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Does AA work? That’s (in part) up to you
Many clinicians refer alcohol-dependent patients to Alcoholics Anonymous, but how effective is AA in reducing drinking? Evidence is elusive—partly because of AA’s tradition of anonymity—but clinician encouragement is among three variables that appear essential to successful AA use.
The pioneer of twelve-step programs (Box 1),1,2 AA is a widely accessible, free adjunct to professional alcohol abuse treatment. This article describes the evidence supporting AA’s efficacy for reducing drinking among persons with alcohol use disorders. We also recommend referral strategies that increase AA participation and discuss special needs of alcohol-dependent patients with comorbid psychiatric disorders.
Alcoholics Anonymous (AA) was founded in 1935 in Akron, OH, by Bill Wilson and Robert Smith, MD, two professionals struggling with alcohol dependence. They joined together to help each other stop drinking.
Their success inspired them to help others, and this mutual-aid society grew under the name Alcoholics Anonymous. AA redefined the then-prevalent view of alcohol dependence as a moral failing, instead conceptualizing it as a disease that can be arrested—but not cured—by alcohol abstinence. The only requirements for AA membership are “a desire to stop drinking,” a respect for maintaining anonymity, and a desire to join a fellowship of mutual support for the goal of abstaining from alcohol.
In 1939, Wilson described AA’s theory and fellowship methods and defined its twelve steps of personal recovery,1 referred to in AA as “The Big Book.” Today, the worldwide fellowship has more than 2 million members, with a male:female ratio of 2:1.2
KEYS TO AA SUCCESS
Besides clinician encouragement, two patient variables—severity of alcohol dependence and self-efficacy—have been associated with successful AA use.
Clinician encouragement. When psychiatrists and other clinicians encourage alcohol-dependent patients to attend AA, the rate of AA use increases and drinking decreases.3-7 When clinicians remain interested in alcohol-dependent patients’ AA use—rather than simply recommending AA—patients are more likely to follow through with a referral and to participate long enough to obtain benefit.
Clinicians play an important role in helping patients benefit from AA referral (Box 2).6 Patients who are personally helped to an AA group will rapidly attend, whereas those only given referral information are unlikely to follow up.7 Moreover, clinicians who encourage patients to attend AA and follow up on that attendance have more patients who attend and participate in AA than do less proactive clinicians.8
Disseminate information about alcohol dependence self-help groups such as AA
Become knowledgeable about local AA options to facilitate referral and cooperation
Invite AA groups to use your institutional or clinic space to hold groups and meetings
Offer appropriate self-help referrals to family members, such as Al-Anon and Al-Ateen family groups
Try to match patient preferences with local AA groups, such as women’s AA, and young people’s AA meetings
Use AA as an adjunct to professional care, rather than stand-alone treatment
Learn about alternatives to 12-step treatments—such as SMART Recovery (a CBT-based treatment), Secular Organization for Sobriety, or Women for Sobriety—for patients who prefer other self-help options
Source: Adapted from Workgroup on Substance Abuse Self-Help Organizations’ expert consensus statement, reference 6.
Self-efficacy. Believing that one can abstain from drinking is associated with being able to reduce one’s drinking. Alcohol-dependent patients with self-efficacy are more likely to use AA, and this trait is believed to be a component of the change process associated with reduced drinking.11,12
HOW EFFECTIVE IS AA?
Randomized, controlled trials (RCTs) may be the “gold standard” for determining any treatment’s efficacy, but constructing an RCT of AA use is complicated. AA does not engage in or support research, which makes AA use difficult to administer as a controlled variable in clinical trials. Also, the variability of AA groups and environments confounds the interpretation of study results and limits their application to populations at large.13
Even so, AA can be effective as an adjunct to professional treatments—such as detoxification—and as aftercare to maintain reduced drinking:
- Kelly’s14 comprehensive review and critical analysis of the main studies through 2003 showed a correlation between professional treatment plus AA attendance and improved outcomes.
- Project MATCH-—a large RCT—also supports AA’s benefits, as reported in smaller, less rigorously controlled studies.4,5
- Kownacki and Shadish15 found poorer 12-month drinking outcomes with AA alone, compared with other treatments or no treatment. Their review assessed attendance as a predictor of alcohol use outcomes, and most subjects were attending AA under court orders. Because AA’s philosophy stresses that members must desire to stop drinking (Table 1), these study results may not apply to the voluntary, motivated individuals who usually use AA.
- Two other meta-analyses9,10 that included nonrandomized studies and RCTs showed that attending AA has modest, favorable effects in reducing drinking and improving psychosocial functioning.
Tonigan et al10 rated 74 studies of alcohol use disorders that measured patients’ affiliation with AA and drinking outcome and/or psychosocial adjustment. Most were cross-sectional inpatient studies; few used collateral interviews or biological measures to confirm self-report data. Most used poor methodology, and their assessments were not psychometrically validated.
Outpatient studies showed positive correlations between AA attendance/involvement and:
- reduced drinking
- improved psychological adjustment and improved family relationships.
All three meta-analyses excluded studies of alcohol-dependent individuals with co-occurring drug use disorders, leaving unaddressed the effect of adjunctive AA in that population.
Table 1
AA’s Twelve Steps of personal recovery
|
| Source: Reprinted with permission, Alcoholics Anonymous World Services (AAWS), Inc. 2005. Permission to reprint does not mean that AAWS has reviewed or approved the contents of this publication, or that AA necessarily agrees with the views expressed herein. |
- 12 sessions of cognitive-behavioral coping skills (CBT)
- 4 sessions of motivational enhancement therapy (MET).
Project MATCH thus found that a twelve-step individual therapy was at least as effective as CBT and MET in reducing post-treatment drinking and maintaining abstinence.
Real-world efficacy. A naturalistic study that resembled Project MATCH enrolled 3,018 male military veterans with substance use disorders across 15 program sites.18 Drug dependence was not excluded, and 51% of the men had co-occurring alcohol and drug dependence.
Participants received inpatient detoxification, followed by 21 to 28 days of intensive twelve-step treatment, CBT, or both. Alcohol and drug abuse declined equally in all three groups, and subjects were referred for outpatient aftercare and self-help groups. After 1 year, involvement in a self-help group predicted better outcome, regardless of the initial treatment.19
Unlike earlier studies,15,20,21 this trial found that individuals with co-occurring psychiatric disorders and those legally mandated to get treatment did as well at 1-year follow-up as those without these variables. It provides additional evidence that twelve-step treatments can reduce substance use across varied populations, including patients with co-occurring alcohol and drug dependence.
AA ATTENDANCE VS. PARTICIPATION
Twelve-step programs appear most effective for individuals who actively participate. This may seem obvious, but most studies of 12-step treatments have monitored meeting attendance rather than engagement. Most studies that separate these variables report that active participation—not passive attendance—correlates with reduced substance use.
Montgomery et al22 followed 66 alcohol-dependent individuals in a 12-step oriented, 28-day residential treatment program and investigated:
- relationships between AA attendance and participation
- drinking outcomes over 31 weeks after treatment.
Similarly, Project MATCH participants involved in AA during the first 6 months after treatment had more-frequent abstinent days in the 7 to 12 months after treatment. AA “involvement” included identifying oneself as an AA member, working the steps, having an AA sponsor, and celebrating sobriety milestones.12
The National Drug Abuse Collaborative Cocaine Treatment Study is the most detailed analysis of self-help use. This multi-site RCT by Weiss and colleagues enrolled 487 individuals for behavioral treatment of cocaine dependence.23
Twelve-step attendance did not predict substance use outcomes, but active participation (such as making coffee for a meeting or reading AA literature) in a given month predicted decreased substance use in the following month. Subjects whose participation increased over the first 3 months showed reduced drug use in the following 3 months. Interestingly, those who participated without attending meetings regularly (such as by reading AA literature or calling a sponsor) benefited as much as those who attended meetings more regularly.
Summary. Actively engaging in 12-step treatment—as measured by identifying with the fellowship and following the steps—appears more important to success than simply attending meetings.
EFFECTIVE AA REFERRALS
To encourage engagement when referring, try to match patients to AA groups attended by persons with whom they feel comfortable (Table 2).24 Adolescents, for example, tend to have more difficulty engaging and remaining in AA than do adults.25 One remedy may be to recommend a Young Person’s AA group composed primarily of adolescents and young adults.
Although AA embraces a spiritual approach to recovery, a person can benefit from participating without having a specific religious affiliation or spiritual beliefs.12,26 The emphasis on spirituality and a “higher power” varies from one AA group to another as well as from region to region. For patients who are uncomfortable with AA’s religiosity, other self-help options for alcohol dependence include SMART Recovery (a CBT-based treatment) and Secular Organization for Sobriety (see Related resources).
Table 2
Matching patients to AA groups:
6 variables to consider
| Variable | Suggestion |
|---|---|
| Socioeconomic status | Match by group location |
| Gender | Women-only groups |
| Age | Young people’s AA |
| Religious content | Beginners’ groups and speaker or topic discussion groups have less-spiritual focus, whereas Step groups and Sunday meetings have more spiritual focus |
| Smoking status | Most groups are smoke-free |
| Drug of choice | Consider AA, Narcotics Anonymous, or a combination of both |
| Source: Reference 29. | |
Some studies20,21—but not all27—suggest that individuals with co-occurring psychiatric disorders have more difficulty participating fully in AA than those without such comorbidity.
