Naltrexone and acamprosate combination in alcohol treatment

The use of Naltrexone and/or acamprosate can be helpful during alcohol treatment, however, to achieve the greatest success, individuals would benefit from incorporating psychological intervention. Evidence-based addiction treatment incorporates cognitive behavior therapy (CBT) which enables individuals to learn ways to cope with cravings and eventually have greater success for alcohol recovery.

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Naltrexone is an opioid antagonist that blocks the reward effects of alcohol consumption. The mechanism of acamprosate is less well-defined, but it may reduce unpleasant feelings (such as anxiety and tension) during withdrawal by blocking NMDA receptors. Previous research shows that acamprosate increases the number of individuals who remain abstinent after alcohol detoxification. Research also shows that naltrexone may reduce relapse and desire to drink in social settings. Naltrexone and acamprosate may both work to effectively reduce craving and relapse in alcohol treatment through different pharmacological pathways. Since both drugs are well-tolerated and show no evidence of dangerous interaction, researchers at the University Hospital of Hamburg in Germany examined the safety of combined naltrexone and acamprosate in alcohol treatment and relapse prevention (Kiefer & Wiedemann, 2004).

The researchers reviewed four pre-clinical and four clinical studies on the tolerability and efficacy of combined naltrexone and acamprosate. The results of the review showed no instance of severe adverse events during combined treatment. The most significant side effects were diarrhea and nausea. The clinical studies suggested that combined treatment is more effective than acamprosate treatment alone as well as placebo. Reviewed clinical studies show that the synergistic effect of combined treatment lasts after 12 weeks of follow-up. This review suggests that the combination of acamprosate and naltrexone in alcohol treatment is efficacious and safe. Individuals who do not respond well to either acamprosate or naltrexone may benefit from combined treatment.

“Studies to date suggest higher efficacy of combined treatment with acamprosate and naltrexone compared to monotherapy, regarding prevention of relapse into heavy drinking and maintenance of abstinence,” the authors conclude. “This added benefit could be explained by subgroups of drug-specific responders, by synergistic effects within each patient, or by a pharmacokinetic interaction. The explorative assessment of potentially discriminating features (nature and intensity of craving, psychopathology, and typology) gives hints on possibly useful differentiations. However, prospective studies with larger sample size are warranted to evaluate the value of matching these subgroups with specific pharmacological interventions.

“Combination treatment appears to be well tolerated, with no severe adverse events reported, although they imply an increased incidence of diarrhea and nausea, perhaps due to a pharmacokinetic interaction. It can be concluded that there is accumulating evidence that the combination of acamprosate and naltrexone is both efficacious and safe. Given the large proportion of alcohol dependent subjects responding insufficiently to monotherapy with either acamprosate or naltrexone with the consequence of early relapse after detoxification, many patients might benefit from enhancing the efficacy of relapse-prevention treatment by combining acamprosate and naltrexone.”

It should be noted that while these medications may ease withdrawal symptoms and reduce the risk of relapse, psychological intervention is often necessary for successful maintenance of alcohol recovery.

Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us? Alcohol and Alcoholism. 2004; 39(6): 542-547.