Current data and guidelines indicate that ongoing antipsychotic medication is critical for avoiding relapse in patients with schizophrenia spectrum disorders, but evidence-based recommendations for the selection of the particular antipsychotic for maintenance treatment are inadequate. Although oral antipsychotics are frequently recommended first-line for practical reasons, long-acting injectable antipsychotics (LAIs) are an important option for addressing adherence concerns from the beginning of the illness. 

The databases and online registers Medline, EMBASE, PsycINFO, CENTRAL, and CINAHL, as well as online registrations, were searched for randomized controlled trials comparing LAIs or oral antipsychotics head-to-head or versus placebo, published up to June 2021. Random-effects pairwise and network meta-analyses were used to pool relative risks and standardized mean differences. Relapse and dropout as a result of adverse events were the major outcomes. For a study, researchers sought to assess research quality, they utilized the Cochrane Risk of Bias tool, and they used the CINeMA technique to assess the confidence in pooled results. 

About 92 (N=22,645) of the 100 qualifying studies produced adequate data for meta-analyses. In terms of relapse prevention, the great majority of the 31 therapies considered outperformed placebo. In comparison to placebo, “high” confidence in the results was observed for amisulpride-oral (OS), olanzapine-OS, aripiprazole-LAI, aripiprazole-OS, paliperidone-OS, and ziprasidone-OS (in decreasing order of effect magnitude). Paliperidone-LAI 1-monthly, iloperidone-OS, fluphenazine-OS, brexpiprazole-OS, paliperidone-LAI 1-monthly, asenapine-OS, haloperidol-OS, quetiapine-OS, cariprazine-OS, and lurasidone-OS all had “moderate” confidence in the results. Tolerability was not considerably worse than placebo, but confidence was low, with only aripiprazole (both LAI and OS) having “moderate” confidence levels. 

Considering that both LAI and oral formulations of these antipsychotics are among the best-performing treatments and have the highest confidence of evidence for relapse prevention, olanzapine, aripiprazole, and paliperidone are the best choices for the maintenance treatment of schizophrenia-spectrum disorders, according to the findings. The conclusion is especially important for low- and middle-income nations with limited resources when just a few drugs are available. Clinical recommendations and national and international drug control regulations can benefit from the findings of the network meta-analysis.