REVIEW OF: London EB et al, J Clin Psychopharmacol 2024;44(5):462–467

STUDY TYPE: Pilot randomized, double-blind, placebo-controlled crossover trial

Aggression and severe behavioral dysregulation in autistic youth are notoriously tough to manage. Risperidone and aripiprazole help but carry steep metabolic risks, and many patients remain treatment resistant. This small pilot trial tested whether high-dose propranolol could calm aggression in autistic adolescents who had failed at least two prior ­medications.

Six teens (ages 12–19, mostly nonspeaking, mean IQ 63) completed both propranolol and placebo phases in a double-blind crossover design. Doses were titrated up to 200 mg 3 times daily (600 mg/day) or until improvement, each phase lasting 6 weeks with a washout in between. Weekly telehealth visits and full cardiac monitoring (ECG, Holter, echo) ensured safety. Main measures were the Clinical Global Impression–Improvement (CGI-I) and the Aberrant Behavior Checklist–Irritability subscale (ABC-C/I).

On propranolol, CGI-I scores improved by about 50% versus placebo (mean 2.5 vs 5.0), and ABC-C/I scores fell 37% (12.2 vs 19.2). Blood pressure stayed stable, and side effects were mild—mostly lethargy and loose stools. One participant’s improvement persisted into the placebo phase, and the tiny sample inflated the apparent effect size, but the results are still encouraging.

CARLAT TAKE
There is a long history of high-dose propranolol for aggression; however, other beta blockers may be better candidates and less likely to create cardiovascular problems or exacerbate asthma. While propranolol may be an alternative for severe, chronic aggression in autistic youth who don’t respond to other approaches, the need for cardiovascular monitoring makes it less practical at high dosages. Before escalating medication, rule out medical causes of pain or distress and use developmental relationship-based, caregiver-mediated strategies. For the hardest cases, propranolol is on our radar, but we want to see larger trials and studies on other beta blockers.