The International Journal of Neuropsychopharmacology
June 7, 2012
Wallace C. Duncan, Simone Sarasso, Fabio Ferrarelli et al.
253 citations
A single infusion of the NMDA receptor antagonist ketamine rapidly reduces depressive symptoms in patients with treatment-resistant major depressive disorder. In 30 patients, ketamine increased electroencephalogram slow wave activity during early non-REM sleep and raised plasma levels of brain-derived neurotrophic factor. The occurrence of high amplitude slow waves and their slope also increased, indicating enhanced synaptic strength. Changes in BDNF levels correlated with changes in EEG parameters, but only in patients who responded to ketamine. This suggests that enhanced synaptic plasticity, reflected by increased slow wave activity and BDNF, is part of the mechanism behind ketamine's rapid antidepressant effects.
The Journal of Clinical Psychiatry
December 6, 2016
Jennifer L. Vande Voort, Elizabeth D. Ballard, David A. Luckenbaugh et al.
67 citations
People with depression who had a reduction in suicidal thoughts after a single ketamine infusion also showed less nighttime wakefulness, measured by EEG, the night after the infusion compared to those whose suicidal thoughts did not improve. The level of wakefulness in responders was similar to that of healthy controls. This suggests that ketamine's effect on suicidal ideation may involve changes in sleep-wake regulation.
Neuropsychiatric Disease and Treatment
October 1, 2018
Wallace C. Duncan, Elizabeth E. Slonena, Nadia S. Hejazi et al.
17 citations
Patients with major depressive disorder who had a brief antidepressant response to ketamine (lasting 24-48 hours) showed blunted 24-hour wrist activity amplitude from baseline through three days post-infusion and a phase advance of activity on day one that returned to baseline by day three. Those with a continued response (over 72 hours) had phase-advanced activity at baseline and day one, plus increased amplitude on days one and three. Nonresponders did not show these patterns. The time course of antidepressant response to ketamine appears linked to underlying biological differences in motor activity timekeeping, which may involve circadian system mechanisms.
Translational Psychiatry
June 4, 2024
Elizabeth D. Ballard, Deanna K Greenstein, Philip T Reiss et al.
16 citations
Ketamine, a drug that modulates the glutamate system, is linked to changes in sleep, depression, and suicidal thoughts. In a randomized, double-blind, crossover trial, 36 people with treatment-resistant major depression and 25 healthy volunteers underwent polysomnography before and after receiving ketamine or placebo. At baseline, those with depression had less total sleep time and shorter REM latency. Ketamine increased slow-wave (delta) brain activity early in the night and both alpha and delta activity later, compared to placebo. However, ketamine did not significantly alter sleep arousal metrics or mediate its antidepressant or anti-suicidal effects through sleep changes. The findings suggest sleep-related variables are part of broader neurobiological shifts after ketamine.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Mina Kheirkhah, Wallace C. Duncan, Qiaoping Yuan et al.
6 citations
People with treatment-resistant depression show higher REM density in the first REM period and shorter REM latency than healthy volunteers, while total night REM density does not differ. Ketamine treatment reduces REM density in the first REM period but does not change total night REM density or REM latency. Baseline REM density in the first REM period moderately predicts whether a person will respond to ketamine, with higher levels indicating greater likelihood of response. This marker could help identify individuals most likely to benefit from ketamine therapy.