Second-generation antipsychotic drugs and short-term mortality: a systematic review and meta-analysis of placebo-controlled randomised controlled trials

This study is registered with PROSPERO, number CRD42016033930.FindingsWe identified 596 randomised controlled trials published between 1978 and 2017, comprising 108 747 participants. 352 studies (comprising 84 988 participants) with mortality data available constituted the main dataset for our meta-analysis. 207 (0·4%) deaths were reported in 53 804 patients on an antipsychotic drug and 99 (0·3%) deaths in 31 184 patients on placebo. 300 (85%) of 352 trials were 13 weeks (3 months) or shorter in duration (median 6 weeks; IQR 4–10). We found no evidence of a difference between antipsychotic drugs and placebo in mortality by any cause (OR 1·19; 95% CI 0·93–1·53), from natural causes (1·29; 0·85–1·94), from suicide (1·15; 0·47–2·81), and from other non-natural causes (1·55; 0·66–3·63). Most subgroup and meta-regression analyses did not indicate any important effect moderators. The exceptions were increased mortality in patients with dementia (OR 1·56; 95% CI 1·10–2·21), in elderly patients (1·38; 1·01–1·89), in aripiprazole-treated patients (2·20; 1·00–4·86), and in studies with a higher proportion of women (regression coefficient 0·025; 95% credible interval 0·010–0·040). However, the effects in elderly patients, aripiprazole-treated patients, and women were mainly based on the included dementia trials. For patients with schizophrenia there was no evidence of an increased mortality risk (OR 0·69; 95% CI 0·35–1·35).Interpr...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research