TOP-PRO study: A randomized double-blind controlled trial of topiramate versus propranolol for prevention of chronic migraine

Abstract

Objective The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine. Background Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence. Methods Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed. Results As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was −5.3 ± 1.2 vs −7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of −1.99 with a 95% confidence interval of −5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups. Conclusion Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile. Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997)

European Headache Federation (EHF) critical reappraisal and meta-analysis of oral drugs in migraine prevention – part 3: topiramate

“…In the direct comparison between topiramate versus other preventive drugs, the evidence is limited. A parallel group, randomized, double-blind controlled study, conducted between May 2019 and February 2021 compared the change in migraine days per 28 weeks at the end of a 24 weeks treatment period in chronic migraine patients treated with topiramate 100 mg/day ( n = 46) or propranolol ( n = 49) [ 46 ]. The reduction in migraine days per month was -5.3 ± 1.2 days within patients treated with topiramate, and − 7.3 ± 1.1 days within patients treated with propranolol, albeit differences were not statistically significant [ 46 ].…”

“…A parallel group, randomized, double-blind controlled study, conducted between May 2019 and February 2021 compared the change in migraine days per 28 weeks at the end of a 24 weeks treatment period in chronic migraine patients treated with topiramate 100 mg/day ( n = 46) or propranolol ( n = 49) [ 46 ]. The reduction in migraine days per month was -5.3 ± 1.2 days within patients treated with topiramate, and − 7.3 ± 1.1 days within patients treated with propranolol, albeit differences were not statistically significant [ 46 ]. In the case of amitriptyline, a parallel group, randomized, double-blind, double dummy study compared topiramate 100 mg/day ( n = 172) versus amitriptyline 25 mg/day ( n = 159), between patients with 3–12 migraine days per month, with no statistically significant differences in the reduction in the number of monthly migraine episodes [ 47 ].…”

Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe

“…Damit wird bei Patienten mit cM vom Gemeinsamen Bundesausschuss (GBA) eine Therapie mit Betablockern, Flunarizin oder Amitriptylin gefordert, deren Wirksamkeit bei der cM nie belegt wurde. Hier gibt es lediglich für Propranolol (160 mg/Tag) erste Daten, dass die Therapieeffekte auf MMD und Alltagsfähigkeit bei Patienten mit chronischer Migräne vergleichbar mit Topiramat (100 mg/Tag) sind [47].…”

Migraine: from pathophysiology to treatment

“…Several open-label studies have also shown a benefit of combining onabotulinumtoxinA with mAbs to CGRP for CM [192][193][194]. A recent head-to-head trial for chronic migraine showed non-inferiority between propranolol and topiramate, with no significant difference in adverse events incidence between the two [195]. Another prospective randomized trial in chronic migraine compared flunarizine 10 mg with topiramate 50 mg daily, showing both drugs had a similar safety profile, with flunarizine being overall more effective [196].…”