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Sweet-liking phenotype, high craving for alcohol moderate strong naltrexone response

Having the sweet-liking phenotype and high craving for alcohol was associated with strong response to naltrexone for alcohol dependence, according to findings from a randomized trial.

“Medications to treat alcohol dependence have been developed, but their effectiveness has been modest, with generally low to medium effect sizes seen in unselected populations. A challenge for clinical research is to identify moderators of response,” James C. Garbutt, MD, of the University of North Carolina at Chapel Hill, and colleagues wrote. “Several moderators have been tentatively identified in the literature as positively associated with the response to the FDA-approved medication naltrexone hydrochloride: high baseline craving for alcohol, increased density of familial alcohol problems, and the Asn40Asp polymorphism in the μ-opioid receptor gene (OPRM1 [rs1799971]). However, none of these factors has been clearly demonstrated in prospective trials to moderate naltrexone response.”

To determine if the sweet-liking phenotype is associated with a high craving for alcohol and improved response to naltrexone for alcohol dependence, researchers conducted a 12-week, double-blind, randomized, placebo-controlled clinical trial among 80 actively drinking individuals. Study participants were randomly assigned by the sweet-liking (n = 22) or sweet-disliking (n = 58) phenotype and by pretreatment high (n = 40) or low (n = 40) craving for alcohol. Researchers defined high craving as higher than the median. Study participants received 50 mg of oral naltrexone hydrochloride or placebo per day with weekly or biweekly brief counseling. The cohort had a mean age of 47 years.

Analysis indicated a nonsignificant effect of naltrexone on heavy drinking, with 4.8 fewer heavy drinking days (P = .07).

The sweet-liking phenotype moderated the effect of naltrexone on heavy drinking, with 6.1 fewer heavy drinking days (P = .02), and abstinence, with 10 more abstinent days (P = .02).

High craving moderated heavy drinking, with 7.1 fewer heavy drinking days (P = .008).

Having both sweet-liking phenotype and high craving was associated with a strong response to naltrexone, with 17.1 fewer heavy drinking days (P < .001) and 28.8 more abstinent days (P = .004), compared with placebo.

“The results of the present trial support the hypothesis that the [sweet-liking] phenotype is a moderator of the response to naltrexone in alcohol dependence and that this effect is most apparent in the presence of a high subjective craving for alcohol. Larger clinical trials in diverse populations of individuals with alcohol dependence will be necessary to confirm these findings,” the researchers concluded. – by Amanda Oldt

Disclosure: Garbutt reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.