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Review
. 2024 Dec 5;25(1):214.
doi: 10.1186/s10194-024-01925-w.

Combining treatments for migraine prophylaxis: the state-of-the-art

Lanfranco Pellesi  1 , David Garcia-Azorin  2   3 , Eloisa Rubio-Beltrán  4 , Wook-Seok Ha  5 , Roberta Messina  6   7 , Raffaele Ornello  8 , Igor Petrusic  9 , Bianca Raffaelli  10   11 , Alejandro Labastida-Ramirez  12 , Ruth Ruscheweyh  13 , Claudio Tana  14 , Doga Vuralli  15   16   17 , Marta Waliszewska-Prosół  18 , Wei Wang  19   20 , William Wells-Gatnik  21
Affiliations
Review

Combining treatments for migraine prophylaxis: the state-of-the-art

Lanfranco Pellesi et al. J Headache Pain. .

Erratum in

  • Correction: Combining treatments for migraine prophylaxis: the state‑of‑the‑art.
    Pellesi L, Garcia-Azorin D, Rubio-Beltrán E, Ha WS, Messina R, Ornello R, Petrusic I, Raffaelli B, Labastida-Ramirez A, Ruscheweyh R, Tana C, Vuralli D, Waliszewska-Prosół M, Wang W, Wells-Gatnik W. Pellesi L, et al. J Headache Pain. 2025 Apr 3;26(1):66. doi: 10.1186/s10194-025-02007-1. J Headache Pain. 2025. PMID: 40181277 Free PMC article. No abstract available.

Abstract

Combination treatments for migraine prophylaxis present a promising approach to addressing the diverse and complex mechanisms underlying migraine. This review explores the potential of combining oral conventional prophylactics, onabotulinumtoxin A, monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway, and small molecule CGRP receptor antagonists (gepants). Among the most promising strategies, dual CGRP inhibition through mAbs and gepants may enhance efficacy by targeting both the CGRP peptide and its receptor, while the combination of onabotulinumtoxin A with CGRP treatments offers synergistic pain relief. Oral non-CGRP treatments, which are accessible and often prescribed for patients with comorbid conditions, provide an affordable and practical option in combination regimens. Despite the potential of these combinations, there is a lack of evidence to support their widespread inclusion in clinical guidelines. The high cost of certain combinations, such as onabotulinumtoxin A with a CGRP mAb or dual anti-CGRP mAbs, presents feasibility challenges. Further large-scale trials are needed to establish safe and effective combination protocols and solidify their role in clinical practice, particularly for treatment-resistant patients.

Keywords: CGRP; Gepants; Onabotulinumtoxin A; Propranolol; Rational polytherapy; Topiramate.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: LP has been employed by Lundbeck in the past two years. DGA has received honoraria for lectures and presentations from AbbVie/Allergan, Eli Lilly, Teva, Lundbeck, and Novartis and has participated in clinical trials as the principal investigator for Pfizer, BioHaven, and Lundbeck. DGA has also received honoraria from the World Health Organization as a subject matter expert. RM reports personal fees from AbbVie, Eli Lilly, Lundbeck, Pfizer, Teva, and Biomedia, outside the submitted work. IP serves as Head of Imaging Section of SN Comprehensive Clinical Medicine. BR reports research grants from Lundbeck, Novartis, the German Research Foundation, the German Migraine and Headache Society, and Else Kröner-Fresenius Stiftung, as well as personal fees from AbbVie/Allergan, Lilly, Lundbeck, Novartis, Perfood, and Teva. RR has received travel grants and/or honoraria from Allergan/AbbVie, Lilly, Lundbeck, Novartis, Pfizer, and Teva. WW serves as Section Editor of SN Comprehensive Clinical Medicine. All authors serve as junior editors of The Journal of Headache and Pain.

Figures

Fig. 1
Fig. 1
Overview of pharmacological treatments which can be used in combination for migraine prophylaxis. CGRP: calcitonin gene-related peptide
See this image and copyright information in PMC

References

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