Psychological Medicine
August 12, 2015
James W. Murrough, Laili Soleimani, Kaitlin E. DeWilde et al.
297 citations
A single infusion of ketamine, compared to midazolam as an active placebo, did not reduce suicidal ideation scores on the Beck Scale for Suicidal Ideation at 24 hours in patients with mood and anxiety disorders who were at elevated risk for suicidal behavior. A significant difference favoring ketamine emerged at 48 hours, but the effect was no longer significant by the end of 7 days. The intervention was well tolerated with no dropouts during the primary assessment period. The findings support the safety and tolerability of ketamine for suicidal ideation but larger studies are needed.
The International Journal of Neuropsychopharmacology
March 17, 2009
Sanjay J. Mathew, James W. Murrough, Marije Aan Het Rot et al.
295 citations
A single intravenous dose of ketamine (0.5 mg/kg) produced rapid antidepressant effects in patients with treatment-resistant major depression, with 65% responding at 24 hours and 54% at 72 hours. Pretreatment with lamotrigine did not reduce ketamine's mild side effects or improve its antidepressant action. In a subsequent randomized trial, riluzole (100-200 mg/day) failed to prevent relapse over 32 days; 80% of riluzole-treated patients relapsed versus 50% on placebo, leading to early termination. Ketamine appears well-tolerated and rapidly effective, but better strategies to sustain its benefits are needed.
Translational Psychiatry
February 17, 2015
James W. Murrough, Katherine A. Collins, Jessica Fields et al.
111 citations
A single low dose of ketamine increases brain activity in the right caudate when people with treatment-resistant depression view happy faces, reversing a baseline deficit compared with healthy volunteers. Twenty patients with treatment-resistant depression not taking other antidepressants underwent fMRI before and 24 hours after receiving intravenous ketamine (0.5 mg per kg of body weight). Twenty matched healthy controls were scanned once. Before ketamine, depressed patients showed reduced neural responses to happy faces in the right caudate. After ketamine, responses to happy faces increased in a similar region. Greater connectivity of the right caudate during positive emotion perception was linked to greater improvement in depression severity. No effects were seen for sad faces.
JAMA Network Open
June 3, 2024
Manish Kumar Jha, Samuel T. Wilkinson, Kamini Krishnan et al.
29 citations
In people with treatment-resistant depression who do not have psychosis, intravenous ketamine works as well as electroconvulsive therapy (ECT) overall. Among outpatients with moderately severe or severe depression, ketamine produced greater improvement in depressive symptoms than ECT. In contrast, inpatients with very severe depression improved more with ECT early in treatment, though by the end of the three-week course both treatments were similarly effective. Higher premorbid intelligence and a diagnosis of posttraumatic stress disorder were linked to greater improvement with ECT, but not with ketamine. These findings may help patients and clinicians decide between the two treatments.
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.
The Journal of Clinical Psychiatry
September 3, 2025
Kristina T. Kumpf, Samuel T. Wilkinson, Bo Hu et al.
In a multisite randomized trial comparing cognitive effects of intravenous ketamine and electroconvulsive therapy (ECT) in patients with treatment-resistant depression, those receiving six ketamine treatments showed superior cognitive functioning after a three-week treatment course compared with those receiving nine ECT sessions. No significant differences in cognitive task performance were associated with response to either treatment. Among responders followed for up to six months, no group differences emerged. Subjective memory measures were mixed: both groups improved on the Squire Memory Complaint Questionnaire, with ketamine recipients reporting greater functional gains, while ketamine-treated patients reported improvements on a global self-evaluation of memory but ECT-treated patients reported a decline. Within the ketamine group, improvements in executive functioning and cognitive flexibility survived adjustment for changes in depression, suggesting partial independence of cognitive and mood effects.
Journal of Affective Disorders
August 15, 2017
James W. Murrough, Elizabeth Wade, Sehrish Sayed et al.
A combination of dextromethorphan and quinidine, given at up to 45/10 mg twice daily for 10 weeks, reduced depression scores in patients with treatment-resistant depression. Twenty patients with unipolar treatment-resistant depression enrolled; six discontinued early. Depression scores on the Montgomery-Asberg Depression Rating Scale dropped by an average of 13 points, and on the Quick Inventory of Depressive Symptomatology by nearly 6 points. Response and remission rates were 45% and 35%, respectively. No treatment-emergent suicidal thoughts, psychosis, or dissociation occurred. The open-label, proof-of-concept design limits conclusions, but results suggest the combination is tolerable and warrants larger placebo-controlled trials.