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Guideline Summary
Guideline Title
Incorporating alcohol pharmacotherapies into medical practice.
Bibliographic Source(s)
Center for Substance Abuse and Treatment. Incorporating alcohol pharmacotherapies into medical practice. Rockville (MD): Substance Abuse and Mental Health Services Administration (SAMHSA); 2009. 110 p. (Treatment improvement protocol (TIP); no. 49).  [108 references]
Guideline Status

This is the current release of the guideline.



Alcohol use disorders (AUDs)

  • Alcohol abuse
  • Alcohol dependence

Note: The following information is not covered in this guideline:

  • Screening and diagnostic assessment for AUDs
  • Detoxification and methods to deal with initial withdrawal symptoms
  • Medical conditions associated with excessive alcohol use, such as cirrhosis
Guideline Category
Clinical Specialty
Family Practice
Internal Medicine
Obstetrics and Gynecology
Intended Users
Advanced Practice Nurses
Physician Assistants
Psychologists/Non-physician Behavioral Health Clinicians
Substance Use Disorders Treatment Providers
Guideline Objective(s)
  • To provide clinical guidelines for the proper use of medications in the treatment of alcohol use disorders (AUDs)
  • To expand access to information about the effective use of these medications, not only in specialty substance abuse treatment programs but also in physicians' offices and other general medical care settings
Target Population

Individuals with alcohol use disorders (AUDs)

Interventions and Practices Considered


  1. Physical exam and laboratory testing
    • Blood/breath/urine alcohol and toxicological screening
    • Biomarkers for alcohol use disorders (AUDs)
    • Complete blood count
    • Testing for vitamin deficiencies
    • Hepatic and renal testing
  2. Psychiatric assessment for psychiatric conditions such as: major depression, generalized anxiety disorder, posttraumatic stress disorder, schizophrenia, and personality disorders)
  3. Substance abuse assessment
    • History of the patient's substance use
    • History of professional treatment or mutual-help group involvement
    • Prior alcohol withdrawal syndrome
  4. Social history
  5. Assessing motivation for change


  1. Medication
    • Acamprosate
    • Disulfiram
    • Oral naltrexone
    • Injectable naltrexone
  2. Combination therapy
  3. Psychosocial interventions
    • Psychosocial therapies
    • Referring for specialty treatment
    • Mutual- or self-help programs
  4. Develop a treatment plan
    • Set goals (abstinence or reduction)
    • Include comprehensive pharmacotherapy plan
  5. Patient education
  6. Monitoring patient progress
    • Monitoring adherence
    • Monitoring abstinence or reduction in alcohol consumption
    • Monitoring craving
    • Monitoring health status and social functioning
    • Monitoring other substances of abuse
  7. Modifying the treatment strategy
  8. Discontinuing pharmacotherapy
Major Outcomes Considered
  • Response to treatment
  • Long-term recovery rate
  • Side effects and adverse effects of drug treatment
  • Quality of life


Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

A lengthy and systematic process was used to identify and synthesize the literature and research that support this Treatment Improvement Protocol (TIP). This TIP literature search was built on—and expanded—a short pharmacotherapy literature review covering 2000–2005, which had been completed for the Center for Substance Abuse Treatment as part of the Screening, Brief Intervention, and Referral to Treatment program. The literature search, done through the National Institute of Medicine's PubMed database, encompassed both clinical and administrative topics. For example, it identified articles concerning physicians' use of pharmacotherapy for alcohol problems, as well as such barriers to use as practitioners’ attitudes and lack of knowledge about these medications. In addition, the Center for Substance Abuse Research (CESAR) conducted a literature search specific to alcohol related disorders and acamprosate in April 2005 (for databases used, see the list below). This search identified 83 relevant articles in the period from 2000 to 2005. These preliminary searches, as well as the experience of literature searches done for earlier TIPs, demonstrated that it would not be necessary to conduct a separate literature search dedicated to administrative topics.

The series of comprehensive searches undertaken for this literature review was started in March 2006. The searches covered the period from 2000 to 2006, with selected articles also retrieved from 1998 to 1999, and focused on (1) research literature concerning medications approved by the Food and Drug Administration (FDA) for medical management of alcohol disorders, as well as combined pharmacotherapies, (2) use of these medications in primary care, including adverse events and selection of appropriate patients, and (3) need for further research and knowledge. The searches, conducted by a professional librarian from CESAR, used the following databases:

PubMed. Search terms included:

  • Alcoholism/drug therapy
  • Alcohol-related disorders/drug therapy
  • Alcohol-related disorders AND each of the following:
    • Acamprosate/Campral (since April 2005)
    • Naltrexone
    • ReVia
    • Antabuse
    • Disulfiram
    • Ondansetron
    • Topiramate
    • Nalmefene
    • Multiple substance abuse
    • Relapse prevention
    • Craving

PsycINFO. Search paths included:

  • (Alcoholism OR Alcohol abuse) AND (Pharmacotherapy OR Drug therapy OR Acamprosate/Campral [since April 2005] OR Naltrexone OR ReVia OR Antabuse OR Disulfiram OR Ondansetron OR Topiramate OR Nalmefene) OR Multiple substance abuse OR Relapse prevention OR Craving.

ETOH. (This Alcohol and Alcohol Problems Science Database, sponsored by the National Institute on Alcohol Abuse and Alcoholism, includes articles from 1972 through December 2003 only.) Search terms included:

  • Ti Pharmacotherapy OR
  • Kw Drug therapy

Academic Search Elite, CINAHL, Health Source Academic, Psychology and Behavior Science, PsycArticles, Social Science Abstracts, Social Index. Search terms included:

  • Alcoholism AND
  • (Pharmacotherapy OR Drug therapy)

While the TIP on alcohol pharmacotherapies was being developed, Vivitrol® (formerly Vivitrex®), a long-acting injectable form of naltrexone, was in the final stages of approval by FDA. To keep apprised of emerging research and updates on the status of the FDA application, the FDA and the manufacturer's Web sites as well as Web search engines were searched regularly for references to this new medication. In April 2006, a targeted literature search was carried out on long-acting naltrexone, which elicited 24 articles specific to this new form of the drug, including articles on an open label trial, randomized controlled clinical trials, and a multicenter, randomized, placebo-controlled pilot study.

