Oral naltrexone and acamprosate, combined with psychosocial interventions, were effective as first-line therapies for alcohol use disorder, according to a systematic review and meta-analysis.
Researchers included studies of at least 12 weeks' duration that compared FDA-approved or off-label medications with placebo or with another medication, published from November 2012 to September 2022. Eligible studies assessed alcohol consumption (defined as return to any drinking, return to heavy drinking, percentage of drinking days, percentage of heavy drinking days, or number of drinks per drinking day); health outcomes including motor vehicle crashes, injuries, quality of life, function, or mortality; or adverse effects of the drugs. Results were published by JAMA on Nov. 7.
Data from 118 clinical trials and 20,976 participants were included. The number needed to treat (NNT) to prevent one person from returning to any drinking was 11 (95% CI, 1 to 32) for acamprosate and 18 (95% CI, 4 to 32) for oral naltrexone. Compared with placebo, oral naltrexone (50 mg/d) significantly reduced rates of return to heavy drinking, with a NNT of 11 (95% CI, 5 to 41). Injectable naltrexone was associated with fewer drinking days over a 30-day treatment period (weighted mean difference, −4.99 days; 95% CI, −9.49 to −0.49 days). The drugs were associated with adverse effects, including gastrointestinal distress (risk ratios, 1.58 [95% CI, 1.27 to 1.97] for diarrhea with acamprosate, 1.73 [95% CI, 1.51 to 1.98] for nausea with naltrexone, and 1.53 [95% CI, 1.23 to 1.91] for vomiting with naltrexone).
The study authors noted that oral naltrexone is more convenient than acamprosate, requiring a single daily dose instead of two tablets three times a day. They added that acamprosate is contraindicated for patients with severe kidney impairment and requires dose adjustments for moderate kidney impairment. However, oral naltrexone is contraindicated for patients with acute hepatitis or liver failure and for those using opioids or who have anticipated need for opioids, and naltrexone can precipitate severe withdrawal for patients dependent on opioid medications.
“Randomized clinical trials that directly compared naltrexone, 50 mg/d, with acamprosate did not consistently [establish] superiority of either medication,” the authors wrote. “Studies of naltrexone had moderate strength of evidence for reducing return to any drinking, return to heavy drinking, percentage of drinking days, and percentage of heavy drinking days at the 50-mg/d oral dose compared with placebo.”