Over the last two decades, several studies have shown the role that the
glutamatergic system plays in the pathophysiology of major depressive disorders
(MDD). This theory is supported mainly by the fact that glutamatergic modulators have
revealed antidepressant effects in animal models as well as in clinical trials. Many of
these compounds have been created to be tested as antidepressants. However, there are
many other compounds used in the treatment of non-depressive illnesses that have
subsequently been discovered to possess antidepressant properties, one such example
being ketamine. Ketamine is an antagonist of the N-methyl-D-aspartate receptor, and it
has shown to improve the symptoms of patients with MDD, including refractory
depression. Laboratory studies have mainly investigated the mechanism of action
responsible for the rapid and prolonged antidepressant effects presented by NMDA
modulators. This chapter will focus on studies which have demonstrated the
antidepressant effects of ketamine, as well as other glutamatergic modulators. Data
from experimental studies and clinical trials have also been included, and these will
demonstrate the biomarkers and mechanisms of action involved behind the effects of
fast acting antidepressants.
Keywords: Biomarkers, D-Cycloserine, Fast antidepressant, Glutamatergic
modulators, Glutamatergic system, Ketamine, Major depressive disorder,
Memantine, N-methyl-D-aspartate, Scopolamine, Sleep deprivation.
