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.
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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-HT1F receptors. Lasmiditan, an agonist at the 5-HT1F 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.
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.