What is the optimal preventive management for chronic migraine in an adult without contraindicating comorbidities?

Optimal Preventive Management for Chronic Migraine

For chronic migraine prevention in adults without contraindications, initiate topiramate 50-100 mg/day as first-line therapy, escalating to onabotulinumtoxinA or CGRP monoclonal antibodies only after topiramate failure or intolerance. 1, 2

First-Line Therapy: Topiramate

Topiramate is the only oral preventive agent with robust randomized controlled trial evidence specifically confirming efficacy in chronic migraine. 1, 2

• Start with 25 mg daily and titrate slowly to target dose of 50-100 mg/day (typically 50 mg twice daily) 1
• Allow an adequate trial period of 2-3 months before assessing efficacy 1
• Topiramate offers the additional advantage of substantially lower cost compared to onabotulinumtoxinA and CGRP monoclonal antibodies 1
• For patients with comorbid obesity, topiramate is particularly beneficial due to associated weight loss 1, 2

Alternative First-Line Option Based on Comorbidities

• If comorbid depression, anxiety, or sleep disturbances are present, consider amitriptyline 30-150 mg/day instead 1, 2
• However, amitriptyline lacks robust RCT evidence specifically for chronic migraine prophylaxis; its efficacy is mainly demonstrated in episodic migraine 1
• Start low and titrate slowly, taking at bedtime to leverage sedating properties 1

Second-Line Therapy: OnabotulinumtoxinA (Botox)

OnabotulinumtoxinA is the only FDA-approved therapy specifically for chronic migraine prophylaxis (defined as 15+ headache days per month, each lasting 4+ hours). 2, 3

• Requires specialist administration following a specific injection protocol 2
• Patients should receive at least 2-3 treatment cycles before being classified as non-responders 2
• Proven to reduce headache days, episodes, severity, and improve quality of life in chronic migraine 2

Third-Line Therapy: CGRP Monoclonal Antibodies

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be reserved for patients who have failed at least 2-3 oral preventive medications. 1, 2

• Administered monthly via subcutaneous injection (or quarterly for fremanezumab) 1, 4
• Fremanezumab dosing: 225 mg monthly or 675 mg every 3 months 4
• Eptinezumab is administered intravenously 5
• Efficacy assessment requires 3-6 months before determining response 1
• Annualized cost is significantly higher at $5,000-$6,000 1
• Strong evidence for prevention of both episodic and chronic migraine 1, 6

Critical Management of Medication Overuse Headache (MOH)

Before establishing any preventive treatment, rule out medication overuse headache, which frequently mimics chronic migraine. 2

• MOH is defined as using acute medications ≥10 days/month for triptans or ≥15 days/month for NSAIDs 1
• Management requires explanation and withdrawal of overused medication; abrupt withdrawal is preferred except for opioids 2
• Limit acute medication use to no more than twice weekly to prevent MOH 1, 2

Acute Treatment Strategy

• First-line acute treatment: NSAIDs (aspirin 650-1000 mg, ibuprofen 400-800 mg, or naproxen sodium 275-550 mg) 2
• Second-line acute treatment: Triptans (naratriptan, rizatriptan, zolmitriptan, or sumatriptan) when NSAIDs fail 2
• Triptans are most effective when taken early while headache is still mild 2
• Avoid acetaminophen alone due to lack of efficacy 2

Treatment Algorithm

1. Confirm chronic migraine diagnosis (15+ headache days/month for >3 months) 2
2. Rule out and address medication overuse headache if present 2
3. Initiate topiramate with gradual titration to 100 mg/day (or amitriptyline if depression/anxiety/sleep disturbance present) 1, 2
4. Evaluate response after 2-3 months 1, 2
5. If topiramate fails or is not tolerated, escalate to onabotulinumtoxinA 2
6. If onabotulinumtoxinA fails, escalate to CGRP monoclonal antibodies 1, 2
7. Provide appropriate acute medications with strict frequency limits (≤2 days/week) 1, 2

Addressing Comorbidities

Chronic migraine is commonly associated with anxiety, depression, sleep disturbances, obesity, and chronic pain conditions—all of which must be identified and treated. 2

• Obesity is an important risk factor for transformation from episodic to chronic migraine 2
• Weight loss can reduce migraine frequency in patients with obesity 2
• Screen and treat obstructive sleep apnea to reduce migraine frequency 2
• Comorbidity management is essential as their alleviation can improve treatment outcomes 2

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training should be offered alongside medication 1
• Identify and modify triggers: sleep hygiene, regular meals, hydration, stress management 1
• Neuromodulatory devices (external trigeminal nerve stimulation, single-pulse transcranial magnetic stimulation) have modest evidence for preventive use 1, 7

Common Pitfalls to Avoid

• Do not use amitriptyline as first-line for chronic migraine without comorbid depression/anxiety/sleep disturbance—topiramate has stronger evidence 1
• Do not fail to recognize medication overuse headache before starting preventive therapy 1, 2
• Do not allow unlimited acute medication use—strict limitation to twice weekly is essential 2
• Do not assess efficacy before adequate trial period (2-3 months for oral agents, 3-6 months for CGRP antibodies) 1, 2
• Do not start with too high a dose, leading to poor tolerability and discontinuation 1
• Beta blockers, candesartan, and amitriptyline lack robust RCT data specifically for chronic migraine, though commonly used in clinical practice 2

Duration and Discontinuation

• After 6-12 months of successful therapy, consider pausing preventive treatment to determine if it can be discontinued 1
• Calculate percentage reduction in monthly migraine days as a useful measure to quantify success 1