Kelly et al20 examined the influence of major depressive disorder (MDD) on AA participation and treatment outcomes in 2,161 men with substance use disorders. During the first year after discharge from inpatient substance-abuse treatment, MDD appeared to have no effect on AA attendance rates or substance abuse outcomes. However, the 110 men with co-occurring MDD showed significantly less social participation in AA—with fewer friends, contacts/calls, and sponsors—and they continued to suffer substantial depression.
This suggests that clinicians could help patients with MDD engage in AA by addressing social anxiety symptoms (how to ask for a sponsor, the importance of establishing and using the AA social network). Carefully monitoring and treating acute depressive symptoms also may enhance AA social participation, especially for patients new to AA.
Impaired social relating is common to many psychiatric disorders—such as psychotic disorders, anxiety disorders, trauma and personality disorders—and social skills training may help other dual-diagnosis patients entering AA. Those with impaired self-control—as with mania or overt psychosis—or inability to maintain interpersonal boundaries are best referred to AA after you stabilize symptoms that would disrupt the group setting.
- Alcoholics Anonymous. General Services Office, PO Box 459, Grand Central Station, New York, NY 10163. Phone (212) 870-3400. www.aa.org
- AA Grapevine: International Journal of Alcoholics Anonymous. http://www.aagrapevine.org.
- National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov
- National Institute on Drug Abuse. http://www.nida.nih.gov/NIDAHome.html
- Cocaine Anonymous. http://www.ca.org
- Narcotics Anonymous. http://www.na.org
- Secular Organizations for Sobriety. http://www.sossobriety.org
- SMART Recovery. http://www.smartrecovery.org
1. Alcoholics Anonymous World Services Inc. Alcoholics Anonymous (4th ed). New York: Alcoholics Anonymous World Services; 2001.
2. Alcoholics Anonymous World Services Inc. AA fact file: what is Alcoholics Anonymous? http://www.aa.org/default/en_about_aa_sub.cfm?subpageid=13&pageid=24.
3. Timko C, Moos RH, Finney JW, Lesar MD. Long-term outcomes of alcohol use disorders: Comparing untreated individuals with those in Alcoholics Anonymous and formal treatment. J Stud Alcohol 2000;61:529-40.
4. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes. Alcohol Clin Exp Res 1998;22(6):1300-11.
5. Project MATCH Research Group. Matching alcoholism treatment to client heterogeneity: Project MATCH post-treatment drinking outcomes. J Stud Alcohol 1997;58:7-29.
6. Humphreys K, Wing S, McCarty D, et al. Self-help organizations for alcohol and drug problems: toward evidence-based practice and policy. J Subst Abuse Treat 2004;26(3):151-8.
7. Sisson RW, Mallams JH. The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings. Am J Drug Alcohol Abuse 1981;8(3):371-6.
8. Humphreys K, Huebsch PD, Finney JW, Moos RH. A comparative evaluation of substance abuse treatment: V. Substance abuse treatment can enhance the effectiveness of self-help groups. Alcohol Clin Exp Res 1999;23(3):558-63.
9. Emrick CD, Tonigan JS, Montgomery H, Little L. Alcoholics Anonymous: what is currently known? In: McCrady BS, Miller WR (eds). Research on Alcoholics Anonymous: opportunities and alternatives. New Brunswick, NJ: Rutgers Center of Alcohol Studies; 1993.
10. Tonigan JS, Toscova R, Miller WR. Meta-analysis of the literature on Alcoholics Anonymous: sample and study characteristics moderate findings. J Stud Alcohol 1996;57:65-72.
11. Morgenstern J, Labouvie E, McCrady BS, et al. Affiliation with Alcoholics Anonymous after treatment: a study of its therapeutic effects and mechanisms of action. J Consult Clin Psychol 1997;65(5):768-77.
12. Connors GJ, Tonigan JS, Miller WR, for the MATCH Research Group. A longitudinal model of intake symptomatology, AA participation and outcome: retrospective study of the Project MATCH outpatient and aftercare samples. J Stud Alcohol 2001;62(6):817-25.
13. Montgomery HA, Miller WR, Tonigan JS. Differences among AA groups: implications for research. J Stud Alcohol 1993;54(4):502-4.
14. Kelly JF. Self-help for substance-use disorders: History, effectiveness, knowledge gaps, and research opportunities. Clin Psychol Rev 2003;23:639-63.
15. Kownacki RJ, Shadish WR. Does Alcoholics Anonymous work? The results from a meta-analysis of controlled experiments. Subst Use Misuse 1999;34(13):1897-1916.
16. Project MATCH Research Group. Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity): rationale and methods for a multisite clinical trial matching patients to alcoholism treatment. Alcohol Clin Exp Res 1993;17(6):1130-45.
17. Project MATCH Research Group. Project MATCH secondary a priori hypotheses. Addiction 1997;92(12):1671-98.
18. Ouimette PC, Finney JW, Moos RH. Twelve-step and cognitive-behavioral treatment for substance abuse: A comparison of treatment effectiveness. J Consult Clin Psychol 1997;65(2):230-40.
19. Ouimette PC, Moos RH, Finney JW. Influence of outpatient treatment and 12-step group involvement on one-year substance abuse treatment outcomes. J Stud Alcohol 1998;59:513-22.
20. Kelly JF, McKellar JD, Moos R. Major depression in patients with substance use disorders: relationship to 12-step self-help involvement and substance use outcomes. Addiction 2003;98:499-508.
21. Bogenschutz MP, Akin SJ. Step participation and attitudes toward 12-step meetings in dual diagnosis patients. Alcohol Treat Q 2001;18:31-46.
22. Montgomery HA, Miller WR, Tonigan JS. Does Alcoholics Anonymous involvement predict treatment outcome? J Subst Abuse Treat 1995;12(4):241-6.
23. Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend 2005;77(2):177-84.
24. Forman RF. One AA meeting doesn’t fit all: 6 keys to prescribing 12-step programs. Current Psychiatry 2002;1(10):16-24.
25. Kelly JF, Myers MG, Brown SA. Do adolescents affiliate with 12-step groups? A multivariate process model of effects. J Stud Alcohol 2002;63:293-304.
26. Winzelberg A, Humphreys K. Should patients’ religiosity influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. J Consult Clin Psychol 1999;67(5):790-4.
27. Ouimette P, Humphreys K, Moos RH, et al. Self-help group participation among substance use disorder patients with posttraumatic stress disorder. J Subst Abuse Treat 2001;20(1):25-32.
Many clinicians refer alcohol-dependent patients to Alcoholics Anonymous, but how effective is AA in reducing drinking? Evidence is elusive—partly because of AA’s tradition of anonymity—but clinician encouragement is among three variables that appear essential to successful AA use.
The pioneer of twelve-step programs (Box 1),1,2 AA is a widely accessible, free adjunct to professional alcohol abuse treatment. This article describes the evidence supporting AA’s efficacy for reducing drinking among persons with alcohol use disorders. We also recommend referral strategies that increase AA participation and discuss special needs of alcohol-dependent patients with comorbid psychiatric disorders.
Alcoholics Anonymous (AA) was founded in 1935 in Akron, OH, by Bill Wilson and Robert Smith, MD, two professionals struggling with alcohol dependence. They joined together to help each other stop drinking.
Their success inspired them to help others, and this mutual-aid society grew under the name Alcoholics Anonymous. AA redefined the then-prevalent view of alcohol dependence as a moral failing, instead conceptualizing it as a disease that can be arrested—but not cured—by alcohol abstinence. The only requirements for AA membership are “a desire to stop drinking,” a respect for maintaining anonymity, and a desire to join a fellowship of mutual support for the goal of abstaining from alcohol.
In 1939, Wilson described AA’s theory and fellowship methods and defined its twelve steps of personal recovery,1 referred to in AA as “The Big Book.” Today, the worldwide fellowship has more than 2 million members, with a male:female ratio of 2:1.2
KEYS TO AA SUCCESS
Besides clinician encouragement, two patient variables—severity of alcohol dependence and self-efficacy—have been associated with successful AA use.
Clinician encouragement. When psychiatrists and other clinicians encourage alcohol-dependent patients to attend AA, the rate of AA use increases and drinking decreases.3-7 When clinicians remain interested in alcohol-dependent patients’ AA use—rather than simply recommending AA—patients are more likely to follow through with a referral and to participate long enough to obtain benefit.
Clinicians play an important role in helping patients benefit from AA referral (Box 2).6 Patients who are personally helped to an AA group will rapidly attend, whereas those only given referral information are unlikely to follow up.7 Moreover, clinicians who encourage patients to attend AA and follow up on that attendance have more patients who attend and participate in AA than do less proactive clinicians.8
Disseminate information about alcohol dependence self-help groups such as AA
Become knowledgeable about local AA options to facilitate referral and cooperation
Invite AA groups to use your institutional or clinic space to hold groups and meetings
Offer appropriate self-help referrals to family members, such as Al-Anon and Al-Ateen family groups
Try to match patient preferences with local AA groups, such as women’s AA, and young people’s AA meetings
Use AA as an adjunct to professional care, rather than stand-alone treatment
Learn about alternatives to 12-step treatments—such as SMART Recovery (a CBT-based treatment), Secular Organization for Sobriety, or Women for Sobriety—for patients who prefer other self-help options
Source: Adapted from Workgroup on Substance Abuse Self-Help Organizations’ expert consensus statement, reference 6.
