaced

8. For patients with opioid use disorder, we recommend offering

one of the following medications considering patient preferences:

• Buprenorphine/naloxone

• Methadone in an Opioid Treatment Program

None, None, 

A, A

[133,135-137,139-

148,151,156,158] 

Additional References:

[132,134,138,149,150,152-

155,157,171,172] 

Strong For Reviewed, Newreplaced
December 2015 Page 96 of 169

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

9. In pregnant women with opioid use disorder for whom

buprenorphine is selected, we suggest offering buprenorphine

alone (i.e., without naloxone) considering patient preferences.

-- [139,166] 

Additional References:

[159-165,167-169] 

Weak For Reviewed, Newadded

10. For patients with opioid use disorder for whom buprenorphine is 

indicated, we recommend individualizing choice of appropriate 

treatment setting (i.e., Opioid Treatment Program or officebased) considering patient preferences.

None Additional References:

[170] 

Strong For Reviewed, Newreplaced

11. For patients with opioid use disorder for whom opioid agonist

treatment is contraindicated, unacceptable, unavailable, or

discontinued and who have established abstinence for a sufficient

period of time (see narrative), we recommend offering:

• Extended-release injectable naltrexone

None, None [173] 

Additional References:

[174] 

Strong For Reviewed, Newreplaced

12. There is insufficient evidence to recommend for or against oral

naltrexone for treatment of opioid use disorder.

None, None [136,176,177] 

Additional References:

[175] 

N/A Reviewed, Newreplaced

13. At initiation of office-based buprenorphine, we recommend

addiction-focused Medical Management (see narrative) alone or

in conjunction with another psychosocial intervention.

C, A, A [51-54,178] 

Additional References:

[55] 

Strong For Reviewed, Newreplaced

14. For patients in office-based buprenorphine treatment, there is 

insufficient evidence to recommend for or against any specific

psychosocial interventions in addition to addiction-focused

Medical Management. Choice of psychosocial intervention should

be made considering patient preferences and provider

training/competence.

None, A [51,181,182] 

Additional References: 

[179,180] 

N/A Reviewed, Newreplaced

15. In Opioid Treatment Program settings, we suggest offering

individual counseling and/or Contingency Management,

considering patient preferences and provider

training/competence.

A [183,184,187,188,191,192]

Additional References:

[170,185,186,189,190] 

Weak For Reviewed, Newreplaced
December 2015 Page 97 of 169

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

16. For patients with opioid use disorder for whom opioid use

disorder pharmacotherapy is contraindicated, unacceptable or

unavailable, there is insufficient evidence to recommend for or

against any specific psychosocial interventions.

None, A [53]

Additional References:

[193] 

N/A Reviewed, Newreplaced

17. There is insufficient evidence to recommend for or against the

use of pharmacotherapy in the treatment of cannabis use

disorder.

-- [194-198] N/A Reviewed, Newadded

18. For patients with cannabis use disorder, we recommend offering

one of the following interventions as initial treatment considering

patient preference and provider training/competence:

• Cognitive Behavioral Therapy

• Motivational Enhancement Therapy

• Combined Cognitive Behavioral Therapy/Motivational

Enhancement Therapy

None [199-203] Strong For Reviewed, Newreplaced

19. There is insufficient evidence to recommend for or against the

use of any pharmacotherapy for the treatment of cocaine use 

disorder or methamphetamine use disorder.

-- [204,206-210,212] 

Additional References:

[205,211] 

N/A Reviewed, Newadded

20. For patients with stimulant use disorder, we recommend offering

one or more of the following interventions as initial treatment

considering patient preference and provider

training/competence:

• Cognitive Behavioral Therapy

• Recovery-focused behavioral therapy

 General Drug Counseling

 Community Reinforcement Approach 

• Contingency Management in combination with one of

the above

None [213,217-

220,222,226,229,230] 

Additional References:

[214-216,221,223-

225,227,228,231] 

Strong For Reviewed, Newreplaced
December 2015 Page 98 of 169

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

21. For patients with substance use disorders in early recovery or

following relapse, we recommend promoting active involvement

in group mutual help programs using one of the following

systematic approaches considering patient preference and

provider training/competence:

• Peer linkage

• Network support

• Twelve-step facilitation

None, A [235,239] 

Additional References:

[232-234,236-238] 

Strong For Reviewed, Newreplaced

22. Among patients in early recovery from substance use disorders or

following relapse, we suggest prioritizing other needs through

shared decision making (e.g., related to other mental health

conditions, housing, supportive recovery environment,

employment, or related recovery-relevant factors) among

identified biopsychosocial problems and arranging services to

address them.

B, None, 

None, None, 

None, None, 

None, None, 

B, None, 

None

[240-242] Weak For Not reviewed, 

Amended

23. We suggest assessing response to treatment periodically and

systematically, using standardized and valid instrument(s)

whenever possible. Indicators of treatment response include 

ongoing substance use, craving, side effects of medication,

emerging symptoms, etc.

None, None, 

None, A, 

None, None, 

None, None, 

None, None, 

None, None

[243,244] Weak For Reviewed, Newreplaced

24. For patients who have initiated an intensive phase of outpatient

or residential treatment, we recommend offering and

encouraging ongoing systematic relapse prevention efforts or

recovery support individualized on the basis of treatment

response.

None [248,249] 

Additional References:

[245-247,250] 

Strong For Not reviewed, 

Amended

25. For patients in substance use disorders specialty care, we

recommend against automatic discharge from care for patients

who do not respond to treatment or who relapse.

None [249] 

Additional References:

[250-253] 

Strong Against Not reviewed, 

Amended

26. For patients with alcohol or opioid use disorder in early

abstinence, we suggest using standardized measures to assess 

the severity of withdrawal symptoms such as Clinical Institute

Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar)

for alcohol or Clinical Opiate Withdrawal Scale (COWS) for

opioids.

B [260,262,269,270] 

Additional References:

[254-259,261,263-268,271]

Weak For Not reviewed, 

Amended
December 2015 Page 99 of 169

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

27. We recommend inpatient medically supervised alcohol

withdrawal management for patients with any of the following

conditions:

• History of delirium tremens or withdrawal seizures 

• Inability to tolerate oral medication

• Co-occurring medical conditions that would pose 

serious risk for ambulatory withdrawal management

(e.g., severe coronary artery disease, congestive heart

failure, liver cirrhosis)

• Severe alcohol withdrawal (i.e., Clinical Institute

Withdrawal Assessment for Alcohol [revised version]

[CIWA-Ar] score ≥20)

• Risk of withdrawal from other substances in addition to

alcohol (e.g., sedative hypnotics)

None, C [272] 

Additional References:

[273,274] 

Strong For Reviewed, Amended

28. We suggest inpatient medically supervised withdrawal for

patients with symptoms of at least moderate alcohol withdrawal

(i.e., Clinical Institute Withdrawal Assessment for Alcohol [revised

version] [CIWA-Ar] score ≥10) and any of the following

conditions:

• Recurrent unsuccessful attempts at ambulatory

withdrawal management

• Reasonable likelihood that the patient will not

complete ambulatory withdrawal management (e.g.,

due to homelessness)

• Active psychosis or severe cognitive impairment

• Medical conditions that could make ambulatory

withdrawal management problematic (e.g., pregnancy,

nephrotic syndrome, cardiovascular disease, lack of

medical support system)

C [272] 

Additional References:

[273,274] 

Weak For Reviewed, Amended

29. We recommend using one of the following pharmacotherapy

strategies for managing alcohol withdrawal symptoms:

• A predetermined fixed medication tapering schedule

with additional medication as needed

• Symptom-triggered therapy where patients are given

medication only when signs or symptoms of withdrawal

occur (e.g., as needed dosing)

A, B [262,275] 

Additional References:

[276,277] 

Strong For Not reviewed, 

Amended
December 2015 Page 100 of 169

Recommendation

2009 

Grade1 Evidence2

Strength of 

Recommendation3

Recommendation 

Category4

30. For treatment of moderate to severe alcohol withdrawal, we

recommend using benzodiazepines with adequate monitoring

because of documented efficacy and high margin of safety.

A [278,279,281] 

Additional References:

[280,282]

Strong For Reviewed, Amended

31. For managing mild to moderate alcohol withdrawal in patients for

whom risks of benzodiazepines outweigh benefits (e.g.,

inadequate monitoring available, abuse liability, or

allergy/adverse reactions), we suggest considering

carbamazepine, gabapentin, or valproic acid as an alternative.

B [278,281] 

Additional References:

[280,282] 

Weak For Reviewed, Newreplaced

32. We recommend against using alcohol as an agent for medically

supervised withdrawal.

D Additional References:

[283-286] 

Strong Against Not reviewed, 

Amended

33. For patients not yet stabilized from opioid use disorder, we

recommend against withdrawal management alone due to high

risk of relapse and overdose (see Recommendations 8 and 11).

B [137,151,290,296] 

Additional References:

[152-154,288,289,291-

295,297-300] 

Strong Against Reviewed, NewReplaced

34. Among patients with opioid use disorder for whom maintenance

agonist treatment is contraindicated, unacceptable, or

unavailable, we recommend using a methadone (in Opioid

Treatment Program only) or buprenorphine taper for opioid

withdrawal management (see Recommendation 11).

None [287,296] 

Additional References:

[179,180] 

Strong For Reviewed, Newreplaced

35. For patients with opioid use disorder for whom methadone and

buprenorphine are contraindicated, unacceptable, or unavailable,

we recommend offering clonidine as a second-line agent for

opioid withdrawal management (see Recommendation 11).

None [301-303] 

Additional References:

[179,180] 

Strong For Reviewed, Newreplaced

36. For patients in need of withdrawal management for sedative

hypnotics, we suggest one of the following:

• Gradually taper the original benzodiazepine

• Substitute a longer acting benzodiazepine then taper

gradually

• Substitute phenobarbital for the addicting agent and

taper gradually

A, None, 

None

Additional References:

[304-307] 

Weak For Not Reviewed, 

Amended
December 2015 Page 101 of 169

Appendix E: 2009 Recommendation Categorization Table 2009 Module1 2009 Section 2009 Number

2009 Recommendation Text2

2009 Grade3

Category4

2015 

Recommendation5

A B 1 Patients in general and mental healthcare settings should be screened for unhealthy alcohol use 

annually.

A Not reviewed, 

Amended

Recommendation 1

A B 2 Use a validated screening questionnaire for past-year unhealthy alcohol use. A Not reviewed, 

Amended 

Recommendation 1

A B 3 Select one of two brief methods of screening: 

 The Alcohol Use Disorders Identification Test Consumption Questions (AUDIT-C) or

 Ask whether patient drank any alcohol in the past year and administer the Single-Item 

Alcohol Screening Questionnaire (SASQ) to assess the frequency of heavy drinking in patients 

who report any drinking. (see Annotation C)

A Not reviewed, 

Amended

Recommendation 1

A B 4 The CAGE questionnaire alone is not a recommended screen for past-year unhealthy alcohol use 

(e.g., risky or hazardous drinking).

D Not reviewed, 

Deleted

--

A B 5 The CAGE questionnaire, used as a self-assessment tool, may be used in addition to an 

appropriate screening method to increase patient’s awareness to unhealthy use or abuse of 

alcohol.

None Not reviewed, 

Deleted

--

A C 1 Consider a screen positive for unhealthy alcohol use if:

 AUDIT-C score (range from 0 to 12) is > 4 points for men or > 3 points for women

B Not reviewed, 

Amended

Recommendation 1

1 The first three columns indicate the location of each recommendation within the 2009 SUD CPG.

2 The 2009 Recommendation Text column contains the wording of each recommendation from the 2009 SUD CPG. 3 The 2009 VA/DoD SUD CPG used the U.S. Preventive Services Task Force (USPSTF) evidence grading system. http://www.uspreventiveservicestaskforce.org The strength of 

recommendations were rated as follows: A- a strong recommendation that the clinicians provide the intervention to eligible patients; B- a recommendation that clinicians provide 

(the service) to eligible patients; C- no recommendation for or against the routine provision of the intervention is made; D- recommendation is made against routinely providing 

the intervention; I- the conclusion is that the evidence is insufficient to recommend for or against routinely providing the intervention. 4 The Category column indicates the way in which each 2009 SUD CPG recommendation was updated. 

5 For recommendations that were carried forward to the 2015 SUD CPG, this column indicates the new recommendation(s) to which they correspond.
December 2015 Page 102 of 169 2009 Module1 2009 Section 2009 Number

2009 Recommendation Text2

2009 Grade3

Category4

2015 

Recommendation5

 Patients report drinking 4 or more (women) or 5 or more (men) drinks in a day in the past 

year on the single-item screening question.

A C 2 Identify contraindications for any alcohol use . Contraindications to alcohol use include:

 Pregnancy or trying to conceive

 Liver disease including hepatitis C

 Other medical conditions potentially exacerbated or complicated by drinking (e.g., 

pancreatitis, congestive heart failure)

 Use of medications with clinically important interactions with alcohol or intoxication (e.g., 

warfarin)

 An alcohol use disorder

C Not reviewed, 

Deleted

--

A D 1 Determine the number of drinks consumed by the patient in a typical week and the maximum 

number of drinks on an occasion in the past month.

None Not reviewed, 

Amended

Recommendation 1

A E 1 Determine whether patient drinks above recommended limits.

 The recommended limits are:

• For men— no more than 14 standard-sized drinks a week and no more than 4

standard-sized drinks on any day

• For women— no more than 7 standard-sized drinks a week and no more than 3

standard-sized drinks on any day

 Standard-sized drinks are: 12 oz beer, 5 oz wine, or 1.5 oz hard liquor.

A Not reviewed, 

Amended

Recommendation 1

A E 2 Contraindications for any alcohol use include:

 Pregnancy or trying to conceive

 Liver disease including hepatitis C

 Other medical conditions potentially exacerbated or complicated by drinking (e.g., 

pancreatitis, congestive heart failure)

 Use of medications with clinically important interactions with alcohol or intoxication (e.g., 

warfarin)

 An alcohol use disorder.

None Not reviewed, 

Deleted

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A F 1 Provide a brief intervention (counseling) for alcohol use, which includes the following 

components:

 Express concern that the patient is drinking at unhealthy levels known to increase his/her 

risk of alcohol-related health problems

 Provide feedback linking alcohol use and health, including:

• Personalized feedback (i.e., explaining how alcohol use can interact with patient’s 

medical concerns [hypertension, depression/anxiety, insomnia, injury, congestive 

heart failure (CHF), diabetes mellitus (DM), breast cancer risk, interactions with

medications]); or

• General feedback on health risks associated with drinking

 Advise:

• To abstain (if there are contraindications to drinking); or

• To drink below recommended limits (specified for patient).

