CLINICAL EFFICACY AND SAFETY OF TRIPTANS VERSUS GEPANTS IN MIGRAINE MANAGEMENT: IMPLICATIONS FOR PHYSICAL ACTIVITY AND QUALITY OF LIFE

Authors

DOI:

https://doi.org/10.31435/ijitss.1(49).2026.4933

Keywords:

Migraine, Triptans, Gepants, CGRP Receptor Antagonists, Physical Activity, Sport Performance

Abstract

Introduction: Migraine is a chronic and disabling neurological disorder that substantially impairs daily functioning and limits participation in physical activity. Pharmacological management must therefore consider not only symptom relief but also safety, tolerability, and the ability to maintain functional and exercise capacity. Triptans have been the standard for acute migraine treatment, whereas calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) have emerged as a newer therapeutic class without vasoconstrictive effects, potentially offering advantages for physically active individuals.

Aim of the study: The aim of this article was to review and compare current evidence on the clinical efficacy, safety, cardiovascular considerations, and functional outcomes associated with triptans and gepants, with particular attention to implications for physically active individuals and sport participation.

Methods and Materials: This narrative review was based exclusively on peer-reviewed full-text scientific articles provided by the author, including randomized controlled trials, long-term safety studies, meta-analyses, and mechanistic investigations related to triptans and CGRP receptor antagonists. Data were synthesized qualitatively with a focus on acute and preventive efficacy, adverse events, cardiovascular and exercise-related findings, and functional or quality-of-life outcomes.

Conclusion: Triptans demonstrate superior acute efficacy in achieving pain freedom and pain relief; however, their vasoconstrictive properties, safety limitations, and low long-term adherence may restrict their suitability for some physically active individuals. Gepants provide clinically meaningful efficacy with a more favorable safety and tolerability profile, preserved exercise capacity, and improved functional outcomes, particularly in preventive treatment settings. These findings support gepants as a valuable therapeutic option for migraine management in patients for whom cardiovascular safety, exercise compatibility, and sustained functional performance are key considerations.

References

Ali, M. D., Gayasuddin Qur, F., Alam, M. S., Alotaibi, N. M., & Mujtaba, M. A. (2023). Global epidemiology, clinical features, diagnosis and current therapeutic novelties in migraine therapy and their prevention: A narrative review. Current Pharmaceutical Design, 29(41), 3295–3311. https://doi.org/10.2174/0113816128266227231205114320

Villar-Martinez, M. D., & Goadsby, P. J. (2022). Pathophysiology and therapy of associated features of migraine. Cells, 11(17), 2767. https://doi.org/10.3390/cells11172767

Yalın, O. Ö., Uluduz, D., Özge, A., Sungur, M. A., Selekler, M., & Siva, A. (2016). Phenotypic features of chronic migraine. The Journal of Headache and Pain, 17, 26. https://doi.org/10.1186/s10194-016-0616-y

La Touche, R., Fierro-Marrero, J., Sánchez-Ruíz, I., Rodríguez de Rivera-Romero, B., Cabrera-López, C. D., Lerma-Lara, S., Requejo-Salinas, N., de Asís-Fernández, F., Elizagaray-García, I., Fernández-Carnero, J., Matesanz-García, L., Pardo-Montero, J., Paris-Alemany, A., & Reina-Varona, Á. (2023). Prescription of therapeutic exercise in migraine, an evidence-based clinical practice guideline. The Journal of Headache and Pain, 24(1), 68. https://doi.org/10.1186/s10194-023-01571-8

Amin, F. M., Aristeidou, S., Baraldi, C., Czapinska-Ciepiela, E. K., Ariadni, D. D., Di Lenola, D., Fenech, C., Kampouris, K., Karagiorgis, G., Braschinsky, M., Linde, M., & European Headache Federation School of Advanced Studies (EHF-SAS). (2018). The association between migraine and physical exercise. The Journal of Headache and Pain, 19(1), 83. https://doi.org/10.1186/s10194-018-0902-y

Reina-Varona, Á., Madroñero-Miguel, B., Fierro-Marrero, J., Paris-Alemany, A., & La Touche, R. (2024). Efficacy of various exercise interventions for migraine treatment: A systematic review and network meta-analysis. Headache, 64(7), 873–900. https://doi.org/10.1111/head.14696

Huang, P. C., Yang, F. C., Chang, C. M., & Yang, C. P. (2020). Targeting the 5-HT1B/1D and 5-HT1F receptors for acute migraine treatment. Progress in Brain Research, 255, 99–121. https://doi.org/10.1016/bs.pbr.2020.05.010

Mitsikostas, D. D., & Tfelt-Hansen, P. (2012). Targeting to 5-HT1F receptor subtype for migraine treatment: Lessons from the past, implications for the future. Central Nervous System Agents in Medicinal Chemistry, 12(4), 241–249. https://doi.org/10.2174/187152412803760627

de Vries, T., Villalón, C. M., & MaassenVanDenBrink, A. (2020). Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans. Pharmacology & Therapeutics, 211, 107528. https://doi.org/10.1016/j.pharmthera.2020.107528

