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Meta-Analysis
. 2024 Jul 24;25(1):119.
doi: 10.1186/s10194-024-01826-y.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol

Jan Versijpt #  1 , Christina Deligianni  2 , Muizz Hussain  3 , Faisal Amin  4 , Uwe Reuter  5 , Margarita Sanchez-Del-Rio  6 , Derya Uluduz  7 , Deirdre Boucherie  8 , Dena Zeraatkar  3 , Antoinette MaassenVanDenBrink #  8 , Simona Sacco  9 , Christian Lampl #  10 , Raquel Gil-Gouveia #  11
Affiliations
Meta-Analysis

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol

Jan Versijpt et al. J Headache Pain. .

Abstract

Objective: The aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis.

Methods: We report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared propranolol with placebo for migraine prophylaxis in adults. The outcomes of interest were informed by the Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in monthly migraine days, the reduction of monthly migraine days, and the number of adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB (risk of bias) 2.0 tool and the certainty of evidence by using the GRADE approach.

Results: Our search yielded twenty trials (n = 1291 patients) eligible for data synthesis and analysis. The analysis revealed a moderate certainty evidence that propranolol leads to a reduction in monthly migraine days versus placebo (-1.27; 95% CI: -2.25 to -0.3). We found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo with a relative risk of 1.65 (95% CI 1.41 to 1.93); absolute risk difference: 179 more per 1,000 (95% CI 113 to 256). We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30).

Conclusions: The present meta-analysis shows that propranolol has a prophylactic role in migraine, with an overall acceptable tolerability profile. Combining these results with its long-standing use and its global availability at a low cost confirms its role as a first line agent in the prophylaxis of migraine.

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Conflict of interest statement

FA reports personal fees for lecturing and/or participating in advisory board for AbbVie, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva. RGG reports honoraria for lectures/presentations from AbbVie/Allergan, Eli Lily, Lundbeck, Novartis, Teva, Organon, Pfizer; participated in clinical trials as the principal investigator for Amgen, Novartis and Lundbeck; received research grants from Novartis. CD has received IHS research fellowship grant and Hellenic Society of Neurology scholarship. AMvdB received honoraria, research and/or travel grants from Allergan/Abbvie, Amgen/Novartis, Eli Lilly, Satsuma and Teva as principal investigator. JV received personal fees and nonfinancial support from Teva, personal fees from Novartis and Lundbeck, and grants and nonfinancial support from Allergan/AbbVie. SS reports personal fees as speaker or advisor for Abbott, Allergan-Abbvie, AstraZeneca, Eli Lilly, Lundbeck, Novartis, NovoNordisk, Pfizer, Teva; research grants from Novartis and Uriach; fees for CME/education from Medscape and Neurodiem Ology Medical Education; Intellectual as president elect European Stroke Organisation, second vice president of the European Headache Federation, specialty chief editor in Headache and Neurogenic Pain for Frontiers in Neurology, associate editor for The Journal of Headache and Pain, assistant editor for Stroke. CL has received consulting fees and honoraria for lectures/presentations from AbbVie/Allergan, Eli Lily, Lundbeck, Novartis and Teva. CL participated in clinical trials as the principal investigator for Eli Lilly. Intellectual as president of the European Headache Federation, associate editor for The Journal of Headache and Pain.

Figures

Fig. 1
Fig. 1
Potential mechanisms of action for the anti-migraine effect of the β1/2 receptor antagonist propranolol. By blocking β-adrenergic receptors, propranolol reduces blood pressure by decreasing sympathetic innervation [6, 7]. Furthermore, blockade of β1-adrenergic receptors in the thalamus may block the trigeminovascular pain pathway, however, there are contradicting findings on the importance of this potential pathway. Propranolol can block capsaicin-mediated vasodilation mediated by the trigeminal nerve, possibly through agonism of presynaptic 5-HT1 receptors [9]. Activation of 5-HT1 receptors can block release of CGRP, leading to reduced vasodilation and nociception
Fig. 2
Fig. 2
Selection of studies for the systematic review
Fig. 3
Fig. 3
Risk of bias assessment
Fig. 4
Fig. 4
Forest plot of analysis comparing propranolol with placebo for the reduction in monthly migraine days
Fig. 5
Fig. 5
Forest plot of analysis comparing propranolol with placebo for 50% responder rate
Fig. 6
Fig. 6
Forest plot of analysis comparing propranolol with placebo for adverse events leading to discontinuation
See this image and copyright information in PMC

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