The International Journal of Neuropsychopharmacology
November 14, 2018
Bashkim Kadriu, Laura Musazzi, Ioline D. Henter et al.
164 citations
Dysfunctional glutamatergic neurotransmission may underlie the pathophysiology of both major depressive disorder and bipolar depression. A single intravenous infusion of the glutamatergic modulator ketamine elicits fast-acting, robust, and relatively sustained antidepressant, antisuicidal, and antianhedonic effects in individuals with treatment-resistant depression. Ketamine's targets include noncompetitive N-methyl-D-aspartate receptor inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid throughput potentiation, and N-methyl-D-aspartate receptor targets on gamma-aminobutyric acid-ergic interneurons. This review describes ketamine and other novel glutamate-based treatments for treatment-resistant depression, including N-methyl-D-aspartate receptor antagonists, glycine binding site ligands, metabotropic glutamate receptor modulators, and other glutamatergic modulators, along with their putative mechanisms and clinically relevant studies.
Translational psychiatry
May 25, 2024
Marta Valenza, Roberta Facchinetti, Carola Torazza et al.
26 citations
Acute stress triggers a rapid response from glial cells—astrocytes and microglia—in the prefrontal cortex of rats, activating the NF-κB pathway and increasing inflammatory cytokines IL-18 and TNF-α. In vulnerable animals, this response persists alongside altered levels of glial proteins S100B, CD11b, and CX43, brain trophic factors BDNF and FGF2, and synaptic proteins MAP2 and PSD95. A single subanesthetic dose of ketamine given 24 hours after stress reversed many of these changes, suggesting it helps restore brain homeostasis. Reactive astrogliosis, changes in trophic factors, and neuronal damage appear to be key determinants of vulnerability to acute traumatic stress, and ketamine shows therapeutic potential against stress-related psychiatric disorders.
October 1, 2020
Laura Musazzi
1 citation
Intranasal esketamine, the (S) enantiomer of ketamine, has been approved for treatment-resistant depression in adults by the FDA and EMA, and will soon be available in Italy. Ketamine is a non-competitive NMDA glutamate receptor antagonist used for over 50 years as an anesthetic and analgesic, but also abused recreationally at high doses. Low-dose ketamine infusions produce rapid and sustained antidepressant effects in severe treatment-resistant patients with only mild dissociative side effects. While repeated intranasal esketamine's efficacy and safety have been demonstrated, the cellular mechanisms behind its antidepressant effect remain unclear. Long-term benefit/risk assessments are missing, but esketamine is the first approved rapid-acting antidepressant with a new mechanism involving glutamate transmission and neuroplasticity.