Archives of General Psychiatry
August 1, 2006
Carlos A. Zarate, Jaskaran B. Singh, Paul J. Carlson et al.
3,762 citations
A single intravenous dose of ketamine, an N-methyl-D-aspartate receptor antagonist, produced rapid and robust antidepressant effects in treatment-resistant major depression. Improvement was significant within 110 minutes and remained so for one week. The effect size was very large after 24 hours and moderate to large after one week. Among 17 subjects, 71% met response and 29% met remission criteria the day after infusion; 35% maintained response for at least one week. These findings suggest a role for glutamatergic modulation in achieving rapid relief from depression.
American Journal of Psychiatry
August 28, 2013
James W. Murrough, Dan V. Iosifescu, Lee C. Chang et al.
1,207 citations
A single intravenous infusion of ketamine produced greater improvement in depression severity 24 hours later than the active placebo midazolam in patients with treatment-resistant major depression. In a randomized controlled trial of 73 participants, the ketamine group scored 7.95 points lower on the Montgomery-Åsberg Depression Rating Scale than the midazolam group. Response rates were 64% for ketamine and 28% for midazolam, with an odds ratio of 2.18 favoring ketamine. The findings support NMDA receptor modulation as a mechanism for rapid improvement in severe, chronic depression, though more information on durability and safety is needed before clinical use.
Journal of Traumatic Stress
January 1, 1998
J. Douglas Bremner, John H. Krystal, Frank W. Putnam et al.
826 citations
A new instrument, the Clinician Administered Dissociative States Scale (CADSS), was developed to measure present-state dissociative symptoms. Initial analyses showed good interrater reliability and construct validity. CADSS scores successfully discriminated patients with dissociative disorders from patients with other psychiatric disorders and from healthy subjects.
JAMA Psychiatry
April 16, 2014
Adriana Feder, Michael K. Parides, James W. Murrough et al.
618 citations
A single intravenous dose of ketamine (0.5 mg/kg) rapidly reduced posttraumatic stress disorder (PTSD) symptom severity more than the active placebo midazolam in patients with chronic PTSD. Twenty-four hours after infusion, the ketamine group showed a mean reduction of 12.7 points on the Impact of Event Scale-Revised compared to midazolam. Ketamine also lessened comorbid depressive symptoms and improved overall clinical presentation. The treatment was generally well tolerated without persistent dissociative symptoms. These results suggest ketamine may offer a novel pharmacologic approach for chronic PTSD, though replication is needed.
Archives of General Psychiatry
March 1, 2000
Amit Anand, Dennis S. Charney, Dan A. Oren et al.
425 citations
A drug that inhibits glutamate release, lamotrigine, reduced several effects of ketamine in healthy adults. Lamotrigine given before ketamine decreased perceptual abnormalities, positive and negative schizophrenia-like symptoms, and learning and memory impairment. However, it increased the immediate mood-elevating effects of ketamine. These findings suggest that glutamate release plays a role in some effects of NMDA receptor blockade and that drugs reducing glutamate release might help treat conditions like schizophrenia, though more research is needed.
The Annual Review of Pharmacology and Toxicology
January 6, 2014
Mark J. Niciu, Ioline D. Henter, David A. Luckenbaugh et al.
166 citations
The NMDA receptor antagonist ketamine produces rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression, contrasting with the modest effects of classic monoaminergic antidepressants that take weeks. Open-label and case studies support these properties. Preclinical research has identified three targets—mTOR, eEF2, and GSK-3—as key to its mechanism. Current efforts focus on prolonging ketamine's effects, developing selective NMDA receptor antagonists without its adverse effects, and identifying biomarkers of its antidepressant action.
American Journal of Geriatric Psychiatry
February 24, 2026
Rachel Fremont, Amelia Karim, Tanya Peguero Estevez et al.
1 citation
In an open-label clinical trial, a single intravenous infusion of ketamine (0.5 mg/kg) was safe and well tolerated in 13 patients with mild cognitive impairment and major depressive disorder. No serious adverse events occurred. Depression severity, measured by the Montgomery-Asberg Depression Rating Scale, dropped from a mean of 27.4 before treatment to 5.7 at 24 hours after the infusion—a large-magnitude improvement. For 8 of the 13 patients, this improvement persisted for up to one month, with a mean score of 12.1 and at least a 50% reduction. These findings suggest ketamine may be effective for depression in this population, but larger randomized controlled trials are needed to confirm efficacy and assess cognitive effects.
medRxiv Preprint Server
April 10, 2021
Agnes Norbury, Sarah B. Rutter, Abigail B. Collins et al.
1 citation
preprint
In a small randomized clinical trial, repeated doses of ketamine improved PTSD symptoms more than midazolam. Brain scans showed that symptom improvement was linked to increased communication between the ventromedial prefrontal cortex and amygdala when viewing emotional faces, especially in those who received ketamine. Ketamine-related improvement was also predicted by decreased activity in the dorsal anterior cingulate during emotional conflict and increased resting-state connectivity between the ventromedial prefrontal cortex and anterior insula. Further analysis indicated that ketamine specifically strengthened the prefrontal cortex's ability to inhibit amygdala responses to threatening social cues, suggesting a normalization of brain circuits involved in fear regulation.