Abstract

THE ROLE KETAMINE, A N-METHYL D-ASPARTATE (NMDA) RECEPTOR ANTAGONIST IN TREATMENT RESISTANCE DEPRESSION (TRD)

Dipesh I. Wadhwani*, Sanket V. Gore, Ashwini K. Bawankule and Twinkle S. Zade

ABSTRACT

Ketamine is a new treatment option providing new hope for TRD. Treatment Resistant Depression (TRD) is a common condition with poor outcomes with a few treatment options. Treatment-resistant depression (TRD) typically refers to incomplete response to antidepressant trial of adequate doses and duration.The administration of ketamine results in a great improvement of depression symptoms. The rapid antidepressant action of the glutamatergic N-methyl-Daspartate (NMDA) receptor antagonist ketamine has great interest among researchers. Ketamine enhaces the presynaptic release of glutamate, results into the higher extracellular levels of glutamate by a combination of disinhibition of the neurotransmitter g-aminobutyric acid (GABA) and blockage of the NMDA receptors to the phencyclidine binding site within the ion channel. This elevation in extracellular glutamate release favours coexpressed a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), resulting in ‗an increased glutamatergic throughput of AMPA relative to NMDA. The glutamatergic system is fundamental for neuroplasticity, which is connected to mood disorders. NMDA receptor activation is part of the process for long-term potentiation, an important form of synaptic plasticity. Synapse-associated proteins and the number of dendritic spines then increase, for example, in the prefrontal cortex, thus reversing the structural and functional deficits resulting from long-term stress exposure. Also, ketamine was also found to be effective in reducing suicidality in TRD samples. This findings provide the substantial evidence for the role of ketamine in treatment resistance depression (TRD).The study proposed ketamine based therapies in the treatment of the treatment resistance depression (TRD) and major depressive disorder (MDD).

Keywords: Ketamine, Treatment resistance depression (TRD), NMDA receptor, Depression, Antidepressants, AMPA receptor.