What are the medication options for preventing migraines in a patient with a history of depression, anxiety, and possibly hypertension?

Migraine Prevention Medication Options

For a patient with depression, anxiety, and possible hypertension, amitriptyline 30-150 mg/day is the optimal first-line preventive medication because it simultaneously treats migraine, depression, and anxiety. 1

First-Line Medication Selection Based on Comorbidities

Best Choice: Amitriptyline

• Amitriptyline (30-150 mg/day) is specifically recommended as the optimal first choice for patients with comorbid depression or anxiety, as it treats both migraine and mood disorders simultaneously. 1
• Start at 10-25 mg at bedtime and titrate slowly by 10-25 mg weekly until clinical benefits are achieved or side effects limit further increases. 1
• Allow an adequate trial period of 2-3 months before determining efficacy. 1
• Common side effects include sedation, dry mouth, and weight gain, but these can be minimized with slow titration. 2

Alternative First-Line Options

If hypertension is confirmed:

• Candesartan is recommended as a first-line agent, particularly useful for patients with comorbid hypertension, providing dual benefit for both conditions. 1
• Propranolol (80-240 mg/day) or timolol (20-30 mg/day) are also first-line treatments with strong evidence for efficacy and can help manage hypertension. 1
• However, beta-blockers may worsen depression in some patients, making them less ideal given the psychiatric comorbidities. 3

If obesity is present:

• Topiramate (100 mg/day, typically 50 mg twice daily) is the preferred first-line treatment for patients with obesity due to its associated weight loss benefits. 1, 4
• Start at 25 mg once daily at bedtime, then increase by 25 mg weekly until reaching the target dose of 100 mg/day to minimize cognitive side effects and paresthesias. 4
• Critical contraindication: Verify pregnancy status before prescribing topiramate, as first-trimester exposure is associated with increased risk of cleft lip/palate (Pregnancy Category D). 4

Second-Line Preventive Medications

If amitriptyline fails or is not tolerated after an adequate 2-3 month trial:

• Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) are second-line options with documented high efficacy. 1, 5

• Absolutely contraindicated in women of childbearing potential due to severe teratogenic effects (neural tube defects). 1, 4

• Alternative beta-blockers including atenolol, bisoprolol, or metoprolol can be considered if propranolol is not tolerated. 1

• Flunarizine (5-10 mg once daily at night) is an effective second-line agent with proven efficacy comparable to propranolol and topiramate. 1

• Critical contraindication: Screen for depression and Parkinson's disease before initiating flunarizine, as it may exacerbate these conditions, particularly in elderly patients. 1

Third-Line: CGRP Monoclonal Antibodies

When 2-3 oral preventive medications have failed or are contraindicated:

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered. 1
• Erenumab 70-140 mg or galcanezumab 120 mg administered monthly via subcutaneous injection. 6, 7
• Efficacy assessment requires 3-6 months, significantly longer than the 2-3 months needed for oral agents. 1
• Annualized cost is $5,000-$6,000, significantly more expensive than oral agents. 1
• Erenumab reduced monthly migraine days by 1.4-1.9 days compared to placebo, with 43-50% of patients achieving ≥50% reduction in migraine frequency. 6
• Galcanezumab reduced monthly migraine days by 1.9-2.0 days compared to placebo, with 59-62% of patients achieving ≥50% reduction in migraine frequency. 7

Implementation Strategy

Starting Preventive Therapy

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases. 1
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects. 1
• Rule out medication overuse headache before starting preventive therapy, defined as using acute medications ≥10 days/month for triptans or ≥15 days/month for NSAIDs. 1

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued. 1
• A useful measure to quantify success is calculating the percentage reduction in monthly migraine days. 1

Critical Pitfalls to Avoid

• Do not start with too high a dose, leading to poor tolerability and discontinuation. 1
• Do not evaluate efficacy before 2-3 months of treatment at target dose (3-6 months for CGRP antibodies). 1, 4
• Do not prescribe valproate/divalproex to any woman of childbearing potential. 1, 4
• Do not fail to recognize medication overuse headache from frequent use of acute medications. 1
• Do not prescribe flunarizine to patients with active depression or Parkinsonism. 1

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training should be offered alongside medication as effective adjuncts for migraine prevention. 1
• Neuromodulatory devices, biobehavioral therapy, or acupuncture can be considered as adjuncts to medication or as stand-alone treatments when medications are contraindicated. 1
• Identifying and modifying triggers such as sleep hygiene, regular meals, hydration, and stress management can be beneficial. 1