Modulating the serotonin system in the treatment of major depressive disorder

CNS Spectr. 2014 Dec;19 Suppl 1:57-67; quiz 54-7, 68. doi: 10.1017/S1092852914000613.


Discuss the theory of modulation of receptor activity or the blockade of the reuptake of multiple neurotransmitter systems for the future treatment of MDD. Major depressive disorder (MDD) is a serious and often crippling psychiatric illness with a high risk of relapse and treatment resistance. In this article, we discuss the role of the serotonergic system in MDD including our current understanding of how various serotonin (5HT) receptors modulate monoamine neurotransmission and behavior. We also discuss how pharmacologic interventions, including novel and existing antidepressants and atypical antipsychotics, may be utilized to adjust serotonergic neurotransmission and provide more effective treatments for patients with MDD.

Keywords: SERT; atypical antipsychotic; serotonin; vilazodone; vortioxetine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Antipsychotic Agents / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / metabolism
  • Humans
  • Receptors, Serotonin / metabolism
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin / metabolism
  • Synaptic Transmission / physiology


  • Antidepressive Agents
  • Antipsychotic Agents
  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Serotonin