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

Christina I. Deligianni*, Simona Sacco, Esme Ekizoglu, Derya Uluduz, Raquel Gil-Gouveia, Antoinette MaassenVanDenBrink, Raffaele Ornello, Margarita Sanchez-del-Rio, Uwe Reuter, Jan Versijpt, Tessa de Vries, Muizz Hussain, Dena Zeraatkar, Christian Lampl

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

8 Citations (Scopus)
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Abstract

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 ClinicalTrials.gov 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.

Original languageEnglish
Article number128
JournalJournal of Headache and Pain
Volume24
Issue number1
DOIs
Publication statusPublished - 19 Sept 2023

Bibliographical note

Funding Information:
This paper was funded by the European Headache Federation (EHF).

Publisher Copyright:
© 2023, Springer-Verlag Italia S.r.l., part of Springer Nature.

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