Flunarizine in the Prevention of Classical Migraine: A Placebo-Controlled Evaluation

Abstract

Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable asset in the prophylaxis of migraine. This was supported by a study in twenty patients with classical migraine who were, after a drug-free running-in phase, orally treated with either placebo or flunarizine (10 mg at night) for three to four months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these three variables, was reduced by 82% in the drug group but increased by 66% in the control patients. Only one patient did not clearly benefit from flunarizine, and the response in another illustrated that flunarizine has to be given for at least four months before its efficacy can be judged in some cases. No side effects occurred.

Systematic Review of Episodic Migraine Prophylaxis: Efficacy of Conventional Treatments Used in Comparisons with Acupuncture

“…A total of 8 randomized controlled trials (RCTs) and 1 Cochrane Review were found. [15][16][17][18][19][20][21][22][23] The RCTs included 6 parallel and 2 crossover designs ( Table 1). Each RCT included males and females and measured the outcome headache frequency (i.e., migraine days, attack frequency, or frequency of migraine attacks) after receiving treatment or placebo at a 3-month follow-up.…”

“…Seven studies reported a significant reduction in headache frequency at a 3-month follow-up in a prophylactic drug treatment group, compared to a control group. [15][16][17][18][19][21][22] Reductions in the frequency of migraine attacks were found by Frenken and Nuijten in 1984 (P = 0.029; flunarizine mean difference [MD]: 1.2; placebo MD: 0.4), 15 Louis in 1981 (P < 0.001; flunarizine pretreatment median: 7 [range: [6][7][8][9][10][11][12][13][14]; flunarizine post-treatment median: 2 [range: 0-5]; placebo pretreatment median: 7 [range: [6][7][8][9][10][11][12]; placebo post-treatment median: 3 [range: 2-5]), 16 Mendenopoulos et al in 1985 (P = 0.033; number-needed-to-treat [NNT]: 1.23), 17 Sørenson et al in 1986 (P = 0.002; NNT: 2.5), 18 Sorge et al in 1988 (P < 0.001; flunarizine MD: 1.7; placebo MD: 0.7), 19 and Andersson et al in 1983 (P < 0.05; flunarizine MD: 1.3; placebo MD: 0.53). 21 Reductions in migraine days were found by Steiner et al .…”

“…The dosage range for the RCTs involving flunarizine were 5-10 mg daily for 12-16 weeks. [15][16][17][18][19][20] Meanwhile, the dosage range for the study included in Linde et al's 2016 review 2 was 10 mg of flunarizine daily for 24 weeks. 9 The dosage range for the RCTs involving metoprolol were 100-200 mg daily for 8-12 weeks.…”

“…The studies included in Linde et al's 2016 review 2,[6][7][8][9][10] and the studies found from the current authors' literature search [15][16][17][18][19][20][21][22][23][24][25] used treatment dosage ranges that were considered similar overall. In fact, with the exception of 1 study, 25 the dosage ranges in Linde et al's 2016 review 2,6-10 were typically greater than or equal to the dosage and duration ranges in the studies found from the current authors' literature search.…”

Migraine: Preventive Treatment

“…The AHCPR Technical Report identified 45 controlled trials of calcium antagonists, including flunarizine (25 trials), nimodipine (11 trials), nifedipine (five trials), verapamil (three trials), cyclandelate (three trials), and nicardipine (one trial) (10). Flunarizine was compared with placebo in eight migraine prevention trials and effect sizes could be calculated for seven studies (107–113) but not the eighth study (114). A meta‐analysis of these seven heterogeneous trials was statistically significant in favour of flunarizine.…”