 Support the patient in choosing a drinking goal, if he/she is ready to make a change

 Offer referral to specialty addictions treatment if appropriate

A Reviewed, NewreplacedRecommendation 2

A G 1 Offer referral to specialty SUD care for addiction treatment if the patient:

 May benefit from additional evaluation of his/her drinking or substance use and related 

problems or from motivational interviewing

 Has tried and been unable to change drinking or substance use on his/her own or does not 

respond to brief intervention

 Has been diagnosed for alcohol or other substance dependence

 Has previously been treated for an alcohol or other substance use disorders

 Has an AUDIT-C score > 8

None Not reviewed, 

Amended

Recommendation 3

A G 2 DoD active duty members involved in an incident in which substance use is suspected to be a 

contributing factor are required to be referred to specialty SUD care for evaluation. Command 

should be contacted to discuss administrative and clinical options if the member refuses to be 

evaluated. (Repeated in other sections)

None Not reviewed, 

Deleted

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A H 1 Agree on a set of specific goals with the patient.

 Review with the patient results of previous efforts of self-change and formal treatment 

experience, including reasons for treatment dropout

 Ask patient about willingness to accept referral

 Consider bringing an addiction specialist into a general medical or mental health visit to 

assist with referral decision

None Not reviewed, 

Deleted

--

A H 2 Patients at high risk for alcohol use disorder but who are not ready for specialty addictions 

treatment should be engaged in monitoring of alcohol-related medical problems in the medical 

setting.

None Not reviewed, 

Deleted

--

A H 3 DoD active duty members involved in an incident in which substance use is suspected to be a 

contributing factor are required to be referred to specialty SUD care for evaluation. Command 

should be contacted to discuss administrative and clinical options if the member refuses to be 

evaluated (see Appendix D).

None Not reviewed, 

Deleted

--

A I 1 Address alcohol at the next medical visit scheduled to address other issues, or schedule a 

separate appointment to specifically address drinking if the patient agrees. 

B Not reviewed, 

Deleted

--

A I 2 Repeat brief intervention at the follow-up visit if the patient has not responded to a previous 

brief intervention. 

B Reviewed, 

Deleted

--

A J 1 Provide positive feedback to patients for decreases in drinking. None Not reviewed, 

Deleted

--

A J 2 Relate changes in drinking to any changes in presenting health conditions. None Not reviewed, 

Deleted

--

A K 1 Advise patients who screen positive for unhealthy alcohol use but who report drinking below 

recommended limits to continue to drink below recommended limits.

None Not reviewed, 

Deleted

--

A L 1 Repeat alcohol screening annually. None Not reviewed, 

Deleted

--

B B 1 Assure patient safety and readiness to cooperate with further assessment by referring the 

patient to an emergency department or appropriate setting for stabilization as needed.

None Not reviewed, 

deleted

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B C 1 Obtain a comprehensive biopsychosocial assessment that includes all of the following:*

 History of the present episode, including precipitating factors, current symptoms and 

pertinent present risks:

• Family history: Family alcohol and drug use history, including past treatment 

episodes; Family social history, including profiles of parents (or guardians or other 

caretakers), home atmosphere, economic status, religious affiliation, cultural 

influences, leisure activities, monitoring and supervision, and relocations; Family 

medical and psychiatric history

• Developmental history, including pregnancy and delivery, developmental

milestones and temperament

• Comprehensive substance use history, including onset and pattern of progression,

past sequelae and past treatment episodes (include all substances, e.g., alcohol,

illicit drugs, tobacco, caffeine, over-the-counter medications, prescription

medications, inhalants)

• Nearly all daily nicotine users are nicotine dependent. Identification and treatment

of co-morbid nicotine dependence may improve recovery rates of other SUDs. For

patients using nicotine, offer and recommend tobacco use cessation treatment.

Use the Clinical Practice Guideline: Treating Tobacco Use Dependence: 2008

Update from the U.S. Department of Health and Human Services available at:

http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf and the

VA/DoD Clinical Practice Guideline for Management of Tobacco Use

• Recent pattern of substance use based on self-report and urine drug screening

• Personal/social history (including housing issues, religious/spiritual affiliation,

cultural influences)

• School history

• Military history

• Marital history

• Peer relationships and friendships

• Leisure activities

• Sexual activity

• Physical or sexual abuse

• Legal/non-judicial punishment history, including past behaviors and their relation

to substance use, arrests, adjudications and details of current status

• Psychiatric history, including symptoms and their relation to substance use, current

and past diagnoses, treatments and providers

None Not reviewed, 

Deleted

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• Medical history, including pertinent medical problems and treatment, surgeries,

head injuries, present medications and allergies

• Review of systems, including present and past medical and psychological

symptoms

 Laboratory tests for infectious diseases (HIV, Hepatitis C, sexually transmitted disease) and 

consequences of substance use (e.g., liver function tests)

 Mental status examination

 Survey of assets, vulnerabilities and supports

 Patient’s perspective on current problems, treatment goals and preferences

*Adapted from ASAM Patient Placement Criteria, 2nd Edition-Revised (ASAM PPC-2R, 2001)

B C 2 Use empathic and non-judgmental (versus confrontational) therapist style, being sensitive to 

gender, cultural and ethnic differences.

None Not reviewed, 

Deleted

--

B D 1 Provide a narrative to consolidate and interpret the information obtained during the assessment 

process.

None Not reviewed, 

Deleted

--

B D 2 Include a diagnostic formulation. None Not reviewed, 

Deleted

--

B D 3 Include past treatment response and patient’s perspective on current problems. None Not reviewed, 

Deleted

--

B D 4 Review the patient’s motivational level, treatment preferences and goals, and consider these 

factors, along with an interdisciplinary perspective and available programming, in 

recommending specific treatment options. 

B Not reviewed, 

Amended

Recommendation 3

B D 5 Present and discuss the treatment options with the patient and significant others. None Not reviewed, 

Deleted

--

B D 6 Determine whether the treatment plan can be implemented in general health care (including 

primary care) based on availability of a willing provider, severity and chronicity of the SUD, active 

involvement with recovery supports in the community, prior treatment response, and patient 

preference and likelihood of adherence.

None Not reviewed, 

Amended

Recommendation 3

B D 7 If treatment in specialty SUD care is appropriate, determine the appropriate initial intensity and 

level of specialty SUD care, based on ASAM patient placement criteria. 

B Reviewed, NewreplacedRecommendation 4

B D 8 If treatment in specialty SUD care is recommended, determine if it is an acceptable mode of 

treatment to the patient.

None Not reviewed, 

Deleted

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B D 9 Involve the patient in prioritizing problems to be addressed in the initial treatment plan, and in 

selecting specific treatment goals, regardless of the level of care selected (see Table B-1).

None Not reviewed,

Deleted

--

B D 10 If the patient does not agree to the treatment plan, provide motivational intervention and offer 

to renegotiate the treatment plan.

None Not reviewed, 

Deleted

--

B D 11 For DoD Active Duty Members:

A treatment team shall convene with the patient and command to review the treatment plan 

and goals.

None Not reviewed, 

Deleted

--

B E 1 Discuss addiction-focused pharmacotherapy options with all patients with opioid and/or alcohol 

dependence.

None Reviewed, Newreplaced

Recommendation 5

Recommendation 6

Recommendation 8

Recommendation 11

Recommendation 12

B E 2 Initiate addiction-focused pharmacotherapy if indicated and monitor adherence and treatment 

response.

None Reviewed, NewreplacedRecommendation 5

Recommendation 6

Recommendation 8

Recommendation 11

Recommendation 12

B F 1 Indicate to the patient and significant others that treatment is more effective than no treatment 

(i.e., “Treatment works”).

None Not reviewed, 

Deleted

--

B F 2 Consider the patient’s prior treatment experience and respect patient preference for the initial 

psychosocial intervention approach, since no single intervention approach has emerged as the 

treatment of choice.

None Not reviewed, 

Deleted

--

B F 3 Regardless of the particular psychosocial intervention chosen, use motivational interviewing 

style during therapeutic encounters with patients and emphasize the common elements of 

effective interventions including: enhancing patient motivation to stop or reduce substance use, 

improving self-efficacy for change, promoting a therapeutic relationship, strengthening coping 

skills, changing reinforcement contingencies for recovery, and enhancing social support for 

recovery.

None Not reviewed, 

Deleted

--

B F 4 Emphasize that the most consistent predictors of successful outcome are retention in formal 

treatment and/or active involvement with community support for recovery.

None Not reviewed, 

Deleted

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B F 5 Use strategies demonstrated to be efficacious to promote active involvement in available 

mutual help programs (e.g., Alcoholics Anonymous, Narcotics Anonymous).

None Reviewed, NewreplacedRecommendation 21

B F 6 Based on locally available expertise, initiate addiction-focused psychosocial interventions with 

empirical support. Consider the following interventions that have been developed into published 

treatment manuals and evaluated in randomized trials:

 Behavioral Couples Counseling

 Cognitive Behavioral Coping Skills Training

 Community Reinforcement Approach

 Contingency Management/Motivational Incentives

 Motivational Enhancement Therapy

 Twelve-Step Facilitation.

None Reviewed, NewreplacedRecommendation 7

Recommendation 14

Recommendation 15

Recommendation 16

Recommendation 18

Recommendation 20

B F 7 Addiction-focused psychosocial interventions should be coordinated with evidence-based 

intervention(s) for other biopsychosocial problems to address identified concurrent problems.

None Reviewed, 

Deleted

--

B F 8 Intervention should be provided in the least restrictive setting necessary for safety and 

effectiveness.

None Reviewed, 

Deleted

--

B G 1 Prioritize and address other coexisting biopsychosocial problems with services targeted to these 

problem areas, rather than increasing intensity of addiction-focused psychosocial treatment 

alone. 

B Not reviewed, 

Amended

Recommendation 22

B G 2 Address transitional housing needs to facilitate access to treatment and promote a supportive 

recovery environment.

None Not reviewed, 

Amended

Recommendation 22

B G 3 Provide social/vocational/legal services in the most accessible setting to promote engagement 

and coordination of care.

None Not reviewed, 

Amended

Recommendation 22

B G 4 Address deferred problems as part of treatment plan updates and monitor emerging needs. None Not reviewed, 

Amended

Recommendation 22

B G 5 Coordinate care with other social service providers or case managers. None Not reviewed, 

Amended

Recommendation 22

B H 1 Prioritize and address other medical and psychiatric co-occurring conditions. None Not reviewed, 

Deleted

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B H 2 Recommend and offer cessation treatment to patients with nicotine dependence. None Not reviewed, 

Deleted

--

B H 3 Treat concurrent psychiatric disorders consistent with VA/DoD clinical practice guidelines (e.g., 

Major Depressive Disorder, Bipolar Disorder, Post Traumatic Stress, Psychoses) including 

concurrent pharmacotherapy.

None Not reviewed, 

Deleted

--

B H 4 Provide or arrange treatment via referral for medical conditions (e.g. management of diabetes, 

chronic heart failure, management of unexplained medical symptoms). (See other VA/DoD 

Clinical Practice Guidelines at: www.healthquality.va.gov)

None Not reviewed, 

Deleted

--

B H 5 Provide multiple services in the most accessible setting to promote engagement and 

coordination of care.

None Not reviewed, 

Deleted

--

B H 6 Monitor and address deferred problems and emerging needs through ongoing treatment plan 

updates.

None Not reviewed, 

Amended

Recommendation 22

B H 7 Coordinate care with other providers. None Not reviewed, 

Amended

Recommendation 22

B I 1 Reassess and document clinical response throughout the course of treatment:

 Daily in the acute inpatient setting, including reevaluation of the continued need for that 

level of care.

 At least weekly in the residential setting, including reevaluation of the continued need for 

that level of care.

 In the outpatient setting:

• Weekly during the first few weeks for a new episode of care

• At least monthly thereafter.

None Reviewed, Newreplaced

Recommendation 23

B J 1 For patients who accomplish their initial goals in early recovery, the treatment team should 

collaborate with the patient to develop a continuing care plan (e.g., aftercare plan) which may 

include:

 Transition to an appropriate alternative specialty care setting (see Annotation L - Aftercare), 

such as PTSD specialty treatment, etc.

 Return to primary care.

None Not reviewed, 

Deleted

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B J 2 For patients who are progressing toward goals, providers should:

 Provide positive feedback and encouragement to remain engaged in specialty SUD care

 Involve patients in identifying the next interim steps toward achieving the goals.

Consider reduced treatment intensity or discontinuing some treatment components based on:

 Accomplishment of treatment goals and objectives

 Full, early remission

 Early problem resolution

 Greater involvement in community support

 Improvements in other associated problem areas.

Coordinate follow-up with the patient's primary medical or behavioral health provider during 

transitions to less intensive levels of care in order to reinforce progress and improve 

monitoring of relapse risks.

None Not reviewed, 

Deleted

--

B K 1 Use the patient’s progress in attaining recovery goals to individualize treatment continuation 

and avoid adopting uniform treatment plans with standardized duration and intensity.

None Reviewed, NewreplacedRecommendation 23

B K 2 Consider patient report of craving and other subjective indications of relapse risk. None Reviewed, NewreplacedRecommendation 23

B K 3 For patients who achieve sustained remission or problem resolution, provide appropriate 

continuity of care and follow-up with providers in the general medical or mental health care 

setting (see Module C).

None Not reviewed, 

Deleted

--

B L 1 Provide continuing care following intensive outpatient or residential rehabilitation (individual, 

group or telephone follow-up).

None Not reviewed, 

Amended

Recommendation 24

B L 2 Consider objective monitoring of substance use and medical consequences. A Reviewed, NewreplacedRecommendation 23

B L 3 Encourage active involvement in community support for recovery (e.g., Alcoholics Anonymous, 

Cocaine Anonymous).

A Reviewed, NewreplacedRecommendation 21
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B L 4 As part of the discharge instructions from the intensive phase, provide the patient a written plan 

to facilitate compliance with aftercare which may include “the basic things I need to do to meet 

my treatment goals,” such as:

 Information on treatment appointments and prescribed medications

 Recognizing relapse warning signs and triggers and appropriate coping responses

 Maintaining contact with recovery support network and identifying mutual help meetings to 

attend.

None Reviewed, 

Deleted

--

B L 5 For DoD Active Duty: Rehabilitation and Referral Services for Alcohol and Drug Abusers, requires 

an individualized aftercare plan designed to identify the continued support of the patient with 

monthly monitoring (minimally) during the first year after inpatient treatment.

None Not reviewed, 

Deleted

--

B M 1 For patients who are not improving, providers should consider either:

 Adding or substituting another medication or psychosocial intervention, or

 Changing treatment intensity by:

• Increasing the intensity of care, or

• Increasing the dose of the medication, or

• Decreasing the intensity to a minimum level of care that is agreeable to the patient

such as monitoring in general health care (see Module C).

None Not reviewed, 

Amended

Recommendation 25

B M 2 If patients drop out of treatment, the treatment team should make efforts to contact the patient 

and re-engage him/her in treatment.

