Acute Migraine: Home Management

Effective outpatient acute treatment is the foundation of migraine care. The principle of stratified care — matching treatment intensity to attack severity — has replaced the outdated step-care approach. Early treatment (within 1 hour of onset) dramatically improves outcomes across all drug classes. Three drug classes now dominate acute migraine therapy: triptans, gepants, and ditans.

Bottom Line

  • Triptans remain first-line for moderate-severe migraine attacks — well-established efficacy, generic availability, 30 years of safety data
  • Gepants (ubrogepant, rimegepant, zavegepant) are first-line alternatives when triptans are contraindicated, poorly tolerated, or ineffective; no vasoconstrictive properties
  • Lasmiditan is an option for patients who cannot use triptans or gepants; sedation and 8-hour driving restriction limit its use
  • Treat early: All acute therapies are significantly more effective when taken within 1 hour of onset
  • Gepants and triptans can be combined or used sequentially in the same day if needed
  • Limit acute medication use to <10 days/month (triptans, gepants) or <15 days/month (NSAIDs) to prevent medication overuse headache

Triptans

Selective 5-HT1B/1D receptor agonists that act through cranial vasoconstriction, inhibition of trigeminal nociceptive transmission, and blockade of neurogenic inflammation. Seven triptans are available, with clinically meaningful differences in speed, route, and consistency.

Comparison

Triptan Routes Onset Key Features
Sumatriptan PO, SC, nasal spray, nasal powder SC: 10-15 min; PO: 30-60 min Most studied; SC formulation is fastest and most effective triptan overall; generic available in all forms
Rizatriptan PO, ODT (orally disintegrating) 30 min Fast oral onset; ODT useful with nausea (still requires GI absorption); reduce dose to 5 mg with propranolol
Eletriptan PO 30-60 min Highest 2-hour response rate among oral triptans (meta-analyses); 40 mg is the maximum single dose (max 80 mg/24h as two 40 mg doses)
Zolmitriptan PO, ODT, nasal spray Nasal: 15 min; PO: 45 min Nasal spray absorbed directly through nasal mucosa (advantage over sumatriptan nasal which is mostly swallowed)
Naratriptan PO 60-120 min Slowest onset but longest half-life (6h); lowest recurrence rate; best tolerated; useful for menstrual migraine mini-prophylaxis
Frovatriptan PO 120 min Longest half-life (25-26h); lowest recurrence; slow onset limits use for acute attacks; most commonly used as menstrual migraine prophylaxis
Almotriptan PO 30-60 min Good balance of efficacy and tolerability; FDA-approved for adolescents (12-17)

Triptan Prescribing Pearls

  • Triptan non-response: Failure of one triptan does not predict failure of another. Try at least 2-3 different triptans before declaring class failure. Switch to a different triptan OR different route.
  • Timing matters: Triptans taken during aura are less effective; take at headache onset. However, triptans are safe in typical aura — the contraindication applies only to hemiplegic or brainstem aura (consensus-based, not evidence-based).
  • Combination: Triptan + NSAID (e.g., sumatriptan 85 mg / naproxen 500 mg — available as Treximet) is more effective than either alone.
  • Recurrence: Headache returns within 24 hours in 15-40% of patients; a second dose is effective; naratriptan/frovatriptan have lowest recurrence.
  • Triptan + gepant same day: Safe to use a gepant if triptan fails (or vice versa). No interaction or safety concern — mechanisms are complementary.

🔴 Triptan Contraindications

  • Coronary artery disease, prior MI, angina
  • Uncontrolled hypertension
  • Prior stroke or TIA
  • Peripheral vascular disease
  • Hemiplegic migraine or migraine with brainstem aura (consensus-based)
  • Within 24 hours of ergots or another triptan
  • Concurrent MAO-A inhibitor use (for some triptans)

Gepants (CGRP Receptor Antagonists)

Small-molecule CGRP receptor antagonists that block the CGRP pathway without vasoconstriction. Unlike triptans, gepants have no cardiovascular contraindications and can be used in patients with vascular risk factors.

