Blockade of postsynaptic serotonin receptors, which differentiates these agents from other drug classes. Nefazodone and trazodone also inhibit serotonin reuptake in the presynaptic neuron and are subclassified as 'serotonin antagonist and reuptake inhibitors.' Nefazodone has demonstrated efficacy in randomize d controlled trials of major depressive disorder, however, this agent was taken off the market in some countries due to concerns about liver toxicity. Trazodone has also demonstrated efficacy in randomized controlled trials of major depressive disorder; however, it is typically used as a sleep agent. Vilazodone is known as a dual action drug, It acts predominantly as a serotonin-reuptake inhibitor and as a partial agonist of 5-HT1A receptors. Serotonin-reuptake and receptor blockers, particularly serotonin antagonist and reuptake inhibitors, should be considered as second-line treatments for depression.