American Journal of Psychiatry
October 3, 2017
S. Wilkinson, Elizabeth D. Ballard, M. Bloch et al.
680 citations
A single dose of ketamine rapidly reduces suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. The effect is moderate to large and partially independent of changes in depressive symptoms. The analysis combined data from 167 participants across 10 studies comparing ketamine to a placebo (saline or midazolam). Ketamine significantly improved clinician-rated and self-reported suicidal ideation, though not on one self-report measure (the Beck Depression Inventory). The authors call for further research on long-term safety and suicide risk reduction 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.
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.
American Journal of Psychiatry
June 24, 2019
E. Dakwar, E. Nunes, C. Hart et al.
179 citations
A single infusion of ketamine, combined with mindfulness-based relapse prevention, helped adults dependent on cocaine stay abstinent longer and reduce cravings. In a trial with 55 participants, 48.2% of those receiving ketamine maintained abstinence over the final two weeks, compared to 10.7% in the control group receiving midazolam. The ketamine group was 53% less likely to relapse or drop out, and their craving scores were 58.1% lower throughout the study. The infusions were well tolerated with no serious adverse events. The authors suggest these results are promising but need replication in a larger sample.
Translational Psychiatry
May 9, 2023
Jared M. Kopelman, T. Keller, Benjamin Panny et al.
57 citations
A single intravenous infusion of ketamine (0.5 mg/kg) in 98 adults with unipolar depression who had not responded to at least one antidepressant was associated with rapid changes in gray matter microstructure measured by diffusion tensor imaging (DTI) 24 hours later. Greater decreases in DTI mean diffusivity, a marker of neuroplasticity enhancement, in several brain regions (left and right BA10, left amygdala) correlated with larger improvements in depression scores, particularly in the ketamine group. In the hippocampus, the relationship was reversed for one depression scale. The findings suggest that ketamine's acute antidepressant effects may involve rapid neuroplastic changes detectable with brain imaging.
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.
European Neuropsychopharmacology
June 2, 2021
A. Feeney, R. Hock, Marlene P. Freeman et al.
33 citations
A single intravenous infusion of ketamine may reduce suicidal ideation in patients with treatment-resistant depression for up to 30 days, but early effects diminish rapidly. In a double-blind randomized trial, 40 patients received ketamine and 16 received midazolam placebo; all had clinically significant suicidal ideation at baseline. By day 30, the ketamine group had a lower mean suicide score (2.03) than the placebo group (3.00). However, among those whose suicidal ideation initially resolved by day 3, there was no significant difference between groups in later scores. Recurrence of suicidal ideation was common in both groups. The findings suggest a possible role for ketamine as an adjunct to standard treatments.
Neuropsychopharmacology
April 19, 2023
N. Murphy, Amanda J. F. Tamman, Marijn Lijffijt et al.
18 citations
A single low-dose infusion of ketamine in older military veterans with treatment-resistant depression temporarily increases the brain's neural complexity, measured by electroencephalogram (EEG) markers Lempel-Ziv complexity and multiscale entropy, within 30 minutes after infusion. These effects vary over time, with some complexity measures decreasing later. However, these changes in complexity were not linked to reductions in depressive symptoms after seven days. The findings suggest that ketamine produces broad, time-varying effects on brain dynamics beyond previously studied gamma oscillations, offering a potential non-linear marker of the drug's action.
JAMA Network Open
May 1, 2023
R. Price, M. Wallace, S. Mathew et al.
9 citations
Automated self-association training may extend the antidepressant effect of a single ketamine infusion beyond one month in people with treatment-resistant depression. This secondary analysis of a randomized clinical trial tested whether a computerized task designed to strengthen positive self-associations could prolong the benefits of ketamine. The results suggest that combining ketamine with this training could help maintain mood improvement for a longer period than ketamine alone.