None Not reviewed, 

Deleted

--

C B 1 Assure patient safety and readiness to cooperate with further assessment by referring the 

patient to an emergency department or appropriate acute care setting for stabilization as 

needed.

None Not reviewed, 

deleted

--

C C 1 Patients with suspected, presumed, or identified substance use disorder (SUD) should receive a 

comprehensive assessment to include:

 Medical history, including pertinent medical problems and treatment, surgeries, head 

injuries, present medications and allergies and family history of substance use

 Physical examination including mental status examination (MSE)

 Laboratory evaluation as indicated.

None Not reviewed, 

Deleted

--

C C 2 Comprehensive substance use history, including onset and pattern of progression, past sequelae 

and past treatment episodes (include all substances, e.g., alcohol, illicit drugs, tobacco, caffeine, 

over-the-counter medications, prescription medications, inhalants).

None Not reviewed, 

Deleted

--
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C C 3 Use empathic and non-judgmental (versus confrontational) therapist style, being sensitive to 

gender, cultural, and ethnic differences.

None Not reviewed, 

Deleted

--

C C 4 DoD active duty members involved in an incident in which substance use is suspected to be a 

contributing factor are required to be referred to specialty SUD care for evaluation. Command 

should be contacted to discuss administrative and clinical options if the member refuses to be 

evaluated (see Appendix D).

None Not reviewed, 

Deleted

--

C D 1 Identify and document any co-occurring disorders (CODs) in patients with substance use 

disorders.

 Psychiatric history, including symptoms and their relation to substance use, current and past 

diagnoses, treatments and providers

 Infectious diseases (HIV, Hepatitis C, sexually transmitted disease)

 Nearly all daily nicotine users are nicotine dependent. Identification and treatment of comorbid nicotine dependence may improve recovery rates of other SUDs. For patients using 

nicotine offer and recommend tobacco use cessation treatment. Use the Clinical Practice 

Guideline: Treating Tobacco Use & Dependence: 2008 Update from the U.S. Department of 

Health and Human Services at 

http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf and the

 VA/DoD Clinical Practice Guideline for Management of Tobacco Use

 Medical COD that may be related to or affected by substance use (e.g., diabetes, 

cardiovascular disease, digestive disorders, skin infections, respiratory disorders).

None Not reviewed, 

Amended

Recommendation 22
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Recommendation5

C D 2 Individuals with SUD should be assessed for any significant, unmet psychosocial needs or 

situational stressors. If the patient is not willing to engage in any addictions focused care, 

provide motivational intervention and determine whether treatment for medical and psychiatric 

problems can be effectively and safely provided. Continue to try to engage the patient in 

addictions treatment (see annotation K).

These include but are not limited to:

 Inadequate or no housing

 Financial difficulties, especially if unable to meet basic needs

 Problematic family relationships or situations (including caregiver burden or domestic 

violence)

 Poor social support

 Religious and spiritual problems

 Occupational problems

 Difficulties with activities of daily living or instrumental activities of daily living

 Any other acute or chronic situational stressors.

None Not reviewed, 

Deleted

--

C E 1 Recognize that feedback about laboratory assessments may improve patients’ motivation to 

change and may serve as a baseline to monitor SUD treatment progress.

None Reviewed, NewreplacedRecommendation 23

C E 2 Review the assessment, including diagnosis, past treatment response and the patient’s 

perspective on current problems; co-occurring disorders related to SUD; the patient’s 

motivational level, treatment preferences and short- and long-term goals.

None Not reviewed, 

Deleted

--

C E 3 Present and discuss with the patient appropriate treatment options in a way that motivates 

ongoing cooperation with the provider and supports subsequent decisions about referral or brief 

intervention.

None Not reviewed, 

Deleted

--

C E 4 Present and discuss the treatment options with the patient and significant others. None Not reviewed, 

Deleted

--

C E 5 Determine which treatments could be offered in general healthcare (including primary care), 

based on availability of a provider, severity and chronicity of the SUD, active involvement with 

recovery supports in the community, prior treatment response, and patient’s preference and 

likelihood of adherence.

None Not reviewed, 

Amended

Recommendation 3

C E 6 Involve the patient in prioritizing problems to be addressed in the initial treatment plan, and in 

selecting specific treatment goals, regardless of the level of care selected (See Table C – 1).

None Not reviewed, 

Deleted

--
December 2015 Page 114 of 169 2009 Module1 2009 Section 2009 Number

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C E 7 If the patient is not willing to engage in any addictions focused care, provide motivational 

intervention and determine whether treatment for medical and psychiatric problems can be 

effectively and safely provided. Continue to try to engage the patient in addictions treatment 

(see annotation K).

None Not reviewed, 

Deleted

--

C F 1 Offer referral to specialty SUD care for addiction treatment if the patient:

 May benefit from additional evaluation or motivational interviewing regarding his/her 

substance use and related problems

 Has tried and been unable to change substance use on his/her own or does not respond to 

repeated brief intervention

 Has been diagnosed with substance dependence

 Has previously been treated for an alcohol or other substance use disorder

 Has an AUDIT-C score of > 8.

A Not reviewed, 

Amended

Recommendation 3

C F 2 DoD active duty members involved in an incident in which substance use is suspected to be a 

contributing factor are required to be referred to specialty SUD care for evaluation. Command 

should be contacted to discuss administrative and clinical options if the member refuses to be 

evaluated (see Appendix D).

None Not reviewed, 

Deleted

--

C G 1 Discuss pharmacotherapy options with all patients with opioid and/or alcohol dependence. None Reviewed, NewreplacedRecommendation 5

Recommendation 6

C G 2 Initiate pharmacotherapy if indicated and monitor adherence and treatment response. None Reviewed, NewreplacedRecommendation 5

Recommendation 6
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Recommendation5

C H 1 Provide a brief intervention (counseling) for Unhealthy Alcohol Use , which includes the 

following components: 

 Express concern that the patient is drinking at unhealthy levels known to increase his/her 

risk of alcohol-related health problems

 Provide feedback linking alcohol use and health, including:

• Personalized feedback (i.e., explaining how alcohol use can interact with the 

patient’s medical concerns [e.g., hypertension, depression/anxiety, insomnia,

injury, diabetes, breast cancer risk, interactions with medications]) OR

• General feedback on health risks associated with drinking.

 Advise:

• To abstain (if there are contraindications to drinking) OR

• To drink below recommended limits (specified for the patient by gender, age and

health status)

 Support the patient in choosing a drinking goal, if he/she is ready to make a change.

A Reviewed, 

Deleted

--

C H 2 Provide medical management in the treatment of alcohol use disorder and consider medical 

management for other substance use disorders that includes: 

 Monitoring self-reported use, laboratory markers and consequences

 Use of medication, adherence monitoring, response to treatment and adverse effects

 Education and referral to community support for recovery (e.g., Alcoholics Anonymous).

C Reviewed, NewreplacedRecommendation 13

C H 3 Offer referral to a specialty addictions program when indicated. None Not reviewed, 

Amended

Recommendation 3

C I 1 Referral to psychosocial rehabilitation services should be offered to individuals with identified, 

unmet psychosocial needs, regardless of the population or setting, and regardless of the type of 

pharmacotherapy or psychotherapy being administered.

None Reviewed, 

Deleted

--
December 2015 Page 116 of 169 2009 Module1 2009 Section 2009 Number

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Recommendation5

C I 2 Prioritize and address other coexisting biopsychosocial problems with services targeted to these 

problem areas, rather than increasing intensity of addiction-focused psychosocial treatment 

alone. 

 Address transitional housing needs to facilitate access to treatment and promote a 

supportive recovery environment

 Provide social/vocational/legal services in the most accessible setting to promote 

engagement and coordination of care

 Address deferred problems as part of treatment plan updates and monitor emerging needs

 Coordinate care with other social service providers or case managers.

B Not reviewed, 

Amended

Recommendation 22

C J 1 Prioritize and address co-occurring medical and psychiatric conditions. None Not reviewed, 

Deleted

--

C J 2 Recommend and offer cessation treatment to patients with nicotine dependence. Use the 

Clinical Practice Guideline: Treating Tobacco Use & Dependence: 2008 Update from the U.S. 

Department of Health and Human Services at: 

http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf and the VA/DoD Clinical 

Practice Guideline for Management of Tobacco Use.

None Not reviewed, 

Deleted

--

C J 3 Treat concurrent psychiatric disorders consistent with VA/DoD clinical practice guidelines (e.g., 

Major Depressive Disorder, Post Traumatic Stress, Bipolar Disorder, Psychoses) including 

concurrent pharmacotherapy.

None Not reviewed, 

Deleted

--

C J 4 Provide multiple services in the most accessible setting to promote engagement and 

coordination of care.

None Reviewed, 

Deleted

--

C J 5 Monitor and address deferred problems and emerging needs through ongoing treatment plan 

updates.

None Reviewed, NewreplacedRecommendation 23

C J 6 Coordinate care with other providers. None Not reviewed, 

Amended

Recommendation 22

C K 1 Reassess response to treatment periodically and systematically, using standardized and valid 

instrument(s) whenever possible. Indicators of treatment response include ongoing substance 

use, craving, side effects of medication, emerging symptoms, etc.

None Reviewed, NewreplacedRecommendation 23

C K 2 Consider obtaining biological markers of recent substance use. None Reviewed, NewreplacedRecommendation 23

C K 3 Assess co-occurring medical problems associated with substance use through history, physical 

exam and appropriate laboratory evaluation.

None Not reviewed, 

Amended

Recommendation 22
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Recommendation5

C L 1 Ask the patient about any use, craving, or perceived relapse risk. None Reviewed, NewreplacedRecommendation 23

C L 2 Provide feedback to patient regarding improvement or deterioration in laboratory assessments 

affiliated with substance use.

None Reviewed, NewreplacedRecommendation 23

C L 3 Encourage abstinence or reduced use, consistent with the patient’s motivation and agreement None Not reviewed, 

Deleted

--

C L 4 Convey openness to discuss any future concerns that may arise and encourage the patient to 

discuss them with you.

None Not reviewed, 

Deleted

--

C M 1 Discuss the patient’s current use of alcohol and other drugs and address any potential problem 

areas, such as recent initiation of use, increase in use, and use to cope with stress.

None Not reviewed, 

Deleted

--

C M 2 Inform patient about potential age- and gender-related problems, such as:

 Abusive drinking or other drug use in the young adult

 Alcohol and other drug use during pregnancy

 Medication misuse or heavy drinking in the older adult.

None Not reviewed, 

Deleted

--

C M 3 Convey openness to discuss any future concerns that may arise and encourage the patient to 

discuss them with you.

None Not reviewed, 

Deleted

--

C M 4 Periodically inquire about alcohol and drug use at future visits. None Not reviewed, 

Deleted

--

C N 1 For patients who are not improving a consideration should be given to either:

 Changing to another medication or intervention; or

 Changing treatment intensity by:

• Increasing the intensity of care, or

• Increasing the dose of the medication, or

• Adding a medication.

None Reviewed, NewreplacedRecommendation 23
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Category4

2015 

Recommendation5

C N 2 For patients who do not stabilize and refuse to engage in any type of ongoing care with any 

provider (e.g., medical, psychiatric, or addiction specialty) episodic attention to substance use 

may be accomplished by the following:

 Provide crisis intervention, as needed

 At any contact initiated by the patient:

• Assess current substance use

• Recommend that the patient accept ongoing care in the most appropriate setting

• Designate a single provider to coordinate care for patients who repeatedly present

in crisis

• Consider involving supportive family members or significant others, if the patient

agrees. For DoD active duty members this may include first line supervisor when

appropriate, and will necessarily include the unit commander

• Initiate involuntary treatment procedures, if imminent threat to safety occurs (e.g.,

suicidal, violent, or unable to care for self).

 Continue to reinforce and endorse increased appropriate engagement and adherence.

None Not reviewed, 

deleted

--

C N 3 Consider consultation with mental health or SUD specialty. None Not reviewed, 

Amended

Recommendation 3

P B 1 Assess opioid dependence using DSM-IV-TR criteria. None Not reviewed, 

Deleted

--

P C 1 Provide access to opioid agonist treatment (OAT) for all opioid dependent patients, under 

appropriate medical supervision and with concurrent addiction-focused psychosocial treatment 

as indicated. 

A Reviewed, NewreplacedRecommendation 8

Recommendation 13

P C 2 Strongly recommend methadone or sublingual buprenorphine/naloxone maintenance as first 

line treatments due to their documented efficacy in improving retention and reducing illicit 

opioid use and craving. 

A Reviewed, NewreplacedRecommendation 8

P C 3 Note: In pregnancy, buprenorphine monotherapy is preferred. None Not reviewed, 

Deleted

--

P D 1 Individualize the choice of setting based on patient characteristics and availability of facilities to 

treat patients with opioid agonist therapy (OAT). 

None Reviewed, NewreplacedRecommendation 10
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P D 2 Appropriate psychosocial interventions should be provided as part of the opioid agonist therapy 

(OAT). 

A Reviewed, NewreplacedRecommendation 14

Recommendation 15

Recommendation 16

P E 1 Opioid Agonist Treatment Program (OATP) and office-based opioid treatment (OBOT) must be 

provided in the context of a complete treatment program that includes:

 Appropriate adjustment of opioid agonist doses to maintain a therapeutic range between 

signs/symptoms of overmedication (e.g., somnolence, miosis, itching, hypotension, and 

flushing) and opioid withdrawal (e.g., drug craving, anxiety, dysphoria, and irritability)

• Usual dosage range for optimal effects: 60–120 mg/day

• Buprenorphine target dose is generally up to 16 mg daily; doses above 32 mg are

rarely indicated. In all cases, except pregnancy, the combination product of

buprenorphine/naloxone should be used.

 Relapse monitoring to promote effective outcomes

 Adequate frequency of toxicology for alcohol and other drugs of abuse. Drug testing for both 

methadone and buprenorphine should also be considered to ensure compliance with the 

prescription and for detection of possible diversion

 Appropriate psychosocial interventions. 

A (for 

specific 

portion 

of the 

rec)

Reviewed, NewreplacedRecommendation 13

P F 1 Consider monitored administration of naltrexone maintenance in highly motivated opioid 

dependent patients. See Table P-3.

C Not reviewed, 

Deleted

--

P F 2 Consider opioid agonist treatment (OAT) or long-term therapeutic community before naltrexone 

as first line approaches for chronic opioid dependent patients

None Not reviewed, 

Deleted

--

P G 1 Prior to starting naltrexone, ensure that the patient is opioid-free as naltrexone is an opioid 

antagonist and may precipitate withdrawal.

None Not reviewed, 

Deleted

--

P G 2 Consider pharmacologically assisted withdrawal (See Module S: Stabilization and Withdrawal 

Management, Annotation F), unless the patient successfully completed a naloxone challenge 

and/or has had at least 7-10 days of verified abstinence.

