Antipsychotics for Primary Alcohol Dependence: A Systematic Review and Meta-Analysis of Placebo-Controlled Trials

Objective: We sought to meta-analytically assess the utility of antipsychotics in patients with primary alcohol dependence.

Data Sources: We searched PubMed, Cochrane Library, and PsycINFO without language restrictions from database inception until December 2012, using the following keywords: (randomized, random, OR randomly) AND (placebo) AND (alcohol dependence) AND (neuroleptic OR antipsychotic OR antidopaminergic OR the names of 34 individual antipsychotics).

Study Selection: Included in this study were randomized, placebo-controlled trials of antipsychotics lasting ≥ 2 weeks in patients with primary alcohol dependence and without schizophrenia or bipolar disorder.

Data Extraction: Two independent evaluators extracted data. Standardized mean difference (SMD), risk ratio (RR), and numbers needed to harm (NNH) ± 95% confidence intervals (CIs) were calculated.

Results: Across 13 double-blind studies, 1,593 patients were randomly assigned to one of the following: amisulpride (1 study, n = 37), aripiprazole (2 studies, n = 163), flupenthixol decanoate (1 study, n = 142), olanzapine (2 studies, n = 62), quetiapine (4 studies, n = 174), tiapride (3 studies, n = 212), or placebo (13 studies, n = 803). Neither pooled nor individual antipsychotics outperformed placebo regarding relapse prevention (pooled RR = 1.05 [95% CI, 0.95 to 1.16], P = .38, 9 studies, n = 1,405). Antipsychotics were similar to placebo regarding heavy drinking days (P = .15), craving (P = .82), and first alcohol consumption time (P = .94). Placebo outperformed pooled antipsychotics regarding number or percentage of abstinent days/lack of drinking days (SMD = 0.17 [95% CI, 0.01 to 0.33], P = .04, 5 studies, n = 918), without significant group differences after removal of 1 outlying flupenthixol decanoate study (P = .24). Individually, flupenthixol decanoate (1 study, n = 281) was inferior to placebo regarding abstinence/drinking days (P = .004), whereas aripiprazole (1 study, n = 30) was superior regarding heavy drinking days (P < .00001). Antipsychotics caused greater all-cause discontinuation than placebo (RR = 1.24 [95% CI, 1.07 to 1.45], P = .005, NNH = 14), especially aripiprazole (P = .01) and flupenthixol decanoate (P = .001). Discontinuation due to intolerability was similar between antipsychotics and placebo (P = .12), but aripiprazole’s risk was higher (P = .003). Drowsiness/sedation (P < .0001, NNH = 9), increased appetite (P = .02, NNH = 14), and dry mouth (P < .0001, NNH = 7) occurred more frequently with pooled antipsychotics.

Conclusions: Except for 1 isolated outcome, the studied antipsychotics did not improve abstinence or reduce drinking or craving in patients with primary alcohol dependence.

J Clin Psychiatry 2013;74(7):e642-e654

© Copyright 2013 Physicians Postgraduate Press, Inc.

Submitted: September 19, 2012; accepted January 11, 2013 (doi:10.4088/JCP.12r08178).

Corresponding author: Christoph U. Correll, MD, Division of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY 11004 ([email protected]).