Annals of medicine
July 3, 2026
Zheping Chen, Yaozhu Wang, Peilin Cong et al.
Patients undergoing acoustic neuroma (AN) surgery often experience postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were...
Journal of Affective Disorders
June 25, 2026
Tse-Hwei Choo, Hanga C Galfalvy, John G Keilp et al.
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...
European Journal of Psychotraumatology
June 15, 2026
V Ursule Taujanskaite, Sunjeev K. Kamboj
Background: State dissociation is commonly assessed using the Clinician Administered Dissociative States Scale (CADSS; 19-items). A briefer CADSS would have many advantages, enabling assessment of transient dissociative states and allowing repeated assessment within short intervals while minimizing participant burden. This is especially relevant in studies of dissociative drugs which cause...
Journal of Affective Disorders
June 8, 2026
Dian‐jeng Li, Tien-Wei Hsu, Te-Chang Changchien et al.
Little is known about esketamine's effectiveness for patients with major depressive disorder (MDD) comorbid substance use disorders (SUD). We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults aged ≥18 years with MDD. Three propensity-score-matched (1:1) cohorts were defined based on treatment: esketamine, antidepressant-only, and repetitive...
Journal of Affective Disorders
June 7, 2026
Lindsay L Benster, Jordan N Kohn, Benjamin Wade et al.
Repetitive transcranial magnetic stimulation (rTMS) and intranasal esketamine are FDA-approved for treatment-resistant depression (TRD), yet comparative real-world data on response trajectories and predictors of outcomes remain limited. A retrospective analysis was performed using electronic medical records from UC San Diego Health. Adults with TRD treated with rTMS (n = 279) or intranasal...
Psychiatry Research
May 12, 2026
Isis Lunsky, Gilmar Gutierrez, Xena Wang et al.
Postpartum Depression (PPD) is a common condition with serious consequences for both mother and baby if left untreated. Currently, few effective strategies exist for prevention of PPD. Ketamine and Esketamine are rapid acting and potent antidepressants, and emerging evidence is showing promising results for PPD. This review searched the MEDLINE, CINAHL, PsycINFO, EMBASE, and Cochrane databases,...
Journal of Affective Disorders
May 6, 2026
Rutger Boesjes, Claudia Oosterveld, Jeanine Kamphuis et al.
1 citation
Ketamine, including its enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine), has demonstrated rapid antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD), yet clinical responses vary widely, highlighting the need to identify mechanisms underlying treatment efficacy and related potential predictors. Growing evidence suggests that alterations in sleep...
Neuropharmacology
May 6, 2026
Taisiia Prosvirova, Wiktoria Podolecka, Jacek Wróbel et al.
Ketamine produces rapid antidepressant effects accompanied by marked changes in fast brain rhythms. High-frequency oscillations (HFO; 130-180 Hz) are an increasingly recognized signature of ketamine across species. However, their relationship to classical gamma activity and their circuit-level organization remain unclear. Using simultaneous multiregion recordings in freely moving male Wistar...
Journal of Affective Disorders
April 28, 2026
Nesreen Sedeek, Carley Rivers, Lucas Williamson et al.
Ketamine produces rapid antidepressant effects in a subset of patients with treatment-resistant depression, yet neuroimaging findings have been difficult to integrate because studies differ in imaging modality, analytic approach, task context, and post-infusion timing. To address this, we conducted a multimodal synthesis of functional magnetic resonance imaging (fMRI) and positron emission...
European Journal of Psychotraumatology
April 1, 2026
Maud Rothärmel, Lila Mekaoui, François Kazour et al.
1 citation
Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression increase the risk of treatment-resistant depression (TRD), with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for TRD, but its efficacy on comorbid TRD-PTSD remains...
American Journal of Psychiatry
March 17, 2021
Roger S McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff et al.
694 citations
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...
JAMA Psychiatry
June 5, 2019
Ella Daly, Madhukar H. Trivedi, Adam Janik et al.
766 citations
Importance: Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. Objective: To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable...
American Journal of Psychiatry
May 21, 2019
Vanina Popova, Ella Daly, Madhukar H. Trivedi et al.
879 citations
OBJECTIVE: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active...
Pharmacological Reviews
June 26, 2018
Panos Zanos, Ruin Moaddel, Patrick J. Morris et al.
1,272 citations
Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these...
American Journal of Psychiatry
April 16, 2018
Carla M. Canuso, Jaskaran Singh, Maggie Fedgchin et al.
666 citations
OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4...
Molecular Psychiatry
March 13, 2018
Panos Zanos, T. Gould
1,112 citations
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine’s widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the...
JAMA Psychiatry
December 27, 2017
Ella Daly, Jaskaran Singh, Maggie Fedgchin et al.
708 citations
Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants: This phase 2, double-blind, doubly randomized, delayed-start,...
American Journal of Psychiatry
October 3, 2017
S. Wilkinson, Elizabeth D. Ballard, Michael H. Bloch et al.
680 citations
Objective Suicide is a public health crisis with limited treatment options. We conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. Method Individual participant data were obtained from 10 of 11 identified comparison intervention studies (using either saline or midazolam as control). The analysis...
Nature
April 24, 2016
Panos Zanos, Ruin Moaddel, Patrick J. Morris et al.
1,602 citations
Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-d-aspartate...
American Journal of Psychiatry
August 28, 2013
James W. Murrough, Dan V. Iosifescu, Lee C. Chang et al.
1,207 citations
OBJECTIVE: Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. METHOD: This was a...
CNS Neuroscience & Therapeutics
April 10, 2013
G. Mion, Thierry Villevieille
690 citations
For more than 50 years, ketamine has proven to be a safe anesthetic drug with potent analgesic properties. The active enantiomer is S(+)-ketamine. Ketamine is mostly metabolized in norketamine, an active metabolite. During "dissociative anesthesia", sensory inputs may reach cortical receiving areas, but fail to be perceived in some association areas. Ketamine also enhances the descending...
Science
August 19, 2010
Nanxin Li, Boyoung Lee, Rongjian Liu et al.
2,875 citations
The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified. We observed...
Journal of Neuroscience
April 15, 1997
Bita Moghaddam, Barbara W. Adams, Anita Verma et al.
1,813 citations
Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal lobe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC function in part by interacting with...
Archives of General Psychiatry
March 1, 1994
John H. Krystal
3,339 citations
BACKGROUND: To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects. Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor. METHODS: Nineteen healthy subjects...