None Not reviewed, 

Deleted

--

P H 1 Provide appropriate dosing, treatment retention- and adherence-enhancing techniques, and 

relapse monitoring to promote effective outcomes.

None Not reviewed, 

Deleted

--

P H 2 Carefully start oral naltrexone at a dose of 25 mg once daily. If no signs of withdrawal occur, the 

dose may be increased to 50 mg daily on the following day. Extended dosing intervals, using 

equivalent weekly doses, may be used for supervised administration (see Table P-4).

None Not reviewed, 

Deleted

--
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P I 1 Identify patients with alcohol dependence that should be considered for addiction-focused 

pharmacotherapy.

None Not reviewed, 

Deleted

--

P J 1 Routinely consider oral naltrexone, an opioid antagonist, and/or acamprosate for patients with 

alcohol dependence. 

Note that in VA, acamprosate is currently a non-formulary medication with criteria for use 

posted at http://vaww.national.cmop.va.gov/PBM/Clinical%20Guidance/Forms/AllItems.aspx

A Reviewed, NewreplacedRecommendation 5

Recommendation 6

P J 2 Medications should be offered in combined with addiction-focused counseling. A Reviewed, NewreplacedRecommendation 5

Recommendation 6

P J 3 Injectable naltrexone should be considered when medication adherence is a significant concern in 

treating alcohol dependence and should be combined with addiction-focused counseling. Note 

that in VA, injectable naltrexone is currently a non-formulary medication with criteria for use 

posted at http://vaww.national.cmop.va.gov/PBM/Clinical%20Guidance/Forms/AllItems.aspx

A Reviewed, NewreplacedRecommendation 5

Recommendation 6

P J 4 If patient does not respond to one of the approved medications, a trial on one of the other 

approved medications is warranted.

None Reviewed, 

Deleted

--

P J 5 Because of the risk of significant toxicity and limited evidence of effectiveness, risk and benefits 

of disulfiram should be considered and disulfiram should only be used when abstinence is the 

goal and when combined with addiction-focused counseling. The informed consent discussion 

with the patient should be documented.

B Reviewed, 

Deleted

--

P J 6 Dosing of these pharmacotherapies should be consistent with medication trials and 

recommendations in appropriate drug references (see Table P-5).

None Reviewed, 

Deleted

--

S B 1 Interview the patient and other collateral informants, where appropriate, about medical and 

mental health history and use of prescription and non-prescription medications before initiating 

extensive diagnostic testing.

None Not reviewed, 

Deleted

--

S B 2 Note any history of recent head trauma. None Not reviewed, 

Deleted

--

S B 3 Order laboratory tests selectively, aiming to detect potential medical causes for the presenting 

symptoms, where indicated by:

 Specific symptoms found on the medical review of systems

 Evidence of unusual symptom profiles

 History of atypical illness course

 Abnormal screen for cognitive status, particularly in the elderly patient.

None Not reviewed, 

Deleted

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Recommendation5

S C 1 Refer patients with problems that require emergency care or urgent action to emergency care 

for further action as needed.

None Not reviewed, 

Deleted

--

S D 1 Assure the patient’s immediate safety and determine the most appropriate setting. None Reviewed, 

Deleted

--

S D 2 Refer for mental health treatment or assure that follow-up appointment is made. None Not reviewed, 

Amended

Recommendation 3

S D 3 Inform and involve someone close to the patient. None Not reviewed, 

Deleted

--

S D 4 Limit access to means of suicide. None Not reviewed, 

Deleted

--

S D 5 Increase contact and make a commitment to help the patient through the crisis. None Not reviewed, 

Deleted

--

S D 6 For comatose patients, maintain airway and adequate ventilation in order to preserve 

respiration and cardiovascular function.

None Not reviewed, 

Deleted

--

S D 7 Emergency procedures should be considered, including the use of gastric lavage for sedative, 

hypnotic, and/or opioid intoxication.

None Not reviewed, 

Deleted

--

S D 8 Emergency pharmacologic interventions should be utilized as appropriate, including the use of 

intravenous naloxone hydrochloride for opioid overdose and flumazenil for benzodiazepine 

overdose.

None Not reviewed, 

Deleted

--

S D 9 Agitation secondary to intoxication from a variety of substances is best initially managed through 

interpersonal approaches and decreasing sensory stimuli rather than additional medications. If 

chemotherapeutic agents are necessary, the short acting IM benzodiazepines (e.g., lorazepam) 

and high potency neuroleptics should be considered

For DoD active duty members: follow DoD and Service-specific policies, as mental 

health/emergency referral is likely mandated.

None Not reviewed, 

Deleted

--
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S E 1 Obtain and document necessary information to classify level of withdrawal and factors that may 

influence the severity of the withdrawal (see Appendix B-6 for a list of withdrawal signs and 

symptoms for the different types of substances):

 Determine type of substance of use

 Determine time since last use

 Determine concurrent use of other substances or prescriptions

 Determine co-occurring medical and/or psychiatric disorders

 Consider past withdrawal experiences.

None Not reviewed, 

Deleted

--

S E 2 Use laboratory results and patient observation to determine the level of tolerance (e.g., high 

blood level in patient who appears to be not intoxicated).

None Not reviewed, 

Deleted

--

S E 3 Use standardized measures to assess the severity of withdrawal symptoms such as CIWA-Ar (see 

Box S-1) or COWS (see Box S-2). 

B Not reviewed, 

Amended

Recommendation 26

S E 4 Evaluate patients using multiple substances (e.g., opioids and sedative-hypnotics) for risk of 

withdrawal from each substance.

None Not reviewed, 

Amended

Recommendation 27

S F 1 Indications for withdrawal management from alcohol or sedative-hypnotics

 Patient with alcohol dependence with observed withdrawal symptoms

 CIWA-Ar score for at least mild withdrawal (>10)

 Patients with dependence on central nervous system depressants, due to the risks of 

untreated withdrawal in severely dependent persons.

None Not reviewed, 

Deleted

--

S F 2 Relative contraindication for medically supervised withdrawal management from alcohol

 Patients with minimal withdrawal symptoms that are not accompanied by complicating cooccurring disorders. Such patients may respond sufficiently to generalized support, 

reassurance, and frequent monitoring.

None Not reviewed, 

Deleted

--

S F 3 Potential indications for medically supervised opioid withdrawal:

 Patient with physical dependence in the absence of clinical indications for ongoing treatment 

(e.g., severe pain disorder)

 Patient with physical dependence accompanied by aberrant or non-adherent behavior (e.g., 

obtaining prescriptions from multiple providers, escalating doses without provider 

consultation, or buying medications on the street)

 Agreement to provide naltrexone for treatment of opioid dependence

 Patient who does not request or want opioid agonist medical therapy but wants nonpharmacologic treatment for opioid dependence.

None Reviewed, 

Deleted

--
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S F 4 Contraindication for opioid withdrawal management:

 Chronic severe opioid dependence. For such patients, first line therapy is methadone or 

sublingual buprenorphine/naloxone maintenance treatment (See Module P - Addiction 

Focused Pharmacotherapy)

 Two or more unsuccessful medically supervised withdrawal episodes within a 12-month 

period. Such patients should be assessed for opioid agonist therapy.

None Reviewed, 

Deleted

--

S F 5 Consider using a structured assessment tool to evaluate and track behaviors suggestive of 

addiction, such as inappropriate medication use, and to increase the provider's confidence in 

determinations of appropriate vs. inappropriate opioid use.

None Reviewed, 

Deleted

--

S F 6 Evaluate opioid dependent patients for severe acute or chronic physical pain that may require 

appropriate short-acting opioid agonist medication in addition to the medication needed to 

prevent opioid withdrawal symptoms (see also VA/DoD Clinical Practice Guideline for 

Management of Chronic Opioid Therapy at: http://www.healthquality.va.gov).

None Reviewed, 

Deleted

--

S G 1 Consider the following indications for inpatient medically supervised withdrawal: 

 Current symptoms of at least mild alcohol withdrawal (e.g., CIWA-Ar score 310)

 History of delirium tremens or withdrawal seizures

 Inability to tolerate oral medication

 Imminent risk of harm to self or others

 Recurrent unsuccessful attempts at ambulatory medically supervised withdrawal

 Reasonable likelihood that the patient will not complete ambulatory medically supervised 

withdrawal (e.g., due to homelessness)

 Active psychosis or severe cognitive impairment

 Chronic liver disease or cardiovascular disease, pregnancy, or lack of medical support system.

C Reviewed, 

Amended

Recommendation 27

Recommendation 28

S H 

(1)

1 Use either of the following two acceptable pharmacotherapy strategies for managing alcohol 

withdrawal symptoms:

 Symptom-triggered therapy where patients are given medication only when signs or 

symptoms of withdrawal appear (e.g., PRN dosing) 

 A predetermined fixed medication dose with gradual tapering over several days may be 

considered for some patients, although it is inferior to symptom-triggered therapy. 

A, B Not reviewed,

Amended

Recommendation 29

S H 

(1)

2 Repeat standardized assessments, such as the CIWA-Ar scale for alcohol withdrawal, to guide 

dosing decisions (e.g., if and when to dose) until stabilized.

None Reviewed, NewreplacedRecommendation 23
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S H 

(1)

3 Consider the following procedures for monitoring ambulatory alcohol withdrawal as safe and 

effective alternatives to inpatient approaches:

 Medical or nursing staff should assess the patient in person, either daily or every other day 

(patient contact may be made by telephone on other days), to include:

• Patient report of any alcohol use the previous day

• Reported medication intake compared to the medication dispensed the previous 

day

• Tremor, restlessness, and previous night’s sleep

• Skin (e.g., color and turgor).

 Urine toxicology or a breathalyzer test of blood alcohol content should be completed.

 If the daily screening is positive for any one of the following, the patient should be medically 

evaluated before initiating or continuing outpatient withdrawal management, or hospital 

admission should be considered:

• Blood sugar≥400 or positive anion gap

• History of recent hematemesis, melena, or other gastrointestinal bleeding disorder

• Bilirubin ≥ 3.0

• Creatinine ≥ 2.0

• Systolic blood pressure ≥ 180 or diastolic blood pressure ≥ 110

• Unstable angina

• Temperature ≥ 101 degrees

• BAC ≥ 0.08 on two outpatient visits.

None Not reviewed, 

Deleted

--

S H 

(1)

4 For inpatient treatment of alcohol withdrawal, use benzodiazepines over non-benzodiazepine 

sedative-hypnotics because of documented efficacy, and a greater margin of safety. 

Benzodiazepines are the drug of choice in this setting, given adequate monitoring, because they 

reduce withdrawal severity, incidence of delirium, and seizures. All benzodiazepines appear to 

be effective, but agents without active metabolites such as lorazepam or oxazepam may be 

preferred in patients with liver impairment. 

A Reviewed, 

Amended

Recommendation 30

S H 

(1)

5 Dose and withdrawal scales should be individualized for each patient. Geriatric patients should 

start with lower doses of benzodiazepines than younger adults. 

A Not reviewed, 

Deleted

--

S H 

(1)

6 For managing mild to moderate alcohol withdrawal, carbamazepine and valproic acid can be 

used as an effective supplement or alternative to benzodiazepines. They may be considered in 

patients that cannot use benzodiazepines (e.g., abuse liability or allergy/adverse reactions). 

B Reviewed, NewreplacedRecommendation 31
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Recommendation5

S H 

(1)

7 Other agents, such as beta-blockers, and clonidine, are generally not considered as appropriate 

monotherapy for alcohol withdrawal, but may be considered in conjunction with 

benzodiazepines in certain patients. 

C Not reviewed, 

Deleted

--

S H 

(1)

8 During and after medically supervised withdrawal, emphasis should be placed on engagement in 

ongoing addiction treatment. 

C Not reviewed, 

Deleted

--

S H 

(1)

9 Use of alcohol as an agent for medically supervised withdrawal is contraindicated. D Not reviewed, 

Amended

Recommendation 32

S H 

(2)

1 Substitute phenobarbital for the addicting agent and taper gradually. 

 The average daily sedative-hypnotic dose is converted to a phenobarbital equivalent and 

divided into 3 doses per day for 2 days (see Appendix E for phenobarbital equivalencies for 

sedative hypnotics).

 Phenobarbital dose should be reduced by 30 mg per day, beginning on day 3.

A Not reviewed, 

Amended

Recommendation 36

S H 

(2)

2 Substitution then tapering: For patients on a shorter acting benzodiazepine, substitute a longer 

acting benzodiazepine at an equivalent dose (e.g., chlordiazepoxide) and taper 10 percent per 

day, over 1 to 2 weeks.

None Not reviewed, 

Amended

Recommendation 36

S H 

(2)

3 Simple tapering: Gradually decrease the dosage of the long-acting substance the patient is 

currently taking.

None Not reviewed, 

Amended

Recommendation 36

S H 

(2)

1 Medically supervised opioid withdrawal is rarely effective as a long-term strategy for treatment 

of opioid dependence because of high relapse rates. Opioid maintenance with 

buprenorphine/naloxone or methadone is the definitive treatment of choice in most cases. 

B Reviewed, NewreplacedRecommendation 33

S H 

(3)

2 If pursuing medically supervised opioid withdrawal, the preferred approaches are initial 

stabilization and subsequent short or extended taper with opioid agonist therapy.

None Reviewed, NewreplacedRecommendation 34

S H 

(3)

3 Set the length of the taper period based on the treatment setting and severity of the 

dependence.

None Not reviewed, 

Deleted

--

S H 

(3)

4 Medically supervised withdrawal can usually be accomplished in 4 to 7 days in an inpatient 

setting, to quickly achieve opioid abstinence prior to treatment in a drug-free setting, preferably 

with initiation of naltrexone.

None Not reviewed, 

Deleted

--
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S H 

(3)

5 Withdrawal using buprenorphine/naloxone:

 Only physicians with a waiver from the US Department of Health and Human Services can 

prescribe buprenorphine/naloxone

 Initial stabilization is accomplished via induction with buprenorphine/naloxone just as it 

would be for maintenance with this agent (See Table S-1). To reduce the risk of precipitated 

withdrawal, the patient must be in sufficient opioid withdrawal to be manifesting objective 

signs of withdrawal prior to starting buprenorphine/naloxone usually at least 8 hours since 

the patient’s last use of heroin or other short-acting opioid or at least 24 and preferably at 

least 48 hours have elapsed since the last use of methadone or other long-acting opioid

 Within 1-3 days, a daily dose of buprenorphine/naloxone should be achieved that eliminates 

signs and symptoms of opioid withdrawal, suppresses opioid craving, and eliminates illicit 

opioid use. This dose could range from 2/0.5 mg per day to 16/4 mg per day and would 

rarely exceed that amount

 Once stabilization has been achieved the dose can be rapidly tapered over 5-7 days. There is 

little evidence that prolonging the taper leads to better results. (If the patient and physician 

prefer a longer taper, there is also no evidence that a longer taper is harmful).

