fluoxetine + trazodone

Fluoxetine + trazodone is a combination of two antidepressant medications, each with distinct mechanisms of action. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin levels by inhibiting its reuptake in the central nervous system. Trazodone is classified as a serotonin antagonist and reuptake inhibitor (SARI); it acts primarily by antagonizing serotonin 5-HT2A and 5-HT2C receptors, weakly inhibiting serotonin reuptake, and also has antihistaminic and alpha-adrenergic blocking properties. This combination may be used in clinical practice for patients with major depressive disorder who have comorbid insomnia or anxiety, as trazodone can help manage sleep disturbances while fluoxetine addresses core depressive symptoms[3][6]. However, combining these drugs increases the risk of adverse effects such as serotonin syndrome due to additive serotonergic activity, excessive sedation, cognitive impairment, QT prolongation (especially in elderly or those with cardiac conditions), and increased plasma concentrations of trazodone and its active metabolite mCPP due to CYP2D6 inhibition by fluoxetine[1][3][4][5][6]. The combination should only be prescribed under close medical supervision.