Science
August 19, 2010
Nanxin Li, Boyoung Lee, Rongjian Liu et al.
2,875 citations
Ketamine, a drug that blocks NMDA receptors, rapidly activates the mTOR pathway in the prefrontal cortex of rats, increasing synaptic signaling proteins and the number and function of new spine synapses. Blocking mTOR signaling prevented ketamine from inducing synaptogenesis and behavioral antidepressant-like responses in depression models. These effects reverse the synaptic deficits caused by stress and may explain ketamine's fast antidepressant action in treatment-resistant depressed patients, which contrasts with the weeks or months needed for standard medications.
Science
October 4, 2012
Ronald S. Duman, George K. Aghajanian
1,613 citations
Depression involves shrinkage of brain regions that regulate mood and cognition, such as the prefrontal cortex and hippocampus, along with reduced neuronal synapses in those areas. Typical antidepressants can reverse some of these deficits but work slowly and have limited effectiveness. Ketamine, a drug that blocks N-methyl-D-aspartate receptors, rapidly (within hours) improves symptoms in patients who do not respond to standard antidepressants. In basic studies, ketamine quickly promotes the formation of new synapses and reverses the synaptic damage caused by chronic stress. These findings suggest that maintaining healthy mood circuit connections is central to depression and its treatment, forming the basis of a synaptogenic hypothesis.
Annual Review of Medicine
October 23, 2014
Chadi G. Abdallah, Gerard Sanacora, Ronald S. Duman et al.
420 citations
Ketamine, a glutamate-based antidepressant, can rapidly alleviate depression within hours of treatment. Replicated evidence shows its rapid and potent effects in treatment-resistant depression. Preclinical and biomarker studies have begun to explain the mechanism behind these rapid effects, offering new insights into depression's biology and identifying potential treatment targets. This article discusses ketamine's efficacy, safety, and tolerability, summarizes depression's neurobiology, reviews the mechanisms of ketamine's rapid antidepressant effects, and considers prospects for next-generation rapid-acting antidepressants.