None Not reviewed, 

Deleted

--
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Recommendation5

S H 

(3)

6 Withdrawal using methadone:

 Withdrawal using methadone can only be performed in the context of a federally licensed 

opioid treatment program where daily medication dispensing can occur. For patients not 

engaged in methadone maintenance through an opioid treatment program, withdrawal 

should be managed with buprenorphine

 Initial stabilization is accomplished via induction with methadone just as it would be for 

maintenance with this agent. Withdrawal signs do not have to be observed prior to starting 

methadone, but with methadone there is risk of medication accumulation, toxicity, and 

overdose. Initial dosing should be very conservative with careful daily observation of the 

patient. Initial daily doses can range from 5 mg to a maximum of 30 mg

 Within days to weeks, a daily dose of methadone should be achieved that eliminates signs 

and symptoms of opioid withdrawal, suppresses opioid craving, and eliminates illicit opioid 

use. This dose could range from 30 mg per day to doses as high as 120 mg per day

 Once stabilization has been achieved, the dose can be gradually tapered over a period of 

weeks to months. Dose decreases of more than 5 -10 mg/day of methadone are generally 

poorly tolerated. In contrast to the evidence with buprenorphine/naloxone, with 

methadone, longer taper periods should be used in the outpatient setting to minimize 

patient discomfort and maximize chances of success

A period of two to three weeks is generally sufficient for short-term outpatient medically 

supervised withdrawal in the most stable and motivated individual. The higher the stabilization 

dose, the longer the taper is likely to take. The taper should proceed more gradually as the dose 

becomes lower.

None Not reviewed, 

Deleted

--

S H 

(3)

7 The 180-day stabilization/medically supervised withdrawal regimen should be considered to 

facilitate work on patients’ early recovery problems, while stabilized on sublingual 

buprenorphine or a relatively low dose (50-60 mg/day) of methadone. Stabilization is followed 

by short-term medically supervised withdrawal from buprenorphine or methadone and 

transition to a drug-free rehabilitation program.

None Not reviewed, 

Deleted

--

S H 

(3)

8 Clonidine, an alpha-adrenergic agonist, can be considered as an adjunctive agent for symptom 

relief during inpatient medically supervised opioid withdrawal; however, outpatient success is 

much lower. If using clonidine, adjunctive medications for anxiety, restlessness, insomnia, 

muscle aches, nausea, and diarrhea can also be prescribed.

None Reviewed, NewreplacedRecommendation 35

S I 1 Identify patients in need of additional withdrawal management or stabilization before 

proceeding with further evaluation or treatment

None Not reviewed, 

Deleted

--
December 2015 Page 128 of 169 2009 Module1 2009 Section 2009 Number

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S I 2 Medically supervised withdrawal is successful to the degree that the patient:

 Is physiologically stable

 Avoids hazardous medical consequences of withdrawal

 Experiences minimal discomfort

 Reports being treated with respect

 Completes the medically supervised withdrawal protocol (e.g., no longer requires medication 

for withdrawal symptom management).

None Not reviewed, 

Deleted

-- 

S J 1 If medically supervised withdrawal is unsuccessful, or treatment engagement is not achieved, 

consider one of the following:

 A more intensive level of care for withdrawal management (e.g., inpatient)

 Identify patients who can benefit from implementation of a care management plan, if 

acceptable to the patient (see Module C, Annotation K).

None Not reviewed, 

Deleted

--
December 2015 Page 129 of 169

Appendix F: Participant List

CDR Jennifer Bodart, PsyD

Director, Clinical Health Behavior Program 

Conditioned-Based Specialty Care Section Clinical 

Support Division Defense Health Agency (DHA) 

Falls Church, VA

LCDR Danyell Brenner, BCD, LCSW, MBA

Navy MSC Social Work Assistant Specialty Leader

Department Head, Directorate of Healthcare and Business

Naval Hospital, Guam

Michael O. Chaffman, PharmD, BCPS

National PBM Clinical Pharmacy Program Manager

Veterans Health Administration Pharmacy Benefits 

Management Services

Hines, IL

Corinne K. B. Devlin, MSN, RN, FNP-BC

Chronic Disease Clinical Practice Guideline Coordinator 

U.S. Army Medical Command Quality Management Division, 

Office of Evidence Based Practice

Fort Sam Houston, TX

Karen Drexler, MD (Co-Chair)

Deputy National Mental Health Program Director, 

Addictive Disorders

Mental Health Services, Office of Patient Care 

Services, VA Central Office

Field-based at Atlanta VA Medical Center

Atlanta, GA

Carol Essenmacher, PMHCNS-BC, DNP, C-TTS

Certified Tobacco Treatment Specialist

Tobacco Cessation Coordinator

Battle Creek VA Medical Center

Battle Creek, MI

Francine Goodman, PharmD, BCPS

National PBM Clinical Pharmacy Program Manager

Veterans Health Administration Pharmacy Benefits 

Management Services

Hines, IL

Adam Gordon, MD, MPH, FACP, FASAM

Internal Medicine and Addiction Medicine

University of Pittsburgh

VA Pittsburgh Healthcare System 

Pittsburgh, PA

Marina Khusid, MD, ND, MSA

Chief of Integrative Medicine

Research Directorate

Deployment Health Clinical Center

Defense Centers of Excellence for Psychological 

Health and Traumatic Brain Injury

Silver Spring, MD

Daniel Kivlahan, PhD (Co-Chair)

National Mental Health Program Director, Addictive Disorders

Mental Health Services, Office of Patient Care Services, VA 

Central Office

Field-based at VA Puget Sound Health Care System

Seattle, WA

Timothy Lacy, MD

Tri-Service Work Flow Team BH Lead

Contract Support (EHRTS)

Defense Health Headquarters

Office of the Chief Information Officer

Silver Spring, MD

CDR Marisol Martinez, PharmD

U.S. Public Health Service

Defense Health Agency

Pharmacy Operations Division

Fort Sam Houston, TX

James R. McKay, PhD

Professor of Psychology in Psychiatry

University of Pennsylvania

Director, VA Center of Excellence in Substance Abuse 

Treatment and Education (CESATE)

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, PA

CH (LTC) Robert Miller, DMin, MDiv, MABMH

Training Manager 

Department of Pastoral Ministry Training

U.S. Army Medical Department Center & School 

Fort Sam Houston, TX

LTC Christopher Perry, MD (Co-Chair)

Director of Psychological Health

Camp Casey, Korea

Renee Redden, MSN, PMHCNS, BC

Clinical Nurse Specialist- Opiate Treatment Program/Addiction 

Recovery Unit/Buprenorphine Program

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, PA
December 2015 Page 130 of 169

Marghani (Gina) Reever, PhD, LCSW

Outpatient Substance Abuse Treatment Team

Mental Health Service Line

Jacksonville VA Outpatient Clinic

Jacksonville, FL

Andrew Saxon, MD

Director, Center of Excellence in Substance Abuse Treatment 

and Education (CESATE)

VA Puget Sound Health Care System

Seattle, WA

CDR Robert M. Selvester, MD 

Family Practice

Naval Air Station Corpus Christi

Corpus Christi, TX

Maj Tracy L. Snyder, MS, RD

Director of Operations

348th Recruiting Squadron (Health Professions)

Air Force Recruiting Service 

Clearfield, UT

Christopher Spevak, MD, MPH, JD

Director Prescription Medication Misuse Program

Deputy Director Wounded Warrior and NCRPI

Walter Reed National Military Medical Center

Professor Georgetown University School of Medicine
December 2015 Page 131 of 169

Appendix G: Conflict of Interest Disclosures Based on Financial 

Relationships with Industry

Work Group 

Member Disclosed Conflict of Interest

Andrew Saxon, MD Received royalties from UpToDate; organizations supplied study medications (Alkermes 

provided extended release naltrexone; Reckitt Benckiser provided Suboxone)
December 2015 Page 132 of 169

Appendix H: Literature Review Search Terms and Strategy

A. Topic-specific Search Terms

The search strategies employed combinations of free-text keywords as well as controlled vocabulary terms 

including (but not limited to) the following concepts. Strategies for each bibliographic database follow this 

table.

Table H-1. EMTREE, Medical Subject Headings (MeSH), PsycInfo, and Keywords 

Concept Controlled Vocabulary Keywords 

General Substance Abuse EMBASE (EMTREE)

'substance abuse'/exp 

'inhalant abuse'/exp 

'intravenous drug abuse'/exp 

'multiple drug abuse'/exp 

'drug dependence'/exp 

'withdrawal syndrome'/exp 

addiction/mj 

'drug abuse'/exp 

MEDLINE (MESH)

exp substance-related disorders/ 

exp substance withdrawal syndrome/

exp drug overdose/

substance abuse, intravenous/

PsycINFO

exp drug abuse/ 

exp drug dependency/ 

exp polydrug abuse/ 

addiction/ 

exp drug addiction/ 

drug(s)

substance

polydrug 

AND abuse

addict(s)

addiction(s)

disorder(s)

misuse

user(s)

AUD EMBASE (EMTREE)

'Alcohol abuse'/exp 

'alcohol use disorder'/exp 

alcoholism/exp 

'drinking behavior'/exp 

'alcohol abstinence'/exp 

'alcohol withdrawal'/exp 

MEDLINE (MESH)

exp alcohol-related disorders/

exp alcohol drinking/ 

exp alcoholics/

PsycINFO 

exp alcohol abuse/ 

exp alcoholism/

exp alcohol intoxication/ 

alcohol withdrawal/

alcohol abuse 

alcohol misuse

alcohol intoxication

alcohol addiction 

alcoholics

alcoholism

drunk

drunken
December 2015 Page 133 of 169

Concept Controlled Vocabulary Keywords 

Opioids and Opioid Use 

Disorder

EMBASE (EMTREE)

'opiate addiction'/exp 

'analgesic agent abuse'/exp 

'narcotic dependence'/exp 

('narcotic analgesic agent'/exp 

MEDLINE (MeSH)

exp opioid-related disorders/ 

exp Analgesics, Opioid/

exp narcotics/

PsycINFO

exp opiates/ 

exp analgesic drugs/ 

exp narcotic drugs/

analgesic

codeine

heroin

hydrocodone 

methadone

morphine 

narcotics

opiates 

opioids

oxycodone 

oxycontin

percocet

vicodin 

AND abuse

addict(s)

addiction(s)

disorder(s)

misuse

user(s)

Other Substances 

(cannabis, stimulants, 

hypnotic sedatives)

EMBASE (EMTREE)

'cannabis'/exp

'cannabis addiction'/exp 

'cocaine'/exp

'cocaine dependence'/exp 

'cannabis use'/exp 

'central stimulant agent'/exp 

'amphetamine'/exp 

'methamphetamine'/exp 

'dexamphetamine'/exp 

'hypnotic sedative agent'/exp 

'sedative agent'/exp 

'barbituric acid derivative'/exp 

'benzodiazepine derivative'/exp

MEDLINE (MeSH) 

exp amphetamine-related disorders/ 

exp cocaine-related disorders/ 

exp marijuana abuse/ 

exp opioid-related disorders/ 

exp inhalant abuse/ 

exp phencyclidine abuse/ OR

exp "hypnotics and sedatives"/ 

exp barbiturates/

exp benzodiazepines/

PsycINFO

Exp amphetamine/

exp barbiturates/

exp benzodiazepines/

exp cocaine/

exp crack cocaine/

exp inhalant abuse/

exp sedatives/ 

exp hypnotic drugs/

Adderall 

Ambien

amphetamine(s)

amytal 

Ativan

barbiturate(s)

barbs 

benzodiazepine(s) 

butalbital

cannabis 

cocaine 

dextroamphetami

ne Dexedrine

diethylamide

downers

eszopiclone

Fiorinal 

Halcion

hypnotic(s)

inhalant(s)

ketamine

librium

LSD 

lysergic acid

lunesta

marijuana 

"meth" 

methamphetamin

e 

nembutal

PCP

phencyclidine 

phenobarbital

roofies 

AND abuse

addict(s)

addiction(s)

disorder(s)

misuse

user(s)
December 2015 Page 134 of 169

Concept Controlled Vocabulary Keywords 

exp marijuana/

exp marijuana usage/

roofinol

salvia 

sedative(s)

seconal 

sonata

stimulant(s)

uppers 

Valium 

Xanax 

Zaleplon

Zolpidem

Pharmacologic 

Treatments (General)

EMBASE (EMTREE)

'drug therapy'/exp 

drug therapy/lnk [floating subheading] 

'drug combination'/exp 

'drug combination'/lnk 

'drugs used in the treatment of 

addiction'/exp

'drug administration'/exp

'drug administration'/lnk

'drug comparison'/exp 

'drug comparison'/lnk

MEDLINE (MESH)

exp drug therapy/ 

drug therapy [Floating Subheading]

PsycINFO

exp drug therapy/

medicine(s)

medication(s)

pharmacotherapeutic

pharmacotherapy

pharmacotherapies

Pharmacologic 

Treatments 

(specific drug classes and 

drugs)

EMBASE (EMTREE)

'opiate agonist'/exp 

'opiate receptor affecting agent'/exp

'alpha adrenergic receptor stimulating 

agent'/exp 

'opiate antagonist'/exp 

MEDLINE(MESH)

exp adrenergic agents/ 

exp adrenergic agonists/ 

exp adrenergic antagonists/

exp dopamine agonists/

PsycINFO

exp narcotic antagonists/ 

exp narcotic agonists/ 

exp narcotic antagonists/ 

exp adrenergic receptors/

exp dopamine agonists/

exp serotonin agonists/ 

exp benzodiazepine agonists/

alcophobin 

acamprosate

antabus

Antabuse

anticol

agonist(s)

atomoxetine

baclofen

buprenorphine 

bupropion

buspirone

citalopram

clonidine 

desipramine

dicupral

disulfiram

divalproex

dronabinol

esperal

fluoxetine
December 2015 Page 135 of 169

Concept Controlled Vocabulary Keywords 

fluvoxamine

gabapentin

guanfacine

guanabenz 

imipramine

LAAM 

Levomethadyl acetate 

lofexidine

methadone

modafinil

nalmefene

naloxone 

naltrexone 

narcotic agonist(s) 

narcotic antagonist(s)

nefazodone

odansetron

olanzapine

opiate agonist(s)

opiate antagonist(s)

paroxetine

quetiapine

Revia

sertraline 

tetrahydrocannabinol

teturam

Topamax

topiramate 

Topimax

valproic acid 

varenicline

Psychosocial Treatments EMBASE (EMTREE)

psychotherapy/exp

'cognitive therapy'/exp counseling/exp 

'Acceptance and commitment 

therapy'/exp 'support group'/exp 

'motivational interviewing'/exp 

'alcohol rehabilitation program'/exp 

'alcoholics anonymous'/exp 

'community based rehabilitation'/exp 

MEDLINE (MeSH)

exp psychotherapy/ 

exp psychotherapy, brief/

exp psychology, applied/ 

exp counseling/ 

exp self-help groups/ 

exp group psychotherapy/

"alcohol sbi"

community reinforcement

community help/group/support

contingency management

counseling

cognitive therapy/counseling

couples therapy/counseling

group therapy/counseling

motivational interview(ing)

mutual help/group/support

psychosocial therapy/counseling

psychotherapy

psychotherapies

psychotherapeutic

behavioral therapy/counseling

motivational therapy/counseling

support group
December 2015 Page 136 of 169

Concept Controlled Vocabulary Keywords 

PsycINFO

exp psychotherapy/ 

exp cognitive therapy/ 

exp couples therapy/ 

exp marriage counseling/

exp family therapy/ 

exp psychotherapeutic processes/ 

exp psychotherapeutic techniques/ 

exp Alcoholics anonymous/ 

psychosocial rehabilitation/ 

exp drug rehabilitation/ exp alcohol 

rehabilitation/ exp motivational 

interviewing/ 

twelve step

12-step

brief 

short 

concise 

abrupt 

time limited

AND advice 

advisory

counsel(ing)

intervention(s)

motivate

motivational

psychotherapy

psychotherapies

psychotherapeutic 

therapy 

therapies 

treatment*

Settings and Treatment 

Intensity

EMBASE (EMTREE)