Agent Acute Dose Onset Key Trial Notes
Ubrogepant 50 or 100 mg PO 60-90 min Ubrogepant for Acute Migraine, ACHIEVE I & II Acute use only; can repeat once after 2h (max 200 mg/day); CYP3A4 interactions (avoid strong inhibitors)
Rimegepant 75 mg PO (ODT) 60 min BHV3000-301, -302, -303 Dual-use: acute AND preventive (75 mg every other day); ODT dissolves on tongue; no food or water needed
Zavegepant 10 mg nasal spray 15-30 min Phase 3 nasal spray trial Fastest gepant onset — comparable to nasal triptans; bypasses GI absorption; dysgeusia (taste disturbance) in ~20%

Zavegepant: The Fast-Acting Gepant

Zavegepant nasal spray offers a significant advantage for patients needing rapid relief without triptan vasoconstrictive effects:

  • Onset: 15-30 minutes — comparable to zolmitriptan nasal spray
  • 2-hour pain freedom: 24% vs 15% placebo (NNT ~11)
  • Bypasses gastric stasis: Useful when nausea/vomiting limits oral intake
  • Main side effect: Dysgeusia (altered/bitter taste) in ~20% of patients — counsel patients to expect this
  • Best for: Patients with CV contraindications to triptans who need fast-acting non-oral therapy

When to Choose a Gepant Over a Triptan

  • Cardiovascular disease, uncontrolled hypertension, prior stroke/TIA, peripheral vascular disease
  • Triptan non-responders or intolerance (chest tightness, significant triptan side effects)
  • Hemiplegic migraine or migraine with brainstem aura (if triptan avoidance preferred)
  • Patient at risk for medication overuse headache — gepants may have lower MOH risk (emerging data)
  • Need for dual acute + preventive therapy (rimegepant every other day)
  • Patient already on a CGRP mAb for prevention — the COURAGE trial showed ubrogepant is effective and well-tolerated when used with CGRP mAbs

Combining Gepants and Triptans

  • Can I take a gepant if my triptan didn’t work? Yes. No pharmacokinetic interaction or safety concern. Mechanisms are different (vasoconstriction vs CGRP blockade).
  • Can I take a triptan if my gepant didn’t work? Yes, if no CV contraindications exist.
  • Can I take them together? Limited data, but no theoretical concern. Some patients use both simultaneously for severe attacks.
  • Practical approach: If triptan provides only partial relief, adding a gepant 2 hours later is reasonable.

Ditans (5-HT1F Agonists)

Lasmiditan

  • Dose: 50 or 100 mg PO (200 mg available but limited additional benefit)
  • Mechanism: Selective 5-HT1F agonist — no vasoconstriction; acts on trigeminal nerve terminals
  • Trial: SAMURAI and SPARTAN — 2-hour pain freedom 28-32% vs 15% placebo
  • No cardiovascular contraindications

🔴 Lasmiditan Limitations

  • CNS side effects: Dizziness (15-17%), somnolence (5-7%), paresthesia — significantly more sedating than triptans or gepants
  • Driving restriction: FDA requires patients not to drive for at least 8 hours after dosing
  • Schedule V controlled substance (low abuse potential but regulatory burden)
  • These limitations have restricted real-world uptake; gepants are generally preferred when triptans are contraindicated
  • Best use case: Patient with CV disease who cannot use triptans, has evening/nighttime migraines, and won’t need to drive

NSAIDs and Simple Analgesics

Appropriate for mild-moderate attacks or as combination therapy with triptans.