Using the search strategy developed for the comprehensive review, updates to this literature review were made in October 2006 and in April 2007. An additional update was made in October 2007, after the text for the literature review had been completed; that update appears as a separate section at the beginning of this Web-site literature review (see "Availability of Companion Documents" field). Continuing updates will be made at 6-month intervals as long as the literature review remains available on the Web site of the Substance Abuse and Mental Health Services Administration's Knowledge Application Program (KAP). Exhibit A-1 of the literature review (see "Availability of Companion Documents" field) provides a tabulation of the articles identified during the initial literature search as well as during the updated searches.

For each citation found, reference information and abstracts were reviewed by the literature reviewer and TIP editors. The reviewers eliminated any citations that focused on preclinical research, including animal studies, and on medications used for detoxification rather than medical management. Citations were also rejected when they concerned use of medications for mental or physical disorders occurring in conjunction with substance use disorders. For example, articles were omitted that focused on medications to treat depression in people with alcohol use disorders. Citations from foreign sources written in English were included because so much significant research on naltrexone and acamprosate has been done in foreign, particularly European, countries. The foreign literature on acamprosate was particularly crucial because acamprosate had been used in 26 countries (with 17 randomized, placebo controlled clinical trials) before 2004, when it was approved for use in the United States. Citations addressing the future directions of pharmacologic treatment were also included, such as the promise of genetic-based research and of selected medications now under development.

After references were selected using these search procedures, the bibliographies or citation lists from these references were reviewed to find older, seminal literature appropriate for this topic. Because disulfiram has been used in the United States for more than 55 years, it was especially important to identify seminal research before 2000. Members of the TIP development panel were asked to suggest earlier research and other articles that would be relevant to the TIP, focusing on the disulfiram literature.

Potentially useful books were identified by chapters appearing in the literature searches and by the TIP chair.

Included with the literature review on the KAP Web site is a 50-item Annotated Bibliography that lists many major and seminal articles on the pharmacotherapy of alcohol disorders. This highly selective list covers articles on each medication currently approved for medical management of alcohol disorders. The literature reviewer assembled an initial list of candidates for this Annotated Bibliography, and the TIP consensus panel of experts reviewed the list and recommended additions and deletions. The Annotated Bibliography represents the final selections recommended by the TIP consensus panel. Because the Annotated Bibliography is limited to only 50 citations, many fine articles could not be included.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus
Subjective Review
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

After selecting a topic, the Center for Substance Abuse Treatment (CSAT) invites staff from Federal agencies and national organizations to be members of a resource panel that reviews an initial draft prospectus and outline and recommends specific areas of focus as well as resources that should be considered in developing the content for the treatment improvement protocol (TIP). These recommendations are communicated to a consensus panel composed of experts on the topic who have been nominated by their peers. In partnership with Knowledge Application Program writers, consensus panel members participate in creating a draft document and then meet to review and discuss the draft. The information and recommendations on which they reach consensus form the foundation of the TIP. A panel chair ensures that the guidelines mirror the results of the group's collaboration.

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

Annual economic costs of alcohol use disorders (AUDs) in the United States have been estimated at approximately $185 billion and include the following:

  • Direct treatment costs
  • Lost earnings
  • Costs of other medical consequences, including premature death
  • Costs of accidents and emergencies
  • Criminal justice costs
Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

A diverse group of experts closely reviews the draft document. Once the changes recommended by these field reviewers have been incorporated, the treatment improvement protocol (TIP) is prepared for publication, in print and online. TIPs can be accessed via the Internet at External Web Site Policy.


Major Recommendations

For specific information on acamprosate, disulfiram, oral naltrexone, and extended-release injectable naltrexone, including rationale for use, how to use, which patients are most appropriate for the medication, and clinical advice, see Chapters 2-5 in the original guideline document.

Initial Assessment

Persons with alcohol use disorders (AUDs) often have physical and social sequelae from excessive alcohol consumption. AUDs influence the incidence, course, and treatment of many medical and behavioral health conditions. Identifying, assessing, and treating AUDs can occur concurrently with assessment and treatment of other medical problems. As noted in Chapter 1 in the original guideline document, a thorough discussion of screening and assessment for AUDs is outside the scope of this treatment improvement protocol (TIP). The reader can refer to resources that are available at External Web Site Policy.

Once an AUD diagnosis has been made, thorough assessments for substance use and social, medical, and psychiatric histories are essential in evaluating the consequences of dependence and identifying problems that can be addressed concurrently with treatment. Evaluation can identify or rule out contraindications to therapy with specific medications. At the very least, a clinician considering a patient's pharmacologic treatment for alcohol dependence should perform a physical exam; order laboratory tests; assess psychiatric status; obtain substance use, treatment, and social histories; and assess motivation for change.

Physical Exam and Laboratory Testing

Because alcohol dependence can harm many organ systems and certain conditions may preclude pharmacotherapy with a particular maintenance medication, a physical exam and laboratory testing should be performed before any treatment is initiated.

Medical complications of excessive alcohol consumption are common and numerous, and TIP 49 cannot discuss them all. However, common medical conditions such as hypertension and gastritis and common psychiatric conditions such as depression can be incited or exacerbated by AUDs. Various patient complaints can be related to alcohol consumption, including dyspepsia, sleep problems, sexual difficulties, depressed mood, and irritability. AUDs also contribute to progression of morbidity for many diseases. For instance, according to a recent review of the literature, excessive alcohol consumption increases the morbidity associated with human immunodeficiency virus (HIV) and viral hepatidies and can complicate medical treatment for these conditions. In addition, existing conditions, such as hepatic or renal disease or pain syndromes, either acute or chronic, may contraindicate treatment with particular maintenance medications.