'alcohol rehabilitation program'/exp 

'rehabilitation'/de 'secondary health 

care'/exp 'health care facility'/de 

'community mental health center'/exp 

'health center'/exp 

'mental health center'/exp

'rehabilitation center'/exp

'residential home'/exp 

'secondary care center'/exp 

'tertiary care center'/exp

'patient referral'/exp 

'primary health care'/exp

'general practitioner'/exp 

MEDLINE (MeSH)

exp Substance Abuse Treatment Centers/

health facilities/ 

exp community health centers/ 

exp community mental health centers/ 

exp outpatient clinics, hospital/ 

exp secondary care centers/ 

exp tertiary care centers/

exp residential facilities/

exp primary health care/ 

exp "Referral and Consultation"/ 

exp "delivery of healthcare"/

PsycINFO

exp Community Mental Health Services/ 

exp Mental Health Services/ 

exp Health Care Services/

exp Treatment Facilities/

ambulatory

center(s)

clinic* 

facility

facilities 

family physician(s)

family practice(s)/practitioner(s)

general practice(s)/practitioner(s)

health center(s)

health centre(s)

inpatient

office

outpatient

primary care 

primary health 

refer 

referral 

referred

rehab*

"secondary care"

setting

specialist(s)

specialty 

"tertiary care"

treatment/care setting(s)* 
December 2015 Page 137 of 169

Concept Controlled Vocabulary Keywords 

exp Psychiatric Hospitals/ 

exp Community Mental Health Centers/

exp clinics/ 

exp psychiatric clinics/

exp walk in clinics/ 

exp Therapeutic Environment/

health care services/

exp "continuum of care"/

exp long term care/ 

exp mental health services/

exp primary health care/

exp mental health programs/ 

exp rehabilitation/ 

exp general practitioners/

Patient selection/criteria EMBASE(EMTREE)

'patient selection'/exp

'disease management'/exp

'practice guideline'/exp 

'patient care planning'/exp

MEDLINE (MeSH)

Exp patient selection/ 

exp disease management/ 

exp Guideline Adherence/ 

exp Guideline/ 

exp Practice Guideline/

PsycINFO

exp Treatment Guidelines/

exp Evaluation Criteria/ 

exp client characteristics/

patient criteria 

patient characteristics

patient selection

Intensity of Care aggressive

intense 

intensive 

intensity

level of care

Levels of care

long term

short term

Measurement Based 

Care

EMBASE (EMTREE)

'self report'/exp

'psychological rating scale'/exp 

'questionnaire'/exp

'biological marker'/exp

parameters/de

'patient monitoring'/de 

'named inventories, questionnaires and 

rating scales'/exp

'self monitoring'/exp

'Patient Health Questionnaire'/exp

"addiction severity index"

assessment

assess

biomarker(s)

brief addiction monitor

continuous assessment 

continuous monitoring

biological measure(s)

instrument(s)

index
December 2015 Page 138 of 169

Concept Controlled Vocabulary Keywords 

MEDLINE (MeSH)

exp self report/ 

exp questionnaires/ 

exp biological markers/

exp monitoring, physiologic/ 

exp psychiatric status rating scales/

exp psychological tests/

exp psychometrics/ 

exp health status indicators/ 

exp "severity of illness index"/ 

PsycINFO

exp measurement/ 

exp test scores/ 

exp testing methods/ 

exp monitoring/

Measurement based care

measure(s)

monitor(s)

patient health questionnaire

PHQ

questionnaire(s)

scale(s)

B. Search Strategies

Table H-2. MEDLINE/PSYCINFO (presented in OVID syntax) 

Set 

Number Concept Search Statement

1 AUD exp Alcohol-Related Disorders/ OR exp Alcohol Drinking/ OR exp 

Alcoholics/exp OR alcohol abuse/ OR exp alcoholism/ OR exp alcohol 

intoxication/ OR alcohol withdrawal/ OR alcoholism.ti,ab. OR (alcohol AND 

(abuse OR misuse OR intoxicat* OR addict*)).ti,ab. OR alcoholics.ti,ab. OR 

drunk.ti,ab. OR drunken.ti,ab.

2 OUD exp opioid-related disorders/ OR ((exp substance-related disorders/ OR exp 

substance withdrawal syndrome/ OR exp drug abuse/ or exp drug 

dependency/ or exp polydrug abuse/ or addiction/ or exp drug addiction/ OR 

exp drug withdrawal/) AND (exp Analgesics, Opioid/ OR exp opiates/ OR exp 

analgesic drugs/ OR exp narcotics/ OR exp analgesics, opioid/OR exp narcotic 

drugs/)) OR ((opiate* OR opiod* OR narcotic* OR hydrocodone OR vicodin OR 

oxycodone OR oxycontin OR percocet OR heroin OR methadone OR morphine 

OR codeine OR analgesic*) AND (abuse OR addict* OR withdrawal OR 

disorder*)).ti,ab.

3 Cannabis, cocaine, and 

stimulant use disorder

exp marijuana abuse/ OR exp amphetamine-related disorders/ OR exp 

Cocaine-Related Disorders/ OR ((exp substance-related disorders/ OR exp 

substance withdrawal syndrome/ OR exp drug abuse/ or exp drug 

dependency/ or exp polydrug abuse/ or addiction/ or exp drug addiction/ OR 

exp drug withdrawal/) AND (exp Cannabis/ OR exp Amphetamine/ OR exp 

Cocaine/ or exp Crack Cocaine/ OR exp Marijuana/ OR exp marijuana usage/ 

exp OR Central Nervous System Stimulants/ OR exp CNS Stimulating Drugs/))

OR

((amphetamine* OR cocaine OR methamphetamine OR dextroamphetamine 

OR Dexedrine OR Adderall OR marijuana OR cannabis OR stimulant* OR 

"meth") ADJ3 (abuse OR misuse OR addict* OR disorder* OR user OR 

users)).ti,ab.
December 2015 Page 139 of 169

Set 

Number Concept Search Statement

4 Sedative hypnotic use 

disorder

(exp "Hypnotics and Sedatives"/ OR exp sedatives/ OR exp hypnotic drugs/ OR 

exp Barbiturates/ OR exp Benzodiazepines/) AND (*substance related 

disorders/ OR substance abuse, intravenous/ or exp substance withdrawal 

syndrome/ OR exp drug abuse/ or exp drug dependency/ or exp addiction/ or 

exp drug addiction/)

OR

((Hypnotic* OR sedative* OR Benzodiazepine* OR barbiturate* OR 

Barbiturates OR Butalbital OR Firoina OR Amytal OR Nembutal OR Seconal OR 

uppers OR Phenobarbital OR barbs OR Ativan OR Halcion OR Librium OR 

Valium OR Xanax OR downers OR Ambien OR zolpidem OR Sonata OR 

zaleplon OR Lunesta OR eszopiclone OR roofies OR roofinol) ADJ3 (abuse OR 

misuse OR addict* OR disorder* OR user OR users)).ti,ab.

5 General substance 

abuse terms

*substance related disorders/ or exp drug overdose/ or substance abuse, 

intravenous/ or exp substance withdrawal syndrome/ OR exp inhalant abuse/ 

OR exp drug abuse/ or exp alcohol abuse/ or exp drug dependency/ or exp 

polydrug abuse/ or exp addiction/ or exp drug abstinence/ or exp drug 

addiction/

OR 

((substance OR substances OR drug OR drugs OR polydrug*) ADJ3 (abuse OR 

misuse OR addict* OR disorder* OR user OR users)).ti,ab.

6 Pharmacotherapy 

(broad terms)

Exp drug therapy/ OR dt.fs. OR pharmacotherap*.ti. OR medicine*.ti. OR 

medication*.ti. 

7 Pharmacotherapy (drug 

terms-alcohol use)

acamprosate OR disulfiram OR naltrexone OR atomoxetine OR baclofen OR 

buspirone OR citalopram OR desipramine OR fluoxetine OR fluvoxamine OR 

gabapentin OR imipramine OR nalmefene OR olanzapine OR ondansetron OR 

paroxetine OR quetiapine OR sertraline OR topiramate OR valproic acid OR 

varenicline

8 Pharmacotherapy (drug 

terms-opioid use)

exp adrenergic agents/ or exp adrenergic agonists/ or exp adrenergic 

antagonists/OR exp Narcotic Antagonists/ OR exp narcotic agonists/ OR exp 

narcotic antagonists/ OR exp adrenergic receptors/ OR buprenorphine OR 

naloxone OR methadone OR naltrexone OR revia OR "LAAM" OR 

'levomethadyl acetate' OR clonidine OR lofexidine OR guanfacine OR 

guanabenz OR (alpha ADJ3 adrenergic) OR ((narcotic* OR opiate OR opioid) 

AND (agonist* OR antagonist*))

9 Pharmacotherapy (drug 

termscannabis/stimulant/coca

ine use)

Bupropion OR divalproex OR nefazodone OR tetrahydrocannabinol OR 

lofexidine OR dronabinol OR modafinil OR baclofen OR exp adrenergic 

agonists/ OR exp narcotic agonists/ OR exp Dopamine Agonists/ or exp 

Serotonin Agonists/ or exp Benzodiazepine Agonists/ or exp Narcotic 

Agonists/OR Exp disulfiram/ OR disulfiram OR esperal OR dicupral OR disulfide 

OR alcophobin OR anticol OR Antabuse OR antabus OR teturam OR 

Topiramate OR topamax OR topimax OR agonist OR agonists

10 Psychosocial Therapies exp psychotherapy/ OR exp psychology, applied/ OR exp Counseling/ OR exp 

self-help groups/ OR exp group psychotherapy/

OR

exp psychotherapy/ or exp cognitive therapy/ or exp couples therapy/ or exp 

marriage counseling/ or exp family therapy/ OR exp psychotherapeutic 

processes/ or exp psychotherapeutic techniques/ exp OR Alcoholics 

anonymous/ OR psychosocial rehabilitation/ or exp drug rehabilitation/ OR 

exp alcohol rehabilitation/ OR exp motivational interviewing/ 

OR

psychotherap*.ti,ab. OR counseling OR ((cognitive OR behavioral OR 

motivational OR couples OR family OR group OR psychosocial) AND 
December 2015 Page 140 of 169

Set 

Number Concept Search Statement

(counseling OR therapy)).ti,ab. OR "community reinforcement" OR 

"contingency management" OR (motivation* ADJ2 interview*) OR (twelve 

ADJ1 step) OR "alcoholics anonymous" OR "narcotics anonymous" OR "self 

help" OR ((mutual OR community) ADJ1 (help OR group* OR support)).ti,ab. 

OR (support ADJ1 group*).ti,ab. OR "12-step"

11 Brief interventions for 

alcohol use

exp Psychotherapy, Brief/ OR (brief OR short OR concise OR abrupt OR 'time 

limited') AND (psychotherapy* OR intervention* OR therapy OR therapies OR 

counsel* OR treatment* OR advice OR advisory OR motivate OR motivational) 

OR "alcohol sbi"

12 Treatment settings exp Substance Abuse Treatment Centers/OR health facilities/ or exp 

community health centers/ or exp community mental health centers/ or exp 

outpatient clinics, hospital/ or exp secondary care centers/ or exp tertiary 

care centers/ or exp residential facilities/ OR exp primary health care/ or exp 

"Referral and Consultation"/ OR exp "delivery of healthcare"/

OR

exp Community Mental Health Services/ or exp Mental Health Services/ or 

exp Health Care Services/ or exp Treatment Facilities/ or exp Psychiatric 

Hospitals/ or exp Community Mental Health Centers/OR exp clinics/ or exp 

psychiatric clinics/ or exp walk in clinics/ OR exp Therapeutic Environment/OR 

health care services/ or exp "continuum of care"/ or exp long term care/ or 

exp mental health services/ or exp primary health care/ or exp mental health 

programs/ or exp rehabilitation/ OR exp general practitioners/

OR 

("primary care" or "primary health" or (family ADJ1 physician*) or (general 

ADJ1 practi*) or (family ADJ1 practi*) or outpatient* or clinic* or ambulatory 

or (health ADJ1 center*) or (health ADJ1 centre*) or office OR specialist* OR

specialty OR rehab* OR inpatient OR "secondary care" OR "tertiary care" OR 

refer OR referral OR referred OR ((setting* OR facility OR facilities OR center 

OF centers) ADJ3 (treatment OR care OR therapy OR therapies))).ti,ab.

13 Patient selection criteria Exp patient selection/ OR exp disease management/ OR exp Guideline 

Adherence/ or exp Guideline/ or exp Practice Guideline/ OR exp Treatment 

Guidelines/OR exp Evaluation Criteria/ OR exp client characteristics/ OR 

((patient ADJ4 (criteria OR characteristic* OR selection)) OR (settin* ADJ3 

(treatment OR care OR therapy OR therapies))).ti,ab.

14 Care Intensity (('short term' OR 'long term' OR intense OR intensive OR intensity OR 

aggressive) ADJ3 (care OR treatment OR therapy OR therapies) OR 'level of 

care' OR 'levels of care').ti,ab.

