What are the recommended treatments for migraine prophylaxis?

Migraine Prophylaxis

For migraine prophylaxis, start with beta-blockers (propranolol 80-240 mg/day, metoprolol, atenolol, or bisoprolol), topiramate (target 100 mg/day), or candesartan as first-line agents, reserving CGRP monoclonal antibodies for patients who fail or cannot tolerate these initial options. 1, 2

Indications for Starting Preventive Therapy

Initiate prophylactic treatment when patients meet any of these criteria:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 1, 2
• Using abortive medications more than twice per week (risk of medication overuse headache) 1, 2
• Contraindication to or failure of acute treatments 1, 2
• Uncommon migraine conditions including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction 1

First-Line Medications

Beta-Blockers

• Propranolol 80-240 mg/day or timolol 20-30 mg/day have the strongest evidence for efficacy 1, 2, 3
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol (use only those without intrinsic sympathomimetic activity) 4, 1
• Particularly useful for patients with comorbid hypertension or anxiety 1

Topiramate

• Target dose is 100 mg/day (typically 50 mg twice daily) 1, 5, 6
• Start at 25 mg/day and titrate by 25 mg weekly to minimize side effects 5, 7
• The 100 mg/day dose provides optimal balance between efficacy and tolerability; 200 mg/day shows no additional benefit but significantly more adverse effects 6, 8
• Reduces migraine frequency by approximately 3.5 days per month compared to placebo 5
• Particularly valuable for patients concerned about weight gain or who are overweight, as it causes weight loss rather than gain 9, 6
• Effective even in chronic migraine with medication overuse 5

Candesartan

• Recommended as first-line, especially useful for patients with comorbid hypertension 4, 1

Second-Line Medications

Use these when first-line agents fail or are contraindicated:

• Amitriptyline 30-150 mg/day - particularly effective for patients with mixed migraine and tension-type headache 1, 2
• Flunarizine - effective where available 4, 1
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day - strictly contraindicated in women of childbearing potential due to teratogenic effects 4, 1, 2

Third-Line Medications: CGRP Monoclonal Antibodies

Reserve for patients who have failed or cannot tolerate first- and second-line options:

• Erenumab, fremanezumab, galcanezumab, or eptinezumab 4, 1
• In Europe, regulatory restrictions limit use to patients in whom other preventive drugs have failed or are contraindicated 4
• Require 3-6 months of treatment before assessing efficacy (longer than traditional preventives) 1

Implementation Strategy

Dosing Principles

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 1, 2
• Allow an adequate trial period of 2-3 months before determining efficacy for traditional preventives 1, 2
• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 1, 2

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1
• Quantify success by calculating the percentage reduction in monthly migraine days 1

Common Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications (≥2 times per week), which interferes with preventive treatment efficacy 1, 2
• Inadequate trial duration (less than 2-3 months) before declaring treatment failure 1, 2
• Starting with too high a dose, leading to poor tolerability and discontinuation 1
• Using valproate in women of childbearing potential - this is an absolute contraindication 4, 1, 2

Topiramate-Specific Considerations

Common Side Effects

• Paresthesia (53% of patients) - most common but rarely causes discontinuation 5, 6
• Cognitive problems - less frequent than paresthesia but more troublesome; manage by slow titration in small increments 9
• Weight loss, decreased appetite, nausea, fatigue, taste perversion 5, 6

Serious Risks

• Metabolic acidosis and renal stones (carbonic anhydrase inhibitor effect) - counsel all patients to maintain hydration 9
• First-trimester exposure associated with cleft lip/palate (Pregnancy Category D) 9
• Acute angle-closure glaucoma - evaluate promptly if sudden onset of blurred vision, visual disturbances, or ocular pain occurs 9

Formulation Considerations

• Extended-release formulations (Qudexy XR, Trokendi XR) provide once-daily dosing with more stable plasma concentrations and potentially fewer cognitive effects compared to immediate-release twice-daily dosing 9

Non-Pharmacological Options

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

• Neuromodulatory devices 4, 1
• Biobehavioral therapy 4, 1
• Acupuncture (though not superior to sham acupuncture in controlled trials) 4, 1
• Limited or no evidence exists for physical therapy, spinal manipulation, dietary approaches, melatonin, magnesium, or riboflavin 4