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Venlafaxine + mirtazapine is a combination of two antidepressant medications used primarily for the treatment of major depressive disorder, particularly in patients with treatment-resistant or refractory depression. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that increases levels of serotonin and norepinephrine in the brain by inhibiting their reuptake. Mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA); it enhances central noradrenergic and serotonergic activity mainly through antagonism of central presynaptic alpha-2 adrenergic inhibitory autoreceptors and heteroreceptors, as well as antagonism at certain serotonin receptors (notably 5-HT2 and 5-HT3). The rationale for combining these agents lies in their complementary mechanisms, which may provide synergistic effects on neurotransmitter systems involved in mood regulation. Clinical studies suggest this combination can yield higher response rates than monotherapy for difficult-to-treat depression, though side effects such as sedation and weight gain are common[1][2][4][6].
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