Alternative Treatment for Migraine When Sumatriptan Fails
Try a different triptan first—specifically rizatriptan 10 mg combined with an NSAID (naproxen 500 mg or ibuprofen 400-600 mg)—as failure of one triptan does not predict failure of another. 1, 2
Why Switch Triptans Works
- Individual triptan response varies significantly between patients, with studies showing that 25-81% of sumatriptan non-responders achieve pain relief when switched to an alternative triptan 3, 4
- Rizatriptan is the preferred first alternative due to its faster onset of action (peak concentration in 60-90 minutes) and availability as an orally disintegrating tablet, which is beneficial for patients with nausea 2
- In a randomized controlled trial, rizatriptan 10 mg achieved 51% pain relief at 2 hours in confirmed sumatriptan non-responders, compared to only 20% with placebo 4
Combination Therapy is Critical
- Always combine the alternative triptan with an NSAID or acetaminophen rather than using it alone, as combination therapy provides greater net benefit than monotherapy 1, 2
- Recommended combinations include: rizatriptan 10 mg + naproxen 500 mg, or rizatriptan 10 mg + ibuprofen 400-600 mg, or rizatriptan 10 mg + acetaminophen 1000 mg 1, 2
- Begin treatment as early as possible during the attack while pain is still mild to maximize efficacy 1, 5
Other Triptan Alternatives
- Zolmitriptan, almotriptan, eletriptan, naratriptan, and frovatriptan are additional options if rizatriptan fails 2
- Naratriptan has the longest half-life, which may decrease headache recurrence 2
- For patients with severe nausea or vomiting, consider intranasal sumatriptan (5-20 mg) or subcutaneous sumatriptan (6 mg), as the route of administration—not just the drug itself—can determine response 5, 2
Escalation to Non-Triptan Options
If all triptans fail after adequate trials (2-3 headache episodes per triptan), escalate in this order:
Second-Line: Dihydroergotamine (DHE)
- DHE has good evidence for efficacy and safety as monotherapy for acute migraine attacks 1, 5
- Available as intranasal spray or parenteral formulation for severe attacks 2
- Critical contraindication: Do not use DHE within 24 hours of any triptan, and avoid in pregnancy, uncontrolled hypertension, or ischemic vascular disease 2
Third-Line: CGRP Antagonists (Gepants)
- Consider rimegepant, ubrogepant, or zavegepant nasal spray for patients who do not tolerate or have inadequate response to combination triptan + NSAID therapy 1
- These are newer agents with proven efficacy but higher cost and less comparative effectiveness data 1, 2
Fourth-Line: Ditan (Lasmiditan)
- Use lasmiditan only for patients who do not tolerate or have inadequate response to all other pharmacologic treatments 1
For Severe Attacks Requiring IV Treatment
- IV metoclopramide 10 mg + IV ketorolac 30 mg is the preferred combination for severe migraine requiring emergency or urgent care treatment 5, 2
- Metoclopramide provides both antiemetic effects and direct antimigraine efficacy 5
- Ketorolac has rapid onset with 6-hour duration and minimal risk of rebound headache 5
Critical Pitfalls to Avoid
- Do not use opioids or butalbital for migraine treatment, as they lead to medication overuse headache, dependency, and loss of efficacy 1, 5
- Limit all acute medications to no more than 2 days per week to prevent medication overuse headache (threshold: ≥10 days/month for triptans, ≥15 days/month for NSAIDs) 1, 2
- Rule out medication overuse headache if the patient is already using acute medications more than twice weekly, as this creates a vicious cycle requiring withdrawal and preventive therapy 2
- Try each new triptan for 2-3 headache episodes before abandoning it, as single-attack failure does not predict overall response 2