Physical Exam

Although physical exam findings may not be specific to alcohol consumption or alcohol disorders, a thorough physical exam can often corroborate clinician suspicions of an AUD and may help with disease monitoring. Patients with AUDs may have no specific abnormal exam findings. However, when present, abnormal exam findings provide evidence of the severity of a patient's AUD. Longstanding alcohol consumption may present with many "classic" physical exam features, including physical manifestations of cirrhosis, encephalopathy, and vitamin deficiencies. Alcohol consumption can incur tachycardia (including supraventricular tachycardias), tremor (hand or tongue), elevated blood pressure, hepatosplenomegaly, a tender liver edge, peripheral neuropathy, spider angiomata, conjunctival injection, and unexplained trauma.

Because AUDs often co-occur with drug use, the physical exam may help the clinician identify comorbid substance use problems. For example, smoking cigarettes frequently co-occurs with excessive alcohol use; smoking, along with alcohol use, may increase heart rate and promote tachyarrhythmias. Needle marks, hard blackened veins, and abscesses in the arms, hips, buttocks, thighs, or calves may indicate concomitant injection drug use. Inhaled drugs, such as crack cocaine, often cause a brown tongue, nasal septum abnormalities, or diffuse wheezes.

Laboratory Testing

In addition to helping healthcare practitioners assess a patient's overall health status, initial laboratory testing can identify the presence of AUDs, alcohol-related damage, and contraindications for use of particular medications. Initial and followup laboratory testing may motivate patients and reinforce their progress in treatment. The following list of useful laboratory tests can identify patients with significant alcohol consumption.

Useful Laboratory Tests

  • Breath or blood alcohol tests
  • Urine toxicology
  • Gamma glutamyltransferase (GGT)
  • Liver function tests, including serum aspartate aminotransferase (AST)
  • Complete blood count
  • Testing for vitamin deficiencies
  • Renal function tests: Standard panel for urea (blood urea nitrogen), electrolytes, and serum creatinine
  • Pregnancy test (women of childbearing age)

Identifying AUDs and Illicit Drug Use

Laboratory tests are more specific than sensitive for detecting alcohol problems, and there is no single laboratory test that is sensitive or specific for AUD diagnoses. Detection of AUDs is improved when laboratory tests are combined with other screening strategies. However, certain tests help healthcare providers identify AUDs and possible alcohol-related abnormalities.

Blood/Breath/Urine Alcohol and Toxicological Screening

Blood alcohol levels and urine/breath tests for alcohol are useful measures of recent alcohol consumption. They determine acute physical or legal incapacity to do specific tasks. Initial laboratory work also should include a urine toxicology screen to assess for other substances.

Biomarkers for AUDs

Alcohol biomarkers are physiological indicators of alcohol exposure or ingestion and may reflect the presence of an AUD. Although tests such as serum carbohydrate-deficient transferrin (CDT) levels are not often used in primary care practice, some evidence suggests that they might be used to screen for chronic alcohol consumption and to monitor consumption during treatment under certain conditions. For example, an increase in CDT over time may suggest an increase in alcohol consumption.

In addition to assessing impairment in liver functioning, aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) can be used as biomarkers because they are often elevated in persons who recently consumed significant amounts of alcohol. Some studies suggest that biomarkers such as AST, GGT, and CDT are most useful for screening when used in combination.

Testing for another biomarker, ethyl glucuronide (EtG) is becoming widely available in the United States and is increasingly being used for screening. This marker is highly sensitive for alcohol. This sensitivity is a potential drawback as well as a strength, as exposure to even small amounts (such as those found in some foods and cosmetic items) can trigger a positive test result.

More detailed information about the use (and misuse) of biomarkers for identifying AUDs and other substance use disorders can be found in the Substance Abuse Treatment Advisory, The Role of Biomarkers in the Treatment of Alcohol Use Disorders.

Identifying Alcohol-Related Damage and Medication Contraindications

Several laboratory tests help healthcare practitioners establish a patient's overall health status as well as identify alcohol-related damage and contraindications for using certain medications.

Complete Blood Count

Alcohol overuse causes anemia and has direct toxic effects on bone marrow. An assessment of hematologic laboratory indices is essential when considering pharmacologic treatment of AUDs. Many persons who are alcohol dependent have macrocytosis, and the mean corpuscular volume is often elevated.

Testing for Vitamin Deficiencies

People with AUDs may not eat well, and several vitamin deficiencies can occur that lead to abnormal cellular functions. Thiamine, folic acid, and pyridoxine deficits are common in people with chronic AUDs, and these deficiencies contribute to abnormal cell growth. Vitamin deficiencies may lead to Wernicke Korsakoff's/amnestic syndrome in patients with severely excessive alcohol consumption.

Hepatic and Renal Testing

Consideration of treatment of AUDs with pharmacotherapy requires the clinician to consider evaluating organ systems that are involved in the metabolism and excretion of these medications. For example, naltrexone and disulfiram should be used with caution in patients with liver disease, and naltrexone and acamprosate should be used with caution in patients with renal impairment. Therefore, hepatic and renal system testing should be done before initiating use of these medications. Finally, all four medications used to treat AUDs are U.S. Food and Drug Administration (FDA) pregnancy category C; women of childbearing age should receive a pregnancy test before pharmacotherapy is initiated.

