What medications and lifestyle modifications are recommended for preventing migraines in a patient with a history of depression or anxiety?

Migraine Prevention in Patients with Depression or Anxiety

For patients with comorbid depression or anxiety, start with amitriptyline 30-150 mg/day as first-line preventive therapy, as it simultaneously treats both migraine and mood disorders. 1, 2

First-Line Preventive Medication Selection

Amitriptyline is the optimal first choice for this specific population because it addresses both conditions with a single agent, improving adherence and avoiding polypharmacy. 2 Start at 30 mg nightly and titrate slowly to 75-150 mg based on response and tolerability. 2

Alternative First-Line Options if Amitriptyline Fails or is Not Tolerated:

• Propranolol 80-240 mg/day (divided doses or extended-release) is highly effective with strong evidence, though it may worsen depression in some patients—monitor mood closely. 1, 3, 2

• Venlafaxine (SNRI) is specifically recommended by the American College of Physicians as first-line therapy and may provide additional benefit for anxiety/depression. 1

• Topiramate 50-100 mg/day has strong efficacy evidence but carries higher adverse event rates including cognitive side effects that may be poorly tolerated in patients with mood disorders. 1, 3

Critical Implementation Strategy

Start low and titrate slowly over 2-3 months before determining efficacy—this is essential as premature discontinuation is a common pitfall. 1, 3, 2 For amitriptyline, begin at 10-30 mg nightly and increase by 10-25 mg every 1-2 weeks. 2

Assess efficacy only after an adequate 2-3 month trial at therapeutic dose—earlier assessment leads to inappropriate medication switching. 1, 3, 2

When First-Line Therapy Fails

If amitriptyline, propranolol, venlafaxine, or topiramate fail after adequate trials:

• Consider CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) administered monthly via subcutaneous injection, though these require 3-6 months for efficacy assessment and cost $5,000-$6,000 annually. 1, 2

• Alternatively, try CGRP antagonist-gepants (atogepant or rimegepant) as oral options before moving to injectable CGRP-mAbs, based on patient preference for oral medications. 1

Essential Lifestyle Modifications

Implement these non-pharmacological interventions alongside medication:

• Cognitive behavioral therapy and biofeedback are effective adjuncts with strong evidence in migraine prevention and directly benefit comorbid anxiety/depression. 2, 4

• Identify and modify triggers: maintain regular sleep schedule (7-8 hours nightly), consistent meal timing, adequate hydration, and stress management techniques. 3, 5, 4

• Regular aerobic exercise 30-45 minutes, 3-5 times weekly, improves both migraine frequency and mood symptoms. 4

Medication Overuse Headache Prevention

Limit acute medication use to ≤2 days per week (≤10 days/month for triptans, ≤15 days/month for NSAIDs) to prevent medication overuse headache, which occurs in two-thirds of chronic migraine patients. 1, 3, 5, 2

If medication overuse is present, abrupt withdrawal is preferred (except for opioids which require tapering), followed by initiation or optimization of preventive therapy. 1

Critical Pitfalls to Avoid

• Do not use valproate/divalproex in women of childbearing potential—it is strictly contraindicated due to teratogenic effects despite strong efficacy evidence. 1, 2

• Screen for worsening depression when using propranolol or topiramate—beta-blockers may exacerbate depression, and topiramate causes cognitive side effects. 1, 2

• Avoid starting at full therapeutic doses—this leads to poor tolerability and premature discontinuation. 1, 2

• Do not assess efficacy before 2-3 months—inadequate trial duration is a common reason for treatment failure. 1, 3, 2

Monitoring and Follow-Up

Schedule follow-up at 4 weeks initially to assess tolerability and side effects, then every 2-3 months to evaluate efficacy using headache diaries tracking attack frequency, severity, and disability. 5, 2

Calculate percentage reduction in monthly migraine days as a quantifiable measure of success—aim for ≥50% reduction. 2

Consider tapering preventive therapy after 6-12 months of successful control to determine if continued treatment is necessary. 2