A randomized placebo-controlled trial of 4 weeks of intranasal oxytocin in 40 autistic men found no improvement in core social symptoms, but did show lasting reductions in repetitive behaviors and avoidance feelings persisting up to 1 year post-treatment.
Benefits lasting 1 year after 4-week treatmentReductions in repetitive behaviors and avoidance feelings persisted up to 1 year after only 4 weeks of daily intranasal oxytocin — suggesting potential neuroplastic effects rather than simple pharmacological action.
What the researchers found
Primary outcome: No significant treatment-specific improvement in social responsiveness (Social Responsiveness Scale). Both oxytocin and placebo groups showed improvement, with no significant between-group difference (self-report p=0.37, informant-rated p=0.19).
Secondary outcomes with significant treatment-specific effects:
- Repetitive Behavior Scale: Reduced self-reported repetitive behaviors in oxytocin group (p=0.04), persisting up to 1 month and even 1 year post-treatment
- State Adult Attachment Measure: Reduced feelings of avoidance toward others (p=0.03), lasting up to 1 year
- Profile of Mood States: Higher reports of vigor (energy, activity, liveliness) in oxytocin group (p=0.03)
These secondary benefits persisted well beyond the 4-week treatment period, suggesting potential long-lasting neuroplastic effects.
Why it matters
This is one of the first oxytocin trials in autism to include long-term follow-up (up to 1 year). While the failure to improve core social symptoms is disappointing, the discovery of lasting effects on repetitive behaviors and avoidance is intriguing because: (1) repetitive behaviors are a core autism feature that significantly impacts quality of life, (2) effects persisting 1 year after only 4 weeks of treatment suggest oxytocin may trigger lasting neural changes rather than just temporary chemical effects, and (3) this shifts the conversation about which autism features oxytocin might actually help.
How the study worked
This was a double-blind, randomized, placebo-controlled, parallel-group pilot trial (Eudract 2014-000586-45). Forty adult men with ASD received either intranasal oxytocin (24 IU once daily in the morning) or placebo for 4 weeks. Assessments were conducted at baseline, immediately post-treatment (~24 hours after last dose), 4 weeks post-treatment, and 1 year post-treatment. Outcomes included self-report and informant-based questionnaires measuring social responsiveness, repetitive behaviors, attachment style, and mood states.
What this study cannot tell us
This is a small pilot study (n=40) with multiple secondary outcome comparisons, increasing the risk of false positive findings. The p-values for significant secondary outcomes (0.03-0.04) would not survive correction for multiple comparisons. Only adult men were included, limiting generalizability to women and children with autism. Self-report measures are inherently subjective, particularly for individuals with ASD who may have difficulty with self-assessment. The strong placebo response in social responsiveness measures is notable and complicates interpretation. The 24 IU dose and once-daily regimen may not be optimal.
How to read the evidence
This is a randomized, double-blind, placebo-controlled trial (the gold standard design) with long-term follow-up. However, it is a small pilot study (n=40), the primary outcome was negative, and the significant secondary findings would not survive multiple comparison correction, placing it at a moderate evidence level with important caveats.
When this study was published
Published in 2020, this study is about 6 years old. The oxytocin-autism field continues to evolve, with ongoing debates about optimal dosing, treatment duration, outcome measures, and which individuals might benefit most.
The bigger picture
Oxytocin has been one of the most studied neuropeptides for autism intervention, with mixed results across trials. This study contributes the important finding that oxytocin's benefits may not lie where researchers initially expected (social cognition) but in adjacent domains (repetitive behaviors, attachment avoidance). The long-lasting effects are particularly significant — most peptide drugs have effects that wear off quickly, but oxytocin may promote neural plasticity that persists long after treatment. This could shift the oxytocin-autism research field toward new outcome measures and treatment paradigms.
Questions still open
- Would a larger trial confirm the long-lasting effects on repetitive behaviors, or are these false positives from multiple comparisons?
- What neural mechanisms explain how 4 weeks of oxytocin could produce behavioral changes lasting a full year?
- Should future oxytocin-autism trials shift primary outcomes from social measures to repetitive behaviors and attachment?
Common questions
Does oxytocin nasal spray help with autism?
Why would effects from a 4-week treatment last for a year?
Read the original research
Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up.
Molecular autism, 11(1), 6
Citation
Bernaerts, Sylvie; Boets, Bart; Bosmans, Guy; Steyaert, Jean; Alaerts, Kaat. (2020). Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up.. Molecular autism, 11(1), 6. https://doi.org/10.1186/s13229-020-0313-1