Motivating Patients for Treatment and Reinforcing Progress

Providing feedback about patients' initial test results, compared with norms, and the health risks associated with these results can be a powerful way to increase patients' motivation and adherence to treatment. Laboratory tests help healthcare providers objectively monitor patients' progress in treatment and provide patients with objective reinforcement by demonstrating biologic evidence of their improving health status.

Psychiatric Assessment

Psychiatric conditions (such as major depression, generalized anxiety disorder, posttraumatic stress disorder, schizophrenia, and personality disorders) frequently co-occur with excessive alcohol consumption. Some psychiatric symptoms resolve with abstinence, and others lessen. Nonetheless, the prescribing professional should assess the patient for these disorders and for suicidal ideation or intent (or refer the patient for assessment). Untreated psychiatric conditions can seriously interfere with a patient's ability to comply with pharmacotherapy and psychosocial treatment for alcohol dependence and can cause the patient preventable suffering. More information on co-occurring psychiatric disorders can be found in TIP 42, "Substance Abuse Treatment for Persons With Co Occurring Disorders".

Substance Use Assessment

After healthcare providers have ascertained that a patient has an AUD, they should obtain an adequate history of the patient's substance use and of prior treatments for AUDs. Providers should determine whether the patient has experienced alcohol withdrawal syndrome because this syndrome can indicate a need for more specialized care than primary care providers can typically provide. More information about alcohol withdrawal and detoxification is in TIP 45, Detoxification and Substance Abuse Treatment. Excerpts of the Quick Guide for Clinicians based on TIP 45 are in Appendix C in the original guideline document.

During the assessment, providers should assess the quantity and frequency of alcohol consumption, patterns of alcohol consumption (e.g., persistent, occasional, binge use), episodes of use, duration of use, and consequences of alcohol consumption. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinician's guide suggests a stepwise approach that consists of assessment of any use, quantity/frequency of use, and harm associated with alcohol consumption. NIAAA's A Pocket Guide for Alcohol Screening and Brief Intervention, a condensed version of the clinician's guide, is in Appendix B. Exhibit 6-2 in the original guideline document lists key questions to quickly assess quantity and frequency of alcohol use, based on a "standard drink" in the United States that contains 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons). More detailed information about what constitutes a standard drink is in Appendix B in the original guideline document.

The history also should include use of substances other than alcohol, especially opioids, as well as the patient's history of use, misuse, or abuse of prescription medications. Misuse of opioid medications may complicate or contraindicate treatment with naltrexone. Abuse of sedatives and tranquilizers may complicate detoxification and treatment.

A complete assessment includes a patient's current involvement in or history of professional treatment or mutual-help group involvement, including the following:

  • Detoxification episodes
  • Pharmacotherapy interventions
  • Specialty substance abuse treatment episodes (including when, where, modality, duration, and outcome)
  • Individual therapy
  • 12-Step (e.g., Alcoholics Anonymous) or other mutual- or self-help program involvement

This information can assist the provider in treatment planning and advocating for psychosocial treatment as an adjunct to pharmacologic treatment for alcohol dependence.

Social History

Understanding a patient's social situation identifies problems that may interfere with treatment and that necessitate referral for ancillary services. Asking a patient basic questions about his or her work, legal, living, and family situations can yield information that is critical to treatment planning:

  • What is the patient's family situation? Who should be included in treatment planning? Who can monitor a patient's medication compliance?
  • Is the patient on probation at work? Could this be a means of motivating medication compliance?
  • What is the patient's living situation? Are extra measures required to ensure medication compliance? Are psychosocial treatment modalities (residential vs. outpatient) recommended?

Assessing Motivation for Change

Before offering treatment for alcohol dependence, providers should assess patients' readiness to change drinking behavior. Through this assessment, patients and providers develop mutually agreeable intervention and treatment plans. Exhibit 6-3 in the original guideline document provides questions that determine patients' readiness for change.

Regardless of patients' readiness to change, they should, at a minimum, be willing to be in a supportive relationship with their healthcare provider. If the relationship is strained by dishonesty or mistrust, initial willingness to take medication and ongoing compliance with a medication regimen may suffer. In addition, patients should be willing to consider adjunctive options including specialty treatment, other independent psychosocial treatment providers, or forms of community support. A review of the literature suggests that although psychosocial interventions increase rates of abstinence and decrease alcohol consumption, a significant proportion of patients relapse to drinking within 1 year. Healthcare providers, however, can play a significant role in motivational enhancement and relapse prevention. More information about stages of change and motivational enhancement is in TIP 35, Enhancing Motivation for Change in Substance Abuse Treatment.

Choosing a Medication

Scant research exists to guide clinicians in choosing the best medication for a particular patient. This lack of guidance results in part from the inconsistent findings of pharmacotherapy efficacy trials among subsets of patient populations. These inconsistent results may be related to the multiple factors associated with the effectiveness of these medications. Further research with larger patient samples is necessary before the proposed relationships can have a definitive influence in the individual decision making process.

Each chapter in this TIP that discusses a particular medication for treating AUDs summarizes the evidence that is available regarding the type of patient most appropriate for the medication; a more detailed discussion of patient–medication matching is found in the TIP's online literature review ( External Web Site Policy). In addition to considering the characteristics that research has indicated may be relevant to choosing a medication, providers need to consider the patient's:

  • Past experience with particular maintenance medications
  • Opinion about which medication may be most helpful
  • Level of motivation for abstinence
  • Medical status and contraindications for each medication
  • History of medication compliance

Exhibit 6-4 in the original guideline document provides a decision grid to help providers make decisions about pharmacotherapy. This grid is based on existing evidence regarding patient–medication matching, medication contraindications, and the clinical experiences of consensus panelists. Exhibit 6-5 in the original guideline document provides a quick-reference guide for comparing maintenance medications.

