What are the recommended treatments for the prevention of migraine?

Prevention of Migraine

For adults with episodic migraine requiring preventive therapy, start with propranolol, topiramate, or amitriptyline as first-line agents, prioritizing based on cost and comorbidities, with propranolol being particularly advantageous for patients with hypertension or anxiety. 1

When to Initiate Preventive Therapy

Consider pharmacologic prevention in patients who:

• Experience severe debilitating headaches despite adequate acute treatment 1
• Use acute medications more than twice weekly (risk of medication-overuse headache) 1
• Have contraindications to or cannot tolerate acute treatments 1
• Experience significant migraine-related disability affecting quality of life 1

There are no evidence-based thresholds for initiating prevention—the decision should be based on individual disability and treatment response patterns. 1

Pre-Pharmacologic Interventions (Essential First Steps)

Before starting medications, address:

• Lifestyle modifications: Regular sleep schedule, adequate hydration, consistent meal timing, and regular physical activity 1
• Trigger identification and avoidance through headache diary use 1
• Adequacy of acute treatment: Ensure patients are using appropriate-strength medications for acute attacks 1
• Behavioral interventions: Cognitive behavioral therapy, relaxation training, or mindfulness-based treatments can reduce migraine frequency 1

First-Line Pharmacologic Options (Prioritized by Cost and Evidence)

Beta-Blockers

• Propranolol 80-240 mg/day (long-acting formulation preferred) 2, 3, 4
• Timolol (FDA-approved for migraine prevention) 4, 5
• Particularly appropriate for patients with comorbid hypertension or anxiety 2
• Contraindicated in asthma, heart failure, or significant bradycardia 2

Anticonvulsants

• Topiramate (FDA-approved, may cause weight loss but risk of cognitive effects) 4, 5, 6
• Divalproex sodium/valproate (FDA-approved but associated with more adverse effects) 4, 5, 6
• Critical warning: Both topiramate and valproate are teratogenic—discuss contraception and folate supplementation with women of childbearing potential 1

Tricyclic Antidepressants

• Amitriptyline (particularly useful with comorbid depression, anxiety, or sleep disorders) 4, 5, 7
• Use cautiously due to anticholinergic effects 6
• Enhanced efficacy when combined with cognitive behavioral therapy in children/adolescents 1

The 2025 American College of Physicians guideline emphasizes cost as a key factor when choosing among these similarly effective first-line options. 1

Second-Line Options (When First-Line Fails or Is Not Tolerated)

If first-line treatments produce inadequate response after 2-3 months or cause intolerable side effects, consider:

• ACE inhibitor: Lisinopril 1, 5
• ARBs: Candesartan or telmisartan 1, 4, 5
• SSRI: Fluoxetine 1
• Calcium channel blocker: Flunarizine 5-10 mg daily (contraindicated in Parkinsonism or depression) 2, 6

These have limited evidence from small studies with high risk of bias but may be effective alternatives. 1

Newer CGRP-Targeted Therapies

• CGRP antagonists (gepants) and CGRP monoclonal antibodies are available but significantly more expensive 1
• Reserve for patients who fail multiple first-line agents or have specific contraindications 1

Critical Implementation Principles

Dosing Strategy

• Start low and titrate slowly until desired outcomes are achieved or side effects emerge 1
• Allow adequate trial period: 2-3 months minimum before declaring treatment failure 1, 2
• Improvement occurs gradually—effects may not be apparent for several weeks 1

Monitoring and Adjustment

• Use a headache diary to track frequency, severity, and medication use 1
• Define success as ≥50% reduction in attack frequency 2
• Switch medications if inadequate response after 2-3 months or earlier if adverse events occur 1

Special Populations

Children and Adolescents:

• Discuss that placebo was as effective as studied medications in many pediatric trials 1
• Evidence supports: amitriptyline combined with cognitive behavioral therapy, topiramate, and propranolol 1
• Consider preventive therapy for frequent or disabling headaches 1

Women of Childbearing Potential:

• Discuss teratogenic risks of topiramate and valproate 1
• Advise effective contraception and folate supplementation 1
• Women with migraine with aura: Avoid combined hormonal contraceptives due to stroke risk; use progestin-only methods 8

Pregnant/Breastfeeding:

• Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation 1
• Magnesium may be particularly useful during pregnancy 6

Common Pitfalls to Avoid

• Do not declare treatment failure before 2-3 months of adequate dosing 1, 2
• Do not allow increased frequency of acute medication use in response to preventive treatment failure—this creates medication-overuse headache 9
• Do not combine topiramate and amitriptyline without trying adequate monotherapy trials first—no added benefit with increased adverse events 1
• Do not ignore medication-overuse headache as a cause of treatment failure—acute medication use >2 days/week requires intervention 1, 9

Treatment Algorithm Summary

1. Optimize lifestyle and acute treatment before starting prevention 1
2. Choose first-line agent based on cost, comorbidities, and patient preference (propranolol, topiramate, or amitriptyline) 1, 4
3. Start low, titrate slowly over 2-3 months 1
4. If inadequate response, switch to different first-line agent or move to second-line options 1
5. Periodically reevaluate the balance of benefits, harms, and costs with the patient 1