What is the role of atogepant and triptans (serotonin receptor agonists) in treating migraines?

Role of Atogepant and Triptans in Treating Migraines

Triptans are second-line therapy for moderate to severe migraine attacks, while atogepant is a preventive treatment for episodic and chronic migraine that can be used concurrently with triptans for acute attacks. 1, 2

Triptans for Acute Treatment

• Triptans (serotonin1B/1D receptor agonists) are the standard second-line therapy for moderate to severe migraine attacks after NSAIDs, with well-documented effectiveness 3, 1
• Triptans work by activating serotonin receptors, causing cranial vessel constriction and inhibiting vasoactive neuropeptide release 1, 4
• Triptans are most effective when taken early in an attack while the headache is still mild, but should not be used during the aura phase 3
• If one triptan is ineffective, others might still provide relief; sumatriptan subcutaneous injection can be useful for patients who rapidly reach peak headache intensity or cannot take oral medications due to vomiting 3

Triptan Administration and Dosing

• Sumatriptan is available in multiple formulations: oral (25mg, 50mg, 100mg), subcutaneous, and intranasal 4
• Maximum sumatriptan dose in a 24-hour period should not exceed 200mg, with doses separated by at least 2 hours 4
• Patients with mild to moderate hepatic impairment should not exceed 50mg per single dose 4

Triptan Contraindications

• Triptans are contraindicated in patients with:
  • History of coronary artery disease or coronary vasospasm 4
  • Wolff-Parkinson-White syndrome or other cardiac conduction disorders 4
  • History of stroke, TIA, or hemiplegic/basilar migraine 4
  • Peripheral vascular disease or ischemic bowel disease 4
  • Uncontrolled hypertension 4
  • Recent (within 24 hours) use of another triptan or ergotamine-containing medication 4

Atogepant for Preventive Treatment

• Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist FDA-approved for the preventive treatment of episodic and chronic migraine 2, 5
• In clinical trials, atogepant significantly reduced monthly migraine days compared to placebo across all tested doses (10mg, 30mg, 60mg daily) 2, 6
• Atogepant demonstrated efficacy in both episodic migraine (4-14 migraine days/month) and chronic migraine (≥15 headache days/month with ≥8 migraine days) 5, 6
• The most common adverse events with atogepant are constipation (6.9-7.7%) and nausea (4.4-6.1%) 6

Atogepant Dosing and Administration

• Atogepant is administered orally once daily for migraine prevention 2
• Effective doses in clinical trials were 10mg, 30mg, and 60mg daily, with the 60mg dose showing the greatest reduction in monthly migraine days 2, 6

Combination Therapy and Drug Interactions

• Atogepant can be safely co-administered with triptans (including sumatriptan) without significant pharmacokinetic interactions 2
• This allows patients to use atogepant for prevention while still having triptans available for breakthrough migraine attacks 2, 5
• Atogepant can also be safely co-administered with common acute migraine treatments including acetaminophen and NSAIDs 2

Treatment Algorithm for Migraine Management

1. First-line acute treatment: NSAIDs (acetylsalicylic acid, ibuprofen, diclofenac potassium) for mild to moderate attacks 3, 1, 7
2. Second-line acute treatment: Triptans for moderate to severe attacks or when NSAIDs provide inadequate relief 3, 1
3. Preventive treatment: Consider atogepant for patients with frequent migraine attacks (4 or more migraine days per month) 2, 6
4. Rescue treatment: For patients who experience relapse after triptan use, consider repeating the triptan dose or combining with fast-acting NSAIDs 3

Important Clinical Considerations

• Limit acute treatments (including triptans) to no more than twice weekly to prevent medication overuse headache 1, 7
• For patients with nausea and vomiting, consider non-oral routes of administration (subcutaneous or intranasal triptans) 1, 7
• Atogepant has shown efficacy in patients with medication overuse headache, reducing both migraine frequency and acute medication use 5
• Triptans remain the mainstay of migraine-specific acute treatment despite newer options like gepants and ditans 8