Combination Therapy

A number of studies have found that treatment outcomes improve when naltrexone is combined with acamprosate or disulfiram, particularly for patients who responded poorly to therapy with any of these medications alone. Another study reported that co-administration of disulfiram improved the action of acamprosate. One study reports that combining acamprosate with naltrexone boosted plasma levels of acamprosate, which may have clinical benefits not achieved by monotherapy with either drug. The Combining Medications and Behavioral Interventions (COMBINE) study did not support the efficacy of combination therapy with acamprosate and naltrexone, although this combination has been used in Europe and Australia with some reported success. More information is needed about the efficacy of this strategy, although it may be worth trying with patients who have not benefited from single-drug therapy.

One placebo-controlled but not randomized trial of acamprosate also prescribed disulfiram to patients who requested it. Patients who received the disulfiram–acamprosate combination had significantly more abstinent days than those who received acamprosate only. However, those who requested disulfiram may have been more motivated. Because patients were not assigned randomly to the disulfiram–acamprosate regimen, it is unclear whether the combination of disulfiram and acamprosate or motivation was responsible for the results. Another study found no advantage for the combination of naltrexone and disulfiram in a randomized, placebo-controlled study of patients with a co-occurring Axis I mental disorder and alcohol dependence, but it did find that active medication with either drug produced greater benefit than placebo in this population.

Although no absolute contraindications exist for using disulfiram with either naltrexone or acamprosate, no clear current evidence indicates that one combination is more efficacious than any of the three agents alone. There is some concern about concurrent use of naltrexone with disulfiram because of the possibility of additive liver toxicity. In addition, disulfiram should not be used unless the patient's goal is complete abstinence, a goal not necessary when treating with naltrexone or acamprosate. Finally, the literature is not clear that combining disulfiram with either naltrexone or acamprosate improves patient outcomes. Therefore, at this time the consensus panel does not recommend using disulfiram in combination with either naltrexone or acamprosate.

Choosing a Psychosocial Intervention

Any pharmacologic treatment for alcohol dependence should be used as an adjunct to, not a replacement for, psychosocial treatment. The literature suggests that the medication–psychosocial therapy combination is more effective than either alone. For example, one group of authors reported the benefits of combining naltrexone and behavioral interventions for alcohol dependence, including longer time to relapse and increased time between relapse episodes.

Psychosocial treatments are likely to enhance compliance with pharmacotherapy; likewise, pharmacotherapies, to the extent that they reduce craving and help maintain abstinence, may make the patient more open to psychosocial interventions.

Types of Psychosocial Therapies

As with pharmacotherapy, there is no psychosocial "magic bullet." However, a number of modalities of psychosocial therapy have been studied and validated for treatment of alcohol use disorders. Medical management (MM) is often practiced by primary care physicians in patients with diabetes and hypertension treatment. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) developed an MM treatment as part of its COMBINE study. MM was designed specifically to accompany pharmacotherapy for AUDs and be delivered by medically trained clinicians in a medical setting. MM provides the structure and materials to enable clinicians to do the following:

  • Provide patients with strategies for taking their medications and staying in treatment
  • Provide educational materials about alcohol dependence and pharmacotherapy
  • Support patients' efforts to change drinking habits
  • Make direct recommendations for changing drinking behaviors

An MM manual is available through NIAAA at External Web Site Policy.

Providers in psychiatric practice may provide psychosocial therapies on site. In the context of the primary care setting, however, delivering particular psychosocial therapies (e.g., group therapy) may be difficult because of time constraints, patient population, and lack of training. Brief interventions, motivational enhancement therapy, and MM treatment are more conducive to primary care settings. Sources of information about these interventions are listed in Exhibit 6-6. If these types of in-office interventions are not effective with a patient, or if the provider does not have the resources to offer them, providers may need to refer the patient for more intensive or specialized services.

Referring Patients for Specialty Treatment

Primary care practitioners may need to refer patients for psychosocial therapies, including to specialty substance abuse treatment programs. Many specialty substance abuse treatment programs provide comprehensive treatment services, either directly or through referrals, that address multiple factors affecting recovery. Such programs address not only immediate withdrawal and craving but management of long-term abstinence through the following:

  • Pharmacotherapy
  • Case monitoring
  • Individual, group, and family/couples counseling and therapy
  • Other psychosocial services (e.g., vocational counseling)
  • Referral to mutual-help groups

The underlying basis for a specialty program is that optimal outcomes are achieved through a range of complementary services and that, as abstinence lengthens, other issues related to alcohol use become clearer and more amenable to treatment.

A practitioner who is planning to treat patients with alcohol dependence should become familiar with a range of local treatment resources. Developing relationships with treatment staff will facilitate smooth referrals and followup. In addition, understanding something about a program's treatment duration, modality, philosophy, and continuing-care options helps the practitioner better match a patient to appropriate treatment; practitioners can prepare the patient for what to expect, enhancing compliance with the referral. Practitioners can find programs in their areas or throughout the United States by using the interactive Substance Abuse Treatment Facility Locator on the Substance Abuse and Mental Health Services Administration (SAMHSA) Web site at External Web Site Policy.

Mutual- or Self-Help Programs

Mutual- or self-help group support can be critical to long-term recovery. The oldest, best-known, and most accessible mutual-help program is Alcoholics Anonymous (AA) ( External Web Site Policy). Patients may resist attending AA meetings and may fear that disclosure of medication use may be unwelcome. Although some AA members may have negative attitudes toward medications, the organization itself supports appropriate medication use. Providers should encourage patients to try different group meetings if they meet with negativity. Lists of local meetings can be obtained from External Web Site Policy and given to patients. Dual Recovery Anonymous ( External Web Site Policy) is a 12-step program for patients with co-occurring psychiatric disorders. Other mutual- or self-help groups include Self Management and Recovery Training ( External Web Site Policy) and Women for Sobriety, Inc. ( External Web Site Policy). Although groups other than AA are not available in every community, they do offer a number of online resources. For patients' family members, there are Al-Anon and Alateen meetings ( External Web Site Policy).

