What is the treatment for intractable migraine?

Treatment of Intractable Migraine

For intractable migraine, immediately initiate preventive therapy with a first-line agent (propranolol, topiramate, or candesartan) while optimizing acute treatment with combination triptan plus NSAID therapy, strictly limiting all acute medications to no more than 2 days per week to prevent medication-overuse headache. 1

Definition and Assessment

Intractable migraine typically refers to patients experiencing two or more attacks per month producing disability for 3+ days, or those requiring acute medications more than twice weekly. 1

Critical first step: Rule out medication-overuse headache (MOH) before escalating therapy, which occurs when acute medications are used ≥10 days/month for triptans or ≥15 days/month for NSAIDs. 1 MOH creates a vicious cycle where increasing medication use paradoxically worsens headache frequency, potentially leading to daily headaches. 1

Acute Treatment Optimization

While initiating preventive therapy, optimize acute treatment strategy:

• Use combination therapy with triptan plus NSAID (e.g., sumatriptan 50-100 mg PLUS naproxen sodium 500 mg), which provides superior efficacy compared to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours. 1

• Take medication early in the attack while pain is still mild for maximum effectiveness. 1

• For rapid progression or severe nausea/vomiting: Use subcutaneous sumatriptan 6 mg, which provides the highest efficacy with onset within 15 minutes and pain relief in 70-82% of patients. 1

• For emergency department or urgent care presentation: Use IV metoclopramide 10 mg plus IV ketorolac 30 mg as first-line combination therapy. 1

Absolute frequency limit: Restrict ALL acute migraine medications to no more than 2 days per week to prevent MOH. 1 This is non-negotiable—patients exceeding this threshold must transition to preventive therapy immediately.

Preventive Therapy: First-Line Options

Initiate preventive therapy immediately for intractable migraine with the goal of reducing attack frequency by ≥50% and restoring responsiveness to acute treatments. 1

Beta-Blockers (Preferred for Most Patients)

• Propranolol 80-240 mg/day is the most strongly evidence-based first-line preventive medication. 1, 2
• Alternative beta-blockers include timolol 20-30 mg/day, metoprolol, atenolol, or bisoprolol. 1, 2
• Contraindications: Asthma, heart block, severe peripheral vascular disease. 2

Topiramate (Preferred for Patients with Obesity or Post-Concussive Migraine)

• Start at 25 mg daily and titrate slowly by 25 mg weekly to minimize side effects, targeting 50-100 mg daily (typically 50 mg twice daily). 1, 3
• Advantages: Weight loss, effective for post-concussive migraine. 3
• Common side effects: Cognitive slowing, paresthesias, kidney stones. 2

Candesartan (Preferred for Patients with Hypertension)

• Candesartan is particularly useful for patients with comorbid hypertension. 1, 2
• Provides dual benefit for both migraine prevention and blood pressure control. 2

Preventive Therapy: Second-Line Options

If first-line agents fail after adequate trial (2-3 months) or are contraindicated:

• Amitriptyline 30-150 mg/day (start at 10-25 mg at bedtime and titrate slowly), particularly effective for patients with mixed migraine and tension-type headache or comorbid insomnia/depression. 1, 2

• Divalproex sodium 500-1500 mg/day or valproate 800-1500 mg/day are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects. 1, 2

Preventive Therapy: Third-Line Options

When first- and second-line agents have failed or are contraindicated:

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, or eptinezumab) should be considered, with efficacy assessed after 3-6 months. 1, 2

• OnabotulinumtoxinA is recommended ONLY for chronic migraine (≥15 headache days per month), not for episodic migraine, and is specifically recommended against for episodic migraine prevention. 2, 4

Implementation Strategy

• Start with low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases. 2

• Allow adequate trial period of 2-3 months before determining efficacy for oral agents; 3-6 months for CGRP monoclonal antibodies; 6-9 months for onabotulinumtoxinA. 1, 2

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects. 2

• Consider tapering or discontinuing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued. 2

Non-Pharmacological Adjuncts

Consider as adjuncts to medication or stand-alone treatments when medications are contraindicated:

• Neuromodulatory devices 1, 2
• Biobehavioral therapy (biofeedback, relaxation training, cognitive-behavioral therapy) 1, 2
• Acupuncture 1, 2

Critical Pitfalls to Avoid

• Failing to recognize MOH from frequent acute medication use—this is the most common reason for treatment failure. 1

• Inadequate duration of preventive trial (less than 2-3 months)—patients and providers often abandon effective treatments prematurely. 2

• Starting with too high a dose—this leads to poor tolerability and discontinuation; always start low and titrate slowly. 2

• Allowing patients to increase frequency of acute medication use in response to treatment failure—this creates the vicious cycle of MOH; instead, transition to preventive therapy while maintaining strict frequency limits. 1

• Not addressing comorbidities that influence treatment selection (e.g., avoiding valproate in women of childbearing potential, choosing beta-blockers for patients with hypertension). 2