IP8 Depression Therapeutics Practice Test

How do serotonin-norepinephrine reuptake inhibitors (SNRIs) differ from SSRIs, and what are common SNRI examples?

They selectively inhibit SERT, with examples including fluoxetine and sertraline.

They block NET but not SERT, with bupropion as an example.

They block both SERT and NET, increasing serotonin and norepinephrine; examples include venlafaxine, duloxetine, desvenlafaxine.

SNRIs differ from SSRIs by blocking both the serotonin transporter and the norepinephrine transporter, which increases levels of both serotonin and norepinephrine in the synapse. This dual reuptake inhibition is the defining feature of SNRIs and underlies their effectiveness for depression and certain pain conditions. Classic examples of this dual action are venlafaxine, duloxetine, and desvenlafaxine. It’s helpful to note that venlafaxine can have dose-dependent effects, with stronger norepinephrine inhibition at higher doses, but the core idea remains dual blockade of SERT and NET. By contrast, SSRIs selectively inhibit SERT and do not significantly affect NET, which is why fluoxetine and sertraline are SSRIs. Other drugs like bupropion primarily inhibit norepinephrine and dopamine reuptake (not serotonin) and thus are not SNRIs. Blocking serotonin receptors would be a different mechanism entirely and does not describe SNRI action.

They block 5-HT receptors as their primary action.