Wang, Z., VanderPluym, J. H., Halker Singh, R. B., Alsibai, R. A., Roellinger, D. L., Firwana, M., & Murad, M. H. (2024). Safety of triptans in patients who have or are at high risk for cardiovascular disease: A target trial emulation. Mayo Clinic Proceedings, 99(11), 1722–1731. https://doi.org/10.1016/j.mayocp.2024.03.023

Lipton, R. B., Croop, R., Stock, E. G., Stock, D. A., Morris, B. A., Frost, M., Dubowchik, G. M., Conway, C. M., Coric, V., & Goadsby, P. J. (2019). Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. The New England Journal of Medicine, 381(2), 142–149. https://doi.org/10.1056/NEJMoa1811090

Robbins, M. S. (2021). Diagnosis and management of headache: A review. JAMA, 325(18), 1874–1885. https://doi.org/10.1001/jama.2021.1640

Karsan, N., & Goadsby, P. J. (2015). CGRP mechanism antagonists and migraine management. Current Neurology and Neuroscience Reports, 15(5), 25. https://doi.org/10.1007/s11910-015-0547-z

Dong, G., Kjærgaard, N. A., Shakibfar, S., & Sessa, M. (2023). Ubrogepant and rimegepant: Systematic review, meta-analysis, and meta-regression of clinical studies. Expert Opinion on Drug Safety, 22(1), 59–70. https://doi.org/10.1080/14740338.2023.2177270

Johnston, K., Popoff, E., Deighton, A., Dabirvaziri, P., Harris, L., Thiry, A., Croop, R., Coric, V., L’Italien, G., & Moren, J. (2022). Comparative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for acute treatment of migraine: A network meta-analysis. Expert Review of Pharmacoeconomics & Outcomes Research, 22(1), 155–166. https://doi.org/10.1080/14737167.2021.1945444

Chiang, C. C., & Schwedt, T. J. (2020). Calcitonin gene-related peptide (CGRP)-targeted therapies as preventive and acute treatments for migraine—The monoclonal antibodies and gepants. Progress in Brain Research, 255, 143–170. https://doi.org/10.1016/bs.pbr.2020.06.019

Yang, C. P., Liang, C. S., Chang, C. M., Yang, C. C., Shih, P. H., Yau, Y. C., Tang, K. T., & Wang, S. J. (2021). Comparison of new pharmacologic agents with triptans for treatment of migraine: A systematic review and meta-analysis. JAMA Network Open, 4(10), e2128544. https://doi.org/10.1001/jamanetworkopen.2021.28544

Ferrari, M. D., Goadsby, P. J., Roon, K. I., & Lipton, R. B. (2002). Triptans (serotonin, 5-HT1B/1D agonists) in migraine: Detailed results and methods of a meta-analysis of 53 trials. Cephalalgia, 22(8), 633–658. https://doi.org/10.1046/j.1468-2982.2002.00404.x

Chen, T. B., Chen, Y. T., Fuh, J. L., Tang, C. H., & Wang, S. J. (2014). Treatment adherence among new triptan users: A 2-year cohort study in Taiwan. The Journal of Headache and Pain, 15(1), 48. https://doi.org/10.1186/1129-2377-15-48

Goadsby, P. J., Wietecha, L. A., Dennehy, E. B., Kuca, B., Case, M. G., Aurora, S. K., & Gaul, C. (2019). Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain, 142(7), 1894–1904. https://doi.org/10.1093/brain/awz134

Kuca, B., Silberstein, S. D., Wietecha, L., Berg, P. H., Dozier, G., Lipton, R. B., & COL MIG-301 Study Group. (2018). Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology, 91(24), e2222–e2232. https://doi.org/10.1212/WNL.0000000000006641

Rissardo, J. P., & Caprara, A. L. F. (2022). Gepants for acute and preventive migraine treatment: A narrative review. Brain Sciences, 12(12), 1612. https://doi.org/10.3390/brainsci12121612

Younis, S., Latysheva, N. V., Danilov, A. B., & Ashina, M. (2024). CGRP receptor antagonists (gepants). Handbook of Clinical Neurology, 199, 51–66. https://doi.org/10.1016/B978-0-12-823357-3.00033-1

Tepper, S. J. (2018). History and review of anti-calcitonin gene-related peptide (CGRP) therapies: From translational research to treatment. Headache, 58(Suppl. 3), 238–275. https://doi.org/10.1111/head.13379

Ailani, J., Lipton, R. B., Goadsby, P. J., Guo, H., Miceli, R., Severt, L., Finnegan, M., Trugman, J. M., & ADVANCE Study Group. (2021). Atogepant for the preventive treatment of migraine. The New England Journal of Medicine, 385(8), 695–706. https://doi.org/10.1056/NEJMoa2035908

