Developments in Psychopharmacology for Major Depressive Disorder

Abstract

After years of emphasizing the same monoamine-based neurotransmitter mechanisms for treating depression, the antidepressant medication pipeline is broadening its reach. While serotonin, norepinephrine, and dopamine remain important treatment targets, researchers are working on compounds targeting their receptors in novel ways, as well as different combinations of monoaminergic actions that they hope will lead to improved efficacy and/or decreased side effects.At the same time, other researchers are focusing on completely different avenues of drug development, such as medications that target glutamate or acetylcholine neurotransmission, opioid receptors, or hormonal systems such as vasopressin and melatonin. Advances in pharmacogenetics also offer the possibility of targeting medications more specifically to individuals depending on their likelihood of response or side effects. This article outlines some promising directions for antidepressant drug development and discusses examples for each that have been undergoing testing.

Novel and Investigational Drugs in Depression

“…Multiple studies have supported the efficacy of vilazodone in the treatment of depression [7][8][9]. Given its unique mechanism of action, vilazodone is often called a serotonin partial agonist reuptake inhibitor (SPARI) [4,[10][11][12][13]. Theories of why this medication has shown to be effective include its 5-HT1A partial agonism which, in combination with serotonin transporter (SERT) inhibition, may lead to rapid and robust elevations of synaptic 5-HT.…”

“…It can be classified as a triple reuptake inhibitor (TRI) or a serotoninnorepinephrine-dopamine reuptake inhibitor with additional pharmacological properties including 5-HT2C, 5-HT3, 5-HT2A, and alpha-1a antagonism [4,38]. This class of drug holds promise for a robust response by targeting three main neurotransmitters without requiring high occupancy of the serotonin transporter, thus potentially reducing some serotonin mediated side effects [11]. According to a Lundbeck release, in vivo rat studies involving tedatioxetine demonstrated increases in acetylcholine, noradrenaline, dopamine, and serotonin levels in brain regions involved in mood regulation.…”