ketamine + venlafaxine

Ketamine + venlafaxine is a combination of two pharmaceutical drugs used primarily in the management of treatment-resistant depression and other mood disorders. Ketamine is a dissociative anesthetic that acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, leading to increased glutamate signaling and rapid antidepressant effects. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that increases synaptic concentrations of serotonin and norepinephrine by inhibiting their reuptake at presynaptic terminals, with some weak inhibition of dopamine reuptake as well. The combination may be considered in clinical practice for patients who have not responded adequately to standard antidepressant therapy alone. Both agents can increase blood pressure and heart rate, so their combined use requires careful monitoring for cardiovascular side effects[1][2][4]. There is evidence suggesting the safety profile of this combination is similar to that seen when ketamine is combined with SSRIs, though transient elevations in blood pressure may occur[4][6]. Venlafaxine may also increase the bioavailability of ketamine due to CYP3A4 inhibition[4].