Acute migraine treatment has evolved substantially with the introduction of ditans (lasmiditan), gepants (rimegepant, ubrogepant), and continued use of triptans and analgesics. Choice depends on patient cardiovascular status, severity, frequency, and prior response patterns. Recognition and treatment of medication overuse headache is increasingly important. This page covers the modern acute migraine and headache armamentarium.

Migraine Acute Treatment Hierarchy

Step 1: Simple Analgesics

  • NSAIDs: ibuprofen 400-800 mg, naproxen 500-1000 mg, diclofenac (oral, IV); first-line for mild-moderate.
  • Acetaminophen: 1000 mg alternative.
  • Combination: acetaminophen + aspirin + caffeine (Excedrin Migraine): mild attacks; caffeine adds modest benefit.

Step 2: Triptans (5-HT1B/1D Agonists)

  • Sumatriptan: SC, oral, intranasal; SC most rapid.
  • Rizatriptan: rapid oral onset; sublingual tablet.
  • Zolmitriptan: oral, intranasal.
  • Eletriptan: more lipophilic; less recurrence.
  • Almotriptan: well-tolerated.
  • Naratriptan, frovatriptan: long half-life; menstrual migraine prophylaxis.
  • Take early in attack for best effect.
  • 2-hour pain freedom: 30-40% with oral triptans.

Triptan Contraindications and Cautions

  • FDA-label contraindications: coronary artery disease (including silent ischemia), uncontrolled hypertension, prior stroke or TIA, peripheral vascular disease, ischemic bowel disease, hemiplegic migraine, and migraine with brainstem aura (basilar-type migraine). The hemiplegic and brainstem-aura listings are formal label contraindications, not just relative cautions — this is the default board-style teaching. Some headache specialists individualize triptan use in selected patients with these subtypes, but this is a specialist decision, not the standard.
  • Pregnancy: limited data; not a formal contraindication.
  • Avoid MAOI + triptan (theoretical serotonin syndrome; rare clinically).
  • SSRI + triptan: low risk despite FDA warning; many patients tolerate.

Step 3: Ditans (5-HT1F Agonists)

  • Lasmiditan (Reyvow): 50-200 mg PO.
  • Selective 5-HT1F; NO vasoconstriction → safer in CAD.
  • Driving restriction: 8 hours after dose due to sedation.
  • Useful when triptans contraindicated by cardiovascular risk.

Step 4: Gepants (CGRP Receptor Antagonists)

  • Rimegepant (Nurtec ODT): 75 mg orally disintegrating; acute treatment AND prevention (every other day).
  • Ubrogepant (Ubrelvy): 50-100 mg PO; acute treatment only.
  • Zavegepant (Zavzpret): intranasal; rapid onset; acute treatment.
  • Mechanism: block CGRP receptor; no vasoconstriction → safe in CAD.
  • Appear to have minimal or lower medication-overuse headache (MOH) liability than older acute agents — but current evidence does not establish zero risk, and frequency of use should still be tracked clinically.
  • Good safety profile; nausea, fatigue common side effects.

Other Acute Options

  • Anti-emetics: metoclopramide, prochlorperazine (parenteral); promethazine; ondansetron.
  • Ergotamines (DHE): dihydroergotamine IV, SC, intranasal; for refractory or status migrainosus; can repeat doses.
  • Steroids: methylprednisolone or dexamethasone for status migrainosus; bridge therapy.
  • Magnesium IV: refractory or status migrainosus.
  • Valproate IV: status migrainosus alternative.
  • Opioids: AVOID for routine migraine; rare emergency use only.

Choice of Triptan

  • Rapid onset: sumatriptan SC, rizatriptan oral, zolmitriptan oral.
  • Less recurrence: eletriptan, frovatriptan.
  • Long half-life (menstrual migraine prophylaxis): naratriptan, frovatriptan.
  • Non-oral route: sumatriptan SC, intranasal triptans.
  • If one triptan fails, try another (different patient response patterns).

Status Migrainosus

  • Severe migraine >72 hours despite typical management.
  • Hydration + antiemetic (IV): prochlorperazine 10 mg or metoclopramide 10 mg.
  • NSAID IV or PO: ketorolac 30-60 mg.
  • Magnesium IV: 1-2 g.
  • Valproate IV: 500-1000 mg.
  • Steroids: methylprednisolone, dexamethasone.
  • DHE IV: 0.5-1 mg q8h.
  • Lidocaine IV: for refractory.
  • Greater occipital nerve block: bupivacaine or lidocaine.

Cluster Headache Acute Treatment

  • Oxygen 100% high-flow: 10-15 L/min via non-rebreather; first-line; abortive in many.
  • Sumatriptan SC: 6 mg; rapid abortive.
  • Sumatriptan intranasal: alternative.
  • Zolmitriptan intranasal: alternative.
  • DHE: alternative.
  • Galcanezumab: FDA-approved for episodic cluster (preventive but acts within days).

Tension-Type Headache Acute Treatment

  • Simple analgesics: NSAIDs, acetaminophen.
  • Combination products (acetaminophen + caffeine).
  • Behavioral approaches: relaxation, biofeedback.
  • Triptans NOT effective for pure tension.

Medication Overuse Headache (MOH)

Definitions

  • Headache ≥15 days/month for >3 months in patients with prior primary headache disorder.
  • Overuse of acute medication:
    • Triptans, ergots, opioids: ≥10 days/month for >3 months.
    • Simple analgesics: ≥15 days/month for >3 months.
  • Bedrock principle: chronic daily headache + acute medication overuse → suspect MOH.

