What is the role of oral gepants (Gepants) and triptans (Triptans) in treating migraines?

Role of Oral Gepants and Triptans in Treating Migraines

Triptans should be used as second-line therapy for migraine after NSAIDs, while gepants are recommended as third-line therapy when triptans fail or are contraindicated. 1

Stepped Care Approach to Migraine Treatment

First-Line Therapy

• NSAIDs with proven efficacy (acetylsalicylic acid, ibuprofen, and diclofenac potassium) should be used as first-line medications for acute migraine treatment 1
• Paracetamol has less efficacy and should only be used in patients intolerant to NSAIDs 1

Second-Line Therapy: Triptans

• Triptans should be offered when over-the-counter analgesics provide inadequate relief 1
• Triptans are most effective when taken early in an attack while headache pain is still mild 1
• Key points for optimal triptan use:
  • No evidence supports using triptans during the aura phase 1
  • If one triptan is ineffective, others might still provide relief 1
  • For patients who rapidly reach peak headache intensity or cannot take oral triptans due to vomiting, sumatriptan by subcutaneous injection is recommended 1
  • Non-oral formulations (nasal sprays, orally disintegrating tablets) are beneficial for patients with significant nausea 2, 3

Third-Line Therapy: Gepants

• Gepants (ubrogepant, rimegepant) should be used when all available triptans fail after an adequate trial period (no or insufficient therapeutic response in at least three consecutive attacks) or when triptans are contraindicated 1
• Rimegepant 75mg has demonstrated efficacy for pain freedom (21.2% vs 10.9% for placebo) and most bothersome symptom freedom (35.1% vs 26.8% for placebo) at 2 hours post-dose 4
• Gepants offer comparable efficacy to NSAIDs with NNT values of 9-12 for pain freedom at two hours 5
• Unlike triptans, gepants have no significant cardiovascular risk and minimal potential for medication-overuse headache 5

Comparative Efficacy and Safety

Triptans

• Well-documented effectiveness for acute migraine treatment 1
• Limitations include:
  • Cardiovascular contraindications 6, 7
  • Incomplete and inconsistent pain relief 6
  • High rates of headache recurrence 6
  • Risk of medication overuse headache with repeated use 1

Gepants

• Efficacy comparable to triptans but with improved cardiovascular safety profile 6, 5
• Particularly valuable for the >20% of migraine patients at increased risk of cardiovascular events 7
• FDA-approved gepants (rimegepant, ubrogepant) have demonstrated statistically significant improvements in pain freedom and most bothersome symptom freedom compared to placebo 4

Special Considerations

Managing Relapse

• Upon relapse (return of symptoms within 48 hours after successful treatment), patients can repeat triptan treatment or combine with fast-acting NSAIDs 1
• Caution: repeating treatment increases risk of medication overuse headache 1

Adjunct Medications

• For patients experiencing nausea/vomiting during attacks, prokinetic antiemetics (domperidone, metoclopramide) are useful adjuncts 1
• Adding an antiemetic is recommended when nausea is a significant component of the migraine 2

Medications to Avoid

• Oral ergot alkaloids (poorly effective and potentially toxic) 1
• Opioids and barbiturates (questionable efficacy, considerable adverse effects, risk of dependency) 1

Practical Algorithm for Treatment Selection

1. Start with NSAIDs (ibuprofen, aspirin, diclofenac) for mild-moderate attacks 1
2. If inadequate response to NSAIDs, prescribe a triptan 1
3. If one triptan fails, try another triptan or a different formulation 1, 2
4. For patients with significant nausea, use non-oral formulations (nasal spray, subcutaneous injection) 2, 3
5. If all triptans fail or are contraindicated, use a gepant (rimegepant, ubrogepant) 1, 4
6. Consider combination therapy (triptan + NSAID) for difficult-to-treat attacks 1