Efficacy of Chronic Intranasal Oxytocin Administration in Individuals with Autism: A Systematic Review and Meta-analysis
Maheen Fatima1, Emaan Athar1, Yusra Tehreem1, Ume Hani1, Ayesha Sarfaraz1, Raghabendra Kumar2, Neeharika Balla3, Shreya Singh Beniwal4
1Quaid-e-Azam Medical CollegeBahawalpur., 2Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal, 3Maharajah's institute of medical sciences, Vizianagaram, AP India 535002, 4Lady Hardinge Medical College,New Delhi-110001
Objective:
To determine whether chronic oxytocin administration improves neural and behavioral outcomes in ASD.
Background:
Autism is an early-onset neurodevelopmental disorder characterized by repetitive and constrictive patterns of behaviors, interests, or activities, as well as difficulties with social interaction and communication. Oxytocin has been proposed as a potential treatment for autism spectrum disorder (ASD) due to its role in social bonding and emotional regulation
Design/Methods:
We performed a comprehensive search on PubMed, Google Scholar, Cochrane Library, and ClinicalTrials.gov from inception to September 2025, searching for RCTs that evaluated the neural, behavioral, and biological outcomes of Chronic oxytocin(more than 4 weeks administration of oxytocin) in patients with autism compared to placebo. The analysis is registered with PROSPERO (CRD420251166227) and followed the PRISMA guidelines. Two independent reviewers screened and extracted data from eligible studies. Outcomes were pooled using Rev-Man (random-effects model) and reported as mean differences (MD) with 95% confidence intervals. Heterogeneity was assessed using I² statistics. The risk of bias was evaluated using Cochrane RoB 2.0.
Results:
The meta-analysis evaluated 9 RCTs, including 415 autistic patients. Chronic oxytocin administration was associated with significant reduction in amygdala-orbitofrontal connectivity by -0.13 units ([95% CI = -0.25 to -0.01], P = 0.04). It did not cause meaningful improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale (RBS-r) (MD = -2.40 [95% CI = -11.80 to 7.00, P = 0.62 and MD = -2.00 [95% CI = -6.31 to 2.31], P = 0.36 ). Salivary oxytocin level showed a non-significant increase of 140.12 [95% CI = 139.16 to 419.40], P = 0.33, with high heterogeneity (I2 = 94%).
Conclusions:
This systemic review and meta analysis indicates that chronic oxytocin administration has significant effect on neural connectivity mainly amygdala-OFC connectivity which in turn has positive impact on avoidance attachment. Further well designed and large RCTS are required to confirm the efficacy.
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