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.
Archives of General Psychiatry
August 1, 2010
Nancy Diazgranados, Lobna Ibrahim, Nancy E. Brutsché et al.
969 citations
A single intravenous dose of ketamine, an N-methyl-D-aspartate-receptor antagonist, produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. Depressive symptoms improved within 40 minutes and remained significantly better than placebo through day 3. The largest drug effect occurred at day 2. Seventy-one percent of subjects responded to ketamine versus 6% to placebo. One subject in each group developed manic symptoms. Ketamine was generally well tolerated, with dissociative symptoms only at the 40-minute point.
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
September 8, 2009
Rodrigo Machado‐Vieira, Peixiong Yuan, Nancy E. Brutsché et al.
154 citations
Ketamine produces rapid antidepressant effects in people with treatment-resistant major depressive disorder, but these effects are not linked to changes in brain-derived neurotrophic factor (BDNF) levels. In 23 adults aged 18 to 65, a single intravenous infusion of ketamine (0.5 mg/kg) significantly improved depression scores on the Montgomery-Asberg Depression Rating Scale within 230 minutes. However, BDNF levels measured at the same time points did not change from baseline, and no association appeared between antidepressant response and BDNF. The findings indicate that ketamine's initial antidepressant action operates through mechanisms other than BDNF.
The International Journal of Neuropsychopharmacology
September 12, 2011
Oz Malkesman, Daniel Austin, Tyson Tragon et al.
91 citations
D-serine, a co-agonist at NMDA receptors, produces antidepressant-like effects in rodents. A single acute dose of D-serine reduced immobility in the forced swim test without affecting motor function, reversed sexual reward-seeking deficits caused by serotonin depletion, and reversed learned helplessness behavior. Mice lacking NMDA receptor NR1 subunits in forebrain excitatory neurons showed a depression-like phenotype and did not respond to D-serine. These findings suggest D-serine has antidepressant-like effects and support the idea of complex glutamatergic dysfunction in depression, though it remains unclear whether D-serine shares a convergent mechanism with NMDA antagonists like ketamine.