First-Line Migraine Preventive Treatments
Beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate (100 mg/day, typically 50 mg twice daily), and candesartan are the first-line treatments for migraine prevention, with propranolol and timolol having the strongest evidence for efficacy. 1
Primary First-Line Options
Beta-Blockers
- Propranolol (80-240 mg/day) and timolol (20-30 mg/day) are recommended as first-line treatments with strong evidence for efficacy. 1
- Alternative beta-blockers include atenolol, bisoprolol, or metoprolol, which can be used if propranolol or timolol are not tolerated. 1
- Propranolol has FDA approval for migraine prophylaxis and demonstrated effectiveness in controlling hypertension and reducing angina episodes in clinical trials. 2
Topiramate
- Topiramate at 100 mg/day (typically dosed as 50 mg twice daily) is recommended as first-line therapy with emerging evidence supporting its efficacy. 1
- No increase in efficacy was observed between 100 and 200 mg/day of topiramate, making 100 mg/day the optimal target dose for most patients. 3
- Treatment with topiramate 100 or 200 mg/day significantly reduced migraine frequency, number of migraine days, and use of acute medications in multicenter randomized controlled trials. 3
- Topiramate should be especially considered for patients concerned about weight gain, currently overweight, or with coexisting epilepsy. 3
- In chronic migraine, topiramate significantly reduced monthly migraine days by 3.5 compared to placebo (-0.2), even in the presence of medication overuse. 4
Candesartan
- Candesartan is recommended as a first-line agent, particularly useful for patients with comorbid hypertension. 1
When to Initiate Preventive Therapy
- Preventive therapy should be considered for patients experiencing ≥2 migraine attacks per month with disability lasting ≥3 days per month. 1
- Patients using abortive medication more than twice per week should be considered for preventive treatment to avoid medication overuse headache. 1
- Patients with contraindications to or failure of acute treatments warrant evaluation for preventive therapy. 1
- Those with uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, or migrainous infarction) are candidates for preventive therapy. 1
Implementation Strategy
Titration and Trial Period
- Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases. 1
- For topiramate, titrate weekly in 25-mg increments to minimize side effects, which are typically mild to moderate and transient. 5, 6
- Allow an adequate trial period of 2-3 months before determining efficacy for oral agents. 1
- Topiramate has shown efficacy as early as the first month of treatment, though full evaluation requires 2-3 months. 5
Monitoring
- Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects. 1
- Monitor for medication overuse, which can interfere with preventive treatment effectiveness. 1
Common Side Effects
Topiramate-Specific Adverse Events
- The most common adverse events are paresthesia (53%), fatigue, decreased appetite, nausea, diarrhea, weight decrease, and taste perversion. 3, 4
- Paresthesia is common early in treatment but rarely causes discontinuation. 7
- Cognitive problems occur less frequently than paresthesia but are more troublesome—these can often be managed by slowly increasing the dose in small increments. 7
- Maintain hydration to reduce risk of renal stones, as migraineurs have increased baseline risk independent of topiramate exposure. 7
- Topiramate is Pregnancy Category D due to increased risk of cleft lip/palate with first-trimester exposure—strictly avoid in women of childbearing potential without adequate contraception. 7
Propranolol-Specific Considerations
- Common beta-blocker side effects include fatigue, bradycardia, and hypotension. 2
- Propranolol increases warfarin bioavailability and prothrombin time when coadministered. 2
Critical Pitfalls to Avoid
- Failing to recognize medication overuse headache from frequent use of acute medications (>2 days/week). 1
- Inadequate duration of preventive trial (less than 2-3 months) before declaring treatment failure. 1
- Starting with too high a dose, leading to poor tolerability and discontinuation. 1
- Not addressing comorbidities that influence treatment selection (e.g., avoiding valproate in women of childbearing potential, selecting candesartan for hypertensive patients). 1