A 36-year-old male has been diagnosed with more severe depression. Which antidepressant is most likely to be prescribed as first-line treatment given his migraines and use of sumatriptan?

• A. Sertraline
• B. Fluoxetine
• C. Citalopram
• D. Lofepramine

Answer: (D)

The key idea is choosing an antidepressant that also helps with the patient’s migraine. Tricyclic antidepressants have a well-established role in migraine prophylaxis, so in someone with depression and comorbid migraines (who is taking sumatriptan), a TCA-based option can offer dual benefit. Lofepramine is a TCA that provides antidepressant effects and tends to have a more tolerable side-effect profile than some older TCAs, with less anticholinergic burden and sedation. This makes it a reasonable first-line choice when migraine management is a consideration and when using triptans.

Sertraline, fluoxetine, and citalopram are effective antidepressants but do not contribute to migraine prevention and, in the context of combination with sumatriptan, carry considerations about serotonin-related interactions. Therefore, the option that best aligns with both mood stabilization and migraine-related needs is the tricyclic antidepressant approach, represented here by lofepramine.