What is the best course of action for a 30-year-old female with a 7-month history of headaches, currently experiencing a severe episode lasting 4 days that is resistant to oral and intravenous (IV) medications, with normal computed tomography (CT) scan and laboratory results?

Management of Refractory Migraine with Normal Imaging

This patient requires hospital admission for status migrainosus with aggressive intravenous therapy using metoclopramide 10 mg IV plus ketorolac 30 mg IV, followed by immediate initiation of preventive therapy given the 7-month history and current treatment failure. 1, 2

Immediate Assessment and Red Flag Exclusion

While the CT is normal, this 30-year-old female with a 4-day severe headache episode requires careful evaluation for secondary causes before proceeding with aggressive migraine treatment:

• Rule out subarachnoid hemorrhage (SAH): A normal CT does not exclude SAH if performed >6 hours from symptom onset or if the patient has new neurological deficits—lumbar puncture should be performed if clinical suspicion remains high 3
• Exclude preeclampsia/eclampsia: Any new headache in a woman of childbearing age with hypertension requires urgent evaluation for preeclampsia 4
• Assess for meningitis: Fever, neck stiffness, or altered mental status mandate CSF examination 5, 6

Acute Treatment Strategy for Status Migrainosus

This 4-day episode resistant to oral and IV medications meets criteria for status migrainosus (migraine lasting >72 hours). The treatment approach differs from typical acute migraine:

First-Line IV Combination Therapy

• Metoclopramide 10 mg IV provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic properties 1, 2
• Ketorolac 30 mg IV (or 60 mg IM if <65 years old) offers rapid onset with 6-hour duration and minimal rebound headache risk 1, 2
• This combination is superior to either agent alone and represents the most evidence-based IV approach for severe refractory migraine 2

Alternative IV Options if First-Line Fails

• Prochlorperazine 10 mg IV has comparable efficacy to metoclopramide with a more favorable side effect profile (21% vs 50% adverse events) 2
• Dihydroergotamine (DHE) IV or intranasal has good evidence for efficacy as monotherapy for acute migraine attacks 1, 2
• Corticosteroids (dexamethasone or prednisone) should be reserved for status migrainosus after other options have failed 4

Critical Medications to Avoid

• Opioids and butalbital-containing compounds should be absolutely avoided—they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 4, 1, 2
• Diphenhydramine is not evidence-based for migraine treatment and should not be included in the "migraine cocktail" 2

Transition to Preventive Therapy

This patient clearly requires preventive therapy given the 7-month history and current treatment failure. The indications are met multiple times over:

Indications for Prevention (All Present in This Case)

• Two or more attacks per month producing disability lasting 3+ days 2
• Failure of acute treatments (demonstrated by 4-day refractory episode) 2
• Use of abortive medication more than twice per week (implied by 7-month history) 2

First-Line Preventive Options

• Propranolol 80-240 mg/day has the most consistent evidence for efficacy and should be the first choice 2
• Topiramate or divalproex sodium are alternatives, though they carry risks of weight gain, hair loss, tremor, and are teratogenic (critical consideration in a 30-year-old female) 2
• Amitriptyline 30-150 mg/day is particularly useful if there is a mixed migraine and tension-type headache pattern 2

Newer Preventive Options

• CGRP monoclonal antibodies should be considered when oral preventives have failed or are contraindicated, with efficacy assessed after 3-6 months 2

Medication Overuse Headache Consideration

Before escalating therapy, assess for medication overuse headache (MOH):

• MOH occurs with acute medication use ≥10 days/month for triptans or ≥15 days/month for NSAIDs/acetaminophen 1, 2
• If MOH is present, the cycle must be broken by withdrawing the overused medication while simultaneously initiating preventive therapy 2
• Do not allow increased frequency of acute medication use in response to treatment failure—this creates a vicious cycle 2

Outpatient Acute Treatment Optimization for Future Episodes

Once the current episode is controlled, optimize the acute treatment strategy:

Mild to Moderate Attacks

• NSAIDs alone: Ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg 1
• Acetaminophen 1000 mg is an alternative 1

Moderate to Severe Attacks

• Combination therapy: Triptan + NSAID is superior to either agent alone 1, 2
• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg provides 130 more patients per 1000 achieving sustained pain relief at 48 hours 2
• Take medication early in the attack while pain is still mild for maximum effectiveness 2

If Triptans Fail or Are Contraindicated

• Gepants (ubrogepant 50-100 mg or rimegepant) are the primary alternative—they have no vasoconstriction and are safe in cardiovascular disease 2
• Lasmiditan 50-200 mg is a second-line alternative but requires an 8-hour driving restriction due to CNS effects 2

Critical Frequency Limitation

Strictly limit all acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication overuse headache. 1, 2 If the patient requires acute treatment more than twice weekly, preventive therapy must be initiated or optimized immediately 2

Disposition and Follow-Up

Hospital Admission Considerations

• This patient with a 4-day refractory episode may benefit from hospitalization, which has been shown to significantly increase responder rates (68% at 6 months vs 12% for outpatient management) and reduce attack frequency and duration 7
• Hospitalization interrupts emotional stress mechanisms that provoke headache attacks and allows for intensive IV therapy 7

Mandatory Headache Specialist Referral

• Referral to a Headache Center should be an integral part of the ED approach—lack of this referral involves a high rate of relapse and new ED visits 8
• The patient requires ongoing management of preventive therapy, which takes 2-3 months for oral agents to show efficacy 2

Common Pitfalls to Avoid

• Do not rely solely on opioids or butalbital compounds—these worsen outcomes and create dependency 4, 1, 2
• Do not delay preventive therapy—this patient has already suffered for 7 months and clearly meets criteria 2
• Do not ignore medication overuse headache—assess frequency of acute medication use before escalating therapy 1, 2
• Do not use traditional "migraine cocktail" components indiscriminately—the evidence supports specific combinations (metoclopramide + ketorolac), not random polypharmacy 2