Self-efficacy. Believing that one can abstain from drinking is associated with being able to reduce one’s drinking. Alcohol-dependent patients with self-efficacy are more likely to use AA, and this trait is believed to be a component of the change process associated with reduced drinking.11,12
HOW EFFECTIVE IS AA?
Randomized, controlled trials (RCTs) may be the “gold standard” for determining any treatment’s efficacy, but constructing an RCT of AA use is complicated. AA does not engage in or support research, which makes AA use difficult to administer as a controlled variable in clinical trials. Also, the variability of AA groups and environments confounds the interpretation of study results and limits their application to populations at large.13
Even so, AA can be effective as an adjunct to professional treatments—such as detoxification—and as aftercare to maintain reduced drinking:
- Kelly’s14 comprehensive review and critical analysis of the main studies through 2003 showed a correlation between professional treatment plus AA attendance and improved outcomes.
- Project MATCH-—a large RCT—also supports AA’s benefits, as reported in smaller, less rigorously controlled studies.4,5
- Kownacki and Shadish15 found poorer 12-month drinking outcomes with AA alone, compared with other treatments or no treatment. Their review assessed attendance as a predictor of alcohol use outcomes, and most subjects were attending AA under court orders. Because AA’s philosophy stresses that members must desire to stop drinking (Table 1), these study results may not apply to the voluntary, motivated individuals who usually use AA.
- Two other meta-analyses9,10 that included nonrandomized studies and RCTs showed that attending AA has modest, favorable effects in reducing drinking and improving psychosocial functioning.
Tonigan et al10 rated 74 studies of alcohol use disorders that measured patients’ affiliation with AA and drinking outcome and/or psychosocial adjustment. Most were cross-sectional inpatient studies; few used collateral interviews or biological measures to confirm self-report data. Most used poor methodology, and their assessments were not psychometrically validated.
Outpatient studies showed positive correlations between AA attendance/involvement and:
- reduced drinking
- improved psychological adjustment and improved family relationships.
All three meta-analyses excluded studies of alcohol-dependent individuals with co-occurring drug use disorders, leaving unaddressed the effect of adjunctive AA in that population.
Table 1
AA’s Twelve Steps of personal recovery
|
| Source: Reprinted with permission, Alcoholics Anonymous World Services (AAWS), Inc. 2005. Permission to reprint does not mean that AAWS has reviewed or approved the contents of this publication, or that AA necessarily agrees with the views expressed herein. |
- 12 sessions of cognitive-behavioral coping skills (CBT)
- 4 sessions of motivational enhancement therapy (MET).
Project MATCH thus found that a twelve-step individual therapy was at least as effective as CBT and MET in reducing post-treatment drinking and maintaining abstinence.
Real-world efficacy. A naturalistic study that resembled Project MATCH enrolled 3,018 male military veterans with substance use disorders across 15 program sites.18 Drug dependence was not excluded, and 51% of the men had co-occurring alcohol and drug dependence.
Participants received inpatient detoxification, followed by 21 to 28 days of intensive twelve-step treatment, CBT, or both. Alcohol and drug abuse declined equally in all three groups, and subjects were referred for outpatient aftercare and self-help groups. After 1 year, involvement in a self-help group predicted better outcome, regardless of the initial treatment.19
Unlike earlier studies,15,20,21 this trial found that individuals with co-occurring psychiatric disorders and those legally mandated to get treatment did as well at 1-year follow-up as those without these variables. It provides additional evidence that twelve-step treatments can reduce substance use across varied populations, including patients with co-occurring alcohol and drug dependence.
AA ATTENDANCE VS. PARTICIPATION
Twelve-step programs appear most effective for individuals who actively participate. This may seem obvious, but most studies of 12-step treatments have monitored meeting attendance rather than engagement. Most studies that separate these variables report that active participation—not passive attendance—correlates with reduced substance use.
Montgomery et al22 followed 66 alcohol-dependent individuals in a 12-step oriented, 28-day residential treatment program and investigated:
- relationships between AA attendance and participation
- drinking outcomes over 31 weeks after treatment.
Similarly, Project MATCH participants involved in AA during the first 6 months after treatment had more-frequent abstinent days in the 7 to 12 months after treatment. AA “involvement” included identifying oneself as an AA member, working the steps, having an AA sponsor, and celebrating sobriety milestones.12
The National Drug Abuse Collaborative Cocaine Treatment Study is the most detailed analysis of self-help use. This multi-site RCT by Weiss and colleagues enrolled 487 individuals for behavioral treatment of cocaine dependence.23
Twelve-step attendance did not predict substance use outcomes, but active participation (such as making coffee for a meeting or reading AA literature) in a given month predicted decreased substance use in the following month. Subjects whose participation increased over the first 3 months showed reduced drug use in the following 3 months. Interestingly, those who participated without attending meetings regularly (such as by reading AA literature or calling a sponsor) benefited as much as those who attended meetings more regularly.
Summary. Actively engaging in 12-step treatment—as measured by identifying with the fellowship and following the steps—appears more important to success than simply attending meetings.
EFFECTIVE AA REFERRALS
To encourage engagement when referring, try to match patients to AA groups attended by persons with whom they feel comfortable (Table 2).24 Adolescents, for example, tend to have more difficulty engaging and remaining in AA than do adults.25 One remedy may be to recommend a Young Person’s AA group composed primarily of adolescents and young adults.
Although AA embraces a spiritual approach to recovery, a person can benefit from participating without having a specific religious affiliation or spiritual beliefs.12,26 The emphasis on spirituality and a “higher power” varies from one AA group to another as well as from region to region. For patients who are uncomfortable with AA’s religiosity, other self-help options for alcohol dependence include SMART Recovery (a CBT-based treatment) and Secular Organization for Sobriety (see Related resources).
Table 2
Matching patients to AA groups:
6 variables to consider
| Variable | Suggestion |
|---|---|
| Socioeconomic status | Match by group location |
| Gender | Women-only groups |
| Age | Young people’s AA |
| Religious content | Beginners’ groups and speaker or topic discussion groups have less-spiritual focus, whereas Step groups and Sunday meetings have more spiritual focus |
| Smoking status | Most groups are smoke-free |
| Drug of choice | Consider AA, Narcotics Anonymous, or a combination of both |
| Source: Reference 29. | |
Some studies20,21—but not all27—suggest that individuals with co-occurring psychiatric disorders have more difficulty participating fully in AA than those without such comorbidity.
Kelly et al20 examined the influence of major depressive disorder (MDD) on AA participation and treatment outcomes in 2,161 men with substance use disorders. During the first year after discharge from inpatient substance-abuse treatment, MDD appeared to have no effect on AA attendance rates or substance abuse outcomes. However, the 110 men with co-occurring MDD showed significantly less social participation in AA—with fewer friends, contacts/calls, and sponsors—and they continued to suffer substantial depression.
This suggests that clinicians could help patients with MDD engage in AA by addressing social anxiety symptoms (how to ask for a sponsor, the importance of establishing and using the AA social network). Carefully monitoring and treating acute depressive symptoms also may enhance AA social participation, especially for patients new to AA.
Impaired social relating is common to many psychiatric disorders—such as psychotic disorders, anxiety disorders, trauma and personality disorders—and social skills training may help other dual-diagnosis patients entering AA. Those with impaired self-control—as with mania or overt psychosis—or inability to maintain interpersonal boundaries are best referred to AA after you stabilize symptoms that would disrupt the group setting.
- Alcoholics Anonymous. General Services Office, PO Box 459, Grand Central Station, New York, NY 10163. Phone (212) 870-3400. www.aa.org
- AA Grapevine: International Journal of Alcoholics Anonymous. http://www.aagrapevine.org.
- National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov
- National Institute on Drug Abuse. http://www.nida.nih.gov/NIDAHome.html
- Cocaine Anonymous. http://www.ca.org
- Narcotics Anonymous. http://www.na.org
- Secular Organizations for Sobriety. http://www.sossobriety.org
- SMART Recovery. http://www.smartrecovery.org
Many clinicians refer alcohol-dependent patients to Alcoholics Anonymous, but how effective is AA in reducing drinking? Evidence is elusive—partly because of AA’s tradition of anonymity—but clinician encouragement is among three variables that appear essential to successful AA use.
The pioneer of twelve-step programs (Box 1),1,2 AA is a widely accessible, free adjunct to professional alcohol abuse treatment. This article describes the evidence supporting AA’s efficacy for reducing drinking among persons with alcohol use disorders. We also recommend referral strategies that increase AA participation and discuss special needs of alcohol-dependent patients with comorbid psychiatric disorders.
Alcoholics Anonymous (AA) was founded in 1935 in Akron, OH, by Bill Wilson and Robert Smith, MD, two professionals struggling with alcohol dependence. They joined together to help each other stop drinking.
Their success inspired them to help others, and this mutual-aid society grew under the name Alcoholics Anonymous. AA redefined the then-prevalent view of alcohol dependence as a moral failing, instead conceptualizing it as a disease that can be arrested—but not cured—by alcohol abstinence. The only requirements for AA membership are “a desire to stop drinking,” a respect for maintaining anonymity, and a desire to join a fellowship of mutual support for the goal of abstaining from alcohol.
