A Risk-Benefit Assessment of Naltrexone in the Treatment of Alcohol Dependence

Abstract

There is a great deal of interest in the use of naltrexone as a treatment for alcohol (ethanol) dependence since there is a rapidly expanding body of evidence to support its efficacy and tolerability in this indication. Naltrexone, a long-acting, nonselective opioid receptor antagonist has been shown to reduce alcohol intake when combined with behavioural treatment. Naltrexone may prevent the return to clinically significant drinking by blocking the pleasurable effects or "high' associated with alcohol drinking. Results from controlled studies showed that in alcohol dependent patients taking naltrexone 50 mg/day in combination with behavioural treatment, relapse rates were reduced by 50% compared with placebo treated patients. Historically, several factors have limited the use of effective pharmacological adjuncts in the treatment of alcohol dependence. These include safety considerations in this vulnerable population, and the fact that some treatment programmes discourage alcohol-dependent patients from taking medications. The most common adverse effects reported with the use of naltrexone at a dosage of 50 mg/day include nausea and vomiting. Naltrexone does not appear to be hepatotoxic in dosages recommended in the treatment of alcohol dependence, i.e. 50 mg/day. Thus, naltrexone appears to offer significant therapeutic benefits at a relatively low risk, when used judiciously and with behavioural treatment for alcohol dependent patients.

Ethanol consumption and reward are decreased in µ-opiate receptor knockout mice

“…Opiate antagonists can reduce human ethanol consumption ) and may be efficacious in the treatment of alcoholism (Berg et al 1996;Kranzler et al 1997Kranzler et al , 1998bMason et al 1999). The mechanisms for these effects are uncertain, however.…”

Effects of naltrexone with nicotine replacement on smoking cue reactivity: preliminary results

“…One possible candidate is naltrexone, a pharmacotherapy that has demonstrated safety and efficacy as an adjunct in the treatment of alcohol dependence (O'Malley et al 1992;Volpicelli et al 1992;Berg et al 1996). Although the mechanisms by which naltrexone works are not well understood, naltrexone's effectiveness has been attributed to its ability to reduce activation of the mesolimbic dopamine system through the antagonism of mu-opiate receptors.…”

A Multi-site Dose Ranging Study of Nalmefene in the Treatment of Alcohol Dependence

“…In addition, naltrexone has been reported to cause reversible, mild-to-moderate liver toxicity in some patients when administered at doses of 150 mg/d or higher. 17,18 Although liver enzyme elevation does not appear to be an issue at the dose approved for treatment of alcohol dependence, naltrexone, nevertheless, has received a black box warning from the FDA due to the risk of hepatic toxicity (Physicians Desk Reference 19 ).…”