What is the role of propranolol (beta blocker) in pediatric patients with migraines?

Propranolol for Pediatric Migraine Prevention

Primary Recommendation

Propranolol is an effective first-line preventive agent for pediatric migraine, dosed at 2-3 mg/kg/day (typically 80-240 mg daily), with evidence supporting its efficacy in reducing headache frequency by more than 50% in approximately 83% of children. 1, 2

Evidence-Based Positioning

• The 2020 American Academy of Neurology guidelines recommend discussing propranolol as one of three evidence-based preventive medications for pediatric migraine (alongside topiramate and amitriptyline combined with cognitive behavioral therapy). 1

• Propranolol has consistent evidence from multiple controlled trials demonstrating efficacy in migraine prevention, with the 2000 American Academy of Family Physicians establishing it as a first-line agent based on 46 controlled studies. 1

• The FDA approves propranolol for migraine prophylaxis, though the efficacy in treating an acute migraine attack that has already started has not been established. 3

Dosing Strategy for Pediatric Patients

• Start with 2-3 mg/kg/day divided into 2-3 doses, with most studies using initial doses around 3 mg/kg/day, then adjusting down to 2 mg/kg/day after the first follow-up visit if response is adequate. 2

• Low-dose propranolol (approximately 0.4 mg/kg/day) combined with nonpharmacologic measures is effective in reducing migraine frequency by >50% in approximately 80% of pediatric patients. 4

• For adults, the effective dose range is 120-240 mg daily, which can guide dosing in older adolescents approaching adult weight. 1

• Extended-release formulations (160 mg once daily) are as effective as divided doses for blood pressure and heart rate control, though pediatric-specific extended-release data are limited. 3

Indications for Preventive Therapy

Initiate propranolol when pediatric patients meet any of these criteria:

• Two or more migraine attacks per month producing disability lasting 3+ days per month. 1
• Use of acute rescue medication more than twice per week. 1
• Failure of or contraindications to acute migraine treatments (ibuprofen, triptans in adolescents). 1
• Frequent school absenteeism, poor quality of life, or recurring emergency room visits. 5

Efficacy Data

• In a prospective randomized trial of 63 children aged 5-15 years, propranolol reduced baseline headache frequency from 13.86 ± 2.11 to 4.23 ± 3.24 attacks per month, with 83% achieving >50% reduction in frequency. 2

• Propranolol significantly outperformed sodium valproate in reducing mean headache frequency per month (p < 0.01), though both drugs similarly reduced headache duration and severity. 2

• One placebo-controlled study demonstrated a number-needed-to-treat of 1.5 (95% CI 1.15-2.1) for achieving a two-thirds reduction in headache frequency. 6

• Complete cessation of headache attacks occurred in 14% of pediatric patients treated with propranolol. 2

Comparative Effectiveness

• Propranolol is preferred over amitriptyline as first-line therapy due to its lower risk of side effects, with both drugs showing equal efficacy (approximately 80% response rate) when combined with nonpharmacologic measures. 4

• Propranolol works better in children without aura compared to those with aura (p = 0.02), whereas amitriptyline shows no difference in response between aura subtypes. 4

• Topiramate may be more effective than propranolol in reducing attack frequency, but should be reserved for second-line use due to higher adverse event rates and teratogenic risk in adolescent females. 1, 7, 5

Critical Counseling Points

High Placebo Response Rate

• Discuss with patients and families that placebo was as effective as the studied medication in many pediatric migraine trials, so shared decision-making about whether to use preventive medication is essential. 1

• This high placebo response (often 50-60%) may reflect the natural fluctuating course of pediatric migraine and the benefit of nonpharmacologic interventions alone. 1

Nonpharmacologic Measures Are Essential

• Always combine propranolol with lifestyle modifications: regular sleep schedule, regular meals with adequate hydration, identification and avoidance of migraine triggers, and addressing acute medication overuse. 1, 7

• The additive effect of nonpharmacologic measures may allow for lower drug doses (0.4 mg/kg/day vs. 2-3 mg/kg/day). 4

Contraindications and Precautions

• Avoid propranolol in children with asthma, significant bradycardia, heart block, or hypotension. 3

• Use caution in children with diabetes, as propranolol may mask hypoglycemic symptoms. 3

• Consider avoiding beta-blockers in patients who developed stroke while on prophylactic therapy, as these agents might worsen intracranial vasoconstriction, though this concern is primarily relevant in children with hemiplegic or basilar migraine. 1

• Beta blockers with intrinsic sympathomimetic activity are ineffective for migraine prevention and should not be used. 1

Adverse Effects

• Minor side effects are fairly well tolerated, with palpitations being the most commonly reported adverse effect in pediatric studies. 2, 5

• Other potential side effects include fatigue, dizziness, bradycardia, and gastrointestinal upset. 3

• Tolerance to propranolol's antimigraine effect was not observed in clinical studies. 8

Treatment Duration and Monitoring

• Maintain treatment for at least 3-6 months to adequately assess response, as most studies evaluated outcomes over 4-6 months. 2, 6

• If inadequate response after 3 months, consider switching to amitriptyline or topiramate rather than increasing propranolol dose beyond 3 mg/kg/day. 1, 2

• Monitor heart rate and blood pressure at follow-up visits, particularly in the first month of therapy. 3

Acute Treatment Considerations

• Propranolol is NOT indicated for treating an acute migraine attack that has already started—its role is purely preventive. 3

• For acute attacks, counsel patients to treat early with ibuprofen as first-line (dosed appropriately for weight), or consider triptans in adolescents (sumatriptan/naproxen oral, zolmitriptan nasal, sumatriptan nasal, rizatriptan ODT, or almotriptan oral). 1, 9

• If nausea or vomiting accompanies the headache, add an antiemetic or consider non-oral triptan formulations. 1, 9