What are the recommended prophylactic medications and lifestyle modifications for a patient experiencing frequent or severe migraines?

Migraine Prophylaxis: Recommended Medications and Lifestyle Modifications

For patients experiencing frequent or severe migraines, initiate prophylactic therapy with propranolol (80-240 mg/day), timolol (20-30 mg/day), or topiramate (50-100 mg/day) as first-line agents, with the specific choice guided by comorbidities and side effect tolerance. 1

Indications for Starting Prophylactic Therapy

Prophylactic treatment should be initiated when patients meet any of the following criteria:

• Two or more migraine attacks per month producing disability lasting 3 or more days 1
• Using acute medications more than twice per week (≥10 days/month for triptans or ≥15 days/month for NSAIDs), which risks medication overuse headache 1
• Contraindications to or failure of acute treatments despite optimized therapy 1
• Uncommon migraine conditions such as hemiplegic migraine, migraine with prolonged aura, or migrainous infarction 1

First-Line Prophylactic Medications

Beta-Blockers

• Propranolol 80-240 mg/day or timolol 20-30 mg/day have the strongest evidence for efficacy and are FDA-approved for migraine prophylaxis 1, 2
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol, though with slightly less robust evidence 1
• Avoid in patients with asthma, heart block, or those who practice competitive sports where beta-blockade impairs performance 1
• Particularly useful for patients with comorbid hypertension or anxiety 1

Topiramate

• Topiramate 50-100 mg/day (typically 50 mg twice daily) is the only medication proven effective in randomized controlled trials specifically for chronic migraine 3, 1
• Optimal choice for patients with comorbid obesity due to associated weight loss 1
• Start at 25 mg/day and titrate by 25 mg weekly to minimize side effects 1
• Common side effects include paresthesias, cognitive slowing, and kidney stones 1

Candesartan

• Candesartan is a first-line agent particularly useful for patients with comorbid hypertension 1
• Provides dual benefit of blood pressure control and migraine prevention 1

Second-Line Prophylactic Medications

Amitriptyline

• Amitriptyline 30-150 mg/day is particularly effective for patients with mixed migraine and tension-type headache or comorbid depression/anxiety 1, 2
• Treats both migraine and mood disorders simultaneously 1
• Side effects include sedation, dry mouth, weight gain, and constipation 1

Valproate/Divalproex

• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day are effective second-line options 1, 2
• Strictly contraindicated in women of childbearing potential due to severe teratogenic effects 1
• Monitor for weight gain, hair loss, tremor, and hepatotoxicity 1

Flunarizine

• Flunarizine 5-10 mg/day (typically 10 mg at night) is an effective second-line agent where available, with efficacy comparable to propranolol and topiramate 1, 4
• Contraindicated in patients with active Parkinsonism, history of extrapyramidal disorders, or current depression 1
• Common side effects include sedation, weight gain, and risk of depression or extrapyramidal symptoms, particularly in elderly patients 1

Third-Line: CGRP Monoclonal Antibodies

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when patients have failed 2-3 oral preventive medications or cannot tolerate them 1

• Administered monthly via subcutaneous injection 1
• Efficacy assessment requires 3-6 months before determining effectiveness 1
• Significantly more expensive ($5,000-$6,000 annually) than oral agents 1
• Excellent safety profile with minimal side effects 1

OnabotulinumtoxinA for Chronic Migraine

OnabotulinumtoxinA (Botox) is the only FDA-approved therapy specifically for chronic migraine prophylaxis (≥15 headache days per month) 3, 1

• Not effective for episodic migraine and specifically recommended against for this indication 1
• Administered by neurologist or headache specialist using the Phase III Research Evaluating Migraine Prophylaxis Therapy protocol 3
• Reduces headache days, episodes, severity, and improves quality of life in chronic migraine 3

Implementation Strategy

Starting and Titrating Prophylactic Therapy

• Start with low doses and titrate slowly until clinical benefits are achieved or side effects limit further increases 1
• Allow an adequate trial period of 2-3 months before determining efficacy for oral agents 1, 2
• For CGRP monoclonal antibodies, assess efficacy only after 3-6 months 1
• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 3, 1

Duration of Therapy

• Continue successful prophylactic treatment for 6-12 months 1
• After this period of stability, consider tapering or discontinuing treatment to determine if it can be stopped 1
• A useful measure of success is calculating the percentage reduction in monthly migraine days 1

Lifestyle Modifications and Non-Pharmacological Options

Modifiable Risk Factors and Triggers

The primary care physician should help patients identify and manage:

• Obesity - weight loss can reduce migraine frequency 3
• Medication overuse - limit acute medications to ≤2 days per week 3, 1
• Caffeine overuse - excessive caffeine can trigger rebound headaches 3
• Obstructive sleep apnea - screen and treat if present 3
• Psychiatric comorbidities - depression and anxiety worsen migraine 3
• Stress management - behavioral interventions help modify responses to stressful events 3

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training are effective adjuncts to medication 1
• Neuromodulatory devices can be considered as adjuncts or stand-alone treatments when medications are contraindicated 1
• Acupuncture may be beneficial, though not superior to sham acupuncture in controlled trials 1
• Sleep hygiene, regular meals, and hydration are foundational lifestyle modifications 1

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications (≥10 days/month for triptans, ≥15 days/month for NSAIDs) 1
• Inadequate duration of preventive trial - stopping before 2-3 months prevents accurate efficacy assessment 1
• Starting with too high a dose - leads to poor tolerability and discontinuation 1
• Using valproate in women of childbearing potential - severe teratogenic risk mandates absolute avoidance 1
• Prescribing onabotulinumtoxinA for episodic migraine - it is only effective for chronic migraine 1
• Not addressing comorbidities that influence treatment selection, such as hypertension, depression, or obesity 1

Treatment Algorithm

1. Confirm indication for prophylaxis (≥2 attacks/month with disability ≥3 days, or acute medication use >2 days/week) 1
2. Rule out medication overuse headache before starting prophylaxis 1
3. Select first-line agent based on comorbidities:
   • Hypertension → propranolol, timolol, or candesartan 1
   • Obesity → topiramate 1
   • Depression/anxiety or mixed headache → amitriptyline 1
   • No specific comorbidity → propranolol or timolol (strongest evidence) 1
4. Start low, titrate slowly, allow 2-3 months for efficacy assessment 1
5. If first-line fails or not tolerated, try alternative first-line agent before moving to second-line 1
6. If 2-3 oral agents fail, consider CGRP monoclonal antibodies 1
7. For chronic migraine specifically, consider onabotulinumtoxinA 3, 1
8. Add non-pharmacological adjuncts throughout (behavioral therapy, trigger management) 1