Dermitzakis, E. V., Rikos, D., Vikelis, M., Xiromerisiou, G., Zisopoulou, S., Rallis, D., Soldatos, P., Vlachos, G. S., Vasiliadis, G. G., & Argyriou, A. A. (2024). Real-world open-label experience with rimegepant for the acute treatment of migraine attacks: A multicenter pilot study. Brain Sciences, 14(12), 1169. https://doi.org/10.3390/brainsci14121169

La Touche, R., Fierro-Marrero, J., Sánchez-Ruíz, I., Rodríguez de Rivera-Romero, B., Cabrera-López, C. D., Lerma-Lara, S., Requejo-Salinas, N., de Asís-Fernández, F., Elizagaray-García, I., Fernández-Carnero, J., Matesanz-García, L., Pardo-Montero, J., Paris-Alemany, A., & Reina-Varona, Á. (2023). Prescription of therapeutic exercise in migraine, an evidence-based clinical practice guideline. The Journal of Headache and Pain, 24(1), 68. https://doi.org/10.1186/s10194-023-01571-8

Juhasz, G., Gecse, K., & Baksa, D. (2023). Towards precision medicine in migraine: Recent therapeutic advances and potential biomarkers to understand heterogeneity and treatment response. Pharmacology & Therapeutics, 250, 108523. https://doi.org/10.1016/j.pharmthera.2023.108523

Liu, W. H., Hu, H. M., Li, C., Shi, Q., Liu, C. H., Liu, A. X., Li, Y. F., Zhang, Y., Mao, P., & Fan, B. F. (2024). Real-world study of adverse events associated with triptan use in migraine treatment based on the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS) database. The Journal of Headache and Pain, 25(1), 206. https://doi.org/10.1186/s10194-024-01913-0

Moriarty, M. A., & Barch, C. A. (2025). Gepants in primary care: A targeted approach to acute and preventive treatment of migraine. Pain and Therapy, 14(4), 1263–1278. https://doi.org/10.1007/s40122-025-00757-z

Lemmens, J., De Pauw, J., Van Soom, T., Michiels, S., Versijpt, J., van Breda, E., Castien, R., & De Hertogh, W. (2019). The effect of aerobic exercise on the number of migraine days, duration and pain intensity in migraine: A systematic literature review and meta-analysis. The Journal of Headache and Pain, 20(1), 16. https://doi.org/10.1186/s10194-019-0961-8

Hutchinson, S., Dodick, D. W., Treppendahl, C., Bennett, N. L., Yu, S. Y., Guo, H., & Trugman, J. M. (2021). Ubrogepant for the acute treatment of migraine: Pooled efficacy, safety, and tolerability from the ACHIEVE I and ACHIEVE II phase 3 randomized trials. Neurology and Therapy, 10(1), 235–249. https://doi.org/10.1007/s40120-021-00234-7

Croop, R., Lipton, R. B., Kudrow, D., Stock, D. A., Kamen, L., Conway, C. M., Stock, E. G., Coric, V., & Goadsby, P. J. (2021). Oral rimegepant for preventive treatment of migraine: A phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet, 397(10268), 51–60. https://doi.org/10.1016/S0140-6736(20)32544-7

Croop, R., Goadsby, P. J., Stock, D. A., Conway, C. M., Forshaw, M., Stock, E. G., Coric, V., & Lipton, R. B. (2019). Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: A randomised, phase 3, double-blind, placebo-controlled trial. Lancet, 394(10200), 737–745. https://doi.org/10.1016/S0140-6736(19)31606-X

Ailani, J., Lipton, R. B., Hutchinson, S., Knievel, K., Lu, K., Butler, M., Yu, S. Y., Finnegan, M., Severt, L., & Trugman, J. M. (2020). Long-term safety evaluation of ubrogepant for the acute treatment of migraine: Phase 3, randomized, 52-week extension trial. Headache, 60(1), 141–152. https://doi.org/10.1111/head.13682

Johnston, K. M., L’Italien, G., Popoff, E., Powell, L., Croop, R., Thiry, A., Harris, L., Coric, V., & Lipton, R. B. (2021). Mapping migraine-specific quality of life to health state utilities in patients receiving rimegepant. Advances in Therapy, 38(10), 5209–5220. https://doi.org/10.1007/s12325-021-01897-2

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Published

2026-03-25

How to Cite

Magdalena Zięba, Szymon Rudawski, & Maja Elertowicz. (2026). CLINICAL EFFICACY AND SAFETY OF TRIPTANS VERSUS GEPANTS IN MIGRAINE MANAGEMENT: IMPLICATIONS FOR PHYSICAL ACTIVITY AND QUALITY OF LIFE. International Journal of Innovative Technologies in Social Science, 2(1(49). https://doi.org/10.31435/ijitss.1(49).2026.4933

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