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

Abstract

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, I (2) = 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, I (2) = 80 %, N = 6, n = 162), positive symptoms (SMD = -0.18, 95 % CI -0.87 to 0.51, p = 0.60, I (2) = 81 %, N = 6, n = 192), and negative symptoms (SMD = -0.34, 95 % CI -0.76 to 0.08, p = 0.12, I (2) = 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, I (2) = 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.

A 12-week randomized controlled trial of twice-daily intranasal oxytocin for social cognitive deficits in people with schizophrenia

“…While these findings need to be interpreted cautiously given the post hoc nature of the analyses, the data suggest a potential advantage for oxytocin on negative symptoms. This is also consistent with a recent meta-analysis which found that, among consecutive-day dosing studies (6 studies, N=192 participants), oxytocin demonstrated significant improvement in negative symptoms in people with schizophrenia (Oya et al, 2015). In addition, Cacciotti-Saija et al (2014) reported a significant dose-response relationship between oxytocin and negative symptoms, suggesting a modest therapeutic effect that was not demonstrated for other symptom domains.…”

The effects of oxytocin and galantamine on objectively-defined vocal and facial expression: Data from the CIDAR study

“…Both medications are associated with mild side effect profiles (Hansen et al, 2008; Oya et al, 2016), are relatively inexpensive, and have shown efficacy in at least some studies (Lee et al, 2013). Unfortunately, data from the CIDAR trial failed to find significant improvements in negative symptom severity or cognitive functioning with either galantamine or oxytocin compared to placebo using standard clinical rating scales or neuropsychological test batteries (Buchanan et al, 2016).…”

Coding errors lead to unsupported conclusions: a critique of Hofmann et al. (2015)

“…They also coded two Brief Psychiatry Reporting Scale (BPRS) outcomes as general psychopathology. Based on the contents of the scale and other meta-analyses on this topic (Oya et al, 2015), this should have either been coded as psychotic symptoms or they should have provided rationale for divergent coding. All four of these outcomes were reported as positive which, in addition to the aforementioned errors, likely inflated their meta-analytic estimates.…”