Providers should have a working knowledge of the most common groups so that they can suggest these groups to their patients and discuss patients' participation.

Developing a Treatment Plan

Setting Goals: Abstinence or Reduction?

Each patient–provider interaction should assess and clarify outcome goals for the patient. A patient initially may seek to reduce alcohol consumption. Another patient may be motivated for total abstinence. Investigations into prescribing of pharmacotherapy employ both alcohol use reduction outcomes and abstinence outcomes to assess the efficacy of medications to treat alcohol dependence. Clinical outcomes to assess progress include the length of time to first drink, time to heavy drinking, cumulative abstinence days, and drinks per drinking episode. Each provider and patient should set an initial goal and be willing to refine that goal as treatment progresses.

If a patient with an AUD is unwilling to be completely abstinent, he or she may be willing to cut down on alcohol use. Practitioners can work with this while noting that abstinence is the safer strategy and has a greater chance of long-term success.

Certain conditions warrant advising a patient to abstain from rather than reduce drinking. As noted in the NIAAA (2006) clinician's guide, these conditions include when drinkers:

  • Are or may become pregnant
  • Are taking a contraindicated medication
  • Have a medical or psychiatric disorder caused or exacerbated by drinking
  • Have an AUD

For those who drink heavily and who do not have an AUD, the practitioner should use professional judgment to determine whether cutting down or abstaining is more appropriate, based on factors such as:

  • A family history of alcohol problems
  • Advanced age
  • Injuries related to drinking

Elements of a Treatment Plan

A comprehensive pharmacotherapy treatment plan for a patient with an AUD should include the following:

  • The medication to be used and a rationale for its use
  • Initial and maintenance dosages
  • A schedule for followup office visits and laboratory testing for monitoring health status and progress
  • Criteria for discontinuing the medication
  • A referral and followup plan for concurrent specialty substance abuse treatment, psychiatric treatment, and/or family therapy
  • A plan for mutual- or self-help group attendance
  • Clarification of family or significant other involvement in treatment
  • A plan for treating alcohol-related or other concurrent conditions

Special attention must be paid to developing a medication compliance plan with the patient. This plan may include the following:

  • Specific strategies for remembering to take medications
  • Using blistercard packs or pill boxes
  • Monitoring medication compliance on an appropriate schedule given the patient's history of compliance with maintenance and other medication regimens
  • Involving the patient's family members in monitoring compliance

Patient Awareness

Patient awareness is critical to successful pharmacotherapy. When starting any new medication, the patient should understand how the medication works and what to expect while taking it. Particularly when prescribing maintenance medications, treatment providers need to offer that information and guidance to patients. Patients also need to understand that alcohol dependence is a chronic medical disorder. They need to know that they may experience protracted effects from their alcohol use, including postacute withdrawal symptoms (e.g., sleep difficulties). When patients do not feel good, it is a challenge to keep them in treatment. Providers should educate patients to manage their concerns and anxieties. Exhibit 6-7 in the original guideline document contains elements of effective patient education, and Exhibit 6-8 in the original guideline document is a brief list of information resources providers can give patients.

Monitoring Patient Progress

As it is with any chronic illness, monitoring of AUDs and pharmacologic treatment is important. Providers should monitor patients' ongoing treatment compliance, abstinence or reduced drinking, levels of craving, health status, social functioning, and use of other substances so that necessary adjustments in treatment plans can be made.

Monitoring Adherence

Several means exist for a provider to monitor patients' compliance with treatment plans, including the following:

  • Tracking patients' record of keeping (or not keeping) appointments for medication monitoring
  • Monitoring prescription refills
  • Noting whether patients are keeping agreements about payment for treatment
  • Requesting periodic status reports from specialty substance abuse treatment programs, psychiatric referrals, and other psychosocial therapy or support

Monitoring Abstinence or Reduction in Alcohol Consumption

The ways in which providers can monitor patients' drinking behavior include the following:

  • Patient self-reports can be useful indicators of treatment success. The provider should discuss with the patient the quantity and frequency of drinking, especially during stressful periods (e.g., holidays, celebrations, major life changes).
  • Laboratory tests may include AST, GGT, CDT, EtG, and urine drug screening.

In addition, providers can use periodic Breathalyzer™ tests (although these detect only for a short period following ingestion) to monitor alcohol intake and provide positive feedback to patients who are successful in maintaining abstinence.

Monitoring Craving

Greatly diminished craving to drink alcohol is an optimum outcome of treatment. To assess craving, a physician can rely largely on the patient's subjective reports, although measures such as the Alcohol Urge Questionnaire may prove useful.

More important than the method of monitoring is consistency in how the patient is asked about craving patterns and trends. Patients should be asked about current craving as well as how they felt over the past week (e.g., as a rating between 1 and 10, with 1 being no craving and 10 the most intense craving the patient has ever experienced). Patients may be asked whether any episodes have caused particular problems for them.

The patterns of craving over time can be useful. Both the provider and the patient can see that the patient's patterns of craving may fluctuate throughout the day and over longer periods; these patterns can assess the appropriateness to continue, adjust, supplement, enhance, or terminate pharmacologic treatment.

Providers should educate the patient about the role of craving in relapse. Learning from and responding optimistically to relapse may increase the patient's motivation to reduce or eliminate alcohol consumption.

