WEEKLY / FEBRUARY 13, 2013, VOL. 3, NO. 6   Send Feedback l View Online
Psychiatric News Update
The Voice of the American Psychiatric Association and the Psychiatric Community
twitter facebook facebook


Pharmacological Treatments for Heavy Drinking

by henry r. kranzler, m.d.

henry r. kranzler m.d.Drinking patterns vary considerably among individuals. However, medical and psychosocial problems increase as average drinking exceeds low levels and the frequency of intoxication increases. Although individuals with an alcohol use disorder (AUD) are often the focus of treatment efforts, heavy drinkers (who may not meet criteria for an AUD) are more numerous and a growing public health concern. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has identified low-risk drinking as weekly consumption of less than 8 drinks for women and 15 drinks for men, with no heavy drinking (i.e., for women, no more than 3 drinks in a day and, for men, no more than 4 drinks in a day). The clinically important adverse effects of heavy drinking suggest that interventions, including pharmacotherapy, are warranted for individuals who regularly exceed the NIAAA guidelines.

The major pharmacological approaches to treat heavy drinking are deterrent medications (e.g., disulfiram), which produce adverse effects when alcohol is consumed, and medications that modify the activity of one or more of the neurotransmitter systems mediating alcohol reinforcement (e.g., opioid antagonists). Disulfiram was the first medication approved by the U.S. Food and Drug Administration (FDA) to treat alcoholism, which occurred prior to the implementation of the rigorous requirements for efficacy that now exist. When combined with alcohol, disulfiram produces a characteristic set of unpleasant signs and symptoms, which are thought to deter drinking. However, in the largest controlled study of disulfiram, its beneficial effects were modest, though it may be more useful among alcoholics with whom special efforts are made to ensure compliance.

The opioid antagonists naltrexone and nalmefene have been approved to treat alcohol dependence in the United States and the European Union, respectively. In 1994, the FDA approved oral naltrexone, based on the results of two single-site studies, which showed it to be efficacious in the prevention of relapse to heavy drinking. The most recent meta-analysis of naltrexone showed that it reduced the risk of any heavy drinking by about 17% relative to placebo and significantly reduced the number of heavy drinking days. Two alternatives to daily naltrexone treatment include a long-acting injectable formulation of naltrexone, which the FDA approved in 2006, and the “targeted” use of the oral medication to high-risk drinking situations. This as-needed approach was the basis for the recent approval of nalmefene by the European Medicines Agency to reduce heavy drinking in alcohol-dependent individuals.

Acamprosate is an amino acid derivative, the safety and efficacy of which have been well demonstrated in Europe. In 2004, the FDA approved acamprosate for clinical use in the United States. A subsequent meta-analysis showed that acamprosate significantly reduced the risk of any drinking and increased the cumulative duration of abstinence. However, placebo-controlled, multicenter trials in the United States, Europe and Australia failed to detect beneficial effects of acamprosate in the treatment of alcohol dependence.

The anticonvulsant topiramate, although not approved to treat alcohol dependence, shows considerable promise in single-site and multi-center trials to reduce heavy drinking. The active medication resulted in significant reductions in drinks/day, drinks/drinking day, drinking days, and heavy drinking days. Although apparently more efficacious than other treatments for heavy drinking, topiramate treatment is associated with a variety of adverse events, which can limit its clinical utility.

In summary, a growing number of medications have been approved to treat alcohol dependence. It appears that these medications also can be used to reduce heavy drinking in individuals whose goal is not to stop drinking completely. This creates a new opportunity for primary care practitioners and psychiatrists to intervene pharmacologically with heavy drinkers. Further research that considers how best to assist heavy drinkers in reducing their drinking is needed to diminish the substantial medical and psychosocial risks associated with this behavior.


1. Babor TF, Kranzler HR, Lauerman RL. Social drinking as a health and psychosocial risk factor: Anstie's limit revisited. In: Galanter M, ed. Recent Developments in Alcoholism. Vol 5. New York, NY: Plenum; 1987:373-402.

2. Kranzler HR, Babor TF, Lauerman RJ. Problems associated with average alcohol consumption and frequency of intoxication in a medical population. Alcohol Clin Exp Res 14:119-126, 1990.

