Ketamine for Treatment-Resistant Depression

1. Front Matter

   Pages i-xix

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2. The History of Ketamine Use and Its Clinical Indications

   • Lee C. Chang, Suman Rajagopalan, Sanjay J. Mathew

   Pages 1-12

3. The Basic and Clinical Pharmacology of Ketamine

   • Elizabeth Wolf Fourcade, Kyle A. B. Lapidus

   Pages 13-29

4. Ketamine: Clinical Studies in Treatment-Resistant Depressive Disorders

   • Pierre Blier, Jean Blier

   Pages 31-42

5. Ketamine and Suicide Risk

   • Elizabeth D. Ballard, Rebecca B. Price

   Pages 43-56

6. Ketamine: Its Safety, Tolerability, and Impact on Neurocognition

   • Janusz K. Rybakowski, Agnieszka Permoda-Osip, Alicja Bartkowska-Sniatkowska

   Pages 57-71

7. Ketamine’s Mechanisms of Rapid Antidepressant Activity: Evidence from Preclinical Studies

   • Gretchen Hermes, Gerard Sanacora

   Pages 73-98

8. Ketamine’s Mechanism of Rapid Antidepressant Activity: Evidence Gleaned from Clinical Studies

   • Lynnette A. Averill, James W. Murrough, Chadi G. Abdallah

   Pages 99-121

9. Ketamine and Electroconvulsive Therapy

   • Colleen K. Loo, Verònica Gálvez

   Pages 123-135

10. Emerging Data for Ketamine in Obsessive-Compulsive, Stress-Related, and Substance Use Disorders

    • Carolyn Ines Rodriguez, Elias Dakwar

    Pages 137-155

This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants.

Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic moleculartargets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose.

This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research. 

• Alcohol and Substance Use
• Anhedonia
• Bipolar Disorder
• Clinical Trials
• Electroconvulsive Therapy
• Glutamate
• Intravenous Medication
• Major Depressive Disorder
• Neuroimaging
• N-methyl-D-aspartate (NMDA) Antagonist
• Obsessive-Compulsive Disorder
• Pharmacokinetics
• Pharmacology
• Pre-Clinical Studies
• Rapid-Acting Antidepressants
• Safety
• Suicide
• Treatment-Resistance
• psychopharmacology

• Baylor College of Medicine and Michael E. Debakey VA Medical Center, Houston, USA

  Sanjay J. Mathew

• National Institute of Mental Health, National Institutes of Health, Bethesda, USA

  Carlos A. Zarate, Jr.

Sanjay J. Mathew, M.D. is the Johnson Family Chair for Research in Psychiatry, Professor with Tenure in the Menninger Department of Psychiatry and Behavioral Sciences, and director of the Mood and Anxiety Disorders Research Program at Baylor College of Medicine. He is a staff psychiatrist at the Michael E. Debakey VA Medical Center in Houston. He completed his psychiatric residency at Columbia University and the New York State Psychiatric Institute, where he also completed a research fellowship in affective and anxiety disorders. Dr Mathew began his faculty career at the Mount Sinai School of Medicine, where he co-founded and directed the Mood and Anxiety Disorders Program. He has led his current program since 2010.

Dr Mathew has published approximately 100 articles in leading scientific journals, and serves on the editorial board of several journals. He is an elected member of the American College of Neuropsychopharmacology and has been selected in Best Doctors every year since 2011.

Carlos A. Zarate, Jr., M.D. is Chief of the Experimental Therapeutics and Pathophysiology Branch at the Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and Clinical Professor of Psychiatry and Behavioral Sciences at George Washington University.
Dr Zarate completed his residency training in psychiatry at the Massachusetts Mental Health Center/Brockton VAMC division of the Consolidated Department of Psychiatry Harvard Medical School, later completing a fellowship in clinical psychopharmacology at McLean Hospital, Massachusetts. He remained on staff there as Director of the Bipolar and Psychotic Disorders Outpatient Services and the director of the New and Experimental Clinic. From 1998 to 2000, Dr Zarate was Chief of the Bipolar and Psychotic Disorders Program at the University of Massachusetts Medical School. In 2001, he joined the Mood and Anxiety Disorders Program at the NIMH. His achievements and awards are numerous, and include the Brain and Behavior Research Foundation Award for Bipolar Mood Disorder Research. Dr Zarate is a fellow of the American College of Neuropsychopharmacology and a member of the Society of Biological Psychiatry. He has published over 280 articles in leading scientific journals and sits on numerous journal review boards. 

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