Family history of alcoholism affects response to drug used to treat heavy drinking

New study in Biological Psychiatry

Philadelphia, PA, September 19, 2007 – Naltrexone is one of four oral medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcoholism. A recent large multicenter research study of alcohol dependence supported by the National Institute of Alcoholism and Alcohol Abuse (NIAAA), the COMBINE Study, suggested that naltrexone produced a modest but significant benefit but another FDA-approved medication, acamprosate, was ineffective. Perhaps consistent with its modest effects in COMBINE, naltrexone is not widely prescribed in the treatment of alcoholism. Yet, clinicians report that naltrexone may have significant benefits for individual patients. To make naltrexone a more useful medication, it would be important to begin to identify groups of patients who might be more or less likely to show a significant clinical benefit from naltrexone prescription and to understand the causes of differential naltrexone efficacy. A new study that will appear in the September 15th issue of Biological Psychiatry suggests that alcohol dependent individuals with a family history of alcohol dependence may be more likely than alcohol dependent individuals without a family history of alcohol dependence to reduce their drinking in the laboratory when prescribed naltrexone.

Krishnan-Sarin and colleagues at the NIAAA Center for the Translational Neuroscience of Alcoholism studied alcohol consumption in the laboratory by alcohol-dependent individuals who were not seeking treatment. The participants were studied in the laboratory after 6 days of treatment with 0 mg (placebo), 50 mg, or 100 mg of naltrexone. The authors discovered that naltrexone decreased drinking in those with a family history of alcoholism and this effect was greatest with the highest naltrexone dose. However, it increased drinking in those without a family history of alcoholism and this effect was greatest at the highest naltrexone dose.

John H. Krystal, M.D., one of the authors, notes that “When studied in large groups, naltrexone appears to have a rather small effect upon the ability to reduce drinking or remain abstinent from alcohol. However, there is growing evidence that there are subgroups of patients who show substantial benefit from naltrexone, even when naltrexone fails to work in the overall trial (see Gueorguieva R et al. Biol Psychiatry. 2007 Jun 1;61(11):1290-5).” According to Suchitra Krishnan-Sarin, Ph.D., the lead author, “The results suggest that family history of alcoholism may be an important predictor of clinical response to naltrexone and could potentially be used to guide clinical practice.” Dr. Krystal agrees, “These data suggest that family history might influence the optimal dosing of naltrexone and the nature of the clinical response.” Their hope is that these findings ultimately can contribute to a better treatment experience for some who are seeking to end their battle with alcohol.

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Notes to Editors:

This article is “Family History of Alcoholism Influences Naltrexone-Induced Reduction in Alcohol Drinking” by Suchitra Krishnan-Sarin, John H. Krystal, Julia Shi, Brian Pittman and Stephanie S. O'Malley. All authors are affiliated with the Department of Psychiatry at Yale University School of Medicine in New Haven, Connecticut. Dr. Krystal is also affiliated with the VA Connecticut Healthcare System in West Haven, Connecticut and he serves as the Editor of Biological Psychiatry. This article appears in Biological Psychiatry, Volume 62, Issue 6 (September 15, 2007), published by Elsevier.

The other referenced article is R. Gueorguieva, R. Wu, B. Pittman, J. Cramer, R.A. Rosenheck, S.S. O’Malley and J.H. Krystal. New Insights into the Efficacy of Naltrexone Based on Trajectory-Based Reanalyses of Two Negative Clinical Trials. Biol Psychiatry. 2007 Jun 1;61(11):1290-5.

Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at (215) 239-3674 or ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.

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This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

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