Abstract
BackgroundNegative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear.MethodsWe conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms.ResultsIn an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40–80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses.ConclusionsThe present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.
Highlights
The clinical manifestations of schizophrenia include positive, disorganized, and negative symptoms (Peralta et al, 1997)
A significant reduction in negative symptoms was found for the highdose subgroup (>40 to IU (40 IU)) (Figure 2), which is consistent with the findings of the dose-response meta-analysis suggesting that the efficacy of intranasal oxytocin increases with high doses of oxytocin
In contrast to the (Williams and Buckner, 2017) as well as the (Zheng et al 2019) meta-analyses that reported the absence of efficacy of intranasal oxytocin on negative symptoms, our meta-analysis suggests a possible trend-level effect on negative symptoms of high-dose oxytocin, even after the exclusion of the Modabbernia study (2013)
Summary
The clinical manifestations of schizophrenia include positive, disorganized, and negative symptoms (Peralta et al, 1997). Methods: We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms. Results: In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. No beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses. Conclusions: The present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required
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