Efficacy and Safety of Olanzapine Long-acting Injection in Schizophrenia and Schizoaffective Disorder: A Systematic Review and Meta-analysis.

Abstract

Olanzapine long-acting injection (LAI) is a second-generation antipsychotic used in patients with schizophrenia-spectrum disorders, particularly those with poor adherence. However, evidence on its comparative efficacy, safety, and tolerability remains limited. We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, ProQuest) were searched through May 2025. We included randomized controlled trials (RCTs), quasi-experimental, and observational studies evaluating olanzapine LAI in adults with schizophrenia or schizoaffective disorder. Risk of bias was assessed using Revised Cochrane Risk-of-Bias Tool for Randomized Trials (Version 2), Risk Of Bias In Non-randomized Studies - of Interventions, and the Newcastle-Ottawa Scale. Data were synthesized using RevMan 5.4. Nine studies (n = 2,915) met inclusion criteria; only two RCTs were eligible for meta-analysis. Olanzapine LAI showed no significant difference from oral olanzapine in reducing Positive and Negative Syndrome Scale scores (mean difference = 1.41; 95% CI: -0.22 to 3.04; p = 0.09) or Clinical Global Impression-Severity scores (mean difference = 0.03; 95% CI: -0.15 to 0.21; p = 0.73). Relapse (OR = 1.15; 95% CI: 0.82 to 1.61), adverse events (OR = 1.12; 95% CI: 0.88 to 1.42), and weight gain were also similar. Across included studies, post-injection delirium/sedation syndrome was reported in 47 participants and resolved without hospitalization or long-term sequelae. Based on low-certainty evidence from limited RCTs, olanzapine LAI appears comparable in efficacy and tolerability to oral olanzapine. It may be considered for patients with adherence difficulties, but careful safety monitoring is required and further head-to-head trials are needed.