In 1939, Wilson described AA’s theory and fellowship methods and defined its twelve steps of personal recovery,1 referred to in AA as “The Big Book.” Today, the worldwide fellowship has more than 2 million members, with a male:female ratio of 2:1.2
KEYS TO AA SUCCESS
Besides clinician encouragement, two patient variables—severity of alcohol dependence and self-efficacy—have been associated with successful AA use.
Clinician encouragement. When psychiatrists and other clinicians encourage alcohol-dependent patients to attend AA, the rate of AA use increases and drinking decreases.3-7 When clinicians remain interested in alcohol-dependent patients’ AA use—rather than simply recommending AA—patients are more likely to follow through with a referral and to participate long enough to obtain benefit.
Clinicians play an important role in helping patients benefit from AA referral (Box 2).6 Patients who are personally helped to an AA group will rapidly attend, whereas those only given referral information are unlikely to follow up.7 Moreover, clinicians who encourage patients to attend AA and follow up on that attendance have more patients who attend and participate in AA than do less proactive clinicians.8
Disseminate information about alcohol dependence self-help groups such as AA
Become knowledgeable about local AA options to facilitate referral and cooperation
Invite AA groups to use your institutional or clinic space to hold groups and meetings
Offer appropriate self-help referrals to family members, such as Al-Anon and Al-Ateen family groups
Try to match patient preferences with local AA groups, such as women’s AA, and young people’s AA meetings
Use AA as an adjunct to professional care, rather than stand-alone treatment
Learn about alternatives to 12-step treatments—such as SMART Recovery (a CBT-based treatment), Secular Organization for Sobriety, or Women for Sobriety—for patients who prefer other self-help options
Source: Adapted from Workgroup on Substance Abuse Self-Help Organizations’ expert consensus statement, reference 6.
Self-efficacy. Believing that one can abstain from drinking is associated with being able to reduce one’s drinking. Alcohol-dependent patients with self-efficacy are more likely to use AA, and this trait is believed to be a component of the change process associated with reduced drinking.11,12
HOW EFFECTIVE IS AA?
Randomized, controlled trials (RCTs) may be the “gold standard” for determining any treatment’s efficacy, but constructing an RCT of AA use is complicated. AA does not engage in or support research, which makes AA use difficult to administer as a controlled variable in clinical trials. Also, the variability of AA groups and environments confounds the interpretation of study results and limits their application to populations at large.13
Even so, AA can be effective as an adjunct to professional treatments—such as detoxification—and as aftercare to maintain reduced drinking:
- Kelly’s14 comprehensive review and critical analysis of the main studies through 2003 showed a correlation between professional treatment plus AA attendance and improved outcomes.
- Project MATCH-—a large RCT—also supports AA’s benefits, as reported in smaller, less rigorously controlled studies.4,5
- Kownacki and Shadish15 found poorer 12-month drinking outcomes with AA alone, compared with other treatments or no treatment. Their review assessed attendance as a predictor of alcohol use outcomes, and most subjects were attending AA under court orders. Because AA’s philosophy stresses that members must desire to stop drinking (Table 1), these study results may not apply to the voluntary, motivated individuals who usually use AA.
- Two other meta-analyses9,10 that included nonrandomized studies and RCTs showed that attending AA has modest, favorable effects in reducing drinking and improving psychosocial functioning.
Tonigan et al10 rated 74 studies of alcohol use disorders that measured patients’ affiliation with AA and drinking outcome and/or psychosocial adjustment. Most were cross-sectional inpatient studies; few used collateral interviews or biological measures to confirm self-report data. Most used poor methodology, and their assessments were not psychometrically validated.
Outpatient studies showed positive correlations between AA attendance/involvement and:
- reduced drinking
- improved psychological adjustment and improved family relationships.
All three meta-analyses excluded studies of alcohol-dependent individuals with co-occurring drug use disorders, leaving unaddressed the effect of adjunctive AA in that population.
Table 1
AA’s Twelve Steps of personal recovery
|
| Source: Reprinted with permission, Alcoholics Anonymous World Services (AAWS), Inc. 2005. Permission to reprint does not mean that AAWS has reviewed or approved the contents of this publication, or that AA necessarily agrees with the views expressed herein. |
- 12 sessions of cognitive-behavioral coping skills (CBT)
- 4 sessions of motivational enhancement therapy (MET).
Project MATCH thus found that a twelve-step individual therapy was at least as effective as CBT and MET in reducing post-treatment drinking and maintaining abstinence.
Real-world efficacy. A naturalistic study that resembled Project MATCH enrolled 3,018 male military veterans with substance use disorders across 15 program sites.18 Drug dependence was not excluded, and 51% of the men had co-occurring alcohol and drug dependence.
Participants received inpatient detoxification, followed by 21 to 28 days of intensive twelve-step treatment, CBT, or both. Alcohol and drug abuse declined equally in all three groups, and subjects were referred for outpatient aftercare and self-help groups. After 1 year, involvement in a self-help group predicted better outcome, regardless of the initial treatment.19
Unlike earlier studies,15,20,21 this trial found that individuals with co-occurring psychiatric disorders and those legally mandated to get treatment did as well at 1-year follow-up as those without these variables. It provides additional evidence that twelve-step treatments can reduce substance use across varied populations, including patients with co-occurring alcohol and drug dependence.
AA ATTENDANCE VS. PARTICIPATION
Twelve-step programs appear most effective for individuals who actively participate. This may seem obvious, but most studies of 12-step treatments have monitored meeting attendance rather than engagement. Most studies that separate these variables report that active participation—not passive attendance—correlates with reduced substance use.
Montgomery et al22 followed 66 alcohol-dependent individuals in a 12-step oriented, 28-day residential treatment program and investigated:
- relationships between AA attendance and participation
- drinking outcomes over 31 weeks after treatment.
Similarly, Project MATCH participants involved in AA during the first 6 months after treatment had more-frequent abstinent days in the 7 to 12 months after treatment. AA “involvement” included identifying oneself as an AA member, working the steps, having an AA sponsor, and celebrating sobriety milestones.12
The National Drug Abuse Collaborative Cocaine Treatment Study is the most detailed analysis of self-help use. This multi-site RCT by Weiss and colleagues enrolled 487 individuals for behavioral treatment of cocaine dependence.23
Twelve-step attendance did not predict substance use outcomes, but active participation (such as making coffee for a meeting or reading AA literature) in a given month predicted decreased substance use in the following month. Subjects whose participation increased over the first 3 months showed reduced drug use in the following 3 months. Interestingly, those who participated without attending meetings regularly (such as by reading AA literature or calling a sponsor) benefited as much as those who attended meetings more regularly.
Summary. Actively engaging in 12-step treatment—as measured by identifying with the fellowship and following the steps—appears more important to success than simply attending meetings.
EFFECTIVE AA REFERRALS
To encourage engagement when referring, try to match patients to AA groups attended by persons with whom they feel comfortable (Table 2).24 Adolescents, for example, tend to have more difficulty engaging and remaining in AA than do adults.25 One remedy may be to recommend a Young Person’s AA group composed primarily of adolescents and young adults.
Although AA embraces a spiritual approach to recovery, a person can benefit from participating without having a specific religious affiliation or spiritual beliefs.12,26 The emphasis on spirituality and a “higher power” varies from one AA group to another as well as from region to region. For patients who are uncomfortable with AA’s religiosity, other self-help options for alcohol dependence include SMART Recovery (a CBT-based treatment) and Secular Organization for Sobriety (see Related resources).
Table 2
Matching patients to AA groups:
6 variables to consider
| Variable | Suggestion |
|---|---|
| Socioeconomic status | Match by group location |
| Gender | Women-only groups |
| Age | Young people’s AA |
| Religious content | Beginners’ groups and speaker or topic discussion groups have less-spiritual focus, whereas Step groups and Sunday meetings have more spiritual focus |
| Smoking status | Most groups are smoke-free |
| Drug of choice | Consider AA, Narcotics Anonymous, or a combination of both |
| Source: Reference 29. | |
Some studies20,21—but not all27—suggest that individuals with co-occurring psychiatric disorders have more difficulty participating fully in AA than those without such comorbidity.
Kelly et al20 examined the influence of major depressive disorder (MDD) on AA participation and treatment outcomes in 2,161 men with substance use disorders. During the first year after discharge from inpatient substance-abuse treatment, MDD appeared to have no effect on AA attendance rates or substance abuse outcomes. However, the 110 men with co-occurring MDD showed significantly less social participation in AA—with fewer friends, contacts/calls, and sponsors—and they continued to suffer substantial depression.
This suggests that clinicians could help patients with MDD engage in AA by addressing social anxiety symptoms (how to ask for a sponsor, the importance of establishing and using the AA social network). Carefully monitoring and treating acute depressive symptoms also may enhance AA social participation, especially for patients new to AA.
Impaired social relating is common to many psychiatric disorders—such as psychotic disorders, anxiety disorders, trauma and personality disorders—and social skills training may help other dual-diagnosis patients entering AA. Those with impaired self-control—as with mania or overt psychosis—or inability to maintain interpersonal boundaries are best referred to AA after you stabilize symptoms that would disrupt the group setting.
