Adjunctive intranasal oxytocin for schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials

Objective: Findings on the efficacy of intranasal oxytocin (IN-OT) in schizophrenia have been inconsistent. This meta-analysis of double-blind randomized controlled trials (RCTs) examined the efficacy and tolerability of adjunctive IN-OT in the treatment of schizophrenia. Methods: Standardized mean differences or risk ratios (SMDs or RRs) with their 95% confidence intervals (CIs) were used to synthesize the results of studies included in the meta-analysis. Results: Ten RCTs (n = 344) with 172 schizophrenia subjects on adjunctive IN-OT [range = 40–80 International Units (IU)/day] and 172 schizophrenia subjects on adjunctive placebo over 2–16 weeks were included. No significant differences regarding total psychopathology measured with the total Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) [8 RCTs, n = 203; SMD: −0.08 (95%CI: −0.53, 0.37), P = 0.74, I ² = 59%] and the positive, negative and general symptom scores [SMD: −0.20 to −0.04 (95%CI: −0.75, 0.36), P = 0.28 to 0.78; I ² = 0% to 72%] were found between the IN-OT and placebo groups. Similarly, subgroup analyses for total psychopathology found no group differences. Dose-response effect analyses showed that only 80 IU/day IN-OT had superiority over placebo in improving total psychopathology (P = 0.02) and positive symptom score (P = 0.01). No group differences between adjunctive IN-OT and placebo regarding discontinuation due to any reason [RR: 1.12 (95%CI: 0.67, 1.88), P = 0.67, I ² = 0%] and adverse drug reactions were found. Conclusions: Although the meta-analysis did not show a positive effect in general, the higher dose of adjunctive IN-OT (80 IU/day) appears to be efficacious and safe in improving total psychopathology and positive symptoms in schizophrenia. Review registration: CRD42017080856