What are the recommended medications and lifestyle modifications for prophylaxis treatment of migraine?

Prophylactic Treatment for Migraine

First-line prophylactic medications for migraine include beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), amitriptyline (30-150 mg/day), topiramate, divalproex sodium (500-1500 mg/day), and candesartan. 1

Indications for Prophylactic Treatment

Prophylactic treatment should be initiated when patients experience:

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

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First-Line Medications

Beta-blockers

• Propranolol: 80-240 mg/day
• Timolol: 20-30 mg/day
• Metoprolol/Atenolol/Bisoprolol: Alternatives with similar efficacy

Beta-blockers are particularly beneficial for patients with comorbid hypertension but should be avoided in patients with asthma, depression, or those who engage in competitive sports due to potential for fatigue. 1, 2

Anticonvulsants

• Topiramate: 50-200 mg/day (typically 100 mg/day)
• Divalproex sodium/Sodium valproate: 500-1500 mg/day

Topiramate has demonstrated efficacy in reducing migraine days in chronic migraine, even in patients with medication overuse. 3 Valproate is contraindicated in women of childbearing potential due to teratogenicity. 1

Antidepressants

• Amitriptyline: 30-150 mg/day

Particularly useful in patients with comorbid depression, anxiety, or tension-type headaches. 1

Angiotensin Receptor Blockers

• Candesartan: 16-32 mg/day

Good option for patients with comorbid hypertension. 1

Second-Line Medications

When first-line treatments fail or are contraindicated, consider:

• Flunarizine: Calcium channel blocker (not available in US)
• Venlafaxine: SNRI antidepressant
• Other calcium channel blockers: Limited evidence

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Third-Line Options

• CGRP monoclonal antibodies: Erenumab, fremanezumab, galcanezumab, eptinezumab
  • Consider when other preventive medications have failed
  • Higher cost but favorable side effect profile
  • Monthly or quarterly injections

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Non-Pharmacological Approaches

These can be used as adjuncts to medication or as alternatives when medications are contraindicated:

• Neuromodulatory devices: Non-invasive options
• Biobehavioral therapy: Relaxation techniques, biofeedback
• Acupuncture: Some evidence of efficacy
• Lifestyle modifications:
  • Regular sleep schedule
  • Regular meals
  • Adequate hydration
  • Regular physical exercise (moderate to intense aerobic)
  • Stress management techniques
  • Weight loss if overweight/obese

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Treatment Protocol

1. Initiation: Start with low dose and gradually titrate to recommended dose as tolerated
2. Duration of trial: Evaluate efficacy after 2-3 months of treatment
3. Monitoring: Have patient maintain headache diary to track frequency, severity, and medication use
4. Continuation: If effective, continue for 6-12 months before attempting to taper
5. Tapering: Gradually reduce dose to find minimum effective dose or discontinue

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Common Pitfalls and Caveats

• Medication overuse: Ensure patient is not overusing acute medications (≥15 days/month for NSAIDs, ≥10 days/month for triptans)
• Inadequate trial period: Allow sufficient time (2-3 months) before declaring treatment failure
• Inadequate dosing: Ensure target therapeutic doses are reached if tolerated
• Unrealistic expectations: Educate patients that goal is ≥50% reduction in frequency, not complete elimination
• Comorbidities: Consider patient's other medical conditions when selecting prophylactic agent
• Pregnancy considerations: Discuss risks of medications during pregnancy and lactation with women of childbearing potential

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Algorithmic Approach to Prophylaxis Selection

1. Assess comorbidities:

   • Hypertension → Beta-blockers or candesartan
   • Depression/anxiety → Amitriptyline
   • Obesity → Avoid medications causing weight gain (consider topiramate)
   • Epilepsy → Topiramate or valproate
   • Women of childbearing potential → Avoid valproate

2. Consider side effect profile:

   • Concern for cognitive effects → Avoid topiramate
   • Concern for weight gain → Avoid amitriptyline, consider topiramate
   • Sedation concerns → Avoid amitriptyline, consider morning dosing of beta-blockers

3. If first agent fails after adequate trial:

   • Switch to different first-line agent from a different class
   • If two first-line agents fail, consider second-line options
   • After multiple failures, consider CGRP monoclonal antibodies

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