What are the treatment options for persistent and recurrent migraines?

Treatment Options for Persistent and Recurrent Migraines

For persistent and recurrent migraines, first-line preventive pharmacologic treatments include beta-blockers (propranolol 80-240 mg/day, timolol 20-30 mg/day), antiseizure medications (topiramate 100 mg/day, divalproex sodium 500-1500 mg/day), and tricyclic antidepressants (amitriptyline 30-150 mg/day), with newer CGRP antagonists and monoclonal antibodies as additional FDA-approved options. 1, 2

Preventive Pharmacologic Treatments

First-Line Options

1. Beta-blockers

   • Propranolol (80-240 mg/day)
   • Timolol (20-30 mg/day)

2. Antiseizure Medications

   • Topiramate (100 mg/day) - Effective for chronic migraine with significant reduction in monthly migraine days 3
   • Divalproex sodium (500-1500 mg/day)
   • Sodium valproate (800-1500 mg/day)

3. Tricyclic Antidepressants

   • Amitriptyline (30-150 mg/day) - Start at 10-25mg at bedtime, increase by 10-25mg every 1-2 weeks 2

4. Angiotensin System Blockers

   • Candesartan (8-32 mg/day)
   • Lisinopril (ACE inhibitor)

Second-Line Options

1. Other Antidepressants

   • Nortriptyline (10-40 mg/day) - Alternative for patients who cannot tolerate amitriptyline 2
   • Venlafaxine (75-150 mg/day)

2. Calcium Channel Blockers

   • Flunarizine (particularly for hemiplegic migraine)

Newer FDA-Approved Options

• CGRP Antagonists (gepants)
• CGRP Monoclonal Antibodies

Acute Treatment Options

Mild to Moderate Attacks

1. Acetaminophen
2. NSAIDs

Moderate to Severe Attacks

1. Triptans

   • Sumatriptan - Provides significant headache relief within 2-4 hours compared to placebo 4
   • Eletriptan - Demonstrates 54-67% headache response rate at 2 hours with 80mg dose 5

2. Antiemetics (for associated symptoms and to enhance absorption of other medications)

3. Ergot Alkaloids

   • Dihydroergotamine (second or third-line therapy)

Complementary Treatments

• Magnesium (400-600mg daily)
• Riboflavin (Vitamin B2) 400mg daily
• Coenzyme Q10
• Petasites
• Feverfew

Non-Pharmacologic Approaches

• Relaxation training
• Thermal biofeedback combined with relaxation training
• Cognitive behavioral therapy
• Regular aerobic exercise
• Maintaining regular sleep schedule
• Regular meals and adequate hydration
• Stress management techniques

Treatment Algorithm

Step 1: Determine Need for Preventive Therapy

Initiate preventive therapy if patient has:

• ≥4 headaches per month
• ≥8 headache days per month
• Debilitating headaches
• Medication-overuse headaches

Step 2: Select Preventive Medication

• For patients without contraindications: Start with propranolol, topiramate, or amitriptyline
• For patients with comorbid depression/anxiety: Consider amitriptyline or venlafaxine
• For patients with comorbid hypertension: Consider propranolol or candesartan
• For patients with comorbid obesity: Consider topiramate (may assist with weight loss)

Step 3: Proper Dosing and Titration

• Start low and titrate slowly (e.g., topiramate starting at 25mg/day, increasing by 25mg weekly to target 100mg/day)
• Allow 6-8 weeks at therapeutic dose to evaluate efficacy
• Target goal: 50% reduction in headache frequency

Step 4: Acute Treatment Plan

• For mild attacks: NSAIDs or acetaminophen
• For moderate-severe attacks: Triptans
• Limit use of simple analgesics to <15 days/month and triptans to <10 days/month to prevent medication overuse headache

Special Considerations

Women of Childbearing Potential

• Avoid valproate and topiramate due to teratogenic effects
• Women with migraine with aura should avoid combined hormonal contraceptives with estrogens due to increased stroke risk

Medication Overuse

• Limit use of simple analgesics to fewer than 15 days/month
• Limit triptans to fewer than 10 days/month
• Consider detoxification protocol for established medication overuse headache

Treatment Failure

• If first preventive medication fails after adequate trial (6-8 weeks), switch to another first-line agent
• If multiple first-line agents fail, consider combination therapy or newer CGRP-targeted therapies

Monitoring

• Evaluate response after 6-8 weeks of treatment
• Monitor for side effects (e.g., dry mouth, sedation, weight gain with TCAs; cognitive effects with topiramate)
• Regular follow-up appointments to adjust treatment plan as needed

Despite the availability of multiple effective treatments, migraine remains underdiagnosed and undertreated, with only a small percentage of eligible patients receiving preventive pharmacologic treatments 1.