Scientific publications

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 2: flunarizine

Sep 19, 2023 | Magazine: Journal of Headache Pain

Christina I Deligianni #  1 , Simona Sacco #  2 , Esme Ekizoglu #  3 , Derya Uluduz #  4 , Raquel Gil-Gouveia  5   6 , Antoinette MaassenVanDenBrink #  7 , Raffaele Ornello  2 , Margarita Sanchez-Del-Rio  8 , Uwe Reuter  9 , Jan Versijpt  10 , Tessa de Vries #  7 , Muizz Hussain  11 , Dena Zeraatkar #  11 , Christian Lampl #  12   13

Objective: Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis.

Methods: A systematic search in MEDLINE, Cochrane CENTRAL, and was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo-controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation.

Results: Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06).

Conclusions: Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large-scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.

CITATION  J Headache Pain. 2023 Sep 19;24(1):128. doi: 10.1186/s10194-023-01657-3