Intranasal Oxytocin for Negative Symptoms of Schizophrenia: Systematic Review, Meta-Analysis, and Dose-Response Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Negative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear. METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms. RESULTS: In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40–80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses. CONCLUSIONS: The present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.