Agent Dose Notes
Ibuprofen 400-800 mg Best evidence among OTC NSAIDs; NNT ~7 for 2h pain-free
Naproxen sodium 500-550 mg Longer half-life; lower recurrence; combination with sumatriptan is synergistic
Diclofenac potassium 50 mg sachet (Cambia) Rapid absorption from powder formulation; RCT-supported; good for patients who prefer non-triptans
Aspirin 900-1000 mg Effervescent formulation preferred (faster absorption); comparable to sumatriptan 50 mg in some trials
Acetaminophen 1000 mg Modest efficacy; reasonable for mild attacks or when NSAIDs contraindicated
Excedrin (ASA + APAP + caffeine) 2 tablets (500 mg ASA + 500 mg APAP + 130 mg caffeine) Caffeine enhances analgesic efficacy; OTC option for moderate attacks; limit use to prevent MOH

Caffeine as an Adjunct

Caffeine (100-200 mg) enhances the efficacy of simple analgesics by ~40% through adenosine receptor antagonism and improved GI absorption. It is included in combination products (Excedrin, Fioricet) for this reason.

  • Can be added to any NSAID or acetaminophen regimen
  • Equivalent to ~1-2 cups of coffee
  • Caution: Regular caffeine use (>200 mg/day) can contribute to medication overuse headache

Antiemetics

Address nausea/vomiting and enhance absorption of oral medications. Also have independent antimigraine efficacy via dopamine receptor blockade.

  • Metoclopramide 10 mg PO/IM: Prokinetic effect improves gastric absorption of oral medications during migraine (gastric stasis is common)
  • Ondansetron 4-8 mg ODT: No antimigraine effect but effective antiemetic; useful when dopamine antagonist side effects are a concern
  • Domperidone 10-20 mg PO: Available outside US; does not cross BBB so less sedation and extrapyramidal risk; useful as pre-treatment before oral triptan

Neuromodulation Devices

FDA-cleared non-pharmacologic options for acute migraine treatment. Particularly useful for patients who want to limit medication use, have contraindications to multiple drug classes, or prefer non-drug approaches.

Device Mechanism Trial Evidence Practical Notes
Cefaly (e-TNS) External trigeminal nerve stimulation via supraorbital electrode e-TNS trial: 2h pain freedom 25.5% vs 18.3% sham (p=0.043); 2h pain relief 69.5% vs 55.2% Worn on forehead; 60-minute acute treatment sessions; also FDA-cleared for prevention (20 min/day)
Nerivio (REN) Remote electrical neuromodulation via upper arm REN for Migraine: 2h pain relief ~67%; also showed preventive benefit with regular use Smartphone-controlled; worn on upper arm; 45-minute treatment sessions; FDA-cleared for ages 12+
gammaCore (nVNS) Non-invasive vagus nerve stimulation via neck PRESTO trial: modest benefit for acute migraine; stronger evidence for cluster headache Handheld device applied to neck; 2-minute treatments; can repeat; also used for cluster headache
sTMS (SpringTMS) Single-pulse transcranial magnetic stimulation RCT-supported for acute treatment and prevention; 2h pain freedom ~39% vs 22% sham Handheld device held to back of head; single pulse delivery; also FDA-cleared for prevention

When to Consider Neuromodulation

  • Medication-averse patients: Prefer non-drug approaches
  • Pregnancy/breastfeeding: When minimizing medication exposure is desired
  • Frequent attacks at risk for MOH: Devices do not contribute to medication overuse
  • Multiple contraindications: Cannot use triptans, gepants, or NSAIDs
  • Adjunctive use: Can be combined with any medication for additive effect
  • Limitations: Lower efficacy than pharmacotherapy; cost and insurance coverage vary; requires device availability during attack

Treatment Selection: Stratified Approach

Attack Severity First Choice Alternative
Mild NSAID (ibuprofen 400-800 mg or naproxen 500 mg) Acetaminophen 1000 mg; aspirin 900 mg + caffeine; neuromodulation device
Moderate Oral triptan; or NSAID + triptan combination Gepant (ubrogepant 100 mg, rimegepant 75 mg)
Severe SC sumatriptan 6 mg; or triptan nasal spray + NSAID Zavegepant nasal spray; or triptan + antiemetic
Severe with vomiting SC sumatriptan; zolmitriptan nasal spray; zavegepant nasal spray Ondansetron ODT first, then oral triptan after 15-20 min
Cardiovascular risk factors Gepant (any); or NSAID alone Lasmiditan 100 mg (if not driving); neuromodulation
Pregnancy Acetaminophen 1000 mg; metoclopramide if needed for nausea Neuromodulation device; sumatriptan (limited data, generally avoided)

