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

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

Anees Bahji  1 , Paxton Bach, Marlon Danilewitz, David Crockford, Daniel J Devoe, Nady El-Guebaly, Richard Saitz
Affiliations

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

Anees Bahji et al. J Addict Med. 2022 Nov-Dec.

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.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
PRISMA flow diagram. PRISMA indicates Preferred Reporting Items for Systematic Reviews and Meta-analyses
FIGURE 2.
FIGURE 2.
Network plot of eligible pharmacotherapy comparisons across all studies for dropouts. Line width corresponds to the number of trials comparing pharmacotherapy pairs. ACA indicates acamprosate; ALC, acetyl-L-carnitine; ARI, aripiprazole; ATE, atenolol; BAC, baclofen; BRO, bromocriptine; CBZ, carbamazepine; CIT, citalopram; DIS, disulfiram; DVP, divalproex; FLU, flupenthixol; FLX, fluoxetine; FVZ, fluvoxamine; GAB, gabapentin; GHB, gamma-hydroxybutyrate; LEV, levetiracetam; LIS, lisuride; NEF, nefazodone; NLM, nalmefene; NTX, naltrexone; NTX-XR, naltrexone extended-release; OND, ondansetron; OXC, oxcarbazepine; PBO, placebo; PRE, pregabalin; RIM, rimonabant; TIA, tiapride; TOP, topiramate.
FIGURE 3.
FIGURE 3.
Forest plot for networkmeta-analysis across randomized controlled trials of pharmacotherapies for alcohol use disorder for (A) Dropouts; (B) Dropouts from Adverse Events [DAE]; (C) Abstinence; and (D) Heavy Drinking. ACA indicates acamprosate; ALC, acetyl-L-carnitine; ARI, aripiprazole; ATE, atenolol; BAC, baclofen; BRO, bromocriptine; CBZ, carbamazepine; CIT, citalopram; DAE, dropouts due to adverse events; DIS, disulfiram; DVP, divalproex; FLU, flupenthixol; FLX, fluoxetine; FVZ, fluvoxamine; GAB, gabapentin; GAL, galantamine; GHB, gamma-hydroxybutyrate; LEV, levetiracetam; LIS, lisuride; NEF, nefazodone; NLM, nalmefene; NTX, naltrexone; NTX-XR, naltrexone extended-release; OND, ondansetron; OXC, oxcarbazepine; PBO, placebo; PRE, pregabalin; RIM, rimonabant; TIA, tiapride; TOP, topiramate.
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