Efficacy and safety of oxytocin augmentation therapy for schizophrenia: an updated systematic review and meta-analysis of randomized, placebo-controlled trials

The aim of this study was to perform a systematic review and an updated and comprehensive meta-analysis of oxytocin augmentation therapy in patients with schizophrenia who received antipsychotic agents. Data published up to 07/11/2015 were obtained from PubMed, PsycINFO, and Cochrane Library databases. We conducted a systematic review and meta-analysis of patients’ data from randomized controlled trials (RCTs) comparing oxytocin with placebo. Relative risk (RR), standardized mean difference (SMD), and 95 % confidence intervals (95 % CI) based on the random-effects model were calculated. We included seven RCTs; the total sample size was 206 patients. Oxytocin was superior to placebo for decreasing the Positive and Negative Syndrome Scale (PANSS) general subscale scores (SMD = −0.44, 95 % CI −0.82 to −0.06, p = 0.02, I2 = 0 %, N = 4, n = 112); however, it was not different from placebo for total symptoms (SMD = −0.46, 95 % CI −1.20 to 0.28, p = 0.22, I2 = 80 %, N = 6, n = 162), positive symptoms (SMD = −0.18, 95 % CI −0.87 to 0.51, p = 0.60, I2 = 81 %, N = 6, n = 192), and negative symptoms (SMD = −0.34, 95 % CI −0.76 to 0.08, p = 0.12, I2 = 55 %, N = 7, n = 214). However, a sensitivity analysis including only oxytocin administration on consecutive days studies was superior to placebo in negative symptoms (SMD = −0.44, 95 % CI −0.87 to −0.01, p = 0.04, I2 = 51 %, N = 6 n = 192). There were no significant differences for all-cause discontinuation (RR = 1.02) and individual side effects such as headache and dizziness between oxytocin and placebo. Oxytocin may improve PANSS general subscale scores in schizophrenia and seems to be well tolerated. However, because the number of studies in the current analysis was small, further study will be required using larger sample sizes.