Clinical predictors of propranolol responsiveness in pediatric migraine: a prospective observational study

Background: This study aimed to evaluate the comparative effectiveness of propranolol therapy and structured behavioral interventions in reducing headache severity in pediatric patients and to identify predictors of treatment response. Methods: In this prospective, single-center study, 178 pediatric patients diagnosed with migraine based on the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria were enrolled. Participants were allocated into two groups according to baseline Pediatric Migraine Disability Assessment Scale (PedMIDAS) scores: Group 1 (PedMIDAS <15, n = 88) received standardized behavioral therapy, while Group 2 (PedMIDAS ≥15, n = 90) received propranolol (1–3 mg/kg/day) for 12 weeks. Primary outcomes were predefined as changes in monthly migraine attack frequency, PedMIDAS scores, and Visual Analog Scale (VAS)-measured headache intensity. Vitamin D deficiency and vitamin B12 deficiency were evaluated as biochemical predictors, and adherence was monitored bi-weekly. Results: Both groups showed significant improvement at week 12. Monthly migraine attacks declined from 3.5± 1.6 to 2.1 ± 1.2 in Group 1 and from 6.4 ± 2.1 to 3.1 ± 1.7 in Group 2. PedMIDAS scores decreased from 8.60 ± 3.25 to 5.75 ± 2.52 and 24.40 ± 9.65 to 16.11 ± 7.72, respectively (p < 0.001 both). VAS scores also improved in both groups with no significant between-group difference in percentage reduction. A ≥50%reduction in attack frequency plus ≥1-grade PedMIDAS improvement defined treatment response. In the propranolol group, response was independently associated with benign paroxysmal vertigo and essential tremor, while vitamin D and vitamin B12 deficiency predicted poorer outcomes. Conclusions: Both propranolol and structured behavioral therapy effectively reduce migraine-related disability and pain in pediatric patients, yielding comparable proportional improvements. The identification of key clinical and biochemical predictors supports a personalized treatment approach, integrating comorbidity screening and nutritional assessment to optimize outcomes. Clinical Trial Registration: ClinicalTrials.gov/NCT07180043, retrospectively registered.