- Beyond the Pain: Rethinking Migraine Care with the RELIEF PLAN Approach
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Sanghyo Ryu
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Headache Pain Res. 2025;26(1):1-2. Published online February 17, 2025
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DOI: https://doi.org/10.62087/hpr.2024.0035
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Citations to this article as recorded by  - The Hidden Risks of Medication Underuse in Migraine Progression
Heui-Soo Moon, Pil-Wook Chung
Headache and Pain Research.2025; 26(3): 209. CrossRef
- Antidepressants in Migraine and Tension-Type Headache Prevention: A Narrative Review and Phenotype-Driven Clinical Framework
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Sanghyo Ryu
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Received September 22, 2026 Accepted October 11, 2026 Published online October 22, 2026
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DOI: https://doi.org/10.62087/hpr.2026.0045
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 Abstract
- Antidepressants retain a clinical role in managing migraine and tension-type headache (TTH), especially in patients with coexisting depression, anxiety, insomnia, or chronic pain. Their direct efficacy in preventing headache, however, varies substantially by agent and should be distinguished from the clinical benefits of treating comorbid conditions. This narrative review examines the evidence, pharmacological characteristics, safety, and practical roles of antidepressants in migraine and TTH. Contemporary evidence appraisal has changed the traditional hierarchy of these drugs. The 2026 American Academy of Neurology/American Headache Society systematic review of episodic migraine prevention found low-confidence evidence suggesting benefit for amitriptyline and fluoxetine, but very-low-confidence evidence for venlafaxine and duloxetine. These ratings require context: the fluoxetine rating depends substantially on a small trial of S-fluoxetine rather than marketed racemic fluoxetine, whereas amitriptyline has an extensive history of clinical use and additional evidence in chronic TTH. Mirtazapine has randomized controlled trial evidence in chronic TTH but insufficient evidence in migraine. Antidepressant selection should therefore account for headache-specific evidence alongside psychiatric comorbidity, sleep, chronic pain, body weight, age, tolerability, drug interactions, and patient preference. Individualized treatment extends beyond antidepressant selection, because behavioral and migraine-specific interventions may address different treatment targets. Separating direct headache-preventive efficacy from the clinical usefulness of treating comorbidities may offer a more rational framework for incorporating antidepressants into contemporary headache practice.
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