A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse

The opioid antagonist, naltrexone, is reported, in single centre studies, t o improve the clinical outcome of individuals with alcohol dependence parti cipating in outpatient psychosocial programmes. This is the first multicent re controlled study to evaluate the efficacy and safety of naltrexone as ad junctive treatment for alcohol dependence or abuse. Patients who met criter ia for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or pl acebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The pr imary efficacy variable was time to first episode of heavy drinking; second ary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transf erase (GGT), and aspartate and alanine aminotransferases. Compliance was as sessed by tablet counts and, in the naltrexone-treated group, by measuremen t of urinary concentrations of 6-beta -naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not comple te the study. In intention-to-treat analyses, there was no difference betwe en groups on measures of drinking. The median reduction from baseline of se rum GGT (P < 0.05) and the reductions in alcohol craving (Obsessive and Com pulsive Drinking Scale: OCDS) were greater in the naltrexone group (P < 0.0 5), from approximately half-way through the study. Of 70 patients (35 place bo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P < 0.05), had g reater median reduction in serum GGT activity (P < 0.05), and greater reduc tion in alcohol craving (OCDS total score: P < 0.05; Obsessive subscale sco re: P < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dep endence/abuse in conjunction with psychosocial therapy, in patients who com ply with treatment.