What is the best course of action for a patient with a severe and prolonged migraine that worsens with positional changes, is unresponsive to oral and intravenous (IV) medications, and awakens from sleep, particularly when laying down or bending over?

Severe Migraine Unresponsive to Oral and IV Medications with Positional Worsening

Critical Red Flag Assessment Required

This presentation demands immediate neuroimaging to rule out secondary headache before proceeding with migraine treatment. Headache that worsens with positional changes (laying down, bending over) and awakens from sleep raises serious concern for increased intracranial pressure from mass lesion, idiopathic intracranial hypertension, or other structural pathology rather than primary migraine 1, 2.

Red Flags Requiring Urgent Evaluation

• Positional worsening (worse when supine or bending) suggests increased intracranial pressure 1
• Awakening from sleep is atypical for migraine and concerning for secondary causes 1
• Failure to respond to both oral and IV medications suggests this may not be migraine 1, 2

If Secondary Causes Are Excluded: Refractory Migraine Management

Immediate ED Treatment for Refractory Migraine

Administer prochlorperazine 10 mg IV plus greater occipital nerve block (GONB) as the highest-level evidence-based combination for refractory migraine in the ED setting 2. This combination addresses both pharmacologic and neuromodulatory approaches with Level A evidence.

First-Line Parenteral Options (Level A/B Evidence)

• Prochlorperazine 10 mg IV is the only medication with "must offer" Level A recommendation for ED migraine treatment 2
• Greater occipital nerve block (GONB) has Level A evidence as highly likely effective for refractory migraine 2
• Dexketoprofen IV or ketorolac 30 mg IV should be offered (Level B) if not already tried 1, 2
• Metoclopramide 10 mg IV should be offered (Level B) for synergistic analgesia beyond antiemetic effects 1, 2

Alternative Parenteral Options

• Sumatriptan 6 mg SC should be offered (Level B) and provides highest efficacy among triptans with 59% complete pain relief at 2 hours 1, 2
• Supraorbital nerve block (SONB) should be offered (Level B) as alternative to GONB 2
• Chlorpromazine IV may be offered (Level C) but has higher adverse event rate (50%) compared to prochlorperazine (21%) 1, 2

What NOT to Use

• Hydromorphone IV must not be offered (Level A) as it is likely ineffective for migraine and risks medication-overuse headache 2
• Paracetamol IV may not be offered (Level C) as it is likely ineffective 2
• Avoid all opioids and butalbital-containing compounds as they lead to dependency, rebound headaches, and loss of efficacy 1, 3, 4

Transition to Preventive Therapy

Immediately initiate preventive therapy as this patient meets multiple criteria for prevention 5, 1, 6:

Indications Present

• Failure of acute treatments (contraindication criterion) 5, 1
• Likely using abortive medication more than twice weekly 5, 1
• Severe attacks producing significant disability 5, 1

First-Line Preventive Medications

• Propranolol 80-240 mg/day has consistent evidence of efficacy with Level A recommendation 5, 1, 7
• Timolol 20-30 mg/day has equivalent efficacy to propranolol 5, 7
• Topiramate 50-100 mg/day (titrate slowly) has strong evidence for prevention 1, 7, 6
• Candesartan is first-line, particularly if hypertension is present 7, 8

Implementation Strategy

• Start at low dose and titrate slowly to minimize adverse effects 1, 7, 6
• Allow adequate trial period of 2-3 months before determining efficacy 5, 1, 7
• Use headache diary to track frequency, severity, and disability 7

Critical Medication-Overuse Headache Assessment

Screen for medication-overuse headache (MOH) before escalating therapy 1, 7. MOH occurs when:

• Triptans or combination analgesics used ≥10 days/month 7
• NSAIDs or simple analgesics used ≥15 days/month 7

If MOH is present, preventive therapy becomes even more critical while strictly limiting acute medication use to no more than 2 days per week 1, 7, 3.

Escalation if First-Line Preventives Fail

If 2-3 oral preventive medications fail after adequate trials, consider CGRP monoclonal antibodies 7:

• Erenumab, fremanezumab, or galcanezumab administered monthly SC 7
• Requires 3-6 months for efficacy assessment 7
• Significantly more expensive ($5,000-$6,000 annually) but may restore responsiveness to acute treatments 7

Common Pitfalls to Avoid

• Do not allow continued frequent use of acute medications in response to treatment failure, as this creates vicious cycle of MOH 1, 7
• Do not dismiss positional worsening and sleep awakening without neuroimaging to exclude secondary causes 1, 2
• Do not use opioids as rescue therapy despite treatment failure, as they worsen long-term outcomes 1, 3, 4, 2
• Do not give up after one preventive fails - failure of one class does not predict failure of others 7