Abstract
Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy.
| Original language | English |
|---|---|
| Pages (from-to) | 774-778 |
| Number of pages | 5 |
| Journal | Neuron |
| Volume | 101 |
| Issue number | 5 |
| DOIs | |
| State | Published - 6 Mar 2019 |
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In: Neuron, Vol. 101, No. 5, 06.03.2019, p. 774-778.
Research output: Contribution to journal › Short survey › peer-review
TY - JOUR
T1 - Ketamine
T2 - A Paradigm Shift for Depression Research and Treatment
AU - Krystal, John H.
AU - Abdallah, Chadi G.
AU - Sanacora, Gerard
AU - Charney, Dennis S.
AU - Duman, Ronald S.
N1 - Funding Information: J.H.K. is supported by the Department of Veterans Affairs (National Center for PTSD), the NIAAA Center for the Translational Neuroscience of Alcohol (P50AA12870), and the the Yale Center for Clinical Investigation (UL1 RR024139). D.S.C. is supported by P01HL131478 (PI, Fayad) and by grants from the Brain and Behavior Research Foundation to collaborating faculty. R.S.D. is supported by NIMH grants MH045481, MH093897, and MH077681 and by the State of Connecticut. Financial disclosures for J.H.K. include the following. The Individual Consultant Agreements listed below are less than $10,000 per year: AstraZeneca Pharmaceuticals; Biogen Idec, MA; Biomedisyn Corporation, Bionomics, Limited (Australia) Boehringer Ingelheim International; Concert Pharmaceuticals; Epiodyne; Heptares Therapeutics, Limited (UK); Janssen Research & Development; L.E.K. Consulting; Otsuka America Pharmaceutical; Perception Neuroscience Holdings; Spring Care; Sunovion Pharmaceuticals; Takeda Industries; Taisho Pharmaceutical. J.H.K. serves on the scientific advisory board for the following: Bioasis Technologies; Biohaven Pharmaceuticals; BioXcel Therapeutics (Clinical Advisory Board); BlackThorn Therapeutics; Broad Institute of MIT and Harvard; Cadent Therapeutics; Lohocla Research Corporation; and Stanley Center for Psychiatric Research at the Broad Institute. J.H.K. stock includes ArRETT Neuroscience, BlackThorn Therapeutics, Biohaven Pharmaceuticals Medical Sciences Spring Care, and Sage Pharmaceuticals. J.H.K. stock options include Biohaven Pharmaceuticals Medical Sciences and Storm Biosciences. J.H.K. income greater than $10,000 includes the following: Editorial Board – Editor – Biological Psychiatry. J.H.K. patents and inventions include the following: (1) Seibyl, J.P., Krystal, J.H., and Charney, D.S. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. US Patent 5,447,948, September 5, 1995; (2) Vladimir, C., Krystal, J.H., and Sanacora, G. Glutamate modulating agents in the treatment of mental disorders. US Patent 8,778,979 B2, July 15, 2014. US Patent Application 15/695,164, filed September 5, 2017. (3) Charney, D., Krystal, J.H, Manji, H., Matthew, S., and Zarate, C. Intranasal administration of ketamine to treat depression. US Application 14/197,767, filed March 5, 2014; US application or Patent Cooperation Treaty (PCT) International application 14/306,382, filed June 17, 2014. (4) Zarate, C., Charney, D.S., Manji, H.K., Mathew, S.J., and Krystal, J.H. Department of Veterans Affairs, Methods for treating suicidal ideation, patent application 14/197.767, filed March 5, 2014 by Yale University Office of Cooperative Research. (5) Arias, A., Petrakis, I., and Krystal, J.H. Composition and methods to treat addiction. Provisional Use Patent application 61/973/961, filed April 2, 2014 by Yale University Office of Cooperative Research. (6) Chekroud, A., Gueorguieva, R., and Krystal, J.H. Treatment selection for major depressive disorder, filed June 3, 2016, USPTO docket number Y0087.70116US00. Provisional patent submission by Yale University. (7) Gihyun, Y., Petrakis, I., and Krystal, J.H. Compounds, compositions and methods for treating or preventing depression and other diseases. US Provisional Patent application 62/444,552, filed January10, 2017 by Yale University Office of Cooperative Research OCR 7088 US01. (8) Abdallah, C., Krystal, J.H., Duman, R., and Sanacora, G. Combination therapy for treating or preventing depression or other mood diseases. US Provisional Patent application 047162-7177P1 (00754) filed on August 20, 2018 by Yale University Office of Cooperative Research, OCR 7451 US01 NON Federal Research Support AstraZeneca Pharmaceuticals provides the drug, Saracatinib, for research related to NIAAA grant “Center for Translational Neuroscience of Alcoholism [CTNA-4]. G.S. has received consulting fees from Alkermes, Allergan, AstraZeneca, Avanier Pharmaceuticals, Axsome