American Journal of Geriatric Psychiatry
February 24, 2026
Rachel Fremont, Amelia Karim, Tanya Peguero Estevez et al.
1 citation
OBJECTIVE: This open-label clinical trial primarily examined the safety and tolerability of ketamine treatment in patients with mild cognitive impairment and Major Depressive Disorder (MCI-D). Preliminary efficacy was also explored. METHODS: The trial was conducted between November 2023 and March 2025. Patients with MCI-D and moderate to severe symptom levels of depression received a single...
The Journal of Clinical Psychiatry
April 2, 2025
Adriana Feder, Oneysha Brown, Sarah B. Rutter et al.
Objective: This open-label clinical trial examined the preliminary efficacy of combining a course of 6 ketamine infusions with a brief, evidence-based exposure-based psychotherapy-written exposure therapy (WET)-in patients with chronic posttraumatic stress disorder (PTSD). Methods: The trial was conducted between June 2021 and October 2023. Patients with chronic PTSD and high-moderate to severe...
Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...
Translational Psychiatry
January 10, 2022
F. Cathomas, L. Bevilacqua, Aarthi Ramakrishnan et al.
44 citations
Ketamine has rapid and sustained antidepressant effects in patients with treatment-resistant depression (TRD). However, the underlying mechanisms of action are not well understood. There is increasing evidence that TRD is associated with a pro-inflammatory state and that ketamine may inhibit inflammatory processes. We thus investigated whole blood transcriptional profiles related to TRD and...
medRxiv Preprint Server
April 10, 2021
Agnes Norbury, Sarah B. Rutter, Abigail B. Collins et al.
1 citation
preprint
Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants...
American Journal of Psychiatry
January 5, 2021
Adriana Feder, Sara Costi, Sarah B. Rutter et al.
239 citations
OBJECTIVE Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first...
Neuron
March 1, 2019
John H. Krystal, Chadi G. Abdallah, Gerard Sanacora et al.
443 citations
Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy. The rapid, profound, and sustainable antidepressant effects of ketamine...
Journal of Affective Disorders
August 15, 2017
James W. Murrough, Elizabeth Wade, Sehrish Sayed et al.
At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan...
Translational Psychiatry
March 21, 2017
Drew D. Kiraly, Sarah R. Horn, Nicholas T. van Dam et al.
182 citations
Abstract A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at...
Psychological Medicine
August 12, 2015
James W. Murrough, Laili Soleimani, Kaitlin E. DeWilde et al.
297 citations
BACKGROUND: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with...
Translational Psychiatry
February 17, 2015
James W. Murrough, Katherine A. Collins, Jessica Fields et al.
111 citations
The glutamate N-methyl-D-aspartate receptor antagonist ketamine has demonstrated antidepressant effects in individuals with treatment-resistant major depressive disorder (TRD) within 24 h of a single dose. The current study utilized functional magnetic resonance imaging (fMRI) and two separate emotion perception tasks to examine the neural effects of ketamine in patients with TRD. One task used...
The Journal of Clinical Psychiatry
September 2, 2014
Le-Ben Wan, Cara F. Levitch, Andrew M. Perez et al.
232 citations
OBJECTIVE: Ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the safety and tolerability of ketamine in this population have not been fully described. Herein we report the largest study to date of the safety, tolerability, and acceptability of ketamine in TRD. METHOD: Data from 205 intravenous (IV) ketamine infusions (0.5...
JAMA Psychiatry
April 16, 2014
Adriana Feder, Michael K. Parides, James W. Murrough et al.
618 citations
IMPORTANCE: Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. OBJECTIVE: To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. DESIGN, SETTING, AND PARTICIPANTS:...
Depression and Anxiety
March 25, 2014
Rebecca B Price, Dan V. Iosifescu, James W. Murrough et al.
342 citations
BACKGROUND: Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit...
The Annual Review of Pharmacology and Toxicology
January 6, 2014
Mark J. Niciu, Ioline D. Henter, David A. Luckenbaugh et al.
166 citations
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant...
The International Journal of Neuropsychopharmacology
October 8, 2013
Colin N. Haile, James W. Murrough, Dan V. Iosifescu et al.
251 citations
Ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), but the magnitude of response varies considerably between individual patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a biomarker of treatment response in depression and has been implicated in the mechanism of action of ketamine. We evaluated plasma BDNF and associations with...
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...
The International Journal of Neuropsychopharmacology
March 17, 2009
Sanjay J. Mathew, James W. Murrough, Marije Aan Het Rot et al.
295 citations
The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-dose intravenous (i.v.) ketamine; (2) test the efficacy of the glutamate-modulating agent riluzole in preventing post-ketamine relapse; and...
Archives of General Psychiatry
August 1, 2006
Carlos A. Zarate, Jaskaran Singh, Paul J. Carlson et al.
3,762 citations
CONTEXT: Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the...
Archives of General Psychiatry
March 1, 2000
Amit Anand, Dennis S. Charney, Dan A. Oren et al.
425 citations
BACKGROUND: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as...
October 1, 1999
R. Andrew Chambers, J. Douglas Bremner, Bita Moghaddam et al.
140 citations
Dissociative cognitive and perceptual alterations commonly occur at the time of traumatization and as an enduring feature of post-traumatic stress disorder (PTSD). After stress exposure, dissociative symptoms are a predictor of the development of PTSD. Recent preclinical data suggest that stress stimulates the cortico-limbic release of glutamate. The glutamate that is released during stress in...
Journal of Traumatic Stress
1998
J. Douglas Bremner, John H. Krystal, Frank W. Putnam et al.
826 citations
The purpose of this study was to develop an instrument for the measurement of present-state dissociative symptoms, the Clinician Administered Dissociative States Scale (CADSS). Reported here are interrater reliability and internal consistency of the CADSS, validity as assessed by comparisons with other instruments for the assessment of dissociation, and sensitivity of the CADSS to discriminate...