Savvy Psychopharmacology

Using SNRIs to prevent migraines in patients with depression

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Practice Points

Ms. D, age 45, has major depressive disorder (MDD), generalized anxiety disorder (GAD), migraines, and hypertension. At a follow-up visit, she says she has been under a lot of stress at work in the past several months and feels her antidepressant is not working well for her depression or anxiety. Ms. D notes that lately she has had more frequent migraines, occurring approximately 4 times per month during the past 3 months. She describes a severe throbbing frontal pain that occurs primarily on the left side of her head, but sometimes on the right side. Ms. D says she experiences nausea, vomiting, and photophobia during these migraine episodes. The migraines last up to 12 hours, but often resolve with sumatriptan 50 mg as needed.

Ms. D takes fluoxetine 60 mg/d for depression and anxiety, lisinopril 20 mg/d for hypertension, as well as a women’s multivitamin and vitamin D3 daily. She has not tried other antidepressants and misses doses of her medications about once every other week. Her blood pressure is 125/80 mm Hg; heart rate is 80 beats per minute; and temperature is 37° C. Ms. D’s treatment team is considering switching her to a medication that can act as preventative therapy for migraines while also treating her depression and anxiety.

Migraine is a chronic, disabling neurovascular disorder that affects approximately 15% of the United States population.1 It is the second-leading disabling condition worldwide and may negatively affect social, family, personal, academic, and occupational domains.2 Migraine is often characterized by throbbing pain, is frequently unilateral, and may last 24 to 72 hours.3 It may occur with or without aura and can be associated with nausea, vomiting, or sensitivity to light.3 Episodic migraines occur <15 days a month, while chronic migraines occur ≥15 days a month.4

Many psychiatric, neurologic, vascular, and cardiac comorbidities are more prevalent in individuals who experience migraine headaches compared to the general population. Common psychiatric comorbidities found in patients with migraines are depression, bipolar disorder, GAD, panic disorder, and posttraumatic stress disorder5; MDD is the most common.4 A person who experiences migraine headaches is 2 to 4 times more likely to develop MDD than one who does not experience migraine headaches.4

First-line treatments for preventing migraine including divalproex, topiramate, metoprolol, propranolol, and timolol.6 However, for some patients with migraines and comorbid depression or anxiety, an antidepressant may be an option. This article briefly reviews the evidence for using antidepressants that have been studied for their ability to decrease migraine frequency.

Antidepressants that can prevent migraine

Tricyclic antidepressants (TCAs) are second- or third-line options for migraine prevention.6 While TCAs have proven to be effective for preventing migraines, many patients are unable to tolerate their adverse effects (ie, anticholinergic effects, sedation).7 TCAs may be more appealing for younger patients, who may be less bothered by anticholinergic burden, or those who have difficulty sleeping.

Serotonin-norepinephrine reuptake inhibitors (SNRIs). There has been growing interest in understanding the potential utility of SNRIs as a preventative treatment for migraines. Research has found that SNRIs are as effective as TCAs for preventing migraines and also more tolerable in terms of adverse effects.7 SNRIs such as venlafaxine and duloxetine are currently prescribed off-label to prevent migraines despite a lack of FDA approval for this indication.8

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