Abstract

Intranasal administration of oxytocin has been shown to enhance social cognition and reduce stress reactivity in healthy individuals, indicating potential therapeutic benefits for mental disorders. However, clinical trials have produced mixed results. Following a systematic search, data were extracted from 42 double-blind, randomized controlled trials comparing symptoms following intranasal oxytocin versus placebo in autism spectrum disorder, schizophrenia spectrum disorders, substance use disorder, and other mental disorders. Random effects meta-analysis of the pooled sample (N = 2185) revealed a small, non-significant overall treatment effect with substantial between-trial heterogeneity (g = 0.17, 95% CI = –0.02 to 0.36, I² = 77.41%). The removal of two outlier studies with extremely large treatment effects in substance use disorder caused a significant moderation by mental disorder category to disappear. However, the removal of these outliers also revealed a significant moderation by biological sex whereby studies with more females showed greater treatment effects. No significant moderation by dose, number of administrations, or psychosocial interventions was detected. Despite promising findings in individual studies, intranasal oxytocin is not currently supported as an evidence-based treatment for mental disorders. Future clinical trials should systematically examine dose-response relations, optimize psychosocial intervention protocols, address the underrepresentation of females, and report individual participant data which will enable meta-analyses to investigate individual differences in treatment response.