What is the best course of action for a 30-year-old female with a 7-month history of migraines, currently experiencing a severe and prolonged right-sided frontal and occipital migraine lasting 19 hours, worsening when laying down, and unresponsive to Tylenol (acetaminophen), ibuprofen, Nurtec (rimegepant), and Maxalt (rizatriptan)?

Immediate Emergency Department Evaluation Required

This patient requires urgent neuroimaging and emergency department evaluation immediately—this is not a typical migraine and represents a potential neurological emergency. 1

Critical Red Flags Present

This 30-year-old woman presents with multiple concerning features that distinguish this from routine migraine:

• Prolonged duration (19 hours) exceeding typical migraine attacks 1
• Worst headache of her life in the context of recent-onset migraine history (only 7 months) 1
• Positional worsening when lying down suggests increased intracranial pressure rather than typical migraine 1
• Complete treatment failure to multiple evidence-based acute therapies (NSAIDs, triptan, and gepant) 2, 1
• Recent-onset migraine pattern (7 months ago) in a 30-year-old warrants investigation for secondary causes 1

Differential Diagnosis Requiring Urgent Exclusion

Before treating this as refractory migraine, the following must be ruled out:

• Cerebral venous sinus thrombosis (positional headache, young woman, can present with migraine-like features) 1
• Idiopathic intracranial hypertension (positional worsening, young woman of childbearing age) 3
• Migrainous infarction (prolonged attack with potential cortical involvement, as documented in similar presentations) 4
• Meningitis or encephalitis (fever, neck stiffness must be assessed) 2
• Intracranial mass or structural lesion (recent-onset headaches, progressive worsening) 1

Immediate Management Steps

1. Emergency Department Workup

• Urgent brain MRI with MR venography to exclude venous sinus thrombosis and structural lesions 1
• Lumbar puncture if imaging is negative and suspicion remains high for increased intracranial pressure or infection 3
• Complete neurological examination documenting any focal deficits 4

2. Acute Treatment in ED Setting (After Excluding Emergencies)

First-line IV combination therapy:

• Metoclopramide 10 mg IV for direct analgesic effects through dopamine receptor antagonism 1, 5
• Ketorolac 30 mg IV for rapid-onset analgesia with 6-hour duration 1, 5

This combination provides superior efficacy compared to either agent alone and represents the most evidence-based approach for severe, refractory migraine in the emergency setting. 1

Alternative if first-line fails:

• Prochlorperazine 10 mg IV has comparable efficacy to metoclopramide with a favorable side effect profile 1, 5
• Dihydroergotamine (DHE) IV or intranasal has good evidence for refractory attacks 2, 5

3. Avoid These Medications

• Do NOT use opioids (hydromorphone, morphine, oxycodone) as they lead to medication-overuse headache, dependency, and rebound headaches with questionable efficacy 1, 6
• Avoid butalbital-containing compounds (like Fioricet/Esgic) which perpetuate medication-overuse headache 6

Critical Pitfall to Avoid

The most dangerous error would be attributing this presentation to "just a bad migraine" without neuroimaging. The combination of recent-onset migraines, worst-ever headache, prolonged duration, positional component, and complete treatment failure mandates exclusion of secondary causes before proceeding with migraine-specific therapy. 1 Young women with new-onset headaches and atypical features have documented cases of serious underlying pathology including cortical laminar necrosis from migrainous infarction. 4

Post-Acute Management (After Emergency Causes Excluded)

Preventive Therapy Indication

This patient meets criteria for preventive therapy: 2

• Two or more attacks per month producing disability lasting 3+ days 2
• Failure of acute treatments (has tried multiple evidence-based options) 2
• Risk of medication overuse (using acute medications frequently) 2, 6

First-line preventive options with strongest evidence:

• Propranolol 80-240 mg/day 2, 1
• Topiramate 50-200 mg/day 1
• Amitriptyline 30-150 mg/day 2
• Divalproex sodium 500-1500 mg/day 2

Medication-Overuse Headache Prevention

• Limit all acute medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache 1, 6
• Initiate preventive therapy immediately to reduce attack frequency and restore responsiveness to acute treatments 1, 7

Bottom Line

Send this patient to the emergency department now for urgent neuroimaging before attempting further acute migraine treatment. The clinical presentation has too many red flags to manage in an outpatient setting. Once secondary causes are excluded, proceed with IV metoclopramide plus ketorolac as the most evidence-based acute treatment, followed by initiation of preventive therapy to break the cycle of frequent attacks. 1