Social Psychiatry, Vol. 52 No. 2, 2024.
Review article
https://doi.org/10.24869/spsih.2024.151
Treatment-Resistant Depression: New Insights into the Etiopathogenesis and the Role of Esketamine in Treatment
Maja Živković
; University of Zagreb School of Medicine, Zagreb, Croatia; University Hospital Centre Zagreb, Zagreb, Croatia
Dino Žujić
; University of Zagreb School of Medicine, Zagreb, Croatia
Alma Mihaljević-Peleš
; University of Zagreb School of Medicine, Zagreb, Croatia; University Hospital Centre Zagreb, Zagreb, Croatia
Abstract
Treatment-resistant depression (TRD) occurs in about 30% of patients with major depressive disorder who have not
achieved an adequate therapeutic response after two or more lines of treatment with antidepressants, provided that they
have taken each selected antidepressant for a sufficient period of time and at the appropriate dose. Numerous factors
are associated with the etiopathogenesis of TRD, one of the significant ones being the neurotransmitter glutamate. In
excessive concentrations in the extracellular space, glutamate causes excitotoxicity, further leading to the release of
proinflammatory cytokines and the development of neuroinflammation. This results in damage to neurons in brain
regions responsible for emotional behavior and mood regulation, which may clinically manifest as TRD. Treating TRD
poses a great challenge for clinicians because, despite the numerous current pharmacological and non-pharmacological
treatment methods, there is a great need for new and more effective treatment strategies. Esketamine represents a new
therapeutic possibility in the treatment of TRD. Unlike traditional antidepressants, it acts as an antagonist to glutamatergic
NMDA receptors, it is administered intranasally, and has acute effects. Due to its unique mechanism of action, it can
be effective in treating TRD by enhancing the signaling of neurotrophic factors and synaptogenesis. Esketamine is
increasingly considered as a welcome new pharmacological strategy in the treatment of TRD, while the inhibition of the
excitotoxic effects of glutamate places this neurotransmitter increasingly at the center of scientific research.
Keywords
Treatment-Resistant Depression; Glutamate; Neuroinflammation; Esketamine
Hrčak ID:
320431
URI
Publication date:
28.8.2024.
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