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. DataSources:We searched PubMed, Cochrane Library, and PsycINFO without language restrictions from database inception until December2012, using the following keywords: (randomized, random, OR randomly) AND (placebo) AND ca/co hol dependence) AND (neuro/eptic OR antipsychotic OR antidopaminergic OR the names of 34 individual a nti psychotics). StudySelection: 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°c confidence intervals (CIs) were calculated. Results: Across 3 double-blind studies, 593 piens were rdndorllly 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% Cl, 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% Cl, QQ1 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% Cl, 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.