Comparison of acamprosate and placebo in long-term treatment of alcohol dependence

Abstract

Summary Background About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence. Methods In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight >60 kg; 1332 mg daily for ≤60 kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. Findings Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n=224) and placebo (n=224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p<0·001, Mantel-Cox). At the end of treatment, 41 (18·3%) acamprosate-treated and 16 (7·1%) placebo-treated patients had been continuously abstinent (p=0·007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138·8 [SD 137·5] vs 103·8 [119·0] days; p=0·012). 148 patients (79 acamprosate, 69 placebo) completed 27 months' follow-up: 27 (11·9%) acamprosate-treated and 11 (4·9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230·8 days (259·1) and 183·0 days (235·2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups. Interpretation Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.