Evidence map›Paper›PMID 37723437›Full record

SynthesisThe journal of headache and pain2023

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 and 4 more

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Review
  9. Drugs for Migraine Prophylaxis.Deutsches Arzteblatt international · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Sexual Dimorphism in Migraine. Focus on Mitochondria.Current pain and headache reports · 2025
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Migraine and Its Treatment from the Medicinal Chemistry Perspective.ACS pharmacology & translational science · 2024
    Review
  20. Health equity, care access and quality in headache - part 2.The journal of headache and pain · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Christina I Deligianni *Department of Neurology, Athens Naval Hospital, Athens, Greece. cdchristina@gmail.com.
Simona Sacco *Department of Biotechnological and Applied Clinical Sciences, University of L´Aquila, L´Aquila, Italy.
Esme Ekizoglu *Department of Neurology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.
Derya Uluduz *Department of Neurology, Istanbul University-Cerrahpasa Medical Faculty, Istanbul, Turkey.
Raquel Gil-GouveiaNeurology Department, Hospital da Luz Headache Center, Hospital da Luz Lisboa, Lisbon, Portugal.
Antoinette MaassenVanDenBrink *Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands.
Raffaele OrnelloDepartment of Biotechnological and Applied Clinical Sciences, University of L´Aquila, L´Aquila, Italy.
Margarita Sanchez-Del-RioDepartment of Neurology, Clinica Universidad de Navarra, Madrid, Spain.
Uwe ReuterDepartment of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany and Universitätsmedizin Greifswald, Greifswald, Germany.
Jan VersijptDepartment of Neurology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.
Tessa de Vries *Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands.
Muizz HussainDepartment of Anesthesia and Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada.
Dena Zeraatkar *Department of Anesthesia and Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada.
Christian Lampl *Department of Neurology and Stroke Unit, Konventhospital Barmherzige Brüder Linz, Linz, Austria.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveNovel 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.

methodsA 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.

resultsFive 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).

conclusionsPublished 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.

Indexed as

Migraine DisordersMigraine with AuraFlunarizineHeadacheHumansResearch DesignTranscription FactorsEHF protein, humanFlunarizineTranscription FactorsFlunarizineMeta-analysisMigraineProphylactic treatment

Identifiers

PMID37723437
PMCPMC10507915

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.