Heterogeneity in response to repeated intranasal oxytocin in schizophrenia and autism spectrum disorders: A meta‐analysis of variance

Abstract

Intranasal oxytocin (OT) has been suggested as a putative adjunctive treatment for patients with schizophrenia and autism spectrum disorders (ASD). Here, we examine available evidence from trials investigating the effects of repeated administrations of intranasal OT on the core symptoms of patients with schizophrenia and ASD, focusing on its therapeutic efficacy and heterogeneity of response (meta-analysis of variance). The repeated administration of intranasal OT does not improve most of the core symptoms of schizophrenia and ASD, beyond a small tentative effect on schizophrenia general symptoms. However, we found significant moderator effects for dose in schizophrenia total psychopathology and positive symptoms, and percentage of included men and duration of treatment in schizophrenia general symptoms. We found evidence of heterogeneity (increased variance) in the response of schizophrenia negative symptoms to intranasal OT compared to placebo, which supports the idea that subgroups of responsive and non-responsive patients might coexist. For other core symptoms of schizophrenia, or any of the core symptom dimensions in ASD, the response to repeated treatment with intranasal OT did not show evidence of heterogeneity.

“Less is more”: a dose-response account of intranasal oxytocin pharmacodynamics in the human brain

“…Intranasal oxytocin, the most widely used method for oxytocin administration in humans, has been suggested as a promising therapeutic strategy for several brain disorders where we currently lack effective treatments (e.g., autism spectrum disorder 1 , schizophrenia 2 , migraine 3 , stroke 4 , obesity 5 , Prader-Willi 6 ). An increasing number of clinical trials have been evaluating the efficacy of specific nominal doses of intranasal oxytocin (for an overview see [7][8][9][10][11] ), yet most studies have been inconclusive at best 11,12 . The lack of unequivocal findings regarding the effects of intranasal oxytocin in trials with human patients contrasts with a flood of evidence showing consistent beneficial effects in animal models 13,14 , where oxytocin is often administered centrally [15][16][17] .…”

Oxytocin—a social peptide? Deconstructing the evidence

“…A recent meta-analysis concluded that repeated administration of intranasal oxytocin had no effect on most core symptoms of schizophrenia, beyond a ‘small tentative effect’ on general symptoms [ 101 ]. However, looking at the heterogeneity in the responses to intranasal oxytocin, the authors suggested that there might be a subgroup of responsive patients.…”

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction

“…Long-term exposure to high concentrations of oxytocin is hypothesized to downregulate the oxytocin-signaling machinery. It attenuates the oxytocinergic effect on brain function, and smaller improvements in the general symptoms of persons with schizophrenia have been reported [246], as demonstrated by the dampening of the response of the amygdala negatively affecting healthy volunteers who received daily intranasal oxytocin for 1 week compared with those who received single doses [247]. The mechanisms underpinning both schizophrenia and the oxytocinergic system have yet to be adequately characterized.…”