edivoxetine + selective serotonin reuptake inhibitor

**Edivoxetine + selective serotonin reuptake inhibitor** is a combination therapy involving **edivoxetine**, a highly selective norepinephrine reuptake inhibitor (NRI), and a **selective serotonin reuptake inhibitor (SSRI)**. This combination was developed to treat major depressive disorder (MDD) in patients with partial response to SSRI monotherapy. Edivoxetine blocks the norepinephrine transporter (NET), increasing noradrenergic neurotransmission, while SSRIs inhibit the serotonin transporter (SERT), increasing serotonergic neurotransmission. The rationale behind combining these drugs was to address symptoms thought to be unresponsive to serotonergic agents alone, such as fatigue and cognitive impairment. Despite a clear pharmacodynamic effect and a safety profile consistent with noradrenergic activation—including increased blood pressure and heart rate, hyperhidrosis, nausea, and dry mouth—multiple large randomized phase III trials found that adjunctive edivoxetine did not improve depression outcomes more than adjunctive placebo when added to SSRIs, and the development was discontinued[1][2][3][4][5][7][8].