title: Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily.
abstract: This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe.
authors.affiliation: Department of Neurology, University Essen, Germany. h.diener@uni-essen.de
authors.forename: H C
authors.initials: HC
authors.lastname: Diener
authors.forename: J
authors.initials: J
authors.lastname: Matias-Guiu
authors.forename: E
authors.initials: E
authors.lastname: Hartung
authors.forename: V
authors.initials: V
authors.lastname: Pfaffenrath
authors.forename: H P
authors.initials: HP
authors.lastname: Ludin
authors.forename: G
authors.initials: G
authors.lastname: Nappi
authors.forename: F
authors.initials: F
authors.lastname: De Beukelaar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005444:Flunarizine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011433:Propranolol / Q000008:administration & dosage* / Q000009:adverse effects; D018709:Statistics, Nonparametric
chemical_list: D011433:Propranolol; D005444:Flunarizine