Propranolol Dosing for Severe Autism Spectrum Disorder
For severe Autism Spectrum Disorder (ASD), propranolol should be initiated at 120 mg/day and titrated up to 400-600 mg/day in divided doses, with close monitoring for cardiovascular effects. 1, 2
Dosing Protocol
Initial Dosing
- Start at lower doses (40 mg three times daily, totaling 120 mg/day)
- Titrate gradually upward in a stepwise fashion
- Monitor vital signs during titration
Target Dosing
- Effective dose range: 120-960 mg/day (mean effective dose: 462 mg/day) 1
- Most patients in clinical studies required 400-600 mg/day for optimal effect
- Maximum studied dose: 600 mg/day (200 mg three times daily) 2
Administration
- Divide total daily dose into three equal doses (TID dosing)
- Administer with food to minimize gastrointestinal side effects
- Maintain consistent dosing schedule to avoid fluctuations in blood levels
Monitoring and Safety
Pre-treatment Assessment
- Complete cardiovascular examination including:
- Blood pressure and heart rate measurements
- Electrocardiogram (ECG)
- Cardiac history assessment
Ongoing Monitoring
- Regular blood pressure and heart rate checks during titration
- Monitor for hypotension (systolic BP <90 mmHg)
- Watch for bradycardia (heart rate <60 bpm)
- Assess for signs of hypoglycemia, especially during periods of reduced food intake
Contraindications
- Sinus bradycardia
- Heart block greater than first-degree
- Cardiogenic shock
- Overt cardiac failure
- Severe hypotension
Clinical Evidence and Efficacy
High-dose propranolol has shown promising results for severe behavioral symptoms in ASD:
- 85% of patients (39 out of 46) showed significant improvement on Clinical Global Impression scale 1
- 50% reduction in aggressive symptoms compared to placebo in controlled trials 2
- Large effect sizes for reduction in irritability (r = -0.64) and global improvement (r = -0.74) 2
While lower doses (0.5-1 mg/kg/day) have been studied for specific symptoms 3, these are insufficient for managing severe behavioral dysregulation in ASD.
Potential Benefits
- Reduction in severe aggression and self-injurious behaviors
- Improvement in emotional, behavioral, and autonomic dysregulation
- Enhanced conversational reciprocity and social communication 4
- Reduced anxiety symptoms 5
Common Side Effects
- Decreased blood pressure (average reduction: 13 mmHg systolic) 2
- Mild sedation
- Sleep disturbances
- Cool extremities
- Potential for hypoglycemia (rare at therapeutic doses)
Important Considerations
- Temporary discontinuation during acute illness, especially with vomiting or diarrhea
- Avoid abrupt discontinuation; taper gradually when stopping treatment
- Consider drug interactions, particularly with other medications affecting blood pressure
- Effectiveness may be seen within 1-2 weeks of reaching therapeutic dose
High-dose propranolol represents a promising treatment option for severe behavioral symptoms in ASD that have been refractory to conventional treatments, with a favorable safety profile when properly monitored.