STUDY SUMMARY
Evidence shows naltrexone can prevent a return to drinking
In a meta-analysis, Jonas et al1 reviewed 123 studies (N = 22,803) of pharmacotherapy for AUD. After excluding 28 studies (seven were the only study of a given drug, one was a prospective cohort, and 20 had insufficient data), 95 randomized controlled trials were included in the analysis. Twenty-two were placebo-controlled for acamprosate (1,000 to 3,000 mg/d), 44 for naltrexone (50 mg/d oral, 100 mg/d oral, or injectable) and four compared the two drugs. Additional studies evaluated disulfiram as well as 23 other off-label medications, such as valproic acid and topiramate.
Two investigators independently reviewed the studies, checking for completeness and accuracy. Studies were also analyzed for bias using predefined criteria; those with high or unclear risk for bias were excluded from the main analysis but included in the sensitivity analysis. Funnel plots showed no evidence of publication bias.
Participants were primarily recruited as inpatients, and in most studies the mean age was in the 40s. Most patients were diagnosed with alcohol dependence based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR); this diagnosis translates to likely moderate to severe AUD in DSM-5. Prior to starting medications, participants underwent detoxification or achieved at least three days of sobriety. Most studies included psychosocial intervention in addition to medication, but the types of intervention varied. The duration of the trials ranged from 12 to 52 weeks.
Researchers analyzed five drinking outcomes—return to any drinking, return to heavy drinking (defined as ≥ 4 drinks/d for women and ≥ 5 drinks/d for men), number of drinking days, number of heavy drinking days, and drinks per drinking day. They also evaluated health outcomes (accidents, injuries, quality of life, function, and mortality) and adverse effects.
Acamprosate and oral naltrexone (50 mg/d) significantly decreased return to any drinking, with a number needed to treat (NNT) of 12 for acamprosate and 20 for naltrexone. Oral naltrexone (50 mg/d) also decreased return to heavy drinking (NNT, 12), while acamprosate did not. Neither medication showed a decrease in heavy drinking days.
In a post hoc subgroup analysis of acamprosate for return to any drinking, the drug appeared to be more effective in studies with a higher risk for bias and less effective in studies with a lower risk for bias. The two studies with the lowest risk for bias found no significant effect.
Disulfiram had no effect on any of the outcomes analyzed.
Of the off-label medications, topiramate showed a decrease in drinking days (weighted mean difference [WMD], –6.5%), heavy drinking days (WMD, –9.0%), and drinks per drinking day (WMD, –1.0).
There were no significant differences in health outcomes for any of the medications. Adverse events were greater in treatment groups than placebo groups. Acamprosate was associated with increased risk for diarrhea (number needed to harm [NNH], 11), vomiting (NNH, 42), and anxiety (NNH, 7). Naltrexone was associated with increased risk for nausea (NNH, 9), vomiting (NNH, 24), and dizziness (NNH, 16).
WHAT’S NEW
Consider prescribing naltrexone to prevent relapse
While previous studies suggested that pharmacotherapy could help patients with AUD remain abstinent, this methodologically rigorous meta-analysis compared the efficacy of several commonly used medications and found clear evidence favoring oral naltrexone. Prescribe oral naltrexone (50 mg/d) to help patients with moderate to severe AUD avoid returning to any drinking or heavy drinking after alcohol detoxification. Acamprosate may also decrease return to drinking, although the evidence is not as strong (the studies with low bias showed no effect).
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