Monitoring Health Status and Social Functioning

Ultimately, the goal of treatment is improved quality of life. It is important to monitor patients' progress over time in the following areas:

  • Health
    • Normalization of previously elevated blood pressure
    • Improvement of liver function
    • Stabilization of related medical problems that the patient was experiencing before treatment (e.g., control of blood glucose, stabilization of asthma, cardiomyopathy, encephalopathy, gastritis, ascites and edema)
    • Signs of increased concern about health care, such as seeing a physician for the first time in years and/or increased compliance with prescribed medication regimens not related to AUD treatment (e.g., asthma or blood pressure medications)
  • Family/social activities
    • Spending more positive time with children and/or spouse
    • Greater involvement/participation with family members
    • Improved intimate relationships
    • Reduced family conflicts
    • Engagement in nondrinking leisure and recreational activities
  • Work/vocational status
    • Obtaining employment if previously unemployed
    • Improved attendance at work
    • Fewer job-related and financial problems
    • Improved job performance
  • Legal status
    • No parole or probation violations (in a patient with legal problems)
    • No new driving-under-the-influence charges
  • Mental status
    • Decreased irritability and anxiety
    • Improved mood
    • Improved sleep
    • Getting appropriate treatment for anxiety disorders, suicidal ideation, depression, or schizophrenia rather than self-medicating with alcohol.

Monitoring Other Substances of Abuse

It is important to address other substances of abuse that pose the same level of concern and possible adverse consequences. The abuse of other substances can be evaluated by random urinalysis collection and testing and self-reports from the patient. Use of illicit substances, tobacco use, and abuse of prescription and nonprescription medications should be addressed. The patient's agreement or resistance to continuing treatment may indicate his or her willingness to consider other substance use a problem.

Modifying the Treatment Strategy

An AUD is a chronic illness that, despite treatment, may wax and wane in intensity over time. Some patients may respond to psychosocial interventions, others to pharmacotherapy. Because a patient may respond to one medication and not to another, the provider should be flexible in modifying the medical regimen based on the patient's needs. Furthermore, a patient may choose to be treated for AUDs to reduce, eliminate, or discourage further escalation of consumption. A patient's goals may change over time, and providers should adapt to these new objectives.

As with patients who receive treatment for other chronic diseases, patients receiving treatment for AUDs may relapse. If this occurs, the provider should consider several options:

  • Increase monitoring of medication adherence
  • Increase the dose of the medication
  • Change the medication
  • Increase or change the intensity of psychosocial treatment to include referring the patient to specialty care
  • Examine social, medical, or behavioral factors that contribute to alcohol consumption

Even after patients and providers have examined the reasons for relapse and have intensified or modified psychosocial treatment or pharmacotherapy, some patients may continue to resist reducing alcohol consumption. A small proportion of patients with AUDs may simply be resistant to treatment. For example, chronic relapsing patients are generally defined as patients who persistently consume alcohol despite regular and intensive social and medical interventions. These patients frequently use emergency services. They may resist or cannot effectively use pharmacological and psychosocial interventions because of poor social or environmental situations or other personal factors. These patients, often labeled as "difficult," contribute to the perception of providers that treating AUDs is unlikely to be successful. Dealing with any chronic condition and changing harmful behavior are difficult. Understanding and accepting these difficulties can help providers keep patients moving forward, even if the pace is slow. Because treatment of chronic relapsing patients is difficult, it should be undertaken by addiction professionals in specialty treatment settings that use a multifaceted approach incorporating social, environmental, medical, behavioral, and motivational interventions.

Discontinuing Pharmacotherapy

Because an AUD is a chronic disorder, patients may need long-term use of medication or more than one episode of pharmacotherapy. In addition, some patients may benefit from using a medication over short periods to help them through a particularly stressful period or a situation that has typically elicited cravings for alcohol (e.g., a patient may want to take disulfiram or naltrexone while visiting family members who drink excessively).

Ideally, the patient and provider will decide together to discontinue pharmacotherapy. A patient may simply stop taking the medication. A patient also may express a desire to discontinue a medication because of side effects or for other reasons, or a patient will need to discontinue medication because of significant negative changes in laboratory findings or physical health status. Otherwise, the patient and provider may consider discontinuing medication under the following conditions:

  • The patient reports substantially diminished craving.
  • The patient has maintained stable abstinence over a sustained period.
  • The patient feels ready to discontinue the medication.
  • The patient is engaged in ongoing recovery, including community supports (such as attendance at mutual-help group meetings).

None of the medications discussed in this TIP are associated with a withdrawal syndrome, and they do not need to be tapered.

Final Clinical Thoughts

Management of the patient with an AUD may be seen as a series of stages:

  • Assessing the patient's suitability for treatment with a medication
  • Determining which medication should be used
  • Providing and/or referring the patient for psychosocial services
  • Assessing the patient's response to medication, including both efficacy (Is it working?) and side effects (Are there problems?).

This process is similar to becoming familiar with any new treatment regimen. AUDs may differ from other common chronic disorders mainly in that health-care providers may perceive that they have few patients with AUDs. However, the pervasiveness of alcohol use and the substantial rates of AUDs in the United States make it extremely unlikely that the clinician is not seeing patients with AUDs. The provider simply may not recognize patients with problem alcohol use.

The availability of effective medications that can decrease rates of problem alcohol use or help patients maintain abstinence is an extremely important step forward in the treatment of AUDs. Physicians should become familiar with these medications, with the features of this patient population, and with the services that, combined with medication, can improve treatment outcome. AUDs are treatable medical conditions, and treatment can improve the patient's health and quality of life.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of evidence supporting the recommendations is not specifically stated.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate pharmacotherapy treatment for patients with alcohol use disorders (AUDs) in medical settings

Potential Harms

Side effects, contraindications and cautions related to the use of acamprosate, disulfiram, oral naltrexone and injectable naltrexone are found in chapters 2-5 respectively of the original guideline document.



