First-Line Medications for Preventive Migraine Treatment
Propranolol (80-240 mg/day), timolol (20-30 mg/day), amitriptyline (30-150 mg/day), divalproex sodium (500-1500 mg/day), sodium valproate (800-1500 mg/day), topiramate (100 mg/day), and angiotensin receptor blockers (candesartan/telmisartan) are the first-line medications recommended for migraine prevention. 1
When to Consider Preventive Treatment
Prophylactic treatment should be initiated when:
- Migraine episodes occur ≥2 times per month
- Attacks are prolonged and disabling
- Poor response to acute treatments
- Quality of life is reduced between attacks 1
First-Line Medication Options and Dosing
Beta-Blockers
- Propranolol: 80-240 mg/day 1
- FDA-approved for migraine prevention
- Demonstrated efficacy in reducing migraine frequency in controlled studies 2
- Timolol: 20-30 mg/day 1
Anticonvulsants
Antidepressants
- Amitriptyline: 30-150 mg/day 1
Other Options
- Angiotensin receptor blockers:
- Candesartan: 8-32 mg daily 1
- Beneficial for patients with comorbid hypertension
- Flunarizine: A calcium channel blocker particularly effective for hemiplegic migraine 1
Treatment Approach
Select appropriate medication based on:
- Patient comorbidities (e.g., hypertension → beta-blockers/candesartan)
- Potential side effect profile
- Patient preferences
Start with low dose and titrate to minimize side effects:
- For topiramate: Begin with 25 mg/day, increase by 25 mg weekly to target 100 mg/day 5
- For propranolol: Start at lower doses and gradually increase to effective range
Evaluate efficacy:
- Target goal is 50% reduction in attack frequency
- Allow 6-8 weeks at therapeutic dose before determining efficacy 1
- If inadequate response, switch to another first-line agent
Monitoring and Side Effects
Common Side Effects by Medication Class:
Beta-blockers: Fatigue, hypotension, bradycardia
- Use with caution in patients with asthma, diabetes, heart block
- Monitor for drug interactions (e.g., propranolol increases warfarin bioavailability) 2
Topiramate: Paresthesia (most common), cognitive dysfunction, weight loss, taste alteration 3, 5
- Paresthesia is dose-related and often the most common cause of discontinuation
- Cognitive side effects may limit use in intellectually demanding professions
Valproate compounds: Weight gain, hair loss, tremor, teratogenicity
- Contraindicated in pregnancy due to birth defect risk 1
Amitriptyline: Sedation, dry mouth, constipation, weight gain
- May be beneficial if migraine is comorbid with insomnia or depression
Special Considerations
Pregnancy and Lactation
- Avoid valproate and topiramate due to teratogenic effects 1
- Women with migraine with aura should avoid combined hormonal contraceptives with estrogens due to increased stroke risk 1
Combination Therapy
- For patients with partial response to monotherapy, consider adding a second preventive agent
- Topiramate has shown efficacy as adjunctive therapy with propranolol or flunarizine 6
Non-Pharmacological Options
Supplements with evidence for migraine prevention:
- Magnesium (400-600 mg daily)
- Riboflavin (400 mg daily)
- Coenzyme Q10 1
Behavioral interventions:
- Cognitive behavioral therapy
- Relaxation training
- Biofeedback
- Regular aerobic exercise 1
Treatment Success Evaluation
- Use headache diary to track frequency, severity, and medication use
- Consider successful prevention as ≥50% reduction in monthly migraine frequency
- If no improvement after 6-8 weeks at therapeutic dose, switch to another first-line agent 1
Remember that preventive treatment should be considered in patients with frequent migraines (≥2 per month) or when attacks significantly impact quality of life, with the goal of reducing attack frequency by at least 50%.