Management

  • Patient education: explain the cycle.
  • Wean overused medication: abrupt or gradual depending on drug (taper opioids; abrupt OK for triptans, NSAIDs).
  • Bridge therapy during withdrawal: steroids (short course), NSAIDs (alternative class), DHE, IV magnesium.
  • Start preventive therapy concurrently.
  • “Crash and recovery” pattern expected over 2-12 weeks.
  • Outcomes: 70-80% improve significantly within 2 months of withdrawal.
  • Recurrence common if patient returns to overuse pattern.

Headache in Special Situations

Pregnancy

  • Acetaminophen: first-line.
  • NSAIDs: avoid third trimester (premature ductus closure); cautious use earlier.
  • Triptans: limited data; some specialists use sumatriptan when needed.
  • Caffeine in moderation OK.
  • Anti-CGRPs: limited data; avoid.
  • Steroids OK short-term.
  • Antiemetics: ondansetron, metoclopramide.

Lactation

  • Acetaminophen, ibuprofen: safe.
  • Sumatriptan: minimal transfer; usually OK.
  • Many opioids: avoid.

Children

  • Acetaminophen, ibuprofen first-line.
  • Triptans approved in adolescents (rizatriptan, sumatriptan, almotriptan, zolmitriptan).
  • Avoid combination analgesics with caffeine.

Elderly

  • NSAIDs cautious (GI, renal, cardiac).
  • Triptans cautious (CV).
  • Lasmiditan, gepants: safer cardiac profile.

Specific Considerations

Triptan + SSRI

  • FDA warning about serotonin syndrome.
  • Clinical incidence very low.
  • Many patients tolerate combination without issue.
  • Counsel patient on signs of serotonin syndrome.

Patent Foramen Ovale (PFO)

  • Strong association with migraine with aura.
  • Closure: mixed evidence for migraine reduction (some trials negative).
  • Reserve for stroke prevention indications.

Estrogen and Migraine

  • Menstrual migraine: more severe, prolonged.
  • Continuous OCP use can help.
  • Migraine with aura + estrogen-containing OCP: stroke risk (especially smokers); avoid.

🔍 Did You Know?

The advent of gepants and ditans as alternatives to triptans has transformed acute migraine therapy for patients with cardiovascular contraindications. For decades, triptans were the most effective acute migraine therapy but were absolutely contraindicated in patients with coronary artery disease, prior stroke, uncontrolled hypertension, or peripheral vascular disease — a substantial portion of older patients. The development of these alternatives now provides effective options: lasmiditan (5-HT1F agonist) targets the trigeminal nerve without intracranial vasoconstriction; rimegepant, ubrogepant, zavegepant (CGRP antagonists) block the CGRP pathway central to migraine pathophysiology with no vasoconstriction. The clinical impact is substantial: older patients with migraine who previously had to suffer through attacks now have effective treatment options, and patients with concurrent CAD can receive evidence-based acute migraine therapy. Additionally, gepants do NOT cause medication overuse headache (a paradoxical advantage over triptans), and rimegepant can be used both acutely AND preventively (every other day) — bridging the acute-preventive divide. The lesson generalizes: understanding pathophysiology drives drug development, and the recognition that migraine is a neurological disease of trigeminovascular pathways (not just vasoconstriction) opened the door to mechanistically distinct therapeutics. For practicing neurologists, the option to choose lasmiditan or a gepant when triptans are contraindicated is one of the most important advances in migraine therapy in 30 years.

Pitfalls and Pearls

  • Triptan early: take at onset of pain for best response.
  • Sumatriptan SC: fastest onset for severe attacks; cluster.
  • Eletriptan: less recurrence.
  • Lasmiditan: no vasoconstriction; safer in CAD; 8-hour driving restriction.
  • Gepants (rimegepant, ubrogepant, zavegepant): no vasoconstriction; lower MOH liability than older acute agents but not proven zero risk.
  • Rimegepant: acute + every other day preventive.
  • Status migrainosus: hydration + antiemetic + NSAID + magnesium + steroids + DHE.
  • MOH: chronic daily headache + acute med overuse; wean + preventive.
  • Cluster headache: oxygen 100% + sumatriptan SC.
  • Pregnancy: acetaminophen first-line; cautious sumatriptan.
  • Children: ibuprofen, acetaminophen first-line; specific triptans approved.
  • Triptan contraindications (FDA label): CAD, uncontrolled HTN, prior stroke/TIA, PVD, ischemic bowel, hemiplegic migraine, migraine with brainstem aura. Hemiplegic and brainstem-aura migraine are formal label contraindications, not soft cautions.
  • Migraine with aura + estrogen OCP: increased stroke risk.
  • Opioids for migraine: AVOID; cause MOH, less effective than alternatives.
  • Greater occipital nerve block: useful for status migrainosus.
  • Acetaminophen + aspirin + caffeine: effective for mild migraine.

References

  1. American Headache Society. The American Headache Society Position Statement on Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019;59(1):1-18.
  2. Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553-622.
  3. Croop R, Goadsby PJ, Stock DA, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine. Lancet. 2019;394(10200):737-745.
  4. Goadsby PJ, Wietecha LA, Dennehy EB, et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142(7):1894-1904.
  5. Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. Lancet Neurol. 2004;3(8):475-483.