What medications treat chronic migraine?

Chronic Migraine Treatment

For chronic migraine (≥15 headache days per month with ≥8 migraine days), initiate preventive therapy with topiramate 100 mg/day or onabotulinumtoxinA 155-195 units every 12 weeks, as these are the only medications with proven efficacy in large-scale placebo-controlled trials specifically for chronic migraine. 1, 2

Defining Chronic Migraine

• Chronic migraine requires headache on ≥15 days per month, with ≥8 days meeting migraine criteria, for at least 3 months, not attributable to medication overuse or other causes 2
• This condition affects 1-3% of the population and produces 4-6 times more disability than episodic migraine 2

First-Line Preventive Medications

Topiramate:

• Target dose is 100 mg/day (50 mg twice daily), which reduces monthly migraine days by approximately 3.5 days compared to placebo 1, 3
• Titrate slowly at 25 mg weekly increments to minimize adverse effects, with dosing flexibility from 50-200 mg/day based on tolerability 1, 4
• The 100 mg/day dose provides optimal balance of efficacy and tolerability; 50 mg/day shows suboptimal efficacy while 200 mg/day causes significantly more adverse effects 3
• Most common adverse effects are paresthesia (51% at 100 mg/day), fatigue (5%), nausea (2%), and cognitive difficulties (2%), occurring predominantly during titration 4, 3
• Particularly beneficial in obese patients due to associated weight loss 5, 6
• Assess efficacy after 2-3 months at therapeutic dose 7

OnabotulinumtoxinA:

• Dose is 155-195 units injected into 31-39 sites every 12 weeks 7
• Proven effective in large-scale placebo-controlled trials specifically for chronic migraine 2
• Assess efficacy after 6-9 months of treatment 7

Second-Line Preventive Options

Beta-blockers:

• Propranolol 80-240 mg/day or metoprolol are effective, particularly in patients with comorbid hypertension 5, 7
• Timolol 20-30 mg/day is also first-line for episodic migraine prevention 5

Tricyclic Antidepressants:

• Amitriptyline 30-150 mg/day at bedtime is the preferred choice when comorbid anxiety, depression, or insomnia are present 5, 6
• Nortriptyline is an alternative with fewer anticholinergic effects 7

Anticonvulsants:

• Divalproex sodium/sodium valproate are first-line options but carry risks of weight gain, hair loss, tremor, and are absolutely contraindicated in women of childbearing potential due to teratogenicity 5, 7

Third-Line Options for Refractory Cases

CGRP Monoclonal Antibodies:

• Erenumab 70-140 mg subcutaneous monthly, fremanezumab 225 mg monthly or 675 mg quarterly, galcanezumab, or eptinezumab 100-300 mg IV quarterly 5, 7
• Reserved for patients who have failed first- and second-line preventive medications 7
• Assess efficacy after 3-6 months 7

Critical Management Principles

Medication Overuse Headache Prevention:

• Strictly limit all acute migraine medications to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 5, 1
• Most chronic migraine patients (78%) meet criteria for acute medication overuse at baseline, which must be addressed 1
• Detoxification therapy is required when medication overuse is present 2

Acute Treatment During Preventive Therapy:

• Continue optimized acute treatment with combination therapy: triptan (sumatriptan 50-100 mg) plus NSAID (naproxen 500 mg) for moderate-to-severe attacks 5
• For severe attacks requiring IV treatment: metoclopramide 10 mg IV plus ketorolac 30 mg IV 5
• NSAIDs alone (ibuprofen 400-800 mg, naproxen 500-825 mg) for mild-to-moderate attacks 5

Treatment Duration and Assessment

• Continue preventive therapy for 6-12 months of successful control before considering discontinuation 7
• Failure of one preventive medication class does not predict failure of others 7
• Set realistic expectations that efficacy requires weeks to months to establish; do not abandon treatment prematurely 7

Common Pitfalls to Avoid

• Do not allow patients to increase acute medication frequency in response to inadequate prevention—this creates a vicious cycle of medication-overuse headache 5
• Avoid opioids and barbiturates due to dependency risk, rebound headaches, and questionable efficacy 5, 7
• Do not use valproate in women of childbearing potential due to severe teratogenic risk 5, 7