Pharmacotherapies for Adults With Alcohol Use Disorders: A Systematic Review and Network Meta-analysis

Anees Bahji; Paxton Bach; Marlon Danilewitz; David Crockford; Daniel J Devoe; Nady El-Guebaly; Richard Saitz

doi:10.1097/ADM.0000000000000992

Pharmacotherapies for Adults With Alcohol Use Disorders: A Systematic Review and Network Meta-analysis

J Addict Med. 2022 Nov-Dec;16(6):630-638. doi: 10.1097/ADM.0000000000000992.

Authors

Anees Bahji¹, Paxton Bach, Marlon Danilewitz, David Crockford, Daniel J Devoe, Nady El-Guebaly, Richard Saitz

Affiliation

¹ From the Department of Psychiatry, University of Calgary, Calgary, AB, Canada (AB, DC, DJD, NEG); British Columbia Centre for Substance Use, Vancouver, BC, Canada (AB, PB); Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada (AB); Department of Medicine, University of British Columbia, Vancouver, BC, Canada (PB); Ontario Shores Centre for Mental Health Sciences, Whitby, ON, Canada (MD); Department of Psychiatry, University of Toronto, Toronto, ON, Canada (MD); Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada (AB, DJD); Department of Community Health Sciences, School of Public Health, Boston University (RS); Department of Medicine, Boston University, Boston, MA (RS); and Clinical Translational Science Institute, Boston University, Boston, MA (RS).

Abstract

Background: We aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders.

Methods: We searched eleven electronic data sources for randomized clinical trials with at least 4 weeks of treatment reporting on alcohol consumption (total abstinence and reduced heavy drinking), dropouts, and dropouts due to adverse events. We conducted network meta-analyses using random-effects, frequentist models, and calculated summary rate ratios (RRs) with 95% confidence intervals (CIs).

Results: We included 156 trials (N = 27,334). Nefazodone (RR = 2.11; 95% CI, 1.42-3.13), aripiprazole (RR = 1.97; 95% CI, 1.36-2.88), carbamazepine (RR = 1.85; 95% CI, 1.03-3.32), and nalmefene (RR = 1.17; 95% CI, 1.01-1.35) were associated with the most dropouts. Baclofen (RR = 0.83; 95% CI, 0.70-0.97) and pregabalin (RR = 0.63; 95% CI, 0.43-0.94) caused fewer dropouts than placebo. Nalmefene (RR = 3.26; 95% CI, 2.34-4.55), fluvoxamine (RR = 3.08; 95% CI, 1.59-5.94), and topiramate (RR=2.18; 95% CI, 1.36-3.51) caused more dropouts from adverse events over placebo. Gamma-hydroxy-butyrate (RR = 1.90; 95% CI, 1.03-3.53), baclofen (RR = 1.80; 95% CI, 1.39-2.34), disulfiram (RR = 1.71; 95% CI, 1.39-2.10), gabapentin (RR = 1.66; 95% CI, 1.04-2.67), acamprosate (RR = 1.33; 95% CI, 1.15-1.54), and oral naltrexone (RR = 1.15; 95% CI, 1.01-1.32) improved total abstinence over placebo (Fig. 3C). For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10-0.35), baclofen (RR = 0.72; 95% CI, 0.57-0.91), acamprosate (RR = 0.78; 95% CI, 0.70-0.86), and oral naltrexone (RR = 0.81; 95% CI, 0.73-0.90) were efficacious against placebo.

Conclusions: The current meta-analyses provide evidence that several medications for AUDs are effective and safe and encourage the expanded use of these medications in the clinical setting. Our review found that acamprosate (2-3 g/d), disulfiram (250-500 mg/d), baclofen (30 mg/d), and oral naltrexone (50 mg/d) had the best evidence for improving abstinence and heavy drinking for patients with AUD.

Prospero: CRD42020208946.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Acamprosate / adverse effects
Adult
Alcoholism* / drug therapy
Baclofen / adverse effects
Disulfiram / adverse effects
Humans
Naltrexone / adverse effects
Network Meta-Analysis
Randomized Controlled Trials as Topic

Substances

Acamprosate
Baclofen
Disulfiram
Naltrexone

Abstract

Publication types

MeSH terms

Substances

Grants and funding