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Paroxetine + venlafaxine is a combination of two antidepressant medications, each with distinct but overlapping mechanisms of action. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin levels by inhibiting its reuptake into presynaptic neurons. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI), which inhibits the reuptake of both serotonin and norepinephrine, thereby increasing their concentrations in the synaptic cleft. This combination may be considered in treatment-resistant depression to potentially leverage both serotonergic and noradrenergic effects for enhanced antidepressant efficacy. However, combining these agents increases the risk of adverse effects such as serotonin syndrome and should only be done under close medical supervision[2][4][5]. There is limited evidence supporting routine use of this specific combination; most clinical data compare their individual efficacy rather than their combined use[1][3].
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