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.

Treatment in a Randomized Multicenter Trial of Acupuncture for Migraine (ART Migraine)

“…Furthermore, a comparison with the data from a large observational study of acupuncture in routine care, which was performed parallel to ART Mi- graine, yielded very similar improvements (manuscript submitted for publication). Response rates in our trial were also comparable to those reported for drugs used for migraine prophylaxis recommended in current guidelines such as beta blockers or calcium channel blockers [12,13]. The surprising finding in ART Migraine is not an inadequate response in the patients who received AC but the great and lasting improvement in many of those patients who received MA.…”

Safety and efficacy of flunarizine in childhood migraine: 11 years’ experience, with emphasis on its effect in hemiplegic migraine

“…This is comparable to the outcome data already available from adult and paediatric studies. 8,18,19 However, of note is the relatively higher rate of therapeutic efficacy in hemiplegic migraine (85% vs 51%) in this cohort. Moreover, as far as we are aware, this is the largest reported cohort of paediatric hemiplegic migraine treated with flunarizine.…”

“…The frequency of attacks was four per month (range 0. [3][4][5][6][7][8][9][10][11][12] in the group with hemiplegia and 12 per month in the remainder.…”

Drug therapy in headache

“…One well-conducted trial shows it to be as effective as propranolol. 48 It is available in the UK on a 'named patient' basis. Ribofl avin (vitamin B2) showed a responder rate of 56% versus 19% on placebo in one small trial, though the baseline attack frequency was very low.…”