What are the next treatment options for a 30-year-old woman with migraines unresponsive to propranolol and amitriptyline?

Treatment Options for Migraine Unresponsive to Propranolol and Amitriptyline

For a 30-year-old non-pregnant woman with migraines unresponsive to propranolol 20mg and amitriptyline 25mg for 6 months, topiramate (50-100mg daily) or candesartan (16-32mg daily) should be the next treatment options.

Evaluation of Current Treatment

Before proceeding to alternative medications, it's important to evaluate the current regimen:

1. Dosage adequacy:

   • The current propranolol dose (20mg) is significantly below the therapeutic range of 80-240mg/day 1
   • Amitriptyline dose (25mg) is below the recommended range of 30-150mg/day 1
   • Consider optimizing current medications before switching:
     • Increase propranolol to 80-160mg daily
     • Increase amitriptyline to 30-100mg daily

2. Medication adherence: Ensure patient is taking medications as prescribed

3. Trigger identification: Verify patient is maintaining a headache diary to identify and avoid triggers 1

Next-Line Medication Options

If optimizing current medications fails, consider these evidence-based alternatives:

First-Line Options:

1. Topiramate:

   • Dosage: 50-100mg oral daily 2, 1
   • Advantages: Strong evidence for efficacy 1, 3
   • Contraindications: Nephrolithiasis, pregnancy, lactation, glaucoma 2
   • Monitoring: Cognitive side effects, paresthesias, weight loss

2. Candesartan:

   • Dosage: 16-32mg oral daily 2, 1
   • Advantages: Good efficacy with favorable side effect profile 1, 4
   • Contraindications: Co-administration of aliskiren 2
   • Monitoring: Blood pressure

Second-Line Options:

1. Flunarizine:

   • Dosage: 5-10mg oral once daily 2
   • Advantages: First-line option in many countries 4, 5
   • Contraindications: Parkinsonism, depression 2
   • Monitoring: Weight gain, mood changes

2. Sodium valproate/Divalproex sodium:

   • Dosage: 600-1,500mg oral daily 2, 1
   • Advantages: Strong evidence for efficacy 3, 6
   • Contraindications: Liver disease, thrombocytopenia 2
   • Absolute contraindication in women of childbearing potential due to teratogenicity 2
   • Monitoring: Liver function, platelets, weight

Third-Line Options:

1. CGRP Monoclonal Antibodies:

   • Options: Erenumab (70-140mg SC monthly), Fremanezumab (225mg SC monthly or 675mg quarterly) 2
   • Advantages: Monthly dosing, favorable side effect profile
   • Considerations: Cost, insurance coverage

2. OnabotulinumtoxinA:

   • Dosage: 155-195 units to 31-39 sites every 12 weeks 2
   • Contraindications: Infection at injection site
   • Best for chronic migraine (≥15 headache days/month)

Non-Pharmacological Approaches

Consider adding these evidence-based complementary approaches:

1. Supplements:

   • Magnesium (400-600mg daily)
   • Riboflavin (400mg daily)
   • Coenzyme Q10 1, 7

2. Behavioral interventions:

   • Cognitive behavioral therapy
   • Relaxation training
   • Biofeedback 1, 3

Treatment Algorithm

1. Optimize current regimen:

   • Increase propranolol to therapeutic dose (80-160mg)
   • Increase amitriptyline to therapeutic dose (30-100mg)
   • Trial for 6-8 weeks

2. If still inadequate response:

   • Add topiramate (starting at 25mg, titrating to 50-100mg daily)
   • OR switch to candesartan (16-32mg daily)
   • Trial for 6-8 weeks

3. If still inadequate response:

   • Consider flunarizine (if available)
   • Consider CGRP monoclonal antibodies
   • Consider onabotulinumtoxinA (if chronic migraine)

Important Considerations

• Target goal: 50% reduction in attack frequency 1
• Adequate trial: 6-8 weeks at therapeutic dose 1, 4
• Medication overuse: Ensure acute medications are limited to ≤10 days/month for triptans and ≤15 days/month for NSAIDs 1
• Avoid: Opioids and butalbital for acute treatment due to risk of medication overuse 1

Common Pitfalls

1. Inadequate dosing: Many treatment failures occur because medications are not titrated to therapeutic doses
2. Insufficient trial duration: Allow 6-8 weeks at therapeutic dose before declaring treatment failure
3. Overlooking lifestyle factors: Ensure regular sleep schedule, hydration, stress management, and regular exercise 1
4. Medication overuse: Excessive use of acute medications can perpetuate headaches
5. Not addressing comorbidities: Anxiety, depression, and sleep disorders can worsen migraines