What is the recommended dosing for propranolol (beta-blocker) in the prophylactic treatment of migraines?

Propranolol Dosing for Migraine Prophylaxis

The recommended dosing for propranolol in migraine prophylaxis is 80-240 mg daily, with most patients achieving optimal results in the 160-240 mg range. 1, 2

Dosing Guidelines

• Start with a low dose (80 mg daily) and gradually increase to minimize side effects 1
• The usual effective dose range is 160-240 mg once daily 2
• For extended-release formulations, dosing is once daily 2
• If using immediate-release formulations, the total daily dose should be divided into multiple administrations 3
• Low doses (approximately 1 mg/kg/day) may be effective in some patients, with fewer than a third requiring higher doses 4

Titration and Duration

• Increase dosage gradually at intervals of 3-7 days until optimal response is achieved 2
• An adequate trial requires 2-3 months as clinical benefits may not become apparent immediately 1
• If satisfactory response is not obtained within 4-6 weeks after reaching the maximal dose, propranolol therapy should be discontinued 2
• When discontinuing treatment, gradually taper the dose over several weeks to avoid rebound effects 2

Indications for Propranolol in Migraine Prevention

• Two or more migraine attacks per month with disability lasting 3+ days per month 3, 1
• Use of acute rescue medications more than twice per week 3, 1
• Failure of or contraindications to acute migraine treatments 1
• Presence of uncommon migraine conditions (e.g., hemiplegic migraine, prolonged aura) 3

Efficacy and Evidence

• Propranolol has consistently demonstrated efficacy in reducing migraine frequency 3, 5
• A recent meta-analysis found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days compared to placebo (RR 1.65,95% CI 1.41 to 1.93) 5
• Propranolol appears more effective for pure migraine, while amitriptyline may be superior for mixed migraine and tension-type headache 3, 1
• Propranolol is considered a first-line agent for migraine prevention along with timolol, amitriptyline, divalproex sodium, and sodium valproate 3

Side Effects and Monitoring

• Common adverse effects include fatigue, depression, nausea, dizziness, and insomnia 3, 1
• These side effects are generally well-tolerated and rarely cause discontinuation 3
• High-quality evidence shows propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo, with an absolute risk difference of 20 more per 1,000 (95% CI 0 to 30) 5
• Monitor for mood changes, sleep disturbances, and cardiovascular effects 1

Important Considerations and Pitfalls

• Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) are ineffective for migraine prevention and should be avoided 3, 1
• Propranolol is contraindicated in patients with bradycardia, heart block, and certain other cardiovascular conditions 1
• When switching from immediate-release to extended-release formulations, retitration may be necessary to maintain effectiveness at the end of the 24-hour dosing interval 2
• Extended-release propranolol is not a simple mg-for-mg substitute for immediate-release tablets 2

Combination Therapy

• Limited evidence suggests that low-dose propranolol (40 mg/day) combined with nortriptyline (20 mg/day) is safe and may be effective 6
• Combined therapy appears to be as safe as monotherapy but requires further investigation with higher doses and longer treatment periods 6