What is the best prophylaxis therapy for migraine?

Best Prophylaxis Therapy for Migraine

Topiramate (100 mg/day) is the best first-line prophylactic therapy for migraine, with the strongest evidence for efficacy and FDA approval specifically for migraine prevention. 1, 2

First-Line Prophylactic Options

Topiramate

• Recommended target dose of 100 mg/day (no additional benefit seen with 200 mg/day) 2
• Only agent with proven efficacy in randomized, placebo-controlled trials specifically for chronic migraine 1
• FDA-approved for migraine prophylaxis with significant reductions in migraine frequency, number of migraine days, and use of acute medications 2
• Common side effects include paresthesia, fatigue, decreased appetite, weight loss, and cognitive disturbances 2, 3
• Efficacy may be seen as early as the first month of treatment, but full evaluation should occur after 2-3 months 4

Beta Blockers

• Propranolol (80-240 mg/day) and timolol (20-30 mg/day) have strong evidence for efficacy 1
• Propranolol extended-release capsules provide once-daily dosing with usual effective dose range of 160-240 mg for migraine prophylaxis 5
• Beta blockers with intrinsic sympathomimetic activity are ineffective for migraine prevention 1
• Common side effects include dizziness, nausea, fatigue, depression, and insomnia 1
• Head-to-head comparison showed topiramate 100 mg/day and propranolol 160 mg/day have similar efficacy profiles 6

Antidepressants

• Amitriptyline (30-150 mg/day) is the only antidepressant with fairly consistent evidence for migraine prevention 1
• May be particularly effective in patients with mixed migraine and tension-type headache 1
• Side effects include weight gain, drowsiness, and anticholinergic symptoms 1
• Fluoxetine has shown some efficacy but with inconsistent results across studies 1

Anticonvulsants

• Divalproex sodium (500-1500 mg/day) and sodium valproate (800-1500 mg/day) have strong evidence for efficacy 1
• Particularly effective in patients with prolonged or atypical migraine aura 1
• Side effects include hair loss, tremor, weight gain, and teratogenic effects 1
• Head-to-head comparison between topiramate and divalproex sodium showed similar efficacy (58% vs 51% of patients achieving >50% reduction in headache frequency) 3

Second-Line Options

Calcium Channel Blockers

• Evidence for verapamil, nifedipine, and nimodipine is of poor quality and suggests only modest effect 1
• No evidence supports the use of diltiazem 1
• Side effects include dizziness, edema, flushing, and constipation 1

OnabotulinumtoxinA (Botox)

• Only FDA-approved therapy specifically for prophylaxis of headache in adults with chronic migraine 1
• Reduces headache days, episodes, severity, and improves quality of life in chronic migraine 1
• Should be administered by a neurologist or headache specialist using established protocols 1

Other Options

• NSAIDs (particularly naproxen) may have modest prophylactic effects 1
• Limited evidence for modest efficacy of hormone therapy, feverfew, magnesium, and riboflavin in certain circumstances 1
• α2-agonist clonidine lacks efficacy; guanfacine has limited evidence for moderate efficacy 1

When to Initiate Prophylactic Therapy

Prophylactic treatment should be initiated when patients have: 1

• Two or more migraine attacks per month producing disability lasting 3+ days per month
• Contraindication to or failure of acute treatments
• Use of abortive medication more than twice per week
• Presence of uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, or migrainous infarction)

Management Approach

1. Start with topiramate at 25 mg daily and increase by 25 mg weekly to target dose of 100 mg/day 2, 7
2. Evaluate efficacy after 2-3 months of treatment at target dose 4
3. If ineffective or poorly tolerated, switch to propranolol (80-240 mg/day) or amitriptyline (30-150 mg/day) 1
4. For patients with chronic migraine (≥15 headache days/month), consider referral for onabotulinumtoxinA treatment 1
5. Monitor and manage modifiable risk factors and triggers (obesity, medication overuse, caffeine use, sleep apnea, psychiatric comorbidities, stress) 1

Important Considerations

• Medication overuse can contribute to transformation from episodic to chronic migraine; limit acute medications to prevent this complication 1
• Maintain a headache diary to monitor frequency, severity, and response to treatment 1
• After a period of stability (typically 6-12 months), consider tapering or discontinuing treatment 1
• When discontinuing prophylactic therapy, gradually taper the medication over several weeks 5