Headache and Pain Research

Review Articles

Gepants for Migraine: An Update on Long-Term Outcomes and Safety Profiles: Soohyun Cho, Kimoon Chang; Headache Pain Res. 2025;26(3):184-192. Published online October 21, 2025; DOI: https://doi.org/10.62087/hpr.2025.0012

6,479 View
58 Download

Abstract PDF: Calcitonin gene-related peptide receptor antagonists, also referred to as gepants, represent a transformative advancement in migraine pharmacotherapy, providing both acute and preventive treatment options without the vasoconstrictive limitations of triptans. Since their initial approval in 2019, gepants have gained widespread clinical adoption, necessitating comprehensive evaluation of their long-term safety and efficacy. This review synthesizes current evidence on four calcitonin gene-related peptide receptor antagonists (rimegepant, atogepant, ubrogepant, and zavegepant) derived from pivotal trials, open-label extension studies, and real-world observational data. Rimegepant demonstrates sustained efficacy and minimal adverse events over 52 weeks, with no evidence of medication-overuse headaches or hepatotoxicity. Atogepant maintains progressive clinical benefits and favorable tolerability for up to 1 year, exhibiting low rates of treatment-emergent adverse events and discontinuation. Ubrogepant remains effective and well-tolerated during long-term intermittent use, with no clinically significant safety signals over extended exposure. Zavegepant, the first intranasal gepant, shows promising long-term tolerability, with the most frequently reported localized adverse event being transient dysgeusia. No consistent hepatic, cardiovascular, or serious systemic toxicity has emerged for any of the agents, and discontinuation rates due to adverse events remain consistently low. Current evidence supports gepants as safe and effective therapies for long-term migraine management, although ongoing surveillance and extended-duration studies remain essential to fully characterize their safety profile, particularly in high-risk populations and combination therapy scenarios. In conclusion, gepants offer a well-tolerated, non-vasoconstrictive alternative for migraine patients who require sustained treatment, representing a significant therapeutic advancement in migraine.

Does Atogepant Offer a Safe and Efficacious Option for Episodic Migraine Prophylaxis? A Systematic Review and Meta-analysis: Ahmed Mostafa Amin, Abdallah Abbas, Samar Ahmed Amer, Hoda Awad, Mahmoud Tarek Hefnawy, Anas Mansour, Mohamed El-Moslemani, Haneen Sabet, Aynur Ozge; Headache Pain Res. 2025;26(1):21-37. Published online February 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0030

5,331 View
46 Download
3 Citations

Migraine, a chronic neurological disorder, imposes a significant burden on individuals and healthcare systems globally. This systematic review and meta-analysis evaluated the efficacy and safety of atogepant in preventing episodic migraine (EM) in adults. A systematic search was conducted in four major databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) up to June 2024. The inclusion criteria targeted randomized controlled trials (RCTs) comparing atogepant to placebo or standard care in patients with EM. Statistical analyses were performed using Review Manager (RevMan) software. Four RCTs with 2,018 patients receiving atogepant and 761 patients receiving placebo or standard care were included. Atogepant significantly reduced monthly migraine days compared to placebo at 10 mg daily (mean difference [MD], –1.16 days; 95% confidence interval [95% CI], –1.60 to –0.73), 30 mg daily (MD, –1.15 days; 95% CI, –1.64 to –0.66), 60 mg daily (MD, –1.48 days; 95% CI: –2.36 to –0.61 days), 30 mg twice daily (MD, –1.30 days; 95% CI, –2.17 to –0.43), and 60 mg twice daily (MD, –1.20 days; 95% CI, –1.90 to –0.50). A ≥50% reduction in migraine days was frequently significantly achieved with atogepant across all dosages. Atogepant was generally well tolerated, though it was associated with higher incidence rates of constipation and nausea compared to placebo. Atogepant is an effective and well-tolerated option for preventing EM, offering patients a noninvasive oral alternative to injectable therapies. Further research is warranted to explore its long-term safety and efficacy in diverse patient populations and refine its role in this field.

Citations

Citations to this article as recorded by

Tension-Type Headache and Primary Stabbing Headache: Primary Headaches Beyond Migraine
Mi-Kyoung Kang
Headache and Pain Research.2025; 26(2): 89. CrossRef
The role of Atogepant in migraine prevention: a systematic review and meta-analysis
Naresh Kumar Ladhwani, Priya Bai, Rohan Lal, Aresha Masood Shah, Sheela Bai, Ghazi Uddin Ahmed, Rimsha Zameer, Varisha Fatima Shaikh, Arsalan Hyder, Sikander Ali, Muhammad Hamza Beg, Maheen Adeeb, Mahir Tesfaye
BMC Neurology.2025;[Epub] CrossRef
Gepants for Migraine: An Update on Long-Term Outcomes and Safety Profiles
Soohyun Cho, Kimoon Chang
Headache and Pain Research.2025; 26(3): 184. CrossRef

New Targeted Drugs for Acute Treatment of Migraine: Heui-Soo Moon, Pil-Wook Chung, Byung-Kun Kim; Korean J Headache. 2023;24(2):56-65. Published online December 31, 2023

955 View
24 Download

Abstract PDF: Acute migraine treatments primarily aim to relieve headache pain and address accompanying symptoms such as photophobia, phonophobia, and nausea. Triptans have traditionally been the first-line treatment for moderate to severe migraine attacks. Nevertheless, they have several limitations, such as causing temporary vasoconstriction of blood vessels, contraindications in patients with cardiovascular issues, and distinctive side effects like chest tightness. Medication overuse is another concern with triptans, prompting research into new antimigraine drugs targeting calcitonin gene-related peptide (CGRP) or 5-HT_1F receptors. Lasmiditan, an agonist at the 5-HT_1F receptor, has emerged as a safe and effective option for abortive treatment in acute migraine attacks. It lacks the vasoconstrictive effects associated with triptans, making it a safer choice for individuals with contraindications to triptans. However, it may lead to central nervous system-related adverse effects, particularly dizziness and paresthesia. Gepants, which are CGRP antagonists, offer an innovative approach by targeting CGRP receptors which is believed to be central in migraine pathophysiology. These medications have demonstrated efficacy in alleviating migraine symptoms, providing alternatives to traditional treatments like triptans and ergots. Ubrogepant and rimegepant are the first approved oral gepants for acute migraine treatment, while Zavegepant is the first approved intranasal gepant. The most common treatment-related adverse events are gastrointestinal symptoms, including nausea. No vascular or hepatic concerns have emerged to date. In this review, we delve into the development of ditans and gepants for acute migraine treatment in adults and discuss their potential advantages and disadvantages in clinical use.

Reiview Article

Zavegepant: Intranasal Drug for Acute Migraine Treatment: Jong-Geun Seo; Korean J Headache. 2023;24(1):17-19. Published online June 30, 2023

500 View
9 Download

Abstract PDF: Calcitonin gene-related peptide (CGRP) is probably the most potent vasodilator in cerebral circulation. The new CGRP-targeted therapy for the treatment of acute treatment are now available for clinical practice. This review article summarized efficacy and safety of zavegepant, which is the first intranasal small molecule CGRP receptor antagonist for acute migraine treatment.

First
Prev
Page of 1
Next
Last

Search