Acamprosate Contraindications

  • Patients with previous hypersensitivity to acamprosate or its components
  • Severe renal impairment (creatinine clearance ≤30 mL/min)

Disulfiram Contraindications

  • Known hypersensitivity to disulfiram or other thiuram derivatives used in pesticides and rubber vulcanization; sulfur or nickel allergy
  • Psychosis
  • Severe myocardial disease and/or coronary occlusion
  • Pregnant or nursing women

Oral Naltrexone Contraindications

  • Current illicit opioid use (as indicated by self-report or a positive urine screen) or buprenorphine (Suboxone® or Subutex®) or methadone maintenance therapy for the treatment of opioid dependence; currently undergoing opioid withdrawal
  • Acute hepatitis or liver failure
  • Anticipated need for opioid analgesics within the next 7 days
  • History of sensitivity to naltrexone, to structurally similar compounds (e.g., naloxone or nalmefene), or to any inactive ingredients in the tablet

Extended-release Injectable Naltrexone Contraindications

  • History of sensitivity to polylactide glycolide (PLG), carboxymethylcellulose, or any components of the diluent
  • Anticipated need for opioid analgesics within the next 30 days
  • Patient obesity

For more information, see the side effects, contraindications and cautions related to the use of acamprosate, disulfiram, oral naltrexone and injectable naltrexone that are found in chapters 2-5 respectively of the original guideline document.

Qualifying Statements

Qualifying Statements
  • The views, opinions, and content expressed herein are those of the expert panel and do not necessarily reflect the views, opinions, or policies of Center for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health Services Administration (SAMHSA), or Health and Human Services (HHS). No official support of or endorsement by CSAT, SAMHSA, or HHS for these opinions or for particular instruments, software, or resources is intended or should be inferred.
  • Although each treatment improvement protocol (TIP) strives to include an evidence base for the practices it recommends, CSAT recognizes that the field of substance abuse treatment is evolving, and research frequently lags behind the innovations pioneered in the field. A major goal of each TIP is to convey "front-line" information quickly but responsibly. For this reason, recommendations proffered in the TIP are based on either panelists' clinical experience or the literature.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Pocket Guide/Reference Cards
Quick Reference Guides/Physician Guides
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Living with Illness
IOM Domain

Identifying Information and Availability

Bibliographic Source(s)
Center for Substance Abuse and Treatment. Incorporating alcohol pharmacotherapies into medical practice. Rockville (MD): Substance Abuse and Mental Health Services Administration (SAMHSA); 2009. 110 p. (Treatment improvement protocol (TIP); no. 49).  [108 references]

Not applicable: The guideline was not adapted from another source.

Date Released
Guideline Developer(s)
Department of Health and Human Services (U.S.) - Federal Government Agency [U.S.]
Substance Abuse and Mental Health Services Administration (U.S.) - Federal Government Agency [U.S.]
Source(s) of Funding

United States Government

Guideline Committee

Treatment Improvement Protocol (TIP) Series 49 Consensus Panel

Composition of Group That Authored the Guideline

Panel Members: Eric C. Strain, M.D., Professor, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (Chair); Adam J. Gordon, M.D., M.P.H., Assistant Professor Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Bankole A. Johnson, M.D., Ph.D., D.Sc., Chairman, Department of Psychiatric Medicine, University of Virginia Health System, Charlottesville, Virginia; Mary Elizabeth McCaul, Ph.D., Professor, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland; Andrew Saxon, M.D., Professor of Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington; Robert Swift, M.D., Ph.D., Professor of Psychiatry and Human Behavior, Brown University Medical School, Center for Alcohol and Addiction Studies, Providence, Rhode Island; Allen Zweben, D.S.W., Professor and Associate Dean for Research and Sponsored Projects, School of Social Work, Columbia University, New York, New York

Expert Advisory Board: Randall T. Brown, M.D., Assistant Professor Department of Family Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Dominic Ciraulo, M.D., Professor and Chairman, Division of Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Scott M. Davis, M.D., Addiction Medicine Physician, Inpatient Medical Services, Betty Ford Center, Rancho Mirage, California; George Kolodner, M.D., CEO and Medical Director, Kolmac Clinic, Silver Spring, Maryland; Henry Kranzler, M.D., Associate Scientific Director, Alcohol Research Center, University of Connecticut Health Center, Farmington, Connecticut; Robert J. Malcolm, Jr., M.D., Associate Dean and Attending Psychiatrist, Institute of Psychiatry, Medical University of South Carolina, Charleston, South Carolina; Barbara J. Mason, Ph.D., Professor, Molecular and Integrative Neurosciences Department, Scripps Research Institute, La Jolla, California; Richard N. Rosenthal, M.D., Chairman, Department of Psychiatry, St. Luke's Roosevelt Hospital Center, New York, New York

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available from the Substance Abuse and Mental Health Services Administration (SAMHSA) Web site External Web Site Policy and the National Library of Medicine Health Services/Technology Assessment (HSTAT) Web site External Web Site Policy.

Print copies: Publications may be ordered from SAMHSA's Web site External Web Site Policy or by calling 1-877-SAMHSA-7 (United States only).

Availability of Companion Documents

The following is available:

  • Incorporating alcohol pharmacotherapies into medical practice: A review of the literature treatment improvement protocol (TIP) series 49 (includes annotated bibliography). Electronic copies: Substance Abuse and Mental Health Services Administration (SAMHSA) Web site External Web Site Policy.
  • KAP keys for clinicians based on TIP 49. Incorporating alcohol pharmacotherapies into medical practice. Electronic copies: Available from the SAMHSA Web site External Web Site Policy.
  • Quick guide for clinicians based on TIP 49. Incorporating alcohol pharmacotherapies into medical practice. Electronic copies: SAMHSA Web site External Web Site Policy.

Print copies: Publications may be ordered from SAMHSA's Web site External Web Site Policy or by calling 1-877-SAMHSA-7 (United States only).

Also, the appendices of the original guideline document External Web Site Policy contain additional implementation tools, including a pocket guide for alcohol screening and brief intervention.

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on July 28, 2010.

Copyright Statement

No copyright restrictions apply.


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