15 Measurement based 

care

Exp *Self Report/ OR exp *Questionnaires/ OR exp *Biological Markers/ OR 

exp*Monitoring, Physiologic/ OR exp *Psychiatric Status Rating Scales OR exp 

*psychological tests/ or exp *psychometrics/ OR exp *health status

indicators/ or exp *"severity of illness index"/ OR exp *measurement/ or exp 

*test scores/ or exp *testing methods/ OR exp*monitoring/

"Measurement based care" OR "addiction severity index" OR "brief addiction 

monitor" OR (measurement ADJ2 care) OR questionnaire*:ti OR scale:ti OR 

scales:ti OR instrument*:ti OR index:ti OR measure*:ti OR monitor*:ti OR 

assessment:ti OR assess:ti OR biomarker*ti OR "PHQ":ti,ab OR "patient health 

questionnaire" OR (continuous ADJ2 (monitor* OR assessment*)) OR

(biological ADJ2 measure*)

16 Combine sets KQ 1 1 AND (6 OR 7)
December 2015 Page 141 of 169

Set 

Number Concept Search Statement

17 Combine sets KQ 2 

(overlaps with KQ 3)

2 AND (6 OR 8)

18 Combine sets KQ 3 

(overlaps with KQ 2)

2 AND 10

19 Combine sets KQ 4 1 AND 11

20 Combine sets KQ 5 1 AND 12 AND (13 OR 14)

21 Combine sets KQ 6 and 

7, and psychosocial 

components of KQs 9 

and 10

(1 OR 2 OR 3 OR 4 OR 5) AND 10

22 Combine sets KQ 8 (1 OR 2 OR 3 OR 4 OR 5) AND 15

23 Combine sets KQs 9, 10, 

and 11; 

3 AND (6 OR 9)

24 For all searches - remove 

unwanted publication 

types/Apply limits

NOT (("column/opinion" OR "comment/reply" OR dissertation OR editorial OR 

letter OR book).dt. OR book.pt.) OR (letter/ or editorial/ or news/ or 

comment/ or case report or case reports/ or note/ or conference paper/) or 

(letter or editorial or news or comment or case reports or conference 

abstract$).pt.

Py:2007-2014; humans; English language

25 For all searches - Limit to 

RCTs or SRs/MetaAnalyses

AND (Randomized controlled trials or random allocation or double-blind 

method or single-blind method or placebos or cross-over studies).de. or 

placebo$.mp. or random$.ti. or crossover$.mp. or cross over.mp. or ((singl* 

or doubl* or tripl* or trebl*) and (blind* or mask* or sham*)).mp. or latin 

square.mp. or ISRTCN or ACTRN* or (NCT* not NCT) or (clinical trials/ and 

random*.ti.) 

OR (

meta analysis/ or (systematic review or meta analysis).md. or (meta-analysis 

or systematic review).ti.

OVID syntax:

$ or * = truncation character (wildcard)

ADJn = search terms within a specified number (n) of words from each other in any order

/ = search as a subject heading (note that terms preceded by an asterisk are searched as a major 

subject headings)

exp = “explodes” controlled vocabulary term (e.g., expands search to all more specific related terms 

in the vocabulary’s hierarchy)

.de. = limit controlled vocabulary heading

.fs. = floating subheading

.hw. = limit to heading word

.md. = type of methodology (PsycINFO)

.mp. = combined search fields (default if no fields are specified)

.pt. = publication type 

.ti. = limit to title 

.tw. = limit to title and abstract fields 
December 2015 Page 142 of 169

Table H-3. Embase 

Set 

Number Concept Search Statement

1 AUD 'Alcohol abuse'/exp OR 'alcohol use disorder'/exp OR alcoholism/exp OR 

'drinking behavior'/exp OR 'alcohol abstinence'/exp OR 'alcohol 

withdrawal'/exp OR alcoholism:ti,ab OR (alcohol near/3 (abuse OR misuse 

OR intoxicat* OR addict*)):ti,ab OR alcoholics:ti,ab OR drunk:ti,ab OR 

drunken:ti,ab

2 OUD 'opiate addiction'/exp OR 'analgesic agent abuse'/exp OR (('drug abuse'/exp 

OR 'drug dependence'/exp OR 'narcotic dependence'/exp OR 

'addiction'/exp) AND ('narcotic analgesic agent'/exp OR opiate* OR opioid* 

OR narcotic* OR hydrocodone OR vicodin OR oxycodone OR oxycontin OR 

percocet OR heroin OR methadone OR morphine OR codeine OR 

analgesic*))

3 Cannabis, cocaine, and 

stimulant use disorder

'cannabis addiction'/exp OR 'cocaine dependence'/exp OR (('drug 

abuse'/exp OR 'drug dependence'/exp OR 'addiction'/exp ) AND 

('cannabis'/exp OR 'cannabis use'/exp OR 'central stimulant agent'/exp OR 

'amphetamine'/exp OR 'methamphetamine'/exp OR 'dexamphetamine'/exp 

OR 'cocaine'/exp))

OR

((amphetamine* OR cocaine OR methamphetamine OR dextroamphetamine 

OR dexamphetamine OR Dexedrine OR Adderall OR marijuana OR cannabis 

OR stimulant* OR "meth") NEAR/3 (abuse OR misuse OR addict* OR 

disorder* OR user OR users)):ti,ab

4 Sedative hypnotic use 

disorder

('hypnotic sedative agent'/exp OR 'sedative agent'/exp OR 'barbituric acid 

derivative'/exp OR 'benzodiazepine derivative'/exp) AND ('substance 

abuse'/exp OR 'drug dependence'/exp OR 'withdrawal syndrome'/exp OR 

addiction/mj) 

OR

((Hypnotic* OR sedative* OR Benzodiazepine* OR barbiturate* OR 

Barbiturates OR Butalbital OR Firoina OR Amytal OR Nembutal OR Seconal 

OR uppers OR Phenobarbital OR barbs OR Ativan OR Halcion OR Librium OR 

Valium OR Xanax OR downers OR Ambien OR zolpidem OR Sonata OR 

zaleplon OR Lunesta OR eszopiclone OR roofies OR roofinol) NEAR/3 (abuse 

OR misuse OR addict* OR disorder* OR user OR users)):ti,ab

5 General substance abuse 

terms

'substance abuse'/exp OR 'inhalant abuse'/exp OR 'intravenous drug 

abuse'/exp OR 'multiple drug abuse'/exp OR 'drug dependence'/exp OR 

'withdrawal syndrome'/exp OR addiction/mj OR ((substance OR substances 

OR drug OR drugs OR polydrug*) NEAR/3 (abuse OR misuse OR addict* OR 

disorder* OR users)):ti,ab

6 Pharmacotherapy (broad 

terms)

'drug therapy'/exp OR drug therapy/lnk OR 'drug combination'/exp OR 'drug 

combination'/lnk OR 'drugs used in the treatment of addiction'/exp OR 'drug 

administration'/exp OR 'drug administration'/lnk OR 'drug comparison'/exp 

OR 'drug comparison'/lnk
December 2015 Page 143 of 169

Set 

Number Concept Search Statement

7 Pharmacotherapy (drug 

terms-alcohol use)

acamprosate OR disulfiram OR naltrexone OR atomoxetine OR baclofen OR 

buspirone OR citalopram OR desipramine OR fluoxetine OR fluvoxamine OR 

gabapentin OR imipramine OR nalmefene OR olanzapine OR ondansetron 

OR paroxetine OR quetiapine OR sertraline OR topiramate OR valproic acid 

OR varenicline

8 Pharmacotherapy (drug 

terms-opioid use)

'opiate agonist'/exp OR 'opiate receptor affecting agent'/exp OR 'alpha 

adrenergic receptor stimulating agent'/exp OR 'opiate antagonist'/exp OR 

buprenorphine OR naloxone OR methadone OR naltrexone OR "LAAM" OR 

'levomethadyl acetate' OR clonidine OR lofexidine OR guanfacine OR 

guanabenz OR (alpha near/3 adrenergic)

9 Pharmacotherapy (drug 

termscannabis/stimulant/cocain

e use)

'disulfiram'/exp OR 'topiramate'/exp OR disulfiram OR esperal OR dicupral 

OR disulfide OR alcophobin OR anticol OR Antabuse OR antabus OR teturam 

OR topiramate OR topamax OR topimax OR Bupropion OR Divalproex OR 

Nefazodone OR Tetrahydrocannabinol OR Lofexidine OR Dronabinol OR 

Modafinil OR 'opiate agonist'/exp OR 'opiate antagonist'/exp OR agonist/exp 

OR Baclofen OR agonist

10 Psychosocial Therapies Psychotherapy/exp OR 'cognitive therapy'/exp OR counseling/exp OR 

'Acceptance and commitment therapy'/exp OR 'support group'/exp OR 

'motivational interviewing'/exp OR 'alcohol rehabilitation program'/exp OR 

'alcoholics anonymous'/exp OR 'community based rehabilitation'/exp OR 

counsel OR counseling OR psychotherap*:ti,ab OR counseling:ti,ab OR 

((cognitive OR behavioral OR motivational OR couples OR family OR group 

OR psychosocial) near/2 (counseling OR therapy)):ti,ab OR 'community 

reinforcement' OR 'contingency management' OR (motivation* near/2 

interview*) OR (twelve NEXT/1 step) OR "alcoholics anonymous" OR 

"narcotics anonymous" OR "self help" OR ((mutual OR community) NEAR/1 

(help OR group* OR support)):ti,ab OR (support NEAR/1 group*):ti,ab OR 

"12-step"

11 Brief interventions for 

alcohol use

'Short course therapy'/exp OR 'motivational interviewing'/exp OR (brief OR 

short OR concise OR abrupt OR 'time limited') near/4 (intervention* OR 

therapy OR therapies OR counsel* OR treatment* OR advice OR advisory OR 

motivate OR motivational) OR "alcohol sbi"

12 Treatment settings 'alcohol rehabilitation program'/exp 'rehabilitation'/de OR 'secondary health 

care'/exp OR 'health care facility'/de OR 'community mental health 

center'/exp OR 'health center'/exp OR 'mental health center'/exp OR 

'rehabilitation center'/exp OR 'residential home'/exp OR 'secondary care 

center'/exp OR 'tertiary care center'/exp OR 'patient referral'/exp OR 

'primary health care'/exp OR 'general practitioner'/exp 

OR

'primary care' or 'primary health' or (family NEXT/1 physician*) or (general 

NEXT/1 practi*) or (family NEXT/1 practi*) or outpatient* or clinic* or 

ambulatory or (health NEXT/1 center*) or (health NEXT/1 centre*) or office 

OR specialist* OR specialty OR rehab* OR inpatient OR 'secondary care' OR 

'tertiary care' OR refer OR referral OR referred OR ((setting* OR facility OR 

facilities OR center OR centers) NEAR/3 (treatment OR care OR therapy OR 

therapies)):ti,ab 

13 Patient selection criteria 'patient selection'/exp OR 'disease management'/exp OR 'practice 

guideline'/exp OR 'patient care planning'/exp OR ((patient NEAR/4 (criteria 

OR characteristic* OR selection)):ti,ab OR (settin* NEAR/3 (treatment OR 

care OR therapy OR therapies):ti,ab
December 2015 Page 144 of 169

Set 

Number Concept Search Statement

14 Care Intensity (('short term' OR 'long term' OR intense OR intensive OR intensity OR 

aggressive) NEAR/3 (care OR treatment OR therapy OR therapies)) OR 'level 

of care' OR 'levels of care'

15 Measurement based care "Measurement based care" OR 'self report'/exp/mj OR 'psychological rating 

scale'/exp/mj OR 'questionnaire'/exp/mj OR 'biological marker'/exp/mj OR 

parameters/de OR 'patient monitoring'/de OR 'named inventories, 

questionnaires and rating scales'/exp/mj OR 'self monitoring'/exp/mj OR 

'Patient Health Questionnaire'/exp/mj OR "addiction severity index" OR 

"brief addiction monitor" OR (measurement NEXT/2 care) OR 

questionnaire*:ti OR scale:ti OR scales:ti OR instrument*:ti OR index:ti OR 

measure*:ti OR monitor*:ti OR assessment:ti OR assess:ti OR biomarker*ti 

OR "PHQ":ti,ab OR "patient health questionnaire" OR (continuous NEAR/2 

(monitor* OR assessment*)) OR (biological NEAR/2 measure*)

16 Combine sets KQ 1 1 AND (6 OR 7)

17 Combine sets KQ 2 

(overlaps with KQ 3)

2 AND (6 OR 8)

18 Combine sets KQ 3 

(overlaps with KQ 2)

2 AND 10

19 Combine sets KQ 4 1 AND 11

20 Combine sets KQ 5 1 AND 12 AND (13 OR 14)

21 Combine sets KQ 6 and 7, 

and psychosocial 

components of KQs 9 and 

10

(1 OR 2 OR 3 OR 4 OR 5) AND 10

22 Combine sets KQ 8 (1 OR 2 OR 3 OR 4 OR 5) AND 15

23 Combine sets KQs 9, 10, 

and 11; 

3 AND (6 OR 9)

24 For all searches - remove 

unwanted publication 

types/Apply limits

NOT ('conference paper'/exp OR 'case study'/exp ('case report' OR book OR 

editorial OR erratum OR letter OR note OR 'short survey')/de OR (book OR 

conference OR editorial OR erratum OR letter OR note OR 'short survey'):it 

OR (book OR 'conference proceeding'):pt)

Limits: Py:2007-2015; humans; English language

25 For all searches - Limit to 

RCTs or Systmatic 

Reviews/Meta-Analyses

AND ('randomized controlled trial'/exp OR 'randomization'/de OR 'double 

blind procedure'/de OR 'single blind procedure'/de OR 'placebo'/de OR 

'crossover procedure'/de OR placebo* OR random*:de,ti OR crossover* OR 

'cross over' OR (singl* OR doubl* OR tripl* OR trebl* AND (blind* OR mask* 

OR sham*)) OR 'latin square' OR isrtcn* OR actrn* OR (nct* NOT nct))

OR

'meta analysis'/de OR 'systematic review'/de OR 'meta analysis':ab,ti OR 

'systematic review':ab,ti

EMBASE.com Syntax:

* = truncation character (wildcard)

NEAR/n = search terms within a specified number (n) of words from each other in any order

NEXT/n = search terms within a specified number (n) of words from each other in the order specified

/ = search as a subject heading
December 2015 Page 145 of 169

exp = “explodes” controlled vocabulary term (e.g., expands search to all more specific related 

terms in the vocabulary’s hierarchy)

mj = denotes a term that has been searched as a major subject heading

:de = search in the descriptors field (controlled terms and keywords)

:lnk = floating subheading

:it,pt. = source item or publication type 

:ti. = limit to title 

:ti,ab. = limit to title and abstract fields

Table H-4. PUBMED (PreMEDLINE) 

Set 

Number Concept Search Statement

1 AUD "Alcohol-Related Disorders"[Mesh] OR alcoholism[tiab] OR 

alcoholics[tiab] OR drunk[tiab] OR drunken[tiab] OR (alcohol[tiab] AND 

(abuse[tiab] OR misuse[tiab] OR intoxicat*[tiab] OR addict*[tiab] OR 

disorder*[tiab] OR dependence[tiab] OR dependent[tiab]))

