What is the appropriate propranolol dosing schedule for adult migraine prophylaxis, including initial dose, titration increments, and maximum daily dose?

Propranolol Dosing for Migraine Prophylaxis

For adult migraine prophylaxis, start propranolol at 80 mg once daily using extended-release formulation, then titrate to a target range of 80-240 mg daily, with most patients achieving adequate control at 160 mg daily. 1, 2

Initial Dosing and Formulation

• Begin with 80 mg once daily of propranolol extended-release capsules, which is the FDA-approved starting dose for migraine prevention 2
• Extended-release formulations are preferred for once-daily dosing and improved adherence 2
• The immediate-release formulation can be divided into 2-3 daily doses if extended-release is unavailable, though this is less convenient 1

Titration Strategy

• Increase the dose gradually at 3-7 day intervals until optimal response is achieved 2
• The usual effective dose range is 160-240 mg once daily 2
• Most patients achieve adequate migraine control at 160 mg daily, making this a reasonable target dose 1
• The maximum dose is 240 mg daily for migraine prophylaxis, though doses up to 320 mg have been studied 2, 1

Duration of Adequate Trial

• Allow 2-3 months at therapeutic dose before declaring treatment failure, as clinical benefits may not become apparent immediately 1
• If no satisfactory response is obtained within 4-6 weeks after reaching maximal dose, discontinue propranolol therapy 2
• An adequate trial requires treating through 2-3 migraine episodes before abandoning therapy 1

Evidence Supporting Lower Doses

• Research demonstrates that low doses (close to 1 mg/kg body weight daily, approximately 40-80 mg) are effective in controlling migraine in 73.5% of patients 3
• Only about one-third of patients require higher doses for adequate control 3
• Starting low minimizes side effects while still providing benefit for many patients 3

Indications for Initiating Prophylaxis

• ≥2 migraine attacks per month producing disability lasting ≥3 days per month 1
• Use of acute rescue medications >2 times per week 1
• Failure of or contraindications to acute migraine treatments 1

Contraindications to Screen For

• Asthma (absolute contraindication) 1
• Bradycardia 1
• Second or third-degree heart block 1
• Cardiac failure 4
• Raynaud disease 4
• Depression (relative contraindication, as propranolol may worsen mood) 4
• Uncontrolled diabetes 1
• Hypersensitivity to propranolol 1

Monitoring and Follow-Up

• No routine monitoring of heart rate or blood pressure is required between appointments if the patient is well and on a stable dose 1
• Follow-up intervals of 2-3 months are appropriate for patients on stable treatment without complications 1
• Monitor for common adverse effects including fatigue, depression, nausea, dizziness, and insomnia 1
• Assess for mood changes and sleep disturbances at each visit 1

Discontinuation Strategy

• Reduce dosage gradually over several weeks when stopping treatment to avoid rebound phenomena 1
• Abrupt discontinuation can be done safely in some cases, but gradual tapering is generally preferred 2

Important Clinical Pitfalls

• Beta-blockers with intrinsic sympathomimetic activity (e.g., pindolol) are ineffective for migraine prevention and should be avoided 1
• Do not switch mg-for-mg from immediate-release to extended-release formulations, as they have different kinetics and produce lower blood levels; retitration may be necessary 2
• Avoid medication overuse headache by ensuring patients do not use acute rescue medications more than twice per week 1
• Extended-release capsules provide sustained release over 24 hours, so effectiveness should be maintained throughout the dosing interval 2

Comparative Effectiveness

• Propranolol and timolol are the only beta-blockers with the strongest evidence for migraine prevention 1
• Propranolol is more effective for pure migraine, while amitriptyline may be superior for mixed migraine and tension-type headache 1
• Other first-line alternatives include amitriptyline, divalproex sodium, sodium valproate, and topiramate 1
• Propranolol is substantially less costly than CGRP antagonists while having similar efficacy 1

Special Populations

• Pregnancy: Propranolol (80-160 mg daily) is the first-line preventive option if prophylaxis is absolutely necessary, though first-trimester exposure may be associated with intrauterine growth restriction 4
• Breastfeeding: Propranolol is the first-choice preventive medication at 80-160 mg daily due to minimal transfer into breast milk 4