Medications to Prevent Migraines
For first-line migraine prophylaxis in adults, use propranolol (80-240 mg/day), metoprolol (50-200 mg/day), topiramate (50-100 mg/day), or valproate (500-1500 mg/day), prioritizing based on cost and tolerability, before considering CGRP monoclonal antibodies or gepants. 1
First-Line Preventive Medications
The most recent and highest-quality evidence from the 2025 American College of Physicians guideline establishes a clear hierarchy based on comparable efficacy but vastly different costs 1:
Recommended Initial Options (in order of preference):
- Beta-blockers: Propranolol (80-240 mg/day) or metoprolol (50-200 mg/day) 2, 3, 1
- Anticonvulsants: Valproate/divalproex sodium (500-1500 mg/day) 2, 1
- Antidepressants: Venlafaxine (SNRI) or amitriptyline (30-150 mg/day) 2, 1
These medications reduce migraine days per month by approximately 1.2-1.4 days compared to placebo 4. The 2025 ACP guideline explicitly recommends trying these less expensive options before CGRP-targeted therapies due to similar net benefits but substantially lower costs 1.
When to Escalate to CGRP-Targeted Therapies:
Use CGRP monoclonal antibodies (erenumab 70-140 mg monthly, fremanezumab 225 mg monthly, galcanezumab, or eptinezumab) or gepants (atogepant, rimegepant) only after inadequate response or intolerance to first-line agents 1, 5.
CGRP therapies reduce migraine days by 1.0-3.8 days per month and are particularly well-tolerated 4, but cost considerations make them second-line unless first-line options fail 1.
Topiramate as Third-Line:
Consider topiramate (50-100 mg/day) only after trials of beta-blockers, valproate, venlafaxine, or amitriptyline AND CGRP therapies have failed 1. While effective (reducing migraine days by 1.4/month 4), topiramate has higher adverse event rates including cognitive impairment, paresthesias, and weight loss 3.
When to Initiate Prophylaxis
Start preventive medication when patients have:
- ≥2 migraine attacks per month causing ≥3 days of disability 2
- Using acute medications >2 times per week 2, 6
- Contraindications or failure of acute treatments 2
- Severe debilitating attacks despite adequate acute treatment 1
Special Populations
Chronic Migraine (≥15 headache days/month):
First-line options include topiramate, onabotulinumtoxinA (155-195 units every 12 weeks to 31-39 sites), or CGRP monoclonal antibodies 3, 5. OnabotulinumtoxinA has strong evidence specifically for chronic migraine 5, 7.
Pregnancy:
Propranolol is the preferred preventive during pregnancy, with amitriptyline as second-line under specialist supervision 3. Avoid topiramate, candesartan, and absolutely contraindicate valproate due to teratogenicity 3.
Children and Adolescents:
Discuss with families that placebo was as effective as medications in many pediatric trials 8. If medication is chosen, consider amitriptyline combined with cognitive behavioral therapy, topiramate, or propranolol 8.
Patients with Comorbidities:
- Hypertension: Candesartan (16-32 mg/day) or beta-blockers 3, 5
- Depression/anxiety: Amitriptyline or venlafaxine 2
- Obesity: Topiramate (causes weight loss) 3
- Mixed migraine and tension-type headache: Amitriptyline superior to propranolol 2
Dosing Strategy and Monitoring
Start low and titrate slowly to minimize adverse effects 3. Initiate at the lowest effective dose and increase gradually until benefits achieved without intolerable side effects 2.
Assess treatment response at 2-3 months after initiation or dose change 3. Key outcomes: attack frequency, severity, and migraine-related disability 3.
Trial duration: Adequate trial requires sufficient time at therapeutic dose—clinical benefit may not appear immediately 2.
Common Pitfalls to Avoid
Medication overuse: Educate patients that using acute medications >2 days/week increases risk of medication overuse headache 5
Premature discontinuation: Improvement occurs gradually; emphasize adherence as effects may take weeks 1
Valproate in women of childbearing potential: Absolutely contraindicated due to teratogenicity 3, 5. Ensure effective contraception and folate supplementation if topiramate used 8
Ignoring cost: CGRP therapies and gepants cost substantially more than traditional preventives with similar efficacy 1
Beta-blocker contraindications: Avoid in asthma, cardiac failure, Raynaud disease, AV block, and depression 3
Duration of Treatment
Consider tapering after sustained improvement over 3-6 months in episodic migraine or 6-12 months in chronic migraine 9. Reevaluate regularly (every 6-12 months) but not at excessively short intervals 3.