Short-acting intramuscular second-generation antipsychotic drugs for acutely agitated patients with schizophrenia spectrum disorders. A systematic review and network meta-analysis

Background: Psychomotor agitation is a common condition in patients with psychotic disorders. One treatment possibility is intramuscular (IM) second-generation antipsychotics. Yet their efficacy in this formulation and for this aim is unclear. This network meta-analysis aims to evaluate the efficacy of short-acting IM second-generation antipsychotic drugs, haloperidol and placebo in patients with diagnosis of schizophrenia and schizophrenia-like disorders that present acute agitation. Methods: We searched the Cochrane Schizophrenia Group Controlled Trials Register, MEDLINE, EMBASE, PsycINFO, Cochrane Library, PubMed, BIOSIS, ClinicalTrials.gov and WHO ICTRP up to November 2018 and PubMed until March 2020. Study selection and outcome extraction were performed independently by two reviewers. Pairwise and network meta-analyses were conducted to compare the different IM second-generation antipsychotics among themselves and with IM haloperidol and placebo. The primary outcome was the number of responders at 2 h after the first injection. Responders at 24 h were also analysed. Results: 10 studies with 1964 patients were included in the meta-analysis. Ziprasidone, olanzapine, aripiprazole and haloperidol were more efficacious than placebo in calming patients at 2 h after administration. Furthermore, olanzapine was superior to aripiprazole. The results at 24 h confirmed the superiority of aripiprazole, olanzapine and haloperidol over placebo, while for ziprasidone no data were available. Conclusions: All second-generation antipsychotics available as intramuscular medications were effective in reducing agitation in people with schizophrenia. Olanzapine was somewhat more efficacious than aripiprazole.