Ketamine, a dissociative anesthetic introduced in the 1960s, has re-emerged as a versatile therapeutic agent extending beyond its traditional perioperative role. Its rapid antidepressant action in treatment-resistant depression and efficacy in acute and chronic pain syndromes have driven what is termed the “ketamine renaissance.” Unlike conventional monoaminergic antidepressants, ketamine...
Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EMBER-MDD) is a non-interventional, investigator-initiated, in-vitro study within the EU Psych-STRATA programme, analyzing biospecimens collected in the randomized INTENSIFY study...
Major depressive disorder, or MDD, is a common cause of disability around the world. Treatment-resistant depression, or TRD, is a tough challenge. Many people do not respond well to treatment, which increases the risk of relapse and suicide. Esketamine is a new treatment that comes as a nasal spray. It works quickly and targets a specific brain receptor. This review looks at research from...
Major depressive disorder (MDD) is a heterogeneous, debilitating disorder. A distinct subgroup within the MDD spectrum is identified to have treatment-resistant depression (TRD). There is an impetus to find alternative treatments for TRD to reduce disease burden and improve quality of life. Psychedelics have been used in the treatment of various psychiatric disorders since the 1950s, with...
Major depressive disorder (MDD) ranks among the foremost contributors to disability worldwide, yet its neurophysiological mechanisms remain poorly understood. Excitation-inhibition (E/I) imbalance has been implicated in MDD pathophysiology, but cortex-wide E/I ratio and its molecular substrates in MDD remain unknown. Resting-state functional magnetic resonance imaging data from 254 MDD patients...
The U.S. Food and Drug Administration (FDA) has increasingly focused on breakthrough molecular mechanisms, rapidly acting medications, and expanded therapeutic indications in the treatment of depression. During this period, psychiatric interventions targeting N-methyl-D-aspartate (NMDA) receptors and intracellular signaling pathways have gained prominence, moving beyond the traditional...
Introduction: Treatment-resistant depression (TRD) is a major public health and societal challenge, associated with persistent symptoms, functional impairment, and increased healthcare and economic burden. Intranasal esketamine has emerged as a rapid-acting adjunctive therapy with a distinct glutamatergic mechanism of action. This systematic review summarizes current evidence on its...
Background: Intranasal esketamine (ESK-NS) is an effective treatment for treatment-resistant depression (TRD), but whether antidepressant outcomes differ by sex and age remains insufficiently explored. Methods: This secondary analysis of the REAL-ESK study included 210 patients with TRD treated with ESK-NS in routine clinical practice and assessed at baseline (T0), one month (T1), and three...
Oral S-ketamine (S-KETPO) is being explored as an alternative to intravenous maintenance treatment (S-KETIV) in treatment-resistant depression (TRD). However, the first-pass effect with S-KETPO significantly alters S-ketamine's bioavailability and the systemic exposure of its active metabolites, raising potential safety and efficacy concerns. This study characterized the pharmacodynamic and...
Depression and its severe outcomes, suicidal ideation and behavior, are exacerbated by stress. A broad literature links dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) stress response system to depression, suicidal ideation and behavior. Our midazolam-controlled clinical trial of subanesthetic, intravenous ketamine infusion for suicidal depressed patients found rapid reduction...