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. 2023 May 19;24(1):56.
doi: 10.1186/s10194-023-01594-1.

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis

Christian Lampl #  1   2 , Antoinette MaassenVanDenBrink #  3 , Christina I Deligianni  4 , Raquel Gil-Gouveia  5   6 , Tanvir Jassal  7 , Margarita Sanchez-Del-Rio  8 , Uwe Reuter  9 , Derya Uluduz  10 , Jan Versijpt  11 , Dena Zeraatkar #  7 , Simona Sacco #  12
Affiliations

The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis

Christian Lampl et al. J Headache Pain. .

Abstract

Objective: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach.

Results: We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events.

Conclusions: (CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.

Keywords: CGRP monoclonal antibodies; Migraine; Network meta-analysis; Systematic review.

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Conflict of interest statement

Dena Zeraatkar and Janvir Jassal report no conflict of interest.

Christian Lampl has received consulting fees and honoraria for lectures/presentations from AbbVie/Allergan, Eli Lilly, Lundbeck, Novartis, Pfizer and Teva. CL participated in clinical trials as the principal investigator for Eli Lilly. Intellectual Christian Lampl is president of the European Headache Federation and associate editor for The Journal of Headache and Pain.

Jan Versijpt received personal fees and nonfinancial support from Teva, personal fees from Novartis and Lundbeck, and grants and nonfinancial support from Allergan/Abbvie. Jan Versijpt serves as a member of the Board of Directors in the European Headache Federation.

Christina I Deligianni has received HIS research fellowship grant, scholarship from Hellenic society of Neurology. Christina I Deligianni serves as a member of the Board of Directors in the European Headache Federation.

Raquel Gil-Gouveia 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, Lundbeck. research grants from Novartis. Raquel Gil-Gouveia serves as a member of the Board of Directors in European Headache Federation.

Antoinette MaassenVanDenBrink received honoraria, research and/or travel grants from Allergan/Abbvie, Amgen/Novartis, Eli Lilly, Satsuma and Teva as principal investigator. Intellectual Antoinette MaassenVanDenBrink is vice-president of the European Headache Federation and associate editor for The Journal of Headache and Pain.

Margarita Sanchez-del-Rio has received consulting fees and honoraria for lectures/presentations from Eli Lily, Lundbeck, Novartis, Teva and Pfizer. Intellectual as Secretary of the European Headache Federation, Review Editor on the Editorial Board of Headache and Neurogenic Pain (specialty section of Frontiers in Neurology). Margarita Sanchez-del-Rio serves as a member of the Board of Directors in the European Headache Federation.

Uwe Reuter has received consulting fees, research grants or fees for presentations from Abbie, Allegan, Amgen, Lilly, Lundbeck, Medscape, Novartis, Pfizer, StreaMedup, Teva and the German Government (BMBF). Uwe Reuter is treasurer of the European Headache Federation.

Derya Uluduz receives honoraria from Allergan-Abbvie, TEVA; consulting fees and honoraria for lectures/presentations from Eli Lily, Novartis, Allergan/Abbvie and Neutec. participated in clinical trials as the sub-investigator for AMGEN, Novartis. Derya Uluduz serves as a member of the Board of Directors in the European Headache Federation.

Simona Sacco 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.

Figures

Fig. 1
Fig. 1
Selection of trials
Fig. 2
Fig. 2
Risk of bias judgements for 50% or more reduction in monthly migraine days
Fig. 3
Fig. 3
Network geometry for 50% or more reduction in monthly migraine days. Each node represents a drug that has been tested in trials. The edges represent direct comparisons of the drugs in trials. The size of the nodes is proportional to the number of patients that have received that drug, and the thickness of the edges is proportional to the number of trials
Fig. 4
Fig. 4
Forest plot displaying results for 50% or more reduction in monthly migraine days
See this image and copyright information in PMC

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