Rationale for combining acamprosate and naltrexone for treating alcohol dependence.
OBJECTIVE
This article provides an evidence-based review of acamprosate and naltrexone, used alone and in combination. Both medications are gaining increasing availability worldwide by prescription for the treatment of alcohol dependence. There is scientific and clinical interest in examining these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes.


METHODS
This article includes a review of the key similarities and differences between acamprosate and naltrexone in the treatment of alcohol dependence; the published double-blind, placebo-controlled trials of acamprosate and naltrexone across a uniform range of outcome criteria to elucidate the differences and similarities in the behavioral effects of these drugs; the two published pharmacokinetic and pharmacodynamic drug interaction studies of acamprosate and naltrexone; and the single-site clinical trial of acamprosate and naltrexone used alone and in combination relative to placebo.


RESULTS
Pharmacokinetic and pharmacodynamic studies report an increase in acamprosate plasma levels with no clinically significant elevation in adverse events when the two drugs are used in combination. Data from dose-response studies for acamprosate alone suggest that the augmentation of acamprosate plasma levels by co-administration of naltrexone may have clinical benefits.


CONCLUSIONS
These factors support investigating the efficacy and safety of combining acamprosate and naltrexone for the treatment of alcohol dependence in a large-scale multisite trial, with evaluation of potential predictors of response to each drug alone and in combination relative to placebo.
Mason
Barbara J
BJ
Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC5, La Jolla, California 92037, USA. mason@scripps.edu
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000437:Alcoholism / Q000188:drug therapy / Q000628:therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; D013654:Taurine; D009271:Naltrexone; D000077443:Acamprosate