Management of Refractory Migraine with Normal Imaging

Immediate Assessment and Red Flag Exclusion

The American College of Neurology recommends ruling out subarachnoid hemorrhage (SAH) with a lumbar puncture if clinical suspicion remains high, even with a normal CT scan, especially if performed more than 6 hours from symptom onset or if the patient has new neurological deficits 1
The American College of Obstetricians and Gynecologists recommends excluding preeclampsia/eclampsia in any new headache in a woman of childbearing age with hypertension 2

The American Headache Society recommends metoclopramide 10 mg IV as a first-line treatment for status migrainosus, providing direct analgesic effects through central dopamine receptor antagonism 3, 4
The American Headache Society recommends ketorolac 30 mg IV as a first-line treatment for status migrainosus, offering rapid onset with 6-hour duration and minimal rebound headache risk 3, 4
The combination of metoclopramide and ketorolac is superior to either agent alone and represents the most evidence-based IV approach for severe refractory migraine 4
Prochlorperazine 10 mg IV has comparable efficacy to metoclopramide with a more favorable side effect profile 4
Dihydroergotamine (DHE) IV or intranasal has good evidence for efficacy as monotherapy for acute migraine attacks 3, 4
Corticosteroids (dexamethasone or prednisone) should be reserved for status migrainosus after other options have failed 2

The American Headache Society recommends preventive therapy for patients with two or more attacks per month producing disability lasting 3+ days, failure of acute treatments, or use of abortive medication more than twice per week 4
Propranolol 80-240 mg/day has the most consistent evidence for efficacy and should be the first choice for preventive therapy 4
Topiramate or divalproex sodium are alternatives, though they carry risks of weight gain, hair loss, tremor, and are teratogenic 4
Amitriptyline 30-150 mg/day is particularly useful if there is a mixed migraine and tension-type headache pattern 4
CGRP monoclonal antibodies should be considered when oral preventives have failed or are contraindicated, with efficacy assessed after 3-6 months 4

The American Headache Society defines medication overuse headache (MOH) as acute medication use ≥10 days/month for triptans or ≥15 days/month for NSAIDs/acetaminophen 3, 4
If MOH is present, the cycle must be broken by withdrawing the overused medication while simultaneously initiating preventive therapy 4

The American Headache Society recommends NSAIDs alone, such as ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg, for mild to moderate attacks 3
Acetaminophen 1000 mg is an alternative for mild to moderate attacks 3
Combination therapy with a triptan and an NSAID is superior to either agent alone for moderate to severe attacks 3, 4
Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg provides sustained pain relief at 48 hours 4
Gepants (ubrogepant 50-100 mg or rimegepant) are the primary alternative to triptans, with no vasoconstriction and safe in cardiovascular disease 4
Lasmiditan 50-200 mg is a second-line alternative but requires an 8-hour driving restriction due to CNS effects 4

The American Headache Society recommends strictly limiting all acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication overuse headache 3, 4
If the patient requires acute treatment more than twice weekly, preventive therapy must be initiated or optimized immediately 4

In individuals with non‑alcoholic fatty liver disease (NAFLD) who have not progressed to cirrhosis, ketorolac is generally safe and does not necessitate dose modification, supporting its use for acute headache management in this population 5.