- Alcoholics Anonymous. General Services Office, PO Box 459, Grand Central Station, New York, NY 10163. Phone (212) 870-3400. www.aa.org
- AA Grapevine: International Journal of Alcoholics Anonymous. http://www.aagrapevine.org.
- National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov
- National Institute on Drug Abuse. http://www.nida.nih.gov/NIDAHome.html
- Cocaine Anonymous. http://www.ca.org
- Narcotics Anonymous. http://www.na.org
- Secular Organizations for Sobriety. http://www.sossobriety.org
- SMART Recovery. http://www.smartrecovery.org
1. Alcoholics Anonymous World Services Inc. Alcoholics Anonymous (4th ed). New York: Alcoholics Anonymous World Services; 2001.
2. Alcoholics Anonymous World Services Inc. AA fact file: what is Alcoholics Anonymous? http://www.aa.org/default/en_about_aa_sub.cfm?subpageid=13&pageid=24.
3. Timko C, Moos RH, Finney JW, Lesar MD. Long-term outcomes of alcohol use disorders: Comparing untreated individuals with those in Alcoholics Anonymous and formal treatment. J Stud Alcohol 2000;61:529-40.
4. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes. Alcohol Clin Exp Res 1998;22(6):1300-11.
5. Project MATCH Research Group. Matching alcoholism treatment to client heterogeneity: Project MATCH post-treatment drinking outcomes. J Stud Alcohol 1997;58:7-29.
6. Humphreys K, Wing S, McCarty D, et al. Self-help organizations for alcohol and drug problems: toward evidence-based practice and policy. J Subst Abuse Treat 2004;26(3):151-8.
7. Sisson RW, Mallams JH. The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings. Am J Drug Alcohol Abuse 1981;8(3):371-6.
8. Humphreys K, Huebsch PD, Finney JW, Moos RH. A comparative evaluation of substance abuse treatment: V. Substance abuse treatment can enhance the effectiveness of self-help groups. Alcohol Clin Exp Res 1999;23(3):558-63.
9. Emrick CD, Tonigan JS, Montgomery H, Little L. Alcoholics Anonymous: what is currently known? In: McCrady BS, Miller WR (eds). Research on Alcoholics Anonymous: opportunities and alternatives. New Brunswick, NJ: Rutgers Center of Alcohol Studies; 1993.
10. Tonigan JS, Toscova R, Miller WR. Meta-analysis of the literature on Alcoholics Anonymous: sample and study characteristics moderate findings. J Stud Alcohol 1996;57:65-72.
11. Morgenstern J, Labouvie E, McCrady BS, et al. Affiliation with Alcoholics Anonymous after treatment: a study of its therapeutic effects and mechanisms of action. J Consult Clin Psychol 1997;65(5):768-77.
12. Connors GJ, Tonigan JS, Miller WR, for the MATCH Research Group. A longitudinal model of intake symptomatology, AA participation and outcome: retrospective study of the Project MATCH outpatient and aftercare samples. J Stud Alcohol 2001;62(6):817-25.
13. Montgomery HA, Miller WR, Tonigan JS. Differences among AA groups: implications for research. J Stud Alcohol 1993;54(4):502-4.
14. Kelly JF. Self-help for substance-use disorders: History, effectiveness, knowledge gaps, and research opportunities. Clin Psychol Rev 2003;23:639-63.
15. Kownacki RJ, Shadish WR. Does Alcoholics Anonymous work? The results from a meta-analysis of controlled experiments. Subst Use Misuse 1999;34(13):1897-1916.
16. Project MATCH Research Group. Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity): rationale and methods for a multisite clinical trial matching patients to alcoholism treatment. Alcohol Clin Exp Res 1993;17(6):1130-45.
17. Project MATCH Research Group. Project MATCH secondary a priori hypotheses. Addiction 1997;92(12):1671-98.
18. Ouimette PC, Finney JW, Moos RH. Twelve-step and cognitive-behavioral treatment for substance abuse: A comparison of treatment effectiveness. J Consult Clin Psychol 1997;65(2):230-40.
19. Ouimette PC, Moos RH, Finney JW. Influence of outpatient treatment and 12-step group involvement on one-year substance abuse treatment outcomes. J Stud Alcohol 1998;59:513-22.
20. Kelly JF, McKellar JD, Moos R. Major depression in patients with substance use disorders: relationship to 12-step self-help involvement and substance use outcomes. Addiction 2003;98:499-508.
21. Bogenschutz MP, Akin SJ. Step participation and attitudes toward 12-step meetings in dual diagnosis patients. Alcohol Treat Q 2001;18:31-46.
22. Montgomery HA, Miller WR, Tonigan JS. Does Alcoholics Anonymous involvement predict treatment outcome? J Subst Abuse Treat 1995;12(4):241-6.
23. Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend 2005;77(2):177-84.
24. Forman RF. One AA meeting doesn’t fit all: 6 keys to prescribing 12-step programs. Current Psychiatry 2002;1(10):16-24.
25. Kelly JF, Myers MG, Brown SA. Do adolescents affiliate with 12-step groups? A multivariate process model of effects. J Stud Alcohol 2002;63:293-304.
26. Winzelberg A, Humphreys K. Should patients’ religiosity influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. J Consult Clin Psychol 1999;67(5):790-4.
27. Ouimette P, Humphreys K, Moos RH, et al. Self-help group participation among substance use disorder patients with posttraumatic stress disorder. J Subst Abuse Treat 2001;20(1):25-32.
1. Alcoholics Anonymous World Services Inc. Alcoholics Anonymous (4th ed). New York: Alcoholics Anonymous World Services; 2001.
2. Alcoholics Anonymous World Services Inc. AA fact file: what is Alcoholics Anonymous? http://www.aa.org/default/en_about_aa_sub.cfm?subpageid=13&pageid=24.
3. Timko C, Moos RH, Finney JW, Lesar MD. Long-term outcomes of alcohol use disorders: Comparing untreated individuals with those in Alcoholics Anonymous and formal treatment. J Stud Alcohol 2000;61:529-40.
4. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes. Alcohol Clin Exp Res 1998;22(6):1300-11.
5. Project MATCH Research Group. Matching alcoholism treatment to client heterogeneity: Project MATCH post-treatment drinking outcomes. J Stud Alcohol 1997;58:7-29.
6. Humphreys K, Wing S, McCarty D, et al. Self-help organizations for alcohol and drug problems: toward evidence-based practice and policy. J Subst Abuse Treat 2004;26(3):151-8.
7. Sisson RW, Mallams JH. The use of systematic encouragement and community access procedures to increase attendance at Alcoholic Anonymous and Al-Anon meetings. Am J Drug Alcohol Abuse 1981;8(3):371-6.
8. Humphreys K, Huebsch PD, Finney JW, Moos RH. A comparative evaluation of substance abuse treatment: V. Substance abuse treatment can enhance the effectiveness of self-help groups. Alcohol Clin Exp Res 1999;23(3):558-63.
9. Emrick CD, Tonigan JS, Montgomery H, Little L. Alcoholics Anonymous: what is currently known? In: McCrady BS, Miller WR (eds). Research on Alcoholics Anonymous: opportunities and alternatives. New Brunswick, NJ: Rutgers Center of Alcohol Studies; 1993.
10. Tonigan JS, Toscova R, Miller WR. Meta-analysis of the literature on Alcoholics Anonymous: sample and study characteristics moderate findings. J Stud Alcohol 1996;57:65-72.
11. Morgenstern J, Labouvie E, McCrady BS, et al. Affiliation with Alcoholics Anonymous after treatment: a study of its therapeutic effects and mechanisms of action. J Consult Clin Psychol 1997;65(5):768-77.
12. Connors GJ, Tonigan JS, Miller WR, for the MATCH Research Group. A longitudinal model of intake symptomatology, AA participation and outcome: retrospective study of the Project MATCH outpatient and aftercare samples. J Stud Alcohol 2001;62(6):817-25.
13. Montgomery HA, Miller WR, Tonigan JS. Differences among AA groups: implications for research. J Stud Alcohol 1993;54(4):502-4.
14. Kelly JF. Self-help for substance-use disorders: History, effectiveness, knowledge gaps, and research opportunities. Clin Psychol Rev 2003;23:639-63.
15. Kownacki RJ, Shadish WR. Does Alcoholics Anonymous work? The results from a meta-analysis of controlled experiments. Subst Use Misuse 1999;34(13):1897-1916.
16. Project MATCH Research Group. Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity): rationale and methods for a multisite clinical trial matching patients to alcoholism treatment. Alcohol Clin Exp Res 1993;17(6):1130-45.
17. Project MATCH Research Group. Project MATCH secondary a priori hypotheses. Addiction 1997;92(12):1671-98.
18. Ouimette PC, Finney JW, Moos RH. Twelve-step and cognitive-behavioral treatment for substance abuse: A comparison of treatment effectiveness. J Consult Clin Psychol 1997;65(2):230-40.
19. Ouimette PC, Moos RH, Finney JW. Influence of outpatient treatment and 12-step group involvement on one-year substance abuse treatment outcomes. J Stud Alcohol 1998;59:513-22.
