What is the recommended maintenance treatment for a patient with frequent or severe migraine attacks, possibly with a history of depression or anxiety?

Maintenance Migraine Treatment

For patients with frequent or severe migraines, particularly those with comorbid depression or anxiety, initiate preventive therapy with amitriptyline 30-150 mg/day as first-line treatment, which addresses both conditions simultaneously. 1

Indications for Preventive Therapy

Preventive therapy should be initiated when any of the following criteria are met:

• Two or more migraine attacks per month with disability lasting ≥3 days 1
• Using acute medications more than twice per week (to prevent medication overuse headache) 1
• Contraindications to or failure of acute treatments 1
• Uncommon migraine conditions such as hemiplegic migraine, prolonged aura, or migrainous infarction 1
• Patient preference for preventive approach over frequent acute treatment 2

First-Line Preventive Medications

The choice depends on comorbidities and patient-specific factors:

For Patients with Depression or Anxiety (Your Scenario)

• Amitriptyline 30-150 mg/day is the optimal first choice, as it treats both migraine and comorbid depression/sleep disturbances 1, 3
• Start at 10-25 mg at bedtime and titrate slowly over 2-3 weeks to minimize side effects 1

For Patients with Hypertension

• Propranolol 80-240 mg/day or timolol 20-30 mg/day address both conditions 1
• Candesartan is particularly useful for comorbid hypertension 1

For Patients with Obesity

• Topiramate 100 mg/day (typically 50 mg twice daily) is preferred due to associated weight loss 3, 1
• Requires slow titration starting at 25 mg/day, increasing by 25 mg weekly to minimize cognitive side effects 4

For Patients Without Specific Comorbidities

• Beta-blockers (propranolol, timolol, metoprolol) have the strongest evidence 1
• Topiramate is equally effective as first-line 1

Second-Line Preventive Medications

When first-line agents fail or are not tolerated:

• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day 1
  • Strictly contraindicated in women of childbearing potential due to teratogenic effects 3, 1
• Venlafaxine for patients with comorbid depression who cannot tolerate amitriptyline 5

Third-Line: CGRP Monoclonal Antibodies

Reserved for patients who have failed 2-3 oral preventive medications:

• Erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection 1, 6
• Efficacy assessment requires 3-6 months before determining effectiveness 1
• Proven beneficial even in patients who failed multiple prior preventives 3
• Significantly more expensive than oral agents (annualized cost $5,000-$6,000) 3

For Chronic Migraine Specifically

If patient has ≥15 headache days per month for ≥3 months:

• Topiramate remains first-line due to lower cost 3
• OnabotulinumtoxinA (Botox) injections every 12 weeks after oral preventives fail 3, 1
• CGRP antibodies after 2-3 preventive failures 3

Implementation Strategy

Dosing Principles

• Start low, titrate slowly to minimize side effects and improve tolerability 1
• Allow 2-3 months for adequate trial of oral medications before declaring failure 1
• For CGRP antibodies, wait 3-6 months before assessing efficacy 1

Monitoring

• Use headache diaries to track frequency, severity, duration, and disability 1
• Calculate percentage reduction in monthly migraine days to quantify success 1
• Goal: ≥50% reduction in monthly migraine days 6

Duration of Therapy

• Continue successful preventive therapy for 6-12 months 1
• After stability, attempt gradual taper to determine if treatment can be discontinued 1
• Some patients require long-term maintenance if migraines return after discontinuation 1

Critical Pitfalls to Avoid

Medication Overuse Headache

• Rule out medication overuse headache before starting preventive therapy 3
• Defined as using acute medications ≥10 days/month for triptans or ≥15 days/month for NSAIDs 3
• Requires withdrawal of overused medication (abrupt withdrawal preferred except for opioids) before preventive therapy will be effective 3

Inadequate Trial Duration

• Do not declare treatment failure before 2-3 months for oral agents 1
• Many patients discontinue prematurely due to initial side effects or lack of immediate benefit 4

Starting Dose Too High

• Rapid titration leads to poor tolerability and treatment abandonment 1
• Particularly important for topiramate (cognitive effects) and amitriptyline (sedation) 4

Ignoring Comorbidities

• Valproate is teratogenic - never use in women of childbearing potential 3, 1
• Beta-blockers worsen depression in some patients - avoid if severe depression 5
• Topiramate causes cognitive slowing - problematic for patients requiring high cognitive function 4

Addressing Comorbid Depression/Anxiety

For your specific patient population:

• Amitriptyline 30-150 mg/day is the optimal first choice as it treats both migraine and mood disorders 3, 1
• Venlafaxine is an alternative SNRI with evidence for both conditions 5
• Avoid beta-blockers as they may worsen depression in susceptible individuals 5
• Recognize that migraine improvement often improves mood and vice versa 3

Non-Pharmacological Adjuncts

Should be offered alongside medication:

• Cognitive behavioral therapy has good evidence for migraine prevention 5
• Biofeedback and relaxation training are effective adjuncts 3, 5
• Identify and modify triggers: sleep hygiene, regular meals, hydration, stress management 3
• Riboflavin 400 mg/day and magnesium have modest evidence as supplements 5