2 OUD "Opioid-Related Disorders"[Mesh] OR ((opioid*[tiab] OR narcotic*[tiab] 

OR hydrocodone[tiab] OR vicodin[tiab] OR oxycodone[tiab] OR 

oxycontin[tiab] OR Percocet[tiab] OR heroin[tiab] OR methadone[tiab] 

OR morphine[tiab] OR codeine[tiab] OR analgesic[tiab]) AND 

(abuse[tiab] OR misuse[tiab] OR intoxicat*[tiab] OR addict*[tiab] OR 

disorder*[tiab] OR dependence[tiab] OR dependent[tiab])) 

3 Cannabis, cocaine, and 

stimulant use disorder

"Amphetamine-Related Disorders"[Mesh] OR "Cocaine-Related 

Disorders"[Mesh] OR "Marijuana Abuse"[Mesh] OR ("Central Nervous 

System Stimulants"[majr] AND "Substance-Related Disorders"[majr]) OR 

((amphetamine*[ti] OR cocaine[ti] OR methamphetamine[ti] OR 

dextroamphetamine[ti] OR Dexedrine[ti] OR Adderall[ti] OR 

marijuana[ti] OR cannabis[ti] OR stimulant*[ti] OR "meth"[ti]) AND 

(abuse[ti]OR misuse[ti] OR addict*[ti] OR disorder*[ti] OR user[ti] OR 

users[ti]))

4 Sedative hypnotic use disorder ("Hypnotics and Sedatives"[Mesh] OR "Barbiturates"[Mesh] OR 

"Benzodiazepines"[Mesh] ) AND ("Substance Abuse, 

Intravenous"[Mesh] OR "Substance Withdrawal Syndrome"[Mesh] OR 

"Substance-Related Disorders"[Mesh]) 

OR

((Hypnotic* OR sedative* OR Benzodiazepine* OR barbiturate*[tiab] OR 

Barbiturates[tiab] OR Butalbital[tiab] OR Firoina OR Amytal OR 

Nembutal OR Seconal OR uppers OR Phenobarbital OR barbs OR Ativan 

OR Halcion OR Librium OR Valium OR Xanax OR downers OR Ambien OR 

zolpidem OR Sonata OR zaleplon OR Lunesta OR eszopiclone OR roofies 

OR roofinol) AND (abuse[tiab] OR misuse[tiab] OR addict*[tiab] OR 

disorder*[ti] OR users[ti]))
December 2015 Page 146 of 169

Set 

Number Concept Search Statement

5 General substance abuse terms "Inhalant Abuse"[Mesh] OR "Substance Abuse, Intravenous"[Mesh] OR 

"Substance Withdrawal Syndrome"[Mesh] OR "Substance-Related 

Disorders"[Mesh] OR ((alcohol[ti] OR substance[ti] OR substances[ti] OR 

drug[ti] OR drugs[ti]) AND (abuse[tiab] OR misuse[tiab] OR addict*[tiab] 

OR disorder*[ti] OR users[ti]))

6 Pharmacotherapy (broad 

terms)

"Drug Therapy"[Mesh] OR "drug therapy" [Subheading] OR 

pharmacotherap* OR ((drug[ti] OR drugs[ti] OR medication*[ti] OR 

prescription*[ti]) AND (treatment*[ti] OR treat[ti] OR treats[ti] OR 

therapy[ti] OR therapeutic*[ti]))

7 Pharmacotherapy (drug termsalcohol use)acamprosate[tiab] OR disulfiram[tiab] OR naltrexone[tiab] OR 

atomoxetine[tiab] OR baclofen[tiab] OR buspirone[tiab] OR 

citalopram[tiab] OR desipramine[tiab] OR fluoxetine[tiab] OR 

fluvoxamine[tiab] OR gabapentin[tiab] OR imipramine[tiab] OR 

nalmefene[tiab] OR olanzapine[tiab] OR ondansetron[tiab] OR 

paroxetine[tiab] OR quetiapine[tiab] OR sertraline[tiab] OR 

topiramate[tiab] OR 'valproic acid'[tiab] OR varenicline[tiab]

8 Pharmacotherapy (drug termsopioid use)"Adrenergic alpha-Agonists"[Mesh] OR "Adrenergic alpha-Agonists" 

[Pharmacological Action] OR buprenorphine[tiab] OR naloxone[tiab] OR 

methadone[tiab] OR naltrexone[tiab] OR "LAAM"[tiab] OR 

'levomethadyl acetate'[tiab] OR clonidine[tiab] OR lofexidine[tiab] OR 

guanfacine[tiab] OR guanabenz[tiab] OR (alpha[tiab] AND 

adrenergic*[tiab])

9 Pharmacotherapy (drug termscannabis/stimulant/cocaine 

use)

Bupropion OR divalproex OR nefazodone OR tetrahydrocannabinol OR 

lofexidine OR dronabinol OR modafinil OR disulfiram OR esperal OR 

dicupral OR disulfide OR alcophobin OR anticol OR Antabuse OR antabus 

OR teturam OR Topiramate OR topamax OR topimax OR agonist OR 

agonists

10 Psychosocial Therapies "Psychotherapy"[Mesh] OR "Self-Help Groups"[Mesh] OR "Couples 

Therapy"[Mesh] OR "Motivational Interviewing"[Mesh] OR 

"Counseling"[Mesh] OR psychotherap*[tiab] OR psychosocial[tiab] OR 

counseling[tiab] OR ((cognitive[tiab] OR behavioral[tiab] OR 

motivational[tiab] OR couples[tiab] OR family[tiab] OR group) AND 

(counseling[tiab] OR therapy[tiab])) OR "community 

reinforcement"[tiab] OR "contingency management"[tiab] OR 

"motivational interview"[tiab] OR "motivational interviewing"[tiab] OR 

"twelve step"[tiab] OR "support group"[tiab] OR "alcoholics 

anonymous" OR "narcotics anonymous" OR "self help" OR ((mutual[ti] 

OR community[ti]) AND (help[ti] OR group*[ti] OR support[ti]))

11 Brief interventions for alcohol 

use

(brief[tiab] OR short[tiab] OR concise[tiab] OR abrupt[tiab] OR 'time 

limited'[tiab]) AND (intervention*[tiab] OR therapy[tiab] OR 

therapies[tiab] OR counsel*[tiab] OR treatment*[tiab] OR advice[tiab] OR 

advisory[tiab] OR motivate[tiab] OR motivational[tiab]) OR "alcohol sbi"

12 Treatment settings "Substance Abuse Treatment Centers"[Mesh] OR "health 

facilities"[Mesh] or "community health centers"[Mesh] OR "community 

mental health centers"[Mesh] OR "Outpatient Clinics, Hospital"[Mesh] 

or "secondary care centers"[Mesh] or "tertiary care centers"[Mesh] OR 

"residential facilities"[Mesh] OR "primary health care"[Mesh] OR 

"Referral and Consultation"[Mesh] OR "delivery of healthcare"[Mesh]

OR

((Primary[tiab] OR secondary[tiab] OR tertiary[tiab] OR general[tiab]) 

AND (care[tiab] OR physician*[tiab] OR practice*[tiab] OR 

practitioner*[tiab])) or outpatient*[tiab] or clinic*[tiab] or 
December 2015 Page 147 of 169

Set 

Number Concept Search Statement

ambulatory[tiab] or "health center"[tiab] or office[tiab] OR 

specialist*[tiab] OR specialty[tiab] OR rehab*[tiab] OR inpatient*[tiab] 

OR refer[tiab] OR referral[tiab] OR referred[tiab] OR ((setting*[tiab] OR 

facility[tiab] OR facilities[tiab] OR center[tiab] OR centers[tiab]) AND 

(treatment[tiab] OR care[tiab] OR therapy[tiab] OR therapies[tiab]))

13 Patient selection criteria (("Patient Selection"[Mesh]) AND "Disease Management"[Mesh]) OR ( 

"Guidelines as Topic"[Mesh] OR "Practice Guidelines as Topic"[Mesh] 

OR "Guideline Adherence"[Mesh] ) (patient[tiab] AND (criteria[tiab] OR 

characteristic*[tiab] OR selection[tiab])) OR (settin*[tiab] AND 

(treatment[tiab] OR care[tiab] OR therapy[tiab] OR therapies[tiab]))

14 Care Intensity (("short term"[tiab] OR "long term"[tiab] OR intense[tiab] OR 

intensive[tiab] OR intensity[tiab] OR aggressive[tiab]) AND (care[tiab] OR 

treatment[tiab] OR therapy[tiab] OR therapies[tiab])) OR "level of 

care"[tiab] OR "levels of care"[tiab]

15 Measurement based care "Self Report"[majr] OR Questionnaires[majr] OR "Biological 

Markers"[majr] OR "Monitoring, Physiologic"[majr] OR "Psychiatric 

Status Rating Scales"[majr] OR "psychological tests"[majr] OR 

psychometrics[majr] OR "health status indicators"[majr] OR "severity of 

illness index"[majr]

OR

"Measurement based care" OR "addiction severity index" OR "brief 

addiction monitor" OR (measurement*[tiab] AND care[tiab]) OR 

questionnaire*[ti] OR scale[ti] OR scales[ti] OR instrument*[ti] OR 

index[ti] OR measure*[ti] OR monitor*[ti] OR assessment[ti] OR 

assess[ti] OR biomarker*[ti] OR "PHQ"[tiab] OR "patient health 

questionnaire" OR (continuous[tiab] AND (monitor*[tiab] OR 

assessment*[tiab])) OR (biological[tiab] AND measure*[tiab])

16 Combine sets KQ 1 1 AND (6 OR 7)

17 Combine sets KQ 2 (overlaps 

with KQ 3)

2 AND (6 OR 8)

18 Combine sets KQ 3 (overlaps 

with KQ 2)

2 AND 10

19 Combine sets KQ 4 1 AND 11

20 Combine sets KQ 5 1 AND 12 AND (13 OR 14)

21 Combine sets KQ 6 and 7, and 

psychosocial components of 

KQs 9 and 10

(1 OR 2 OR 3 OR 4 OR 5) AND 10

22 Combine sets KQ 8 (1 OR 2 OR 3 OR 4 OR 5) AND 15

23 Combine sets KQs 9, 10, and 

11; 

3 AND (6 OR 9)

24 For all searches - remove 

unwanted publication 

types/Apply limits

NOT (case reports[pt] OR comment[pt] OR editorial[pt] OR letter[pt] OR 

news[pt] OR "Textbooks" [pt] OR "Book Reviews"[pt]OR "Book 

Illustrations"[pt])

Limits: Py:2007-2015; humans; English language

25 For all searches - Limit to RCTs 

or Systematic Reviews/MetaAnalyses

AND ((Random*[tiab] OR randomized[tiab] OR RCT*[tiab]) OR

(meta-analysis[tiab] OR meta-analysis[pt] OR systematic*[tiab] OR 

"systematic review"[tiab]))
December 2015 Page 148 of 169

Set 

Number Concept Search Statement

26 Limit to "In process" citations 

[i.e. citations that have not yet 

been indexed and therefore 

may not have been captured in 

the MEDLINE search]

AND ("inprocess"[sb] OR publisher[sb] OR pubmednotmedline[sb])

PubMed syntax:

[Mesh] = search as a subject heading

[majr] = search as a major subject heading

* = truncation character (wildcard)

[ti] = limit to title field

[tiab] = limit to title and abstract fields

[tw] = text word 
December 2015 Page 149 of 169

Appendix I. Acronym List

Abbreviation Definition

AA Alcoholics Anonymous

AHRQ Agency for Healthcare Research and Quality

ASAM American Society of Addiction Medicine

AUD alcohol use disorder

AUDIT-C Alcohol Use Disorders Identification Test - Consumption

AUDIT-PC Alcohol Use Disorders Identification Test Primary Care

AWS alcohol withdrawal syndrome

BAL blood alcohol level

BCT Behavioral Couples Therapy

BI brief intervention

BT behavioral therapy

CBT Cognitive Behavioral Therapy

CDC Centers for Disease Control and Prevention

CENTRAL The Cochrane Central Register of Controlled Trials

CIWA-Ar Clinical Institute Withdrawal Assessment for Alcohol (revised version)

CKD chronic kidney disease

CM Contingency Management

Cmax maximum concentration

CMI chronic multisymptom illness

CNS central nervous system

COR contracting officer's representative

COWS Clinical Opiate Withdrawal Scale

CPG clinical practice guideline

CRA Community Reinforcement Approach

CrCl creatinine clearance

DATA 2000 Drug Addiction Treatment Act of 2000

DEA Drug Enforcement Administration

DoD Department of Defense

DODD Department of Defense Directive

DSM Diagnostic and Statistical Manual of Mental Disorders

DSM-IV Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition

DSM-IV-TR Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision

DSM-5 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

EBPWG Evidence-Based Practice Work Group

FDA Food and Drug Administration

GRADE Grading of Recommendations Assessment, Development and Evaluation

HCG human chorionic gonadotropin

HIPAA Health Insurance Portability and Accountability Act

HTA Health Technology Assessment Database
December 2015 Page 150 of 169

Abbreviation Definition

KQ key question

LARS Luebeck Alcohol Withdrawal Risk Scale-11

m meter(s)

MDD major depressive disorder

MeSH Medical Subject Headings

MET Motivational Enhancement Therapy

mg milligram(s) 

MI motivational interviewing

mL milliliter(s) 

MMT methadone maintenance therapy

mTBI mild traumatic brain injury

NA Narcotics Anonymous

NIAAA National Institute on Alcohol Abuse and Alcoholism

NICE National Institute for Health and Care Excellence

NIDA National Institute on Drug Abuse

NS Network Support

OAT opioid agonist therapy

OBOT Office-based Opioid Therapy

OTP Opioid Treatment Program

OUD opioid use disorder

PACT Patient-aligned Care Team

PAWSS Prediction of Alcohol Withdrawal Severity Scale

PC-MHI Primary Care-Mental Health Integration

PCT person-centered therapy

PDMP prescription drug monitoring program

PHQ-9 Patient Health Questionnaire

PICOTS population, intervention, comparison, outcome, timing and setting

PRN as needed

PTSD posttraumatic stress disorder

QTc the heart rate corrected time from the start of the Q wave to the end of the T wave

RCT randomized controlled trial

SAMHSA Substance Abuse and Mental Health Services Administration

SASQ Single Item Alcohol Screening Questionnaire

SAWS Short Alcohol Withdrawal Scale

SDM shared decision making

SR systematic review

SUD substance use disorders

TAU treatment as usual

TJC The Joint Commission

TSF 12-Step Facilitation
December 2015 Page 151 of 169

Abbreviation Definition

U.S. United States

USPSTF U.S. Preventive Services Task Force

VA Department of Veterans Affairs
December 2015 Page 152 of 169

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