20. Kelly JF, McKellar JD, Moos R. Major depression in patients with substance use disorders: relationship to 12-step self-help involvement and substance use outcomes. Addiction 2003;98:499-508.
21. Bogenschutz MP, Akin SJ. Step participation and attitudes toward 12-step meetings in dual diagnosis patients. Alcohol Treat Q 2001;18:31-46.
22. Montgomery HA, Miller WR, Tonigan JS. Does Alcoholics Anonymous involvement predict treatment outcome? J Subst Abuse Treat 1995;12(4):241-6.
23. Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug Alcohol Depend 2005;77(2):177-84.
24. Forman RF. One AA meeting doesn’t fit all: 6 keys to prescribing 12-step programs. Current Psychiatry 2002;1(10):16-24.
25. Kelly JF, Myers MG, Brown SA. Do adolescents affiliate with 12-step groups? A multivariate process model of effects. J Stud Alcohol 2002;63:293-304.
26. Winzelberg A, Humphreys K. Should patients’ religiosity influence clinicians’ referral to 12-step self-help groups? Evidence from a study of 3,018 male substance abuse patients. J Consult Clin Psychol 1999;67(5):790-4.
27. Ouimette P, Humphreys K, Moos RH, et al. Self-help group participation among substance use disorder patients with posttraumatic stress disorder. J Subst Abuse Treat 2001;20(1):25-32.
Acamprosate: For discomfort of early alcohol abstinence
Acamprosate, a gamma-aminobutyric acid (GABA) analogue used worldwide to treat alcohol dependence, is available in this country (Table 1). The agent appears to reduce discomfort—including restlessness, anxiety, dysphoria, and insomnia—common within the first 6 months of alcohol abstinence. In clinical trials, it prolonged abstinence in alcohol-dependent patients who completed an initial detoxification and were receiving relapse prevention treatment.
HOW IT WORKS
Acamprosate’s chemical structure resembles both GABA and taurine, an endogenous amino acid derivative that enhances GABA-ergic activity.1 The drug’s synthetic structure facilitates its passage across the blood-brain barrier, and the brain mediates its major effect.
Table 1
Acamprosate: Fast facts
| Brand name: |
| Campral |
| Class: |
| GABA analogue |
| FDA-approved indication: |
| Maintaining abstinence in alcohol-dependent patients |
| Approval date: |
| July 29, 2004 |
| Manufacturer: |
| Forest Pharmaceuticals |
| Dosing form: |
| 333-mg tablets |
| Recommended dosage: |
| Adults age |
The mechanisms by which acamprosate promotes abstinence in alcohol dependence are unknown. The drug may bind to N-methyl-D-aspartate (NMDA) glutamate receptors and work as a partial antagonist, but direct ligand activity does not appear to cause most of its central actions. Rather, acamprosate interacts with glutamate and GABA to normalize the hyperexcitability that accompanies early abstinence (Table 2).
Table 2
Acamprosate’s proposed mechanisms of action*
| Neurotransmitter interactions | Pharmacologic effect | Clinical effect |
| Glutamatergic system (NMDA receptor) | Blocks increased glutamate release in nucleus accumbens during alcohol withdrawal; may bind to receptor site as partial antagonist | Decreased arousal, craving, and dysphoria associated with early abstinence |
| GABAergic system (GABAAreceptor) | Normalizes alcohol-induced decrease in basal GABA concentrations in nucleus accumbens | Same as above |
| Neuromodulator interactions | ||
| Taurine | Increases extracellular taurine concentrations in nucleus accumbens; taurine shifts the glutamate/GABA balance in favor of GABAergic activity | Mimics increase in taurine seen with acute alcohol intake, likely facilitating GABA normalization |
| * Based on animal models of alcohol dependence | ||
| Source: reference 3 | ||
PHARMACOKINETICS
Acamprosate’s bioavailability is relatively poor (11%), so it is prescribed to be taken three times daily. Although patients in clinical practice often have trouble following frequent daily dosing schedules, subjects in one study reportedly had little difficulty adhering to this regimen.2
Acamprosate’s half-life is approximately 13 hours, and it reaches peak plasma concentrations in 3.5 to 9.5 hours. Pharmaceutical studies indicate that food does not significantly affect absorption.
Although 666 mg tid has shown efficacy in clinical trials, the blood level at which acamprosate becomes therapeutic has not been determined.
The drug reaches steady-state blood levels within 1 week, meaning it will not be fully effective for 5 to 7 days but may still reach therapeutic blood levels during that time. Advise patients that adverse effects may not clear for 5 to 7 days after discontinuation.
Acamprosate does not bind with plasma proteins, so it will not interact with drugs that do. The drug, which is renally excreted in an unmetabolized state, has not been found to interact adversely with commonly prescribed antidepressants, anxiolytics, antipsychotics, alcohol, or disulfiram.3 How acamprosate interacts with renally excreted drugs such as lithium is unknown.
In two studies following 24 healthy volunteers4 and 23 alcohol-dependent patients,5 concomitant naltrexone, 50 to 100 mg/d, and acamprosate, 2 to 3 g/d, increased acamprosate plasma concentrations as much as 25%, but did not change plasma levels of naltrexone or its major metabolite. Naltrexone might delay gastric emptying, thereby increasing acamprosate absorption.
EFFICACY
Acamprosate with psychosocial treatment increased total abstinent days in:
- 15 randomized, controlled trials (RCT) conducted in Europe6
- a meta-analysis of 12 methodologically comparable RCTs conducted in Europe7
- an open-label trial in France that studied acamprosate as an adjunct to treatment-as-usual in primary care settings.2
Acamprosate may improve patient retention in substance abuse treatment, which predicts favorable outcomes.7 Patients receiving acamprosate and treatment-as-usual reported fewer alcohol-related problems and improved quality of life compared with treatment-as-usual alone.2 Reduced subjective craving for alcohol is difficult to study and has not been sufficiently shown.
Combined pharmacotherapy. It is unclear whether acamprosate and naltrexone or disulfiram are more effective than acamprosate alone.3,6,7
In one multi-center, placebo-controlled trial, a subgroup of severely alcohol-dependent patients sought acamprosate/disulfiram therapy. The combination was shown to be safe and increased total abstinent days compared with acamprosate or disulfiram alone, but effectiveness could not be determined because of the self-selection bias of those who requested combined pharmacotherapy.
In one 12-week RCT,8 naltrexone/acamprosate therapy was more effective than acamprosate alone—but not more effective than naltrexone alone—in reducing time to first drink and relapse to heavy drinking.
The multi-center COMBINE (Combining Medications and Behavioral Interventions) study,9 funded by the National Institute on Alcohol Abuse and Alcoholism, is comparing the efficacy of naltrexone, acamprosate, and both agents when given with low-intensity psychosocial treatment or moderate-intensity, alcohol-specific psychosocial treatment. Preliminary safety, tolerability, and adherence results with the acamprosate/naltrexone combination have been promising. Efficacy findings are expected later this year.
SAFETY
Acamprosate is contraindicated in patients with severely compromised renal function (creatinine clearance
The drug is safe for patients with mild to moderate alcohol-related liver disease as defined by the Child-Pugh classification of hepatic impairment.10 For a patient with severe liver disease, consult his or her gastroenterologist to gauge risks and benefits, as acamprosate can cause adverse GI effects.
Acamprosate has not been tested in children or the elderly, although one study suggests efficacy in alcohol-dependent adolescents ages 16 to 19.7. The agent’s safety during pregnancy or lactation is unknown.
TOLERABILITY
Acamprosate has been well-tolerated in clinical trials. Discontinuation rates because of adverse effects have been similar in treatment and placebo groups.7
GI side effects are most common, with overall rates of 17% and 11% among acamprosate and placebo groups, respectively.7 Diarrhea may be transient and may also resolve with a reduced dosage.6
Slightly higher rates of suicidal ideation were reported among patients taking acamprosate vs those taking placebo (1.4 % vs. 0.5% in short-term [10 Screen all patients taking acamprosate for suicidal ideation or behavior.
Other reported side effects include headache, abdominal pain, nausea and vomiting, dyspepsia, flatulence, pruritus, rash, drowsiness, and dizziness. Acamprosate has no abuse potential and low potential for toxicity in overdose. Higher acamprosate plasma levels during combined acamprosate/naltrexone treatment may increase risk of diarrhea.9
CLINICAL IMPLICATIONS
Drinking alcohol while taking acamprosate will not make a patient sick, which makes it an alternative for patients who fear the harsh effects of “slipping up” while taking disulfiram.
Also, acamprosate does not interact with prescription opioids. By contrast, naltrexone is contraindicated in patients taking opioids for pain.
Related resources
- Campral Web site. www.campral.com
- National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov
- National Institute on Drug Abuse. www.nida.nih.gov
Drug brand names
- Acamprosate • Campral
- Disulfiram • Antabuse
- Naltrexone • ReVia
Disclosure
Drs. Connery and Weiss receive research/grant support from Ortho-McNeil Pharmaceutical. Dr. Weiss is also a speaker for Forest Laboratories.
1. Dahchour A, De Witte P. Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog Neurobiol 2000;60:343-62.
2. Kiritze-Topor P, Huas D, Rosenzweig C, et al. A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care. Alcohol Alcohol 2004;39:520-7.
3. Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us? Alcohol Alcohol 2004;39:542-7.
4. Mason BJ, Goodman AM, Dixon RM, et al. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology 2002;27:596-606.
5. Johnson BA, O’Malley SS, Ciraulo DA, et al. Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J Clin Psychopharmacol 2003;23:281-93.
6. Overman GP, Teter CJ, Guthrie SK. Acamprosate for the adjunctive treatment of alcohol dependence. Ann Pharmacother 2003;37:1090-9.
7. Carmen B, Angeles M, Ana M, Maria AJ. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction 2004;99:811-28.
8. Kiefer F, Jahn H, Tarnaske T, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 2003;60:92-9.
9. The COMBINE study research group. Testing combined pharmacotherapies and behavioral interventions in alcohol dependence: rationale and methods. Alcohol Clin Exp Res 2003;27:1107-22.
10. Campral prescribing information. Available at: http://www.campral.com. Accessed Jan. 7, 2005.
Acamprosate, a gamma-aminobutyric acid (GABA) analogue used worldwide to treat alcohol dependence, is available in this country (Table 1). The agent appears to reduce discomfort—including restlessness, anxiety, dysphoria, and insomnia—common within the first 6 months of alcohol abstinence. In clinical trials, it prolonged abstinence in alcohol-dependent patients who completed an initial detoxification and were receiving relapse prevention treatment.
HOW IT WORKS
Acamprosate’s chemical structure resembles both GABA and taurine, an endogenous amino acid derivative that enhances GABA-ergic activity.1 The drug’s synthetic structure facilitates its passage across the blood-brain barrier, and the brain mediates its major effect.
Table 1
Acamprosate: Fast facts
| Brand name: |
| Campral |
| Class: |
| GABA analogue |
| FDA-approved indication: |
| Maintaining abstinence in alcohol-dependent patients |
| Approval date: |
| July 29, 2004 |
| Manufacturer: |
| Forest Pharmaceuticals |
| Dosing form: |
| 333-mg tablets |
| Recommended dosage: |
| Adults age |
The mechanisms by which acamprosate promotes abstinence in alcohol dependence are unknown. The drug may bind to N-methyl-D-aspartate (NMDA) glutamate receptors and work as a partial antagonist, but direct ligand activity does not appear to cause most of its central actions. Rather, acamprosate interacts with glutamate and GABA to normalize the hyperexcitability that accompanies early abstinence (Table 2).
Table 2
Acamprosate’s proposed mechanisms of action*
| Neurotransmitter interactions | Pharmacologic effect | Clinical effect |
| Glutamatergic system (NMDA receptor) | Blocks increased glutamate release in nucleus accumbens during alcohol withdrawal; may bind to receptor site as partial antagonist | Decreased arousal, craving, and dysphoria associated with early abstinence |
| GABAergic system (GABAAreceptor) | Normalizes alcohol-induced decrease in basal GABA concentrations in nucleus accumbens | Same as above |
| Neuromodulator interactions | ||
| Taurine | Increases extracellular taurine concentrations in nucleus accumbens; taurine shifts the glutamate/GABA balance in favor of GABAergic activity | Mimics increase in taurine seen with acute alcohol intake, likely facilitating GABA normalization |
| * Based on animal models of alcohol dependence | ||
| Source: reference 3 | ||
PHARMACOKINETICS
Acamprosate’s bioavailability is relatively poor (11%), so it is prescribed to be taken three times daily. Although patients in clinical practice often have trouble following frequent daily dosing schedules, subjects in one study reportedly had little difficulty adhering to this regimen.2
Acamprosate’s half-life is approximately 13 hours, and it reaches peak plasma concentrations in 3.5 to 9.5 hours. Pharmaceutical studies indicate that food does not significantly affect absorption.
Although 666 mg tid has shown efficacy in clinical trials, the blood level at which acamprosate becomes therapeutic has not been determined.
The drug reaches steady-state blood levels within 1 week, meaning it will not be fully effective for 5 to 7 days but may still reach therapeutic blood levels during that time. Advise patients that adverse effects may not clear for 5 to 7 days after discontinuation.
Acamprosate does not bind with plasma proteins, so it will not interact with drugs that do. The drug, which is renally excreted in an unmetabolized state, has not been found to interact adversely with commonly prescribed antidepressants, anxiolytics, antipsychotics, alcohol, or disulfiram.3 How acamprosate interacts with renally excreted drugs such as lithium is unknown.
In two studies following 24 healthy volunteers4 and 23 alcohol-dependent patients,5 concomitant naltrexone, 50 to 100 mg/d, and acamprosate, 2 to 3 g/d, increased acamprosate plasma concentrations as much as 25%, but did not change plasma levels of naltrexone or its major metabolite. Naltrexone might delay gastric emptying, thereby increasing acamprosate absorption.
EFFICACY
Acamprosate with psychosocial treatment increased total abstinent days in:
- 15 randomized, controlled trials (RCT) conducted in Europe6
- a meta-analysis of 12 methodologically comparable RCTs conducted in Europe7
- an open-label trial in France that studied acamprosate as an adjunct to treatment-as-usual in primary care settings.2
Acamprosate may improve patient retention in substance abuse treatment, which predicts favorable outcomes.7 Patients receiving acamprosate and treatment-as-usual reported fewer alcohol-related problems and improved quality of life compared with treatment-as-usual alone.2 Reduced subjective craving for alcohol is difficult to study and has not been sufficiently shown.
Combined pharmacotherapy. It is unclear whether acamprosate and naltrexone or disulfiram are more effective than acamprosate alone.3,6,7
In one multi-center, placebo-controlled trial, a subgroup of severely alcohol-dependent patients sought acamprosate/disulfiram therapy. The combination was shown to be safe and increased total abstinent days compared with acamprosate or disulfiram alone, but effectiveness could not be determined because of the self-selection bias of those who requested combined pharmacotherapy.
In one 12-week RCT,8 naltrexone/acamprosate therapy was more effective than acamprosate alone—but not more effective than naltrexone alone—in reducing time to first drink and relapse to heavy drinking.
The multi-center COMBINE (Combining Medications and Behavioral Interventions) study,9 funded by the National Institute on Alcohol Abuse and Alcoholism, is comparing the efficacy of naltrexone, acamprosate, and both agents when given with low-intensity psychosocial treatment or moderate-intensity, alcohol-specific psychosocial treatment. Preliminary safety, tolerability, and adherence results with the acamprosate/naltrexone combination have been promising. Efficacy findings are expected later this year.
SAFETY
Acamprosate is contraindicated in patients with severely compromised renal function (creatinine clearance
The drug is safe for patients with mild to moderate alcohol-related liver disease as defined by the Child-Pugh classification of hepatic impairment.10 For a patient with severe liver disease, consult his or her gastroenterologist to gauge risks and benefits, as acamprosate can cause adverse GI effects.
Acamprosate has not been tested in children or the elderly, although one study suggests efficacy in alcohol-dependent adolescents ages 16 to 19.7. The agent’s safety during pregnancy or lactation is unknown.
TOLERABILITY
Acamprosate has been well-tolerated in clinical trials. Discontinuation rates because of adverse effects have been similar in treatment and placebo groups.7
GI side effects are most common, with overall rates of 17% and 11% among acamprosate and placebo groups, respectively.7 Diarrhea may be transient and may also resolve with a reduced dosage.6
Slightly higher rates of suicidal ideation were reported among patients taking acamprosate vs those taking placebo (1.4 % vs. 0.5% in short-term [10 Screen all patients taking acamprosate for suicidal ideation or behavior.
Other reported side effects include headache, abdominal pain, nausea and vomiting, dyspepsia, flatulence, pruritus, rash, drowsiness, and dizziness. Acamprosate has no abuse potential and low potential for toxicity in overdose. Higher acamprosate plasma levels during combined acamprosate/naltrexone treatment may increase risk of diarrhea.9
CLINICAL IMPLICATIONS
Drinking alcohol while taking acamprosate will not make a patient sick, which makes it an alternative for patients who fear the harsh effects of “slipping up” while taking disulfiram.
Also, acamprosate does not interact with prescription opioids. By contrast, naltrexone is contraindicated in patients taking opioids for pain.
Related resources
- Campral Web site. www.campral.com
- National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov
- National Institute on Drug Abuse. www.nida.nih.gov
Drug brand names
- Acamprosate • Campral
- Disulfiram • Antabuse
- Naltrexone • ReVia
Disclosure
Drs. Connery and Weiss receive research/grant support from Ortho-McNeil Pharmaceutical. Dr. Weiss is also a speaker for Forest Laboratories.
Acamprosate, a gamma-aminobutyric acid (GABA) analogue used worldwide to treat alcohol dependence, is available in this country (Table 1). The agent appears to reduce discomfort—including restlessness, anxiety, dysphoria, and insomnia—common within the first 6 months of alcohol abstinence. In clinical trials, it prolonged abstinence in alcohol-dependent patients who completed an initial detoxification and were receiving relapse prevention treatment.
HOW IT WORKS
Acamprosate’s chemical structure resembles both GABA and taurine, an endogenous amino acid derivative that enhances GABA-ergic activity.1 The drug’s synthetic structure facilitates its passage across the blood-brain barrier, and the brain mediates its major effect.
