Intranasal administration of oxytocin has been shown to enhance social cognition and reduce stress reactivity in healthy individuals, suggesting therapeutic potential 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 disorders, and other mental disorders. Random effects meta-analysis of the pooled sample (N = 1922) revealed a small, non-significant overall treatment effect with substantial between-trial heterogeneity (g = 0.17, 95% CI -0.05, 0.38, I² = 77.4%). Removing two outlier studies with very large treatment effects in substance use disorders reduced the pooled estimate and eliminated heterogeneity (g = 0.05, 95% CI -0.03, 0.12, I² = 0.0%). Analyzing mental disorder subgroups separately revealed a small, significant effect in schizophrenia spectrum disorders (g = 0.12, 95% CI 0.01, 0.23). Removing outliers uncovered moderation by biological sex, whereby studies with more females showed greater effects (b = 0.0043, p =.02). No significant moderation by dose, number of administrations, psychosocial interventions, or participant age was detected. Findings demonstrate a promising signal in schizophrenia spectrum disorders and potentially important sex differences. However, trial methods seldom aligned with optimal protocols. Future trials should systematically examine dose-response relations, optimize psychosocial interventions, address female underrepresentation, and report individual participant data to enable future meta-analyses to investigate individual differences in treatment response.
Bonnieux et al. (Fri,) studied this question.