What are the recommended treatments for migraine prevention?

Migraine Prevention: Evidence-Based Recommendations

First-Line Preventive Medications

For adults with frequent migraines (≥2 attacks per month with significant disability), initiate preventive therapy with propranolol 80-240 mg/day or topiramate 100 mg/day as first-line agents, based on the most recent guideline evidence. 1

Beta-Blockers (Preferred First-Line)

• Propranolol (80-240 mg/day) is the most strongly recommended first-line agent, particularly beneficial for patients with comorbid hypertension or anxiety 1, 2
• Propranolol is FDA-approved specifically for migraine prophylaxis and has the strongest evidence base among all preventive medications 3
• Timolol (20-30 mg/day) is equally effective with consistent evidence 4, 2
• Metoprolol, atenolol, and nadolol have limited but supportive evidence as alternatives 4, 5
• Critical caveat: Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) are ineffective and should not be used 4

Anticonvulsants (First-Line with Major Restrictions)

• Topiramate (100 mg/day) is effective but strictly contraindicated in women of childbearing potential due to teratogenic effects 1
• Divalproex sodium (500-1500 mg/day) or sodium valproate (800-1500 mg/day) are effective but carry the same strict contraindication in women of childbearing potential 1, 2
• Common pitfall: Failing to counsel women about teratogenic risks and ensure effective contraception before prescribing these agents 1

Angiotensin Receptor Blockers (First-Line Alternative)

• Candesartan is an effective first-line agent, especially useful for patients with comorbid hypertension 1, 5

Second-Line Preventive Medications

Tricyclic Antidepressants

• Amitriptyline (30-150 mg/day) is the only antidepressant with consistent evidence for migraine prevention 4, 1
• Particularly useful for patients with comorbid depression, anxiety, sleep disorders, or mixed migraine/tension-type headache 4, 1
• More effective than propranolol specifically in patients with mixed migraine and tension-type headache 4
• Common side effects: drowsiness, weight gain, and anticholinergic symptoms (dry mouth, constipation, urinary retention) 4

Third-Line Options: CGRP Monoclonal Antibodies

• Consider CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) when first- and second-line treatments have failed or are contraindicated 1
• These agents require 3-6 months to assess efficacy 6

Clear Indications for Preventive Therapy

Initiate preventive therapy when patients meet any of these criteria:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 4, 1
• Use of acute medications more than twice weekly (risk of medication-overuse headache) 4, 1
• Contraindication to or failure of acute treatments 4
• Presence of uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, migrainous infarction) 4

Critical Implementation Principles

Dosing Strategy

• Start low and titrate slowly to minimize side effects and improve tolerability 1, 2
• Allow a minimum of 2-3 months at therapeutic dose before declaring treatment failure 1, 2
• For oral preventive agents, efficacy requires 2-3 months; for CGRP antibodies, 3-6 months 6

Success Criteria

• Define treatment success as ≥50% reduction in monthly migraine days 1
• Also consider improvements in attack severity, disability, and quality of life 6

Non-Pharmacologic Approaches (Adjunctive)

Behavioral Interventions

• Cognitive behavioral therapy and relaxation training are effective non-pharmacologic approaches 2, 5
• Biofeedback combined with relaxation training has good evidence for efficacy 6

Lifestyle Modifications (Essential for All Patients)

• Maintain regular sleep patterns, adequate hydration, regular physical activity, and stress management 2, 7
• Identify and avoid migraine triggers (environmental factors, dietary triggers, hormonal changes) 8
• Common pitfall: Failing to address lifestyle factors before or alongside medication therapy 8

Nutraceuticals (Evidence-Based Supplements)

• Riboflavin (vitamin B2) has efficacy in more than one randomized trial 7, 6
• Magnesium citrate is probably effective and particularly useful during pregnancy 7, 6
• Coenzyme Q10 has limited evidence but favorable safety profile 7, 6

Special Population: Women of Childbearing Potential

Absolutely avoid topiramate and valproate in women of childbearing potential unless effective contraception is ensured and folate supplementation is provided 1, 2

• Preferred options for this population: propranolol, amitriptyline, or magnesium 7

Common Pitfalls to Avoid

• Discontinuing treatment too early before therapeutic effect is achieved (minimum 2-3 months required) 1, 2
• Not starting at low doses and gradually titrating, leading to unnecessary side effects and poor adherence 1, 2
• Failing to address medication overuse, which can lead to rebound headaches and treatment failure 2
• Prescribing teratogenic medications (topiramate, valproate) to women of childbearing potential without adequate counseling and contraception 1

Algorithm for Sequential Treatment

1. First attempt: Propranolol 80-240 mg/day (or timolol 20-30 mg/day) for 2-3 months at therapeutic dose 1, 2
2. If contraindicated or ineffective: Topiramate 100 mg/day (if not childbearing potential) OR candesartan (if hypertensive) for 2-3 months 1
3. If first-line fails: Amitriptyline 30-150 mg/day, especially if comorbid tension-type headache or sleep disorder 1, 2
4. If all oral agents fail: CGRP monoclonal antibodies, assessed over 3-6 months 1, 6