Autism spectrum disorder (ASD) is characterized by impairments in social communication and restricted and repetitive behaviors, with a high incidence of comorbid anxiety.  We conducted a double-blinded placebo-controlled trial of the beta-adrenergic antagonist propranolol in ASD.  Herein, we report initial results of the patients completing the open-label extension phase for the primary outcome measure of social communication and, secondarily, language and anxiety.

Propranolol is widely utilized for performance anxiety and public speaking anxiety.  We previously reported single-dose psychopharmacological challenge studies revealing significant benefits from propranolol on a structured social interaction task and language tasks in ASD. 

ASD patients (age 7-24) were enrolled, titrated to 100mg propranolol daily in divided doses over 12-weeks (body weight adjusted in children), monitoring social interaction, and secondarily anxiety, language, and overall ASD severity.  Forty seven participants completed the 12-week open label extension. In this initial analysis, separate Clinician Global Clinical Impression-Severity (CGI-S) scales are reported for social interaction as well as for verbal communication, anxiety, and overall ASD severity. 

For the primary outcome, CGI-S for social interaction was 4.01 (±0.80sdev)(1-7, 7=most severe) at baseline, decreasing to 3.75(±0.82sdev) at week-12 (t(46)=4.47, p<0.001, Cohen's d=0.65).  For secondary outcomes, baseline CGI-S for anxiety was 3.92 (±0.89sdev), decreasing to 3.40 (±1.01sdev)(t(46)=5.40, p<0.001, Cohen's d=0.79), baseline CGI-S for verbal communication was 3.22 (±0.81sdev), decreasing to 3.04 (±0.78sdev) (t(46)=2.92, p=0.005, Cohen's d=0.43), and baseline CGI-S for overall ASD severity was 3.90 (±0.54sdev) at baseline, decreasing to 3.57 (±0.68sdev) (t(12)=3.13, p=0.003, Cohen's d=0.46). 

Initial analysis of open label extension data from the propranolol trial in ASD suggests promising results for social interaction, as well as the secondary outcomes of anxiety, language, and overall severity. While quite promising, firm conclusions should be deferred for completion of analysis of the double-blind trial data, and analysis of psychophysiological data to identify best responders.