Abstract
Rationale
Autism spectrum disorder (ASD) is characterized by impaired social communication and is also frequently characterized by co-occurring anxiety. Propranolol is widely utilized to treat performance and public speaking anxiety. Single-dose psychopharmacological challenge studies suggested benefits using propranolol for verbal tasks and social interaction.
Objective
We conducted a double-blinded, placebo-controlled trial of the β-adrenergic antagonist propranolol in ASD for social interaction, anxiety, and language.
Methods
Seventy-four participants with ASD, age 7–24 years, were enrolled and randomized to a 12-week course of propranolol or placebo, with blinded assessments at baseline, 6 weeks, and 12 weeks. The primary outcome was the General Social Outcome Measure-2 (GSOM-2) for social interaction, and secondary outcomes were the Clinician Global Clinical Impression-Improvement (CGI-I) ratings independently conducted for social interaction, anxiety, and language at 6 weeks and 12 weeks.
Results
Sixty-nine participants completed the 12-week visit. No significant effect of drug was found for the GSOM-2 or the CGI-I for social interaction or language. CGI-I for anxiety showed greater improvement with propranolol at the 12-week time point (p = 0.045, odds ratio = 2.58 (95% CI = 1.02–6.52). Expected decreases in heart rate and blood pressure were observed with propranolol, and side effects were uncommon.
Conclusions
Propranolol did not impact social interaction measures or language, but there were indications of a beneficial effect for anxiety. This will need confirmation in a larger multicenter trial, monitoring markers or characteristics to identify those participants most likely to respond to propranolol for anxiety, and determine whether there is a subset of participants that are responsive for other previously reported outcomes.
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Data Availability
Requests can be made to the corresponding author for de-identified data from this study. All reasonable requests will be accommodated.
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Acknowledgements
We would like to thank our statistical consultants Dr. James Patrie and Dr. Greg Petroski for their contribution and the participants and their families for their time and effort. We would also like to thank Dr. John Hall for serving as our data safety monitor.
Funding
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Autism Research Program under Award No. W81XWH-16–1-0321. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense Congressionally Directed Medical Research Programs.
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Dr. Beversdorf serves as a consultant for YAMO Pharma, Impel Pharma, Scioto Biosciences, and Stalicla Biosciences, not related to this work.
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Beversdorf, D.Q., Ferguson, B., Hunter, S. et al. Randomized controlled trial of propranolol on social communication and anxiety in children and young adults with autism spectrum disorder. Psychopharmacology 241, 19–32 (2024). https://doi.org/10.1007/s00213-023-06452-1
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DOI: https://doi.org/10.1007/s00213-023-06452-1