Clinical Inquiries

How effective are pharmacologic agents for alcoholism?

Hunt RR, Nashelsky J, Chavey W. J Fam Pract 2002 Jun;51(6):577.

Evidence-based Answer

Naltrexone (ReVia) and nalmefene (Revex) are the most effective agents for treating alcoholism. Acamprosate is effective but not available in the United States. Serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), and lithium work best in patients with alcoholism and comorbid depression, anxiety, or bipolar disorder. Disulfiram (Antabuse) decreases drink frequency, but is no better than placebo for other outcomes. Greater effectiveness is achieved when pharmacologic agents are combined with either counseling or Alcoholics Anonymous programs. (Grade of recommendation: B, based on multiple randomized controlled studies with short and incomplete follow-up of patients.)

Evidence-based Summary

Naltrexone (50 mg qd), nalmefene (10–80 mg qd), and acamprosate (dose based on patient weight) are all superior to placebo and other agents such as the SSRIs, disulfiram, and serotonergic agents in reducing relapse rates and the phenomena of craving and in increasing abstinence rates.1-6 For example, naltrexone reduces relapse rates by one half to two thirds.4,6 However, these outcomes apply only to patients who completed the study protocol; noncompleters accounted for up to more than 50% of study participants. When compared with placebo, nalmefene taken for 3 to 24 months significantly reduced relapse without affecting abstinence rates or cravings.3 When compared with placebo, disulfiram failed to significantly increase abstinence rates or decrease relapse rates or cravings.2

In European studies, acamprosate taken for 3 to 24 months significantly increased abstinence rates, but did not significantly decrease relapse or cravings as compared with placebo.3 Fifteen studies evaluating serotonergic agents, lithium, and SSRIs (including citalopram, viqualine, fluoxetine, and others) taken for 2 to 12 weeks have shown promise for increasing abstinence rates and decreasing cravings in alcoholic patients with coexisting psychiatric conditions such as depression, anxiety, and bipolar disorder.2,7,8 Studies combining pharmacologic intervention with Alcoholics Anonymous’s 12-step program or psychological interventions showed the most significant effects on decreasing cravings and relapse rates and increasing abstinence rates.2,3,6,9-12

Clinical Commentary

The most important consideration in the pharmacologic therapy of alcoholism is to remember that pharmacologic therapy is merely adjunctive and should be combined with ancillary services designed to assist in recovery. All of the medications described above have shown some efficacy, but comparative data is scarce. The choice of a particular agent may be made on the basis of cost, acceptance by the patient, and co-morbid conditions. Disulfiram costs approximately one-third as much as naltrexone and may be more familiar to some patients.

Recommendations from Others

According to the American Society of Addiction Medicine, patients who comply with a combination of medication, education, and counseling have favorable short-term and long-term benefits.1 Naltraxone and acamprosate effectively reduce cravings and increase abstinence.

Figures

Grade of recommendation based on the evidence
Agent Decreased cravings at 6 & 12 months Increased abstinence rates 6 & 12 months Decreased relapse rates at 6 & 12 months Comorbidities: alcoholism with anxiety, depression, or bipolar disorder
Naltrexone B B B D
Nalmefene C C B D
Serotonergics D D D B
SSRIs D D D B
Disulfiram C C C D
Lithium D D D B
Acamprosate B B C D
Based on the Oxford Center for Evidence-based Medicine Levels of Evidence (May 2001).

References

  1. Garbutt JC, West SL, Carey TS, Lohr KN, Crews FTnull Pharmacological treatment of alcohol dependence: a review of the evidence. 1999. Volume 281. Page(s): 1318-25.
  2. Fiellin DA, Reid MC, O’Connor PGnull New therapies for alcohol problems: application to primary care. 2000. Volume 8. Page(s): 227-37.
  3. Chick J, Anton R, Checinski Ket al. A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. 2000. Volume 35. Page(s): 587-93.
  4. O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville Bnull Naltrexone and coping skills therapy for alcohol dependence. A controlled study. 1992. Volume 9. Page(s): 881-7.
  5. Mason BJ, Salvato FR, Williams LD, Ritvo EC, Cutler RBnull A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. 1999. Volume 56. Page(s): 719-24.
  6. O’Connor PG, Farren CK, Rounsaville BJ, O’Malley SSnull A preliminary investigation of the management of alcohol dependence with naltrexone by primary care providers. 1997. Volume 103. Page(s): 477-82.
  7. Fawcett J, Clark DC, Gibbons RDet al. Evaluation of lithium therapy for alcoholism. 1984. Volume 45. Page(s): 494-9.
  8. Merry J, Reynolds C, Bailey J, Coppen Anull Prophylactic treatment of alcoholism by lithium carbonate. A controlled study. 1976. Volume 1. Page(s): 481-2.
  9. Srisurapanont M, Jarusuraisin Nnull Opioid antagonists for alcohol dependence (Cohrane Review). In: The Cochrane Library, Issue 4, 2001. Oxford, England: Update Software..
  10. O’Malley SS, Jaffe AJ, Chang Get al. Six-month follow-up of naltrexone and psychotherapy for alcohol dependence. 1996. Volume 53. Page(s): 217-24.
  11. No author listed. Principles of Addiction Medicine. Graham AW, Schultz TK, Wilford BB, eds..
  12. Jaffe AJ, Rounsaville B, Chang G, Schottenfeld RS, Meyer RE, O’Malley SSnull Naltrexone, relapse prevention, and supportive therapy with alcoholics: an analysis of patient treatment matching. 1996. Volume 64. Page(s): 1044-53.