What is the recommended dosing, titration schedule, efficacy monitoring, contraindications, cautions, side effects, and alternative prophylactic therapies for propranolol in an adult patient with migraine?

Propranolol for Migraine Prophylaxis

Recommended Dosing and Titration

Start propranolol at 80 mg daily and titrate to a target range of 80–240 mg daily, with most patients achieving adequate control at 160 mg daily. 1

• Begin with 80 mg daily (or as low as 40 mg daily in patients concerned about tolerability) and increase gradually every 2–4 weeks until clinical benefit is achieved or side effects limit further increases. 1, 2
• The FDA-approved dosing range is 80–240 mg daily, with strong evidence supporting efficacy across this spectrum. 1, 3
• Approximately 73.5% of patients respond to low doses (≤1 mg/kg body weight daily, typically 40–80 mg), and fewer than one-third require higher doses to control migraine attacks. 2
• Allow an adequate trial period of 2–3 months at therapeutic dose before declaring treatment failure, as clinical benefits may not become apparent immediately. 1, 4

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Indications for Initiating Propranolol Prophylaxis

Propranolol is indicated as first-line preventive therapy for patients with ≥2 migraine attacks per month producing disability for ≥3 days, or those using acute rescue medications more than twice weekly. 1, 4

• Additional indications include failure of or contraindications to acute migraine treatments, and uncommon migraine conditions such as hemiplegic migraine or migraine with prolonged aura. 4
• Propranolol is the beta-blocker with the strongest evidence for migraine prevention and carries FDA approval for this indication. 1, 5
• It is substantially less costly than CGRP monoclonal antibodies while demonstrating similar efficacy, making it the preferred first-line agent from both clinical and economic perspectives. 1

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Efficacy Monitoring

Assess treatment response at 2–3 months after initiation using headache diaries to track attack frequency, severity, duration, and disability. 1, 4

• A successful response is defined as ≥50% reduction in monthly migraine days. 4
• Continue regular follow-up at 6–12 month intervals to reassess efficacy, adverse events, and adherence. 1
• Consider pausing preventive therapy after 6–12 months of successful control to determine if discontinuation is feasible. 4
• When stopping propranolol, reduce dosage gradually over several weeks to avoid rebound phenomena. 1

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Contraindications

Propranolol is absolutely contraindicated in patients with bradycardia, second- or third-degree heart block, hypersensitivity to propranolol, and hypoglycemic episodes. 1

• Additional contraindications include asthma, uncontrolled diabetes, and severe cardiovascular disease. 1
• Beta-blockers with intrinsic sympathomimetic activity (e.g., pindolol, acebutolol) are ineffective for migraine prevention and should be avoided. 1

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Common Side Effects and Cautions

Common adverse effects include fatigue, depression, nausea, dizziness, and insomnia; monitor for mood changes and sleep disturbances at follow-up visits. 1

• Side effects intensify as the dose is increased, and approximately 5–10% of patients discontinue treatment due to intolerable adverse reactions. 2
• No routine monitoring of heart rate or blood pressure is required between appointments if the patient is well. 1
• Propranolol demonstrates better tolerability than topiramate, with 157 fewer discontinuations due to adverse events per 1000 treated people. 1

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Comparative Effectiveness and Treatment Selection

Propranolol is superior for pure migraine, while amitriptyline is more effective for mixed migraine and tension-type headache. 1

• Propranolol and timolol are the only beta-blockers with the strongest evidence for migraine prevention; other first-line alternatives include topiramate, divalproex sodium, and sodium valproate. 1, 5
• Propranolol is as effective and safe as calcium antagonists, other beta-blockers, and a variety of other drugs used for migraine prophylaxis, though long-term efficacy data beyond 3 months are lacking. 3
• Metoprolol, atenolol, and nadolol have moderate evidence supporting their use as alternative beta-blockers when propranolol is not tolerated. 4

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Alternative Prophylactic Therapies

First-Line Alternatives

• Topiramate 50–100 mg daily is the only oral preventive with strong RCT evidence for chronic migraine and is preferred in patients with obesity due to associated weight loss. 4
• Amitriptyline 30–150 mg daily is optimal for patients with comorbid depression, anxiety, or sleep disturbances, though it lacks robust evidence for chronic migraine. 4
• Candesartan is an effective first-line agent, particularly useful for patients with comorbid hypertension. 4

Second-Line Alternatives

• Divalproex sodium 500–1500 mg daily or sodium valproate 800–1500 mg daily are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects. 4, 5
• Gabapentin has fair evidence of effectiveness but should only be considered if propranolol fails or is contraindicated. 1, 5

Third-Line Alternatives

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when 2–3 oral preventives have failed or are contraindicated, with efficacy assessed after 3–6 months. 4
• OnabotulinumtoxinA is the only FDA-approved therapy specifically for chronic migraine (not episodic migraine) and should be used when three oral preventives have failed, with efficacy evaluated after 6–9 months. 4

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, relaxation training, and acupuncture can be offered alongside medication as effective adjuncts for migraine prevention. 4
• Identifying and modifying triggers (sleep hygiene, regular meals, hydration, stress management) can reduce migraine frequency. 4

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Critical Pitfalls to Avoid

• Do not allow patients to use acute migraine medications more than 2 days per week (≤10 days per month), as this creates medication-overuse headache and interferes with preventive therapy effectiveness. 4, 1
• Do not declare treatment failure before completing a 2–3 month trial at therapeutic dose, as clinical benefits may be delayed. 1
• Do not start with excessively high doses, as this leads to poor tolerability and discontinuation; begin at 80 mg daily and titrate gradually. 1
• Do not use beta-blockers with intrinsic sympathomimetic activity (e.g., pindolol), as they are ineffective for migraine prevention. 1