title: Mortality Risk Associated With Long-acting Injectable Antipsychotics: A Systematic Review and Meta-analyses of Randomized Controlled Trials.
abstract: Long-acting injectable (LAI) antipsychotics (LAI-APs) have several advantages over oral medications, but deaths reported in Japan during the early post-marketing phase vigilance period have raised safety concerns. We conducted a series of meta-analyses to assess whether LAI-APs affect the mortality of patients with schizophrenia. Three categorical meta-analyses of randomized controlled trials (RCTs) were performed to compare all-cause death (primary outcome) and death due to suicide: individual and pooled LAI-APs vs placebo, individual and pooled LAI-APs vs oral antipsychotics (OAPs), and head-to-head comparisons of LAI-APs. The risk ratios (RRs) and 95% CIs were calculated. We identified 52 RCTs (53 comparisons; total participants = 17 416, LAI-APs = 11 360, OAP = 3910, and placebo = 2146; mean study duration [wk]: LAI-APs vs placebo = 28.9, LAI-APs vs OAPs = 64.5). Neither pooled nor individual LAI-APs (aripiprazole, fluphenazine, olanzapine, paliperidone, and risperidone) differed from the placebo regarding the incidences of all-cause death (pooled LAI-APs: RR = 0.64, P = .37) and death due to suicide (pooled LAI-APs: RR = 0.98, P = .98). However, in a subgroup meta-analysis of only short-duration RCTs (≤13wk), pooled LAI-APs exhibited a trend toward lower incidence of all-cause death than placebo (RR = 0.29, P = .08). Pooled LAI-APs (aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, risperidone, and zuclopenthixol) did not differ from pooled OAPs regarding all-cause death (pooled LAI-APs: RR = 0.71, P = .30) and death due to suicide (pooled LAI-APs: RR = 0.94, P = .91). Individual LAI-APs and OAPs were associated with similar risks of death. Data for head-to-head comparisons of individual LAI-APs were insufficient. In conclusion, there was no significant difference between LAI-APs and placebo or OAPs regarding all-cause death and death due to suicide.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D003692:Delayed-Action Preparations / Q000009:adverse effects*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy* / Q000401:mortality*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations
keywords: long-acting injectable antipsychotics; meta-analysis; mortality; schizophrenia; systematic review