High-dose propranolol decreases aggression in young people with autism

As many as two-thirds of individuals with autism spectrum disorder (ASD) experience challenging symptoms of irritability, including aggression and self-injury. The antipsychotics risperidone and aripiprazole are approved for the treatment of irritability associated with ASD; however, their adverse effects can compromise long-term use in many patients. Based on longstanding case reports showing promising results for the beta-blocker propranolol in reducing challenging symptoms in ASD, investigators conducted a randomized, double-blind, placebo-controlled crossover trial to evaluate the feasibility of high-dose propranolol for treating aggression in patients with ASD. The investigators recruited youths and young adults aged 12 to 30 with ASD and a history of severe and chronic aggression, self-injury, and disruptive behaviors that interfere with daily activities. Participants were required to have had an inadequate trial of at least two psychotropic medications, including at least one antipsychotic. Dosing of propranolol started at 10 mg three times a day and could be increased until adequate therapeutic response was achieved, to a maximum dose of 200 mg three times a day. Most study visits were conducted via telehealth in order to minimize patient schedule disruption. The primary outcomes were change in scores on the Clinical Global Impression-Improvement (CGI-I) and Aberrant Behavior Checklist-Community (ABC-C) scales from baseline to study endpoint. Six participants with a mean age of 16 years were enrolled. The investigators found that propranolol resulted in mean reductions of 50% in scores on the CGI-I and 37% in scores on the ABC-C. Effect sizes were large for both measures: –0.74 for the CGI-I and –0.64 for the ABC-C. “As this was a feasibility pilot study, we had a small sample that limits the generalization of our results to a wider population, and therefore, until a placebo-controlled, double-blind study with an adequate number of subjects is conducted, the clinical value of this report is limited,” the study's authors wrote. [London, E., et al. (2024). J Clin Psychopharmacol. https://doi.org/10.1097/JCP.0000000000001895]