Table 1
Acamprosate: Fast facts
| Brand name: |
| Campral |
| Class: |
| GABA analogue |
| FDA-approved indication: |
| Maintaining abstinence in alcohol-dependent patients |
| Approval date: |
| July 29, 2004 |
| Manufacturer: |
| Forest Pharmaceuticals |
| Dosing form: |
| 333-mg tablets |
| Recommended dosage: |
| Adults age |
The mechanisms by which acamprosate promotes abstinence in alcohol dependence are unknown. The drug may bind to N-methyl-D-aspartate (NMDA) glutamate receptors and work as a partial antagonist, but direct ligand activity does not appear to cause most of its central actions. Rather, acamprosate interacts with glutamate and GABA to normalize the hyperexcitability that accompanies early abstinence (Table 2).
Table 2
Acamprosate’s proposed mechanisms of action*
| Neurotransmitter interactions | Pharmacologic effect | Clinical effect |
| Glutamatergic system (NMDA receptor) | Blocks increased glutamate release in nucleus accumbens during alcohol withdrawal; may bind to receptor site as partial antagonist | Decreased arousal, craving, and dysphoria associated with early abstinence |
| GABAergic system (GABAAreceptor) | Normalizes alcohol-induced decrease in basal GABA concentrations in nucleus accumbens | Same as above |
| Neuromodulator interactions | ||
| Taurine | Increases extracellular taurine concentrations in nucleus accumbens; taurine shifts the glutamate/GABA balance in favor of GABAergic activity | Mimics increase in taurine seen with acute alcohol intake, likely facilitating GABA normalization |
| * Based on animal models of alcohol dependence | ||
| Source: reference 3 | ||
PHARMACOKINETICS
Acamprosate’s bioavailability is relatively poor (11%), so it is prescribed to be taken three times daily. Although patients in clinical practice often have trouble following frequent daily dosing schedules, subjects in one study reportedly had little difficulty adhering to this regimen.2
Acamprosate’s half-life is approximately 13 hours, and it reaches peak plasma concentrations in 3.5 to 9.5 hours. Pharmaceutical studies indicate that food does not significantly affect absorption.
Although 666 mg tid has shown efficacy in clinical trials, the blood level at which acamprosate becomes therapeutic has not been determined.
The drug reaches steady-state blood levels within 1 week, meaning it will not be fully effective for 5 to 7 days but may still reach therapeutic blood levels during that time. Advise patients that adverse effects may not clear for 5 to 7 days after discontinuation.
Acamprosate does not bind with plasma proteins, so it will not interact with drugs that do. The drug, which is renally excreted in an unmetabolized state, has not been found to interact adversely with commonly prescribed antidepressants, anxiolytics, antipsychotics, alcohol, or disulfiram.3 How acamprosate interacts with renally excreted drugs such as lithium is unknown.
In two studies following 24 healthy volunteers4 and 23 alcohol-dependent patients,5 concomitant naltrexone, 50 to 100 mg/d, and acamprosate, 2 to 3 g/d, increased acamprosate plasma concentrations as much as 25%, but did not change plasma levels of naltrexone or its major metabolite. Naltrexone might delay gastric emptying, thereby increasing acamprosate absorption.
EFFICACY
Acamprosate with psychosocial treatment increased total abstinent days in:
- 15 randomized, controlled trials (RCT) conducted in Europe6
- a meta-analysis of 12 methodologically comparable RCTs conducted in Europe7
- an open-label trial in France that studied acamprosate as an adjunct to treatment-as-usual in primary care settings.2
Acamprosate may improve patient retention in substance abuse treatment, which predicts favorable outcomes.7 Patients receiving acamprosate and treatment-as-usual reported fewer alcohol-related problems and improved quality of life compared with treatment-as-usual alone.2 Reduced subjective craving for alcohol is difficult to study and has not been sufficiently shown.
Combined pharmacotherapy. It is unclear whether acamprosate and naltrexone or disulfiram are more effective than acamprosate alone.3,6,7
In one multi-center, placebo-controlled trial, a subgroup of severely alcohol-dependent patients sought acamprosate/disulfiram therapy. The combination was shown to be safe and increased total abstinent days compared with acamprosate or disulfiram alone, but effectiveness could not be determined because of the self-selection bias of those who requested combined pharmacotherapy.
In one 12-week RCT,8 naltrexone/acamprosate therapy was more effective than acamprosate alone—but not more effective than naltrexone alone—in reducing time to first drink and relapse to heavy drinking.
The multi-center COMBINE (Combining Medications and Behavioral Interventions) study,9 funded by the National Institute on Alcohol Abuse and Alcoholism, is comparing the efficacy of naltrexone, acamprosate, and both agents when given with low-intensity psychosocial treatment or moderate-intensity, alcohol-specific psychosocial treatment. Preliminary safety, tolerability, and adherence results with the acamprosate/naltrexone combination have been promising. Efficacy findings are expected later this year.
SAFETY
Acamprosate is contraindicated in patients with severely compromised renal function (creatinine clearance
The drug is safe for patients with mild to moderate alcohol-related liver disease as defined by the Child-Pugh classification of hepatic impairment.10 For a patient with severe liver disease, consult his or her gastroenterologist to gauge risks and benefits, as acamprosate can cause adverse GI effects.
Acamprosate has not been tested in children or the elderly, although one study suggests efficacy in alcohol-dependent adolescents ages 16 to 19.7. The agent’s safety during pregnancy or lactation is unknown.
TOLERABILITY
Acamprosate has been well-tolerated in clinical trials. Discontinuation rates because of adverse effects have been similar in treatment and placebo groups.7
GI side effects are most common, with overall rates of 17% and 11% among acamprosate and placebo groups, respectively.7 Diarrhea may be transient and may also resolve with a reduced dosage.6
Slightly higher rates of suicidal ideation were reported among patients taking acamprosate vs those taking placebo (1.4 % vs. 0.5% in short-term [10 Screen all patients taking acamprosate for suicidal ideation or behavior.
Other reported side effects include headache, abdominal pain, nausea and vomiting, dyspepsia, flatulence, pruritus, rash, drowsiness, and dizziness. Acamprosate has no abuse potential and low potential for toxicity in overdose. Higher acamprosate plasma levels during combined acamprosate/naltrexone treatment may increase risk of diarrhea.9
CLINICAL IMPLICATIONS
Drinking alcohol while taking acamprosate will not make a patient sick, which makes it an alternative for patients who fear the harsh effects of “slipping up” while taking disulfiram.
Also, acamprosate does not interact with prescription opioids. By contrast, naltrexone is contraindicated in patients taking opioids for pain.
Related resources
- Campral Web site. www.campral.com
- National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov
- National Institute on Drug Abuse. www.nida.nih.gov
Drug brand names
- Acamprosate • Campral
- Disulfiram • Antabuse
- Naltrexone • ReVia
Disclosure
Drs. Connery and Weiss receive research/grant support from Ortho-McNeil Pharmaceutical. Dr. Weiss is also a speaker for Forest Laboratories.
1. Dahchour A, De Witte P. Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog Neurobiol 2000;60:343-62.
2. Kiritze-Topor P, Huas D, Rosenzweig C, et al. A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care. Alcohol Alcohol 2004;39:520-7.
3. Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us? Alcohol Alcohol 2004;39:542-7.
4. Mason BJ, Goodman AM, Dixon RM, et al. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology 2002;27:596-606.
5. Johnson BA, O’Malley SS, Ciraulo DA, et al. Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J Clin Psychopharmacol 2003;23:281-93.
6. Overman GP, Teter CJ, Guthrie SK. Acamprosate for the adjunctive treatment of alcohol dependence. Ann Pharmacother 2003;37:1090-9.
7. Carmen B, Angeles M, Ana M, Maria AJ. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction 2004;99:811-28.
8. Kiefer F, Jahn H, Tarnaske T, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 2003;60:92-9.
9. The COMBINE study research group. Testing combined pharmacotherapies and behavioral interventions in alcohol dependence: rationale and methods. Alcohol Clin Exp Res 2003;27:1107-22.
10. Campral prescribing information. Available at: http://www.campral.com. Accessed Jan. 7, 2005.
1. Dahchour A, De Witte P. Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog Neurobiol 2000;60:343-62.
2. Kiritze-Topor P, Huas D, Rosenzweig C, et al. A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care. Alcohol Alcohol 2004;39:520-7.
3. Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us? Alcohol Alcohol 2004;39:542-7.
4. Mason BJ, Goodman AM, Dixon RM, et al. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology 2002;27:596-606.
5. Johnson BA, O’Malley SS, Ciraulo DA, et al. Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J Clin Psychopharmacol 2003;23:281-93.
6. Overman GP, Teter CJ, Guthrie SK. Acamprosate for the adjunctive treatment of alcohol dependence. Ann Pharmacother 2003;37:1090-9.
7. Carmen B, Angeles M, Ana M, Maria AJ. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction 2004;99:811-28.
8. Kiefer F, Jahn H, Tarnaske T, et al. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 2003;60:92-9.
9. The COMBINE study research group. Testing combined pharmacotherapies and behavioral interventions in alcohol dependence: rationale and methods. Alcohol Clin Exp Res 2003;27:1107-22.
10. Campral prescribing information. Available at: http://www.campral.com. Accessed Jan. 7, 2005.