Objective To find the safety of long-acting injectable antipsychotics (LAIs) compared to each other, and/or placebo in the treatment of schizophrenia (SCZ) and/or schizoaffective disorder (SZA). Methods We performed a systematic review and a network meta-analysis of randomized controlled trials (RCTs) comparing the safety of LAIs versus other LAIs or placebo in adults diagnosed with SCZ or SZA. The primary outcomes were treatment emergent adverse events (TEAEs), serious treatment emergent adverse events (STEAEs), and deaths. The secondary outcomes included treatment discon-tinuations due to adverse events and all-cause discontinuations. Results Seventeen RCTs were included (n=7,908). There were no significant differences between LAIs and placebo in the risk of pre-senting TEAEs. LAIs had a significant lower risk of presenting STEAEs except for aripiprazole. No significant differences in deaths were found. LAIs showed a significant protective effect against all-cause discontinuation, except for haloperidol. Only aripiprazole had a sig-nificantly lower risk of treatment discontinuation due to adverse events. Conclusion We found no significant differences in the risk of presenting TEAEs between LAIs and placebo. The majority of LAIs had a significantly lower risk of presenting STEAEs than placebo. Development of international guidelines for the report of safety outcomes re-lated to antipsychotics especially for LAIs in clinical trials could minimize report and interpretation biases and improve the accuracy of posterior meta-analysis.
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