What medications are recommended for patients experiencing more than 15 migraines per month?

Medications for Chronic Migraine (≥15 Headaches per Month)

For patients with more than 15 migraines per month (chronic migraine), initiate preventive therapy with CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) as first-line treatment, given their strong evidence base and favorable tolerability profile. 1

First-Line Preventive Medications

CGRP Monoclonal Antibodies (Strongest Evidence)

• Erenumab, fremanezumab, and galcanezumab have "strong for" recommendations for chronic migraine prevention based on network meta-analysis of 6,979 patients demonstrating significant reductions in monthly migraine days and acute medication use 1
• These agents reduce migraine headache days by approximately 2-4.8 days per month compared to baseline 1, 2
• Galcanezumab specifically reduced monthly migraine headache days by 4.8 days (vs. 2.7 for placebo) in chronic migraine patients over 3 months 2
• Administered as monthly subcutaneous injections with minimal systemic side effects 1
• Critical caveat: Erenumab carries postmarketing warnings for development or worsening of hypertension—monitor blood pressure 1

OnabotulinumtoxinA

• FDA-approved specifically for chronic migraine (≥15 headache days/month) 3
• Administered as injections every 12 weeks 3
• Particularly useful when CGRP antibodies are contraindicated or ineffective 3

Second-Line Preventive Options

Topiramate

• "Weak for" recommendation for both episodic and chronic migraine 1
• Only traditional preventive medication with randomized placebo-controlled trial evidence specifically in chronic migraine patients 1
• Start at 25 mg daily, titrate slowly to 100-200 mg daily in divided doses 1
• Common side effects include cognitive slowing, paresthesias, weight loss, and kidney stones 1

Atogepant (Oral Gepant)

• "Weak for" recommendation for episodic migraine prevention 1
• Meta-analysis of 2,466 patients showed statistically significant reductions in monthly migraine and headache days 1
• Oral administration may improve adherence compared to injectable therapies 1

Third-Line Options (Limited Evidence in Chronic Migraine)

The following medications have evidence primarily in episodic migraine but are commonly used off-label for chronic migraine 1:

• Beta-blockers: Propranolol (80-240 mg/d), timolol (20-30 mg/d), metoprolol 1
• Tricyclic antidepressants: Amitriptyline (30-150 mg/d at bedtime) 1
• Other antiepileptics: Divalproex sodium 1
• ACE inhibitors/ARBs: Lisinopril, candesartan 4

Critical Management Considerations

Medication Overuse Headache Screening

• Assess for medication overuse before initiating preventive therapy: triptans/ergots/combination analgesics ≥10 days/month for ≥3 months, or simple analgesics ≥15 days/month for ≥3 months 3
• Medication overuse perpetuates chronic migraine and reduces preventive therapy effectiveness 3

Treatment Initiation Strategy

• Start preventive medications at low doses and titrate slowly over 2-3 months to assess clinical benefit while minimizing adverse effects 1, 4
• Do not abandon therapy prematurely—full benefit may take 2-3 months to manifest 1
• Limit acute medication use to ≤2 days per week to prevent medication overuse headache 5

Acute Treatment Considerations

• Continue appropriate acute therapy alongside preventive treatment 1
• First-line acute treatment: NSAIDs (ibuprofen 400-800 mg, naproxen sodium) for mild-moderate attacks 5
• Triptans for moderate-severe attacks (sumatriptan 50-100 mg orally or 6 mg subcutaneously) 5
• Add antiemetics (metoclopramide 10 mg or prochlorperazine 10-25 mg) when nausea is prominent 5
• Avoid opioids and butalbital—these worsen medication overuse headache risk 5

When to Refer to Specialist

Refer patients with chronic migraine (≥15 headache days/month) to neurology or headache specialist for 1, 3:

• Failure of first-line preventive therapy
• Diagnostic uncertainty
• Medication overuse headache requiring detoxification
• Consideration of advanced therapies (CGRP antibodies, onabotulinumtoxinA)

Common Pitfalls to Avoid

• Do not wait for an arbitrary threshold before initiating prevention—focus on functional impairment and treatment response 3
• Do not withhold preventive therapy from patients with significant disability even if they have fewer than 15 headache days per month 3
• Do not use preventive medications designed for episodic migraine without recognizing limited evidence in chronic migraine—only topiramate has specific chronic migraine trial data among traditional agents 1
• Do not forget to address lifestyle triggers: sleep hygiene, hydration, regular meals, stress management 5