Objective This study evaluated whether intramuscular (IM) ketamine is non‐inferior to intranasal (IN) esketamine for treatment‐resistant depression (TRD) and assessed differences in safety and healthcare costs. Methods In a retrospective, observational sequential cohort at the VA San Diego, 179 Veterans with TRD received eight treatments of either IN esketamine ( n = 89) or IM ketamine ( n =...
Ketamine promotes spine growth on the apical dendrites of pyramidal neurons in the prefrontal cortex (PFC), which are critical for its behavioral effects. Follow-up studies show that brain-derived neurotrophic factor (BDNF) signaling is critical for these effects. In this context, we sought to determine if microglial BDNF contributes to the synaptic and behavioral effects of ketamine....
ABSTRACT: Introduction Ketamine and esketamine have reemerged as promising interventions for treatment-resistant depression (TRD), yet debate persists regarding the clinical relevance of acute dissociative experiences. This secondary exploratory analysis examined the relationship between dissociative experiences induced by subcutaneous esketamine and antidepressant response in patients with...
Neuroinflammation, particularly Toll-like receptor 4 (TLR4)-mediated signaling, plays a critical role in the pathophysiology of depression. This study aimed to investigate the mechanisms by which S-ketamine (S-ket) and S-hydroxynorketamine (S-HNK) modulate TLR4 and peroxisome proliferator-activated receptor alpha (PPARα) signaling in the prefrontal cortex (PFC) to exert antidepressant effects....
Over the past two decades, ketamine has emerged as a rapid-acting antidepressant, especially among patients with treatment-resistant depression. As an N-methyl-d-aspartate glutamate receptor antagonist, ketamine has reshaped the understanding of the underlying neurobiological mechanisms of depression treatment. Ketamine induces a transient state of enhanced neuroplasticity and likely...
Introduction Treatment-resistant major depressive disorder with high-risk suicidal ideation is a psychiatric emergency that requires rapid and effective intervention. Although intranasal esketamine and intermittent theta-burst stimulation (iTBS) are time-efficient therapeutic options, clinical reports describing their combined use in an accelerated inpatient schedule are limited, particularly...
Treatment-resistant depression (TRD) represents an unmet challenge, accounting for disproportionate morbidity, disability, and healthcare burden in depression. Limitations of monoaminergic antidepressants have prompted a conceptual shift toward models emphasizing impaired neuroplasticity, synaptic dysfunction, and network dysregulation. This expert review synthesizes preclinical, translational,...
NeuropharmacologyJuly 1, 2026Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.1 citation
N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...
Background and Objective Ketamine and esketamine have emerged as effective and rapid-acting interventions for treatment-resistant depression. Nevertheless, the best-suited candidates for these treatments are not clear. As such, the ability to personalize treatment selection and parameters would likely improve therapeutic response. This systematic review synthesized the literature on clinical...
Background. Ketamine provides rapid but short-lived antidepressant effects for treatment-resistant depression (TRD). To prolong this response, ketamine-assisted therapy (KAT) combines the drug's pharmacological effects with psychotherapy. Aim. This study aims to analyze scientific evidence regarding the synergistic interaction between ketamine's pharmacological effects and modern...