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. (C) 2018 Elsevier B.V. All rights reserved.