Gene Variant Predicts Medication Response in Patients with Alcohol Dependence
News Feb 08, 2008
Patients with a certain gene variant drank less and experienced better overall clinical outcomes than patients without the variant while taking the medication naltrexone, according to an analysis of participants in the National Institutes of Health's 2001-2004 COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) Study.
About 87 percent of patients with the variant who received naltrexone experienced good outcomes, compared with about 49 percent of those who received a placebo. About 55 percent of patients without the variant experienced a good outcome regardless of whether they received naltrexone or placebo.
Good outcome was defined as abstinence or moderate drinking without related problems, according to an article in the Feb. 4 issue of the "Archives of General Psychiatry."
Drinking alcohol increases the release of endogenous opioids, compounds that originate in the body and promote a sense of pleasure or well-being. An opioid antagonist, naltrexone blocks brain receptors for endogenous opioids, making it easier for patients to remain abstinent or stop quickly in the event of a slip.
In clinical studies, naltrexone has been shown to reduce relapse and craving for alcohol in some but not all treated patients. Earlier studies had suggested that a specific DNA variant of the opioid receptor gene (OPRM1) might have role in patients' response to naltrexone.
The researchers successfully genotyped 911 of the available patients and conducted their initial analysis in 604 who are white, 135 of whom were found to carry the genetic variant. Approximately 15 to 25 percent of humans carry the variant, with considerable variation among ethnicities.
As in the COMBINE clinical trial, drinking variables evaluated in the pharmacogenetic study included the percentage of days abstinent from alcohol, the percentage of heavy drinking days, and clinical outcome during 16 weeks of active treatment.
In addition to naltrexone or placebo, all patients received medical management (nine brief, structured outpatient sessions delivered by a health professional) and some also received a combined behavioral intervention (integrated cognitive-behavioral and motivational enhancement therapies, together with techniques to enhance mutual-help participation).
The researchers found that, compared with patients who do not carry the variant, white variant carriers who received naltrexone fared substantially better than other groups on all measures, including almost a 6 times greater likelihood of good clinical outcome. Extending the clinical outcome measure to variant carriers of all ethnicities reduced the benefit to just over a 3 times greater likelihood of good outcome.
The researchers found no gene-medication interaction in patients who received specialized alcohol counseling, leading to them to conclude that genotyping for the variant may be most useful when naltrexone is used without intensive counseling.
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