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**Brexpiprazole + duloxetine** is a combination of two approved psychiatric medications used for the treatment of major depressive disorder, typically where brexpiprazole acts as adjunctive therapy to other antidepressants. **Brexpiprazole** is a second-generation (atypical) antipsychotic and serotonin-dopamine activity modulator whose mechanism includes partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors, and antagonist activity at serotonin 5-HT2A, 5-HT2B, 5-HT7, and multiple adrenergic receptors. **Duloxetine** is a serotonin-norepinephrine reuptake inhibitor (SNRI) that increases levels of serotonin and norepinephrine by inhibiting their reuptake, with minor inhibition of dopamine reuptake. The combination is used to address symptoms of depression resistant to monotherapy, leveraging complementary mechanisms of action: brexpiprazole modulates monoaminergic receptor activity, while duloxetine raises monoamine levels in the synaptic cleft by blocking reuptake. There is a clinically significant drug interaction between the two, warranting careful monitoring for side effects such as serotonin syndrome and CNS effects[1][3][6][7].
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