mirtazapine + paroxetine

Mirtazapine + paroxetine is a combination of two antidepressant medications used in the management of major depressive disorder (MDD), particularly in patients who do not respond adequately to initial monotherapy. Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts primarily as an antagonist at central presynaptic alpha-2 adrenergic inhibitory autoreceptors and heteroreceptors, increasing norepinephrine and serotonin release. It also antagonizes serotonin 5-HT2 and 5-HT3 receptors, enhancing serotonergic neurotransmission via 5-HT1A receptors. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin levels by inhibiting its reuptake into presynaptic neurons. The combination has been studied for efficacy in patients with MDD who show early non-response to SSRI monotherapy; however, evidence suggests no significant advantage over monotherapy with either agent alone[2]. Caution is warranted due to the risk of serotonin syndrome when these drugs are combined[1].