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.
Molecular Psychiatry
October 3, 2018
M. Fava, M. Freeman, M. Flynn et al.
438 citations
Intravenous ketamine at 0.5 mg/kg and 1.0 mg/kg produces rapid antidepressant effects in adults with treatment-resistant depression, with most improvement seen one day after a single 40-minute infusion. Lower doses (0.1 mg/kg and 0.2 mg/kg) did not show consistent benefit. The study compared four ketamine doses against an active placebo (midazolam) in 99 outpatients across six U.S. sites. Higher doses caused more dissociative symptoms and temporary blood pressure increases, but infusions were generally well tolerated. The findings indicate a range of effective subanesthetic doses, with no clear advantage for doses below 0.5 mg/kg.
Depression and Anxiety
March 25, 2014
Rebecca B Price, Dan V. Iosifescu, James W. Murrough et al.
342 citations
A single subanesthetic dose of intravenous ketamine reduced explicit suicidal thoughts and implicit associations between self and escape in adults with treatment-resistant major depression more than the active placebo midazolam. Twenty-four hours after infusion, 53% of ketamine-treated patients scored zero on all three explicit suicide measures, compared with 24% of the midazolam group. The reductions in explicit suicidal cognition were largest in those with higher baseline suicidal thoughts and were partly explained by decreases in other depressive symptoms. The findings suggest ketamine may offer rapid relief from suicidal cognition beyond what a psychoactive placebo provides.
New England Journal of Medicine
May 24, 2023
A. Anand, S. Mathew, G. Sanacora et al.
263 citations
For treatment-resistant major depression without psychosis, intravenous ketamine is at least as effective as electroconvulsive therapy (ECT). In a randomized trial with 403 patients, 55.4% of those receiving ketamine and 41.2% of those receiving ECT showed a 50% or greater reduction in depression scores over three weeks. ECT was linked to a notable decline in memory recall after three weeks (average decrease of 9.7 points on a memory test vs. 0.9 points with ketamine), with gradual recovery during follow-up. Quality-of-life improvements were similar between groups. Ketamine caused dissociation, while ECT led to musculoskeletal side effects.
The International Journal of Neuropsychopharmacology
October 8, 2013
Colin N. Haile, James W. Murrough, Dan V. Iosifescu et al.
251 citations
In patients with treatment-resistant depression, ketamine increased blood levels of brain-derived neurotrophic factor (BDNF) in those who responded to the drug, compared to non-responders, 240 minutes after infusion. Higher BDNF levels were strongly linked to lower depression scores at multiple time points up to 72 hours. No such associations appeared in patients given the anesthetic midazolam. The findings support BDNF as a marker of ketamine's antidepressant effects.
The Journal of Clinical Psychiatry
September 2, 2014
Le-Ben Wan, Cara F. Levitch, Andrew M. Perez et al.
232 citations
Ketamine given intravenously at 0.5 mg/kg over 40 minutes was safe and well tolerated in a large group of patients with treatment-resistant depression. Across 205 infusions in 97 participants, the antidepressant response rate was 67%. Only about 2% of infusions were stopped due to adverse effects, and the overall dropout rate was 3%. Common temporary side effects in the first four hours included drowsiness, dizziness, poor coordination, blurred vision, and feeling strange or unreal. About one third of participants had changes in blood pressure or heart rate. There were small but significant increases in psychotomimetic and dissociative symptoms, but no lasting psychotic effects, medical complications, or increased substance use among those followed long-term.
Contemporary Clinical Trials
February 1, 2019
S. Mathew, S. Wilkinson, Murat Altinay et al.
54 citations
Electroconvulsive therapy (ECT) and ketamine show similar response rates for treatment-resistant depression, but a head-to-head comparison in a large, well-powered trial has been lacking. This protocol describes a non-inferiority trial randomizing 400 patients with treatment-resistant depression to receive either ECT thrice weekly or intravenous ketamine twice weekly for 3-5 weeks. The primary outcome is the proportion of responders based on a patient-reported depression scale. The study is designed to determine whether ketamine retains at least 90% of ECT's treatment effect. Results will inform patient choice, clinical practice, and insurance policies.
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.
Contemporary clinical trials communications
December 1, 2019
Brittany O'Brien, Charles E. Green, Rayan K. Al Jurdi et al.
10 citations
Over eleven million U.S. Veterans are 65 or older, and nearly 20% of that group experiences clinically significant depression. Existing medications often work poorly for late-life depression, especially when it is treatment-resistant. Ketamine offers a potentially rapid-acting option, but few studies have tested it in older adults. This ongoing trial uses an adaptive randomization design to compare the safety, tolerability, efficacy, and durability of three different low doses of intravenous ketamine against a single dose of an active placebo (midazolam) in older depressed veterans. As the study proceeds, Bayesian adaptive randomization shifts the odds of assignment toward the more promising dose conditions.