Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. — VialBase Research

Summary

Because oxytocin had been proposed as a treatment for the social deficits of autism spectrum disorder (ASD) without its safety having been formally established in that population, this systematic review set out to characterize the side-effect profile of long-term intranasal oxytocin against placebo. The authors searched PubMed, Embase, the Cochrane Library, and International Pharmaceutical Abstracts for all randomized controlled trials of intranasal oxytocin in ASD published before 1 January 2017 that reported safety data, extracted the relevant data, and pooled it to estimate risk ratios for the most common adverse events, supplemented by a descriptive analysis of severe adverse events. Five trials met criteria, comprising 223 participants — 123 who received oxytocin and 100 who received placebo. The most frequently reported adverse events were nasal discomfort (14.3%), irritability (9.0%), tiredness (7.2%), diarrhea (4.5%), and skin irritation (4.5%). Critically, none of these common events was statistically associated with treatment allocation on meta-analysis (all P-values > 0.1), meaning they occurred at comparable rates on placebo. Five severe adverse events were reported across the literature: aggression (one in placebo, two in oxytocin) and seizures (one in placebo, one in oxytocin). The authors concluded that the available evidence supports intranasal oxytocin as well tolerated and safe for use in the ASD population, while stating explicitly that larger clinical trials are still required to establish whether it is actually effective.

Key Findings

• Five randomized controlled trials pooled, totaling 223 participants: 123 assigned to oxytocin and 100 to placebo, all published before 1 January 2017
• Most common adverse events across the trials: nasal discomfort 14.3%, irritability 9.0%, tiredness 7.2%, diarrhea 4.5%, skin irritation 4.5%
• On meta-analysis of pooled data, none of these common adverse events was statistically associated with treatment allocation (all P-values > 0.1) — the events occurred at similar rates on placebo
• Five severe adverse events were reported in total: aggression (one on placebo, two on oxytocin) and seizures (one on placebo, one on oxytocin) — numerically small and not clearly attributable to oxytocin, but worth noting given the neurological nature of both
• The local, nasal-route events (nasal discomfort, skin irritation) are the ones most directly tied to the delivery method rather than systemic peptide activity
• Authors’ conclusion is explicitly split: the safety data support tolerability, but efficacy in ASD remains unestablished and requires larger trials

Relevance to Oxytocin

This is the main safety reference anyone should reach for when evaluating repeated intranasal Oxytocin use, and its findings are genuinely reassuring on tolerability: the common complaints — nasal discomfort, tiredness, irritability, mild GI upset, skin irritation — occurred at rates statistically indistinguishable from placebo, and severe events were rare and distributed across both arms. Two limitations must travel with that reassurance. First, the evidence base is thin: 223 pooled participants across five trials is a small foundation on which to declare a chronically dosed peptide safe, and rare harms would not be detectable at that sample size. Second, this review addresses safety only — the authors themselves note that efficacy for ASD is not established, so the paper cannot be cited as support for oxytocin working, only as evidence that it did not obviously hurt the people studied. That distinction matters because oxytocin’s FDA approval covers obstetric use; every intranasal application discussed here is off-label.

Citation

Cai Q, Feng L, Yap KZ. Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. Psychiatry and clinical neurosciences. 2018;72(3):140-151. doi:10.1111/pcn.12627.

See Also

• Parent compound: Oxytocin