Treatment-resistant depression (TRD) remains a major clinical challenge in psychiatric practice and affects a substantial proportion of patients with major depressive disorder (MDD). It is commonly defined as failure to achieve remission after at least two adequately conducted antidepressant trials. TRD is associated with persistent functional impairment, increased morbidity, reduced quality of...
Introduction: Treatment-resistant depression (TRD) represents a significant clinical challenge, particularly when associated with suicidal ideation. Intranasal esketamine has emerged as an effective therapeutic option in refractory cases, while monoamine oxidase inhibitors (MAOIs) remain relevant in the management of severe and resistant conditions. Objective: To describe the clinical course of...
Background: Depression is a significant mental health condition affecting numerous individuals worldwide, leading to disability within society and posing a heightened risk of suicide, thereby diminishing overall quality of life. Depression, often a contributing factor in suicides, is associated with various prevalent medical conditions such as obesity, diabetes, stroke, Parkinson's disease, and...
PsychopathologyMarch 27, 2026Xiaoran Ding, Yaping Wu, Juan Yang et al.1 citation
Ketamine has emerged as a promising rapid-acting antidepressant with distinct advantages for the treatment of treatment-resistant depression (TRD). Its therapeutic effects are mediated through multi-target modulation of the glutamatergic system. Unlike conventional antidepressants, ketamine exerts a markedly faster onset of action; however, its long-term safety profile and potential risk of...
Medicine AdvancesMarch 27, 2026Thomas Edward Cutting, Richard Evans Hartman
ABSTRACT Numerous studies have demonstrated the efficacy of (R, S)‐ketamine as a treatment for post‐traumatic stress disorder (PTSD), treatment‐resistant depression, and comorbid occurrences of these conditions. The (R) and (S) stereoisomers of ketamine have also demonstrated efficacy in attenuating stress and depressive symptoms, with (R)‐ketamine demonstrating reduced abuse potential and side...
Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no...
The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline,...
Major depressive disorder (MDD) is a highly prevalent psychiatric illness for which rapid-acting antidepressants such as ketamine provide only transient benefit. Because κ-opioid receptor (KOR) signaling contributes to stress-related dysphoria and impaired neuroplasticity, we examined whether KOR antagonism could prolong ketamine’s antidepressant-like effects in a mouse model of adolescent...
To investigate the regulatory role of glutamatergic neurons in the medial prefrontal cortex (mPFC) in the antidepressant effects of esketamine. A total of 150 male C57BL/6J mice were randomly divided into 15 groups (n=10). The mice subjected to the chronic restraint stress (CRS), and those exhibiting depressive-like behaviors following CRS received either esketamine or saline treatment, and...
BACKGROUND: Intranasal esketamine has recently emerged as an innovative treatment option for treatment-resistant depression (TRD). This retrospective, uncontrolled study aimed to evaluate the real-world effectiveness of esketamine in an naturalistic inpatient setting and explore demographic and clinical factors associated with treatment response. METHODS: We conducted a chart review of 101...