What are the treatment options for a female patient of reproductive age experiencing severe migraines around periods without relief on Elavil (amitriptyline) and gabapentin?

Treatment of Severe Perimenstrual Migraines Refractory to Amitriptyline and Gabapentin

For severe perimenstrual migraines failing amitriptyline and gabapentin, initiate perimenstrual short-term prophylaxis with frovatriptan 2.5 mg twice daily or naratriptan 1 mg twice daily starting 2 days before expected menstruation and continuing for 5 days, combined with naproxen 500 mg twice daily during the same period. 1

Immediate Management Strategy

Short-Term Perimenstrual Prophylaxis (First-Line)

• Frovatriptan has the strongest evidence among triptans for perimenstrual prevention, with four randomized controlled trials demonstrating efficacy when taken twice daily during the perimenstrual window 2
• Naratriptan 1 mg twice daily is an alternative, supported by two randomized studies showing statistically significant reduction in perimenstrual attacks 2
• Naproxen sodium 500 mg twice daily can be combined with triptans or used alone, with proven efficacy in perimenstrual migraine prevention 1, 2
• Begin treatment 2 days before expected menstruation and continue for 5 days total 1

Acute Treatment Optimization

• Rizatriptan has the best overall evidence for acute treatment of menstrual migraine, with pain-free responses of 33-73% at 2 hours and sustained pain relief of 63% between 2-24 hours 2
• Sumatriptan and rizatriptan show similar efficacy (61-63% pain freedom at 2 hours) for acute menstrual migraine attacks 2
• Menstrual migraines are typically more severe, longer-lasting, and more resistant to treatment than non-menstrual attacks 2

Daily Preventive Treatment Escalation

Since amitriptyline (second-line agent) and gabapentin (second-line with less evidence) have failed, escalate to more effective options 1, 3:

Third-Line Options (Highest Efficacy)

• OnabotulinumtoxinA 155-195 units to 31-39 sites every 12 weeks is highly effective for chronic migraine in women and should be strongly considered 1, 4
• CGRP monoclonal antibodies (erenumab 70-140 mg subcutaneous monthly, or fremanezumab 225 mg monthly/675 mg quarterly) represent newer generation treatments with high efficacy in women 1, 4

First-Line Agents Not Yet Tried

• Propranolol 80-160 mg daily in long-acting formulations remains a first-line option if not contraindicated 1
• Topiramate 50-100 mg daily is effective for overall migraine reduction and specifically reduces perimenstrual migraine frequency by approximately 46%, including attacks with and without aura 1, 5

Critical Contraindications and Warnings

Reproductive Age Considerations

• Topiramate is contraindicated in pregnancy due to teratogenic effects and should be used with effective contraception in women of childbearing potential 1, 6
• Sodium valproate is absolutely contraindicated in women of childbearing potential due to high rates of fetal anomalies 1, 4, 6
• Topiramate has minimal effect on oral contraceptives at doses below 200 mg/day, unlike other antiepileptic drugs 2, 6

Hormonal Considerations

• Combined hormonal contraceptives are contraindicated if the patient has migraine with aura due to increased stroke risk 1
• Continuous use of combined hormonal contraceptives (without hormone-free intervals) may benefit women with pure menstrual migraine without aura 1

Practical Implementation Algorithm

1. Immediate step: Add perimenstrual prophylaxis with frovatriptan 2.5 mg twice daily + naproxen 500 mg twice daily for 5 days starting 2 days before menses 1, 2

2. Optimize acute treatment: Switch to rizatriptan for breakthrough attacks given superior evidence in menstrual migraine 2

3. If inadequate response after 2-3 months: Escalate daily prevention to third-line agents (onabotulinumtoxinA or CGRP antibodies) given failure of second-line medications 1, 4

4. Alternative if third-line unavailable: Trial topiramate 50-100 mg daily (if appropriate contraception in place) or propranolol 80-160 mg daily if not previously tried 1, 5

Monitoring and Follow-Up

• Evaluate treatment response at 2-3 months using headache calendars to track attack frequency, severity, and disability 1
• Monitor for medication overuse (limit acute treatments to <10 days/month for triptans, <15 days/month for NSAIDs) 1
• Perimenstrual migraines specifically respond to topiramate with similar percentage reductions during and outside the perimenstrual period (-45.9% vs -46.1%) 5