Next Line Treatment for Migraine After NSAIDs: Triptans and Their Mechanism of Action
For patients with migraine attacks who did not respond to NSAIDs, triptans are the recommended next-line therapy, which work by selectively binding to serotonin (5-HT1B/1D) receptors, causing vasoconstriction of cranial blood vessels and inhibition of pro-inflammatory neuropeptide release. 1
Mechanism of Action of Triptans
Triptans function through three primary mechanisms:
Cranial vasoconstriction: Triptans activate 5-HT1B receptors on blood vessels, causing vasoconstriction of abnormally dilated cerebral blood vessels during migraine attacks
Inhibition of neuropeptide release: By activating 5-HT1D receptors on trigeminal nerve terminals, triptans block the release of inflammatory substances like calcitonin gene-related peptide (CGRP)
Inhibition of pain transmission: Triptans reduce pain signal transmission in the trigeminal nucleus caudalis
Triptan Options
The American College of Physicians specifically recommends the following triptans 1:
- Rizatriptan: Demonstrated efficacy with 33% of pediatric patients achieving pain freedom at 2 hours compared to 24% with placebo 2
- Zolmitriptan
- Naratriptan
Clinical Considerations for Triptan Use
- Timing is critical: Triptans are most effective when taken early in the migraine attack, before central sensitization develops 3
- Efficacy in moderate-to-severe migraines: Triptans are first-line for moderate-to-severe migraines, while NSAIDs are first-line for mild-to-moderate attacks 4
- Contraindications: Triptans should not be used in patients with cardiovascular disease or risk factors 1
- Route of administration: For patients with significant nausea/vomiting, non-oral routes (nasal sprays, subcutaneous injections) may be more effective 1, 3
Alternative Next-Line Options
If triptans are contraindicated or ineffective, other options include:
- CGRP antagonists (gepants): Ubrogepant has demonstrated efficacy with 21.8% of patients achieving pain freedom at 2 hours compared to 14.3% with placebo 5
- Dihydroergotamine (DHE): Recommended for refractory migraines 1
- Combination therapy: Combining a triptan with an NSAID has demonstrated better efficacy than either agent alone 6
Management of Associated Symptoms
For migraines with significant nausea/vomiting, add:
- Metoclopramide: 10 mg IV or orally 20-30 minutes before or with primary medication
- Prochlorperazine: 25 mg orally or suppository (max 3 doses/24 hours) 1
Important Cautions
- Avoid regular use of opioids and butalbital-containing analgesics due to risk of dependence and medication overuse headache 1
- If all treatments fail despite optimization, consider referral to a neurologist or headache specialist 1
- Approximately 90% of migraine patients can be effectively managed in primary care with proper medication selection and dosing 1