Which antidepressant is known to be an antagonist at the 5-HT2A receptor?

Trazodone is recognized as an antagonist at the 5-HT2A receptor. This action is one of the key mechanisms through which trazodone exerts its antidepressant effects. By blocking the 5-HT2A receptors, trazodone can lead to increased serotonergic neurotransmission and may also contribute to its sedative effects, making it useful in treating depression, particularly in patients who also experience insomnia.

In contrast, other medications listed do not primarily work as 5-HT2A antagonists. Venlafaxine primarily functions as a serotonin-norepinephrine reuptake inhibitor and does not have significant antagonistic effects on the 5-HT2A receptor. Bupropion is a norepinephrine-dopamine reuptake inhibitor that does not interact notably with 5-HT2A receptors. Sertraline, while it is a selective serotonin reuptake inhibitor (SSRI), does not exhibit 5-HT2A antagonism as its key mechanism of action. Therefore, trazodone stands out for its unique profile among these antidepressants regarding the 5-HT2A receptor blockade.