Neuron
March 1, 2019
J. Krystal, C. Abdallah, G. Sanacora et al.
443 citations
Ketamine represents a new class of rapid-acting antidepressants effective for treatment-resistant mood disorders. Its development grew from a revised understanding of depression's biology. Research into how ketamine works is providing fresh insights into antidepressant mechanisms and challenging established views on the neurobiology of depression. The drug's fast, strong, and lasting effects on depressive symptoms appear ready to change how depression is treated.
Neuropsychopharmacology
July 24, 2023
J. Krystal, E. Kavalali, L. Monteggia
229 citations
Ketamine, a drug that blocks NMDA receptors in the brain, produces rapid antidepressant effects in people with depression and treatment-resistant depression. This finding has led to new treatments for mood disorders and has advanced understanding of the brain's neurobiology and the synaptic plasticity mechanisms that make ketamine effective. This review covers the clinical aspects of ketamine's rapid antidepressant action, the synaptic and circuit mechanisms behind it, and how these insights can guide future research toward more effective treatments for neuropsychiatric disorders.
Neuropsychopharmacology
February 24, 2020
C. Abdallah, L. Averill, R. Gueorguieva et al.
181 citations
Ketamine produces rapid antidepressant effects within 24 hours, thought to involve mTORC1 activation. In a double-blind crossover trial, 20 depressed patients received either rapamycin (an mTORC1 inhibitor) or placebo before ketamine. Rapamycin did not block ketamine's 24-hour antidepressant effects. Over two weeks, rapamycin prolonged ketamine's benefits: response rates were 41% with rapamycin versus 13% with placebo, and remission rates were 29% versus 7%. These findings question whether systemic or local mTORC1 blockade matters and suggest rapamycin may extend ketamine's effects, potentially informing mechanisms of depression relapse.
JAMA Network Open
May 1, 2020
K. Beck, Guy Hindley, F. Borgan et al.
179 citations
Ketamine administration produces transient psychopathological effects in both healthy volunteers and patients with schizophrenia, with the nature and severity of these effects varying according to experimental factors such as dose, route of administration, and participant characteristics. The meta-analysis quantifies these outcomes, showing that ketamine reliably induces psychotic-like symptoms, dissociation, and cognitive impairments in healthy individuals, while its effects in patients with schizophrenia are more complex and may involve both symptom exacerbation and potential therapeutic benefits depending on the context.
JAMA psychiatry
March 1, 2019
Gihyun Yoon, I. Petrakis, J. Krystal
152 citations
Naltrexone pretreatment does not interfere with the antidepressant effects of ketamine. In the study, participants who received naltrexone before ketamine treatment showed similar reductions in depressive symptoms as those who received a placebo before ketamine. The findings suggest that ketamine's antidepressant action does not depend on the opioid system, contrary to some previous theories.
JAMA psychiatry
October 19, 2022
T. Rhee, S. Shim, B. Forester et al.
139 citations
A systematic review and meta-analysis of six clinical trials involving 340 patients with major depressive episodes found that electroconvulsive therapy (ECT) was more effective than ketamine for reducing depression severity in the acute phase, with a standardized mean difference of -0.69 favoring ECT. No significant differences were observed between the two treatments for cognition, memory, or serious adverse events. Ketamine carried lower risks of headache and muscle pain, while ECT carried lower risks of blurred vision, vertigo, diplopia, and dissociative symptoms. The findings suggest ECT may be superior, but treatment decisions should be individualized.
Proceedings of the National Academy of Sciences of the United States of America
November 27, 2023
J. Krystal, Alfred P. Kaye, S. Jefferson et al.
66 citations
Ketamine represents a new type of antidepressant that works quickly, helps people whose depression has not responded to other treatments, and reduces the chance of relapse. Its development came from a new understanding of depression's biology, and studying how ketamine works has deepened knowledge of depression and related conditions. Twenty-five years after the first findings on ketamine for depression were presented, this review examines what has been learned and suggests future ways to improve rapid-acting antidepressant therapy.
Journal of Psychiatric Research
December 24, 2014
Ke Xu, J. Krystal, Y. Ning et al.
65 citations
Ketamine, a drug that blocks NMDA glutamate receptors, produces symptoms resembling schizophrenia. Analyzing the Positive and Negative Syndrome Scale (PANSS) in four groups—135 healthy people given ketamine or saline, 187 chronic ketamine abusers, 154 early-course schizophrenia patients, and 522 chronic schizophrenia patients—revealed five similar symptom dimensions (positive, negative, cognitive, depressed, excitement/dissociation) across all groups. The chronic ketamine group's symptom structure more closely matched the schizophrenia groups than the acute ketamine group did. Symptoms were milder in ketamine users than in schizophrenia patients (Cohen's d = 0.7). The findings suggest ketamine-induced psychosis shares symptom dimensions with schizophrenia, though confounding factors warrant caution.