Therapeutics, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Hoffmann–La Roche, Intra-Cellular Therapies, Janssen, Merck, Minerva Neurosciences, Naurex, Navitor Pharmaceuticals, Novartis, Noven Pharmaceuticals, Otsuka, Perception Neuroscience, Praxis Therapeutics, Sage Pharmaceuticals, Servier Pharmaceuticals, Taisho Pharmaceuticals, Teva, Valeant, and Vistagen Therapeutics. He has also received research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Hoffmann–La Roche, Merck, Naurex, and Servier Pharmaceuticals. No-cost medication was provided to G.S. for an NIH-sponsored study by Sanofi-Aventis. In addition, he holds shares in Biohaven Pharmaceuticals Holding Company and is a co-inventor on the patent “Glutamate agents in the treatment of mental disorders” (patent 8778979) and is a co-inventor on. US Provisional Patent application 047162-7177P1 (00754), Combination therapy for treating or preventing depression or other mood diseases, filed August 20, 2018 by Yale University Office of Cooperative Research OCR 7451 US01. D.S.C. is Dean of the Icahn School of Medicine at Mount Sinai (ISMMS) and co-inventor on patents related to ketamine outlined below. If ketamine gains regulatory approval, both D.S.C. and ISMMS stand to benefit financially. ISMMS also is seeking to license ketamine as a treatment for PTSD. D.S.C. holds a share of the following patents: Intranasal administration of ketamine to treat depression, US patent 9,592,207, issued March 14, 2017; Methods for treating suicidal ideation, US patent 9,539,220, issued January 10, 2017; Intranasal administration of ketamine to treat depression, US patent 8,785,500, issued July 22, 2014; Systems and methods for treating a psychiatric disorder, US patent 10,123,737, issued November 13, 2018, US CON Patent application 16/189,059; and related foreign patent applications Systems and methods for treating a psychiatric disorder, Provisional Patent application 62/649,469; Brain plasticity following cognitive-emotional training, US CON Patent application 14/974,576; and related foreign patent applications, Method for treating post traumatic stress disorder (PTSD), US serial number 14/889,746; and Treatment of mood and anxiety disorders and Intranasal Administration of ketamine to treat depression, US CON Patent applications 15/379,013 and 15/417,689. R.S.D. has served as a consultant for Janssen, Taisho, Naurex, and Aptinyx and has received research support from Lilly, Taisho, Allergan, Janssen, Naurex, Aptynix, Navitor, and Relmada. C.G.A. served as a consultant for and/or on advisory boards for Genentech, Janssen, and FSV7 and as editor of Chronic Stress for Sage Publications, Inc. C.G.A. filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed August 20, 2018). G.S. has received consulting fees from Alkermes, Allergan, AstraZeneca, Avanier Pharmaceuticals, Axsome Therapeutics, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Hoffmann–La Roche, Intra-Cellular Therapies, Janssen, Merck, Minerva Neurosciences, Naurex, Navitor Pharmaceuticals, Novartis, Noven Pharmaceuticals, Otsuka, Perception Neuroscience, Praxis Therapeutics, Sage Pharmaceuticals, Servier Pharmaceuticals, Taisho Pharmaceuticals, Teva, Valeant, and Vistagen Therapeutics. He has also received research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Hoffmann–La Roche, Merck, Naurex, and Servier Pharmaceuticals. No-cost medication was provided to G.S. for an NIH-sponsored study by Sanofi-Aventis. In addition, he holds shares in Biohaven Pharmaceuticals Holding Company and is a co-inventor on the patent Glutamate agents in the treatment of mental disorders, patent 8778979. Funding Information: J.H.K. is supported by the Department of Veterans Affairs (National Center for PTSD), the NIAAA Center for the Translational Neuroscience of Alcohol (P50AA12870), and the the Yale Center for Clinical Investigation (UL1 RR024139). D.S.C. is supported by P01HL131478 (PI, Fayad) and by grants from the Brain and Behavior Research Foundation to collaborating faculty. R.S.D. is supported by NIMH grants MH045481, MH093897, and MH077681 and by the State of Connecticut. Publisher Copyright: © 2019
PY - 2019/3/6
Y1 - 2019/3/6
N2 - Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy.
AB - Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy.
UR - http://www.scopus.com/inward/record.url?scp=85061999597&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2019.02.005
DO - 10.1016/j.neuron.2019.02.005
M3 - Short survey
C2 - 30844397
AN - SCOPUS:85061999597
SN - 0896-6273
VL - 101
SP - 774
EP - 778
JO - Neuron
JF - Neuron
IS - 5
ER -