Migraine Management After Triptan Failure
After failing an adequate trial of triptans, gepants (ubrogepant or rimegepant) should be used as third-line therapy for acute migraine treatment. 1
Treatment Algorithm Following Triptan Failure
Step 1: Verify Adequate Triptan Trial
Before abandoning triptans entirely, ensure the following:
- Try a different triptan or formulation if only one triptan has been attempted, as individual response is idiosyncratic and one triptan failure does not predict failure of all triptans 1, 2
- Consider alternative delivery routes including subcutaneous injection (6 mg sumatriptan), intranasal spray, or orally disintegrating tablets, particularly for patients with rapid peak intensity or severe vomiting 3, 1
- Confirm early administration during the attack while pain is still mild, as timing significantly impacts efficacy 1
Step 2: Third-Line Therapy - Gepants
Gepants (ubrogepant, rimegepant) are the recommended next step when all available triptans have failed after adequate trials or when triptans are contraindicated. 1
The American Academy of Neurology specifically positions gepants as third-line therapy in the stepped care approach: NSAIDs first, triptans second, gepants third 1
Step 3: Combination Therapy Considerations
For difficult-to-treat attacks, consider:
- Triptan plus fast-acting NSAID combination for patients who had partial response to triptans 1
- Prokinetic antiemetics (domperidone, metoclopramide) as adjuncts when nausea is prominent 1
Critical Medications to AVOID
Do NOT use the following agents due to poor efficacy and safety concerns:
- Oral ergot alkaloids - poor efficacy and potential toxicity 1
- Opioids/barbiturates - poor efficacy, risk of medication overuse headache, and progression to chronic migraine 1, 4
- Compounds containing butalbital - high risk of medication overuse and chronification 4
Important Caveats
Medication Overuse Prevention
- Limit acute medication use to no more than 2 days per week to prevent medication overuse headache and daily headaches 3
- For patients with frequent headaches (>10 days per month), reserve acute treatments only for the most disabling episodes 4
Contraindications to Monitor
Before prescribing any acute migraine therapy, exclude:
- Ischemic heart disease or previous myocardial infarction
- Uncontrolled hypertension
- Basilar or hemiplegic migraine
- History of stroke or TIA
- Peripheral vascular disease 3
When Gepants Are Unavailable
If gepants are not accessible in your region, verify local formulary availability before prescribing, as medication access varies significantly between countries 3. In such cases, optimizing combination therapy with triptans plus NSAIDs may be the best available option 1.