When to Go to the ED

🔴 Advise ED Evaluation When:

  • Worst headache of life or thunderclap onset
  • Headache with fever, neck stiffness, or rash
  • New neurologic deficits that do not resolve with the aura
  • Headache unresponsive to 2 doses of acute treatment at home
  • Persistent vomiting preventing medication use and causing dehydration
  • Headache lasting >72 hours (approaching status migrainosus)
  • First or worst headache in a patient >50 years old

Medication Overuse Prevention

Frequency Limits to Discuss With Patients

  • Triptans / gepants / combination analgesics: <10 days per month
  • Simple analgesics (NSAIDs, acetaminophen): <15 days per month
  • Opioids / barbiturates: Avoid entirely if possible; <8 days/month absolute maximum
  • Neuromodulation devices: No limit — do not contribute to MOH
  • If acute medication is needed ≥4 days/month, initiate preventive therapy
  • Track with a headache diary; patients often underestimate medication frequency

Trial Comparison Table

Trial Year Agent 2h Pain Freedom Key Notes
Ubrogepant for Acute Migraine 2019 Ubrogepant 50/100 mg 19-21% vs 12% placebo First FDA-approved gepant for acute use
ACHIEVE I & II 2020 Ubrogepant 25-100 mg Functional recovery 40% vs 30% Confirmed PRO benefits; high satisfaction rates
BHV3000-301/302/303 2019-2021 Rimegepant 75 mg ODT 19-21% vs 12% placebo Also approved for prevention (every other day dosing)
Zavegepant Phase 3 2022 Zavegepant 10 mg nasal 24% vs 15% placebo Fastest gepant onset (15-30 min); dysgeusia in 20%
SAMURAI/SPARTAN 2019 Lasmiditan 100-200 mg 28-32% vs 15% placebo No CV contraindications; 8h driving restriction
COURAGE 2023 Ubrogepant + CGRP mAb N/A (satisfaction endpoint) 70-73% satisfied; confirms safety of combination
e-TNS (Cefaly) 2021 External trigeminal stimulation 25.5% vs 18.3% sham 2h pain relief 69.5% vs 55.2%
REN for Migraine 2023 Remote electrical neuromodulation Pain relief 67% Also showed preventive benefit with regular use
Ferrari meta-analysis 2001 Oral triptans (53 trials) Eletriptan 80 mg highest (30%) Established triptan class efficacy hierarchy

References

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  3. Lipton RB, et al. Ubrogepant achieves early and sustained pain relief (ACHIEVE I & II). Headache. 2020;60(10):2098-2109.
  4. Croop R, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine. Lancet. 2019;394(10200):737-745.
  5. Lipton RB, et al. Zavegepant nasal spray for acute treatment of migraine. Lancet Neurol. 2023;22(5):378-388.
  6. Goadsby PJ, et al. Trial of lasmiditan for acute treatment of migraine (SAMURAI/SPARTAN). N Engl J Med. 2019;380(11):1001-1011.
  7. Ailani J, et al. Ubrogepant and CGRP mAb combination (COURAGE). Headache. 2023;63(5):611-621.
  8. Tassorelli C, et al. External trigeminal nerve stimulation for acute migraine (e-TNS). Neurology. 2021;96(12):e1687-e1698.
  9. Yarnitsky D, et al. Remote electrical neuromodulation for migraine (REN). Cephalalgia. 2023;43(2):1-12.
  10. Ferrari MD, et al. Oral triptans in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668-1675.
  11. Lipton RB, et al. Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) study. JAMA. 2000;284(20):2599-2605.