3. National Institute on Alcohol Abuse and Alcoholism:

4. Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, James KE, Lacoursiere RB, Lee KK, Lowenstam I, Maany I, Neiderhiser D, Nocks JJ, Shaw S. Disulfiram treatment of alcoholism. A Veterans Administration cooperative study. JAMA 256:1449-1455, 1986.

5. Chick J, Gough K, Falkowski W, Kershaw P, Hore B, Mehta B,Ritson B, Ropner R, Torley D. Disulfiram treatment of alcoholism. Brit J Psychiatry 161:84-89, 1992.

6. Brewer C. Controlled trials of Antabuse in alcoholism: the importance of supervision and adequate dosage. Acta Psychiatr Scand Suppl. 369:51-8, 1992.

7. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 49:881-887, 1992.

8. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876-880, 1992.

9. Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. (8):CD001867, 2010.

10. Kranzler HR, Tennen H, Penta C, Bohn MJ. Targeted naltrexone treatment of early problem drinkers. Addict Behav 22:431-436, 1997.

11. Kranzler HR, Armeli S, Tennen H, Blomqvist O, Oncken C, Petry N, Feinn R. Targeted naltrexone for early problem drinkers. J Clin Psychopharmacol 23:294-304, 2003.

12. Kranzler HR, Tennen H, Armeli S, Chan G, Covault J, Arias A, Oncken C. Targeted naltrexone for problem drinkers. J Clin Psychopharmacol 29:350-357, 2009.

13. Mann K, Bladström A, Torup L, Gual A, van den Brink W. Extending the treatment options in alcohol dependence: A randomized controlled study of as-needed nalmefene. Biol Psychiatry. 2012 Dec 10. doi:pii: S0006-3223(12)00942-0. 10.1016/j.biopsych.2012.10.020. [Epub ahead of print]

14. Gual A, He Y, Torup L, van den Brink W, Mann K. ESENSE 2: A randomised, double-blind, placebo-controlled study of nalmefene, as-needed use in alcohol dependent patients. Alcohol Clin Exp Res 36:246A, 2012.

15. van den Brink W, Sørensen P, Torup L, Mann K, Gual A. Long-term efficacy, tolerability, and safety of nalmefene as-needed in alcohol-dependence: A randomized, double-blind, placebo-controlled study. Alcohol Clin Exp Res 36:247A, 2012.

16. Rösner S, Hackl-Herrwerth A, Leucht S, Lehert P, Vecchi S, Soyka M. Acamprosate for alcohol dependence. Cochrane Database Syst Rev (9):CD004332, 2010.

17. Mason BJ, Goodman AM, Chabac S, Lehert P. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J Psychiatr Res 40:383-393, 2006.

18. Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence–The COMBINE Study: a randomized controlled trial. JAMA. 295:2003-2017, 2006.

19. Mann K, Lemenager T, Hoffmann S, Reinhard I, Hermann D, Batra A, Berner M, Wodarz N, Heinz A, Smolka MN, Zimmermann US, Wellek S, Kiefer F, Anton RF; The PREDICT Study Team. Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study. Addict Biol. 2012 Dec 12. doi: 10.1111/adb.12012. [Epub ahead of print]

20. Morley KC, Teesson M, Reid SC, Sannibale C, Thomson C, Phung N, Weltman M, Bell JR, Richardson K, Haber PS. Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial. Addiction. 101:1451-62, 2006.

21. Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 361:1677-1685, 2003.

22. Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O'Malley SS, Swift RM; Topiramate for Alcoholism Advisory Board; Topiramate for Alcoholism Study Group. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 298:1641-1651, 2007.

23. Miranda R Jr, MacKillop J, Monti PM, Rohsenow DJ, Tidey J, Gwaltney C, Swift R, Ray L, McGeary J. Effects of topiramate on urge to drink and the subjective effects of alcohol: a preliminary laboratory study. Alcohol Clin Exp Res 32:489-497, 2008.

Henry R. Kranzler, M.D., is a professor of psychiatry at the Perelman School of Medicine of the University of Pennsylvania. He is the co-editor of Clinical Manual of Addiction Psychopharmacology, published by American Psychiatric Publishing. APA members may purchase the book at a discount here.

>>Back to Newsletter



 subscribe to blog rss

>>subscribe to blog via email

Copyright © 2013 American Psychiatric Association. All rights reserved.