What can be prescribed for a patient with intractable migraine?

Treatment for Intractable Migraine

For intractable migraine, initiate or optimize preventive therapy immediately with first-line agents (propranolol 80-240 mg/day, timolol 20-30 mg/day, topiramate 50-100 mg/day, or candesartan), while simultaneously treating acute attacks with IV metoclopramide 10 mg plus IV ketorolac 30 mg, limiting acute therapy to no more than twice weekly to prevent medication-overuse headache. 1

Defining Intractable Migraine and Indications for Preventive Therapy

Intractable migraine warrants preventive therapy when patients experience: 2

• Two or more migraine attacks per month producing disability lasting 3 or more days
• Use of rescue medication more than twice per week (this pattern creates medication-overuse headache and worsening frequency) 2, 1
• Failure of acute treatments or contraindications to such treatments
• Uncommon migraine conditions such as prolonged aura, migrainous infarction, or hemiplegic migraine 2

The critical pitfall is allowing patients to increase acute medication frequency in response to treatment failure—this creates a vicious cycle of medication-overuse headache. Instead, transition immediately to preventive therapy. 1

First-Line Preventive Medications

Beta-blockers are the primary first-line option: 2, 3

• Propranolol 80-240 mg/day has the strongest evidence for efficacy 2, 3
• Timolol 20-30 mg/day is equally effective 2, 3
• Common adverse effects (dizziness, nausea, fatigue, depression, insomnia) are generally well-tolerated 2
• Contraindicated in patients with asthma, heart block, or those who practice competitive sports 1

Topiramate 50-100 mg/day (typically 50 mg twice daily): 3, 4

• Particularly effective for chronic migraine, reducing migraine days by 3.5 days per month compared to placebo 4
• Effective even in the presence of medication overuse 4
• Most common adverse effects: paresthesia (53%), nausea (9%), dizziness (6%), fatigue (6%), anorexia (6%) 4
• Titrate slowly at 25 mg weekly to minimize side effects 4

Candesartan is highly effective, especially for patients with comorbid hypertension. 3

Second-Line Preventive Medications

Amitriptyline 30-150 mg/day: 2, 3

• Superior to propranolol for patients with mixed migraine and tension-type headache 2
• Adverse effects include weight gain, drowsiness, and anticholinergic symptoms 2

Divalproex sodium 500-1,500 mg/day or sodium valproate 800-1,500 mg/day: 2, 3

• Particularly effective for prolonged or atypical migraine aura 2
• Strictly contraindicated in women of childbearing potential due to teratogenic effects (neural tube defects) 2, 3
• Adverse effects: hair loss, tremor, weight gain 2

Implementation Strategy

Initiation protocol: 2, 3

1. Start with a low dose and increase slowly until benefits are achieved or adverse effects limit further increases
2. Allow an adequate trial of 2-3 months before determining efficacy—clinical benefits may not become apparent earlier 2, 3
3. Use headache diaries to track attack frequency, severity, duration, and treatment response 3
4. After 6-12 months of successful therapy (defined as ≥50% reduction in monthly migraine days), consider tapering to determine if treatment can be discontinued 2, 3

Acute Treatment During Preventive Therapy Initiation

While establishing preventive therapy, treat acute attacks with: 1

IV combination therapy (first-line for severe attacks):

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV provides rapid pain relief with minimal rebound headache risk 1
• Metoclopramide provides both antiemetic effects and direct analgesic effects through dopamine receptor antagonism 1
• Ketorolac has rapid onset (approximately 15 minutes) with 6-hour duration 1

Oral options for moderate attacks:

• Triptans (sumatriptan, rizatriptan, naratriptan, zolmitriptan) for moderate-to-severe attacks 1
• NSAIDs (naproxen 500-825 mg, ibuprofen 400-800 mg) for mild-to-moderate attacks 1

Critical frequency limitation: Restrict all acute medications to no more than 2 days per week to prevent medication-overuse headache. 1, 3

Third-Line Options When First- and Second-Line Fail

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab): 3

• Reserved for patients who have failed or cannot tolerate first- and second-line options
• Require 3-6 months for adequate efficacy assessment (longer than oral agents) 3

OnabotulinumtoxinA: 3

• Recommended only for chronic migraine (≥15 headache days per month), not episodic migraine
• Requires 6-9 months for adequate efficacy assessment 1

Common Pitfalls to Avoid

• Inadequate trial duration: Failing to wait 2-3 months before declaring treatment failure 2, 3
• Starting dose too high: Leading to poor tolerability and premature discontinuation 3
• Not recognizing medication-overuse headache: Frequent acute medication use (>2 days/week) interferes with preventive treatment efficacy 1, 3
• Using valproate in women of childbearing potential: Absolute contraindication due to teratogenic effects 2, 3
• Allowing continued frequent acute medication use: This perpetuates the cycle of intractable migraine 1