- This review updates a prior review of pharmacotherapy for alcohol-use disorders (AUDs) published in 2014.
- Evidence continues to be strongest for the use of oral naltrexone at the 50 mg dose, with moderate strength of evidence across multiple outcomes, as well as relative ease of use as a once daily oral medication and an NNT of 11.
- The prior report found uncertain benefit for injectable naltrexone, but the addition of a new RCT conducted in a population experiencing homelessness resulted in positive outcomes for a reduction in drinking days and in heavy drinking days, with low SOE.
- With potential for contraindications as noted in the full report, acamprosate and topiramate also have evidence for benefit with moderate SOE, but decisions will be affected by ease of use, including the need to take multiple pills over the course of a day and the side effect profile. The NNT for acamprosate was 18.
- Since the last report, the addition of 11 new studies of baclofen have demonstrated low strength of evidence for reducing return to any drinking and studies of gabapentin demonstrated low strength of evidence for reducing return to heavy drinking.
- No new eligible studies were found for disulfiram, so our assessment of that drug remains that relatively limited evidence from well-controlled trials does not adequately support the efficacy of disulfiram compared with placebo for preventing return to any drinking or for other alcohol consumption outcomes.
- Very little evidence exists to evaluate the effectiveness of the use of medications for AUDs among specific populations.
- Most of the studies took place in specialty outpatient clinics; only 1 study was carried out in primary care. Therefore, there are too few studies to assess the effectiveness of medications in this setting or to characterize differences between specialty outpatient clinics and primary care populations.
Background. Unhealthy alcohol use is the third leading preventable cause of death in the United States, accounting for 145,000 deaths annually. Only 4.3 percent of Americans who reported having an alcohol-use disorder (AUD) indicated they received any AUD treatment in the past year; 1 percent were prescribed an approved medication as part of treatment, despite evidence of effectiveness for some pharmacotherapies.
Methods. We updated a 2014 Agency for Healthcare Research and Quality (AHRQ) report on pharmacotherapy for AUD treatment, following AHRQ Evidence-based Practice Center Guidance. We assessed efficacy and comparative effectiveness of specific medications for improving consumption outcomes (KQ1) and health outcomes (KQ2). We assessed harms (KQ3) and sought to identify evidence for the use of pharmacotherapy to treat AUDs in primary care (KQ4) and among subgroups (KQ5). When possible, we conducted quantitative analyses using random-effects models to estimate pooled effects. When quantitative analyses could not be conducted, we used qualitative approaches.
Results. We included 117 studies (154 articles) in our review, which included 81 studies (106 articles) from the 2014 review and 36 studies (48 articles) published since then. Studies generally included counseling co-interventions in all study groups, and the benefits observed reflect the added benefit of medications beyond those of counseling and placebo. Oral naltrexone at the 50 mg dosage had moderate strength of evidence for reducing return to any drinking, return to heavy drinking, percent drinking days and percent heavy drinking days. The addition of a new RCT of injectable naltrexone conducted in a population experiencing homelessness resulted in positive outcomes for a reduction in drinking days and heavy drinking days with low SOE. Acamprosate had moderate strength of evidence for a significant reduction in return to any drinking and reduction in drinking days. Topiramate had moderate SOE for several outcomes as well, but with a greater side effect profile. Two other medications demonstrated low strength of evidence for benefit in at least one consumption outcome - baclofen (reduced return to any drinking) and gabapentin (reduced return to heavy drinking). With no new studies on disulfiram, there remains inadequate evidence for efficacy compared to placebo for preventing return to any drinking or for other alcohol consumption outcomes. No new eligible studies provided head-to-head comparisons.
Conclusions. Oral naltrexone at the 50 mg oral dose had moderate strength of evidence across multiple outcomes and relative ease of use as a once-daily oral medication. Acamprosate and topiramate also have evidence of benefit, but have more potential contraindications, a less desirable side effect profile (topiramate) and are less convenient to take. Clinicians and patients may also want to consider which treatment outcomes are most important when choosing between the two. Current data are largely insufficient for understanding health outcomes. Finally, there is very little research to assess the use of medications for AUDs among subgroups (9 studies) or in primary care settings (1 study).