KETAMINE FOR DEPRESSION: WHAT PSYCHOLOGISTS NEED TO KNOW Raquel G. Bennett A Clinical Research Project submitted to the Faculty of the American School of Professional Psychology, at Argosy University, San Francisco Bay Area in partial fulfillment of the requirements for the degree of Doctor of Psychology Alameda, California April, 2014 ___________________________________ ________________ Pauline Lytle, Ph.D., Chairperson Date ___________________________________ ________________ Nicola Wolfe, Ph.D., Member Date ABSTRACT KETAMINE FOR DEPRESSION: WHAT PSYCHOLOGISTS NEED TO KNOW By Raquel G. Bennett The emphasis of this study was on the role of the psychologist in patient care and/or as a member of a research team with respect to ketamine as a novel treatment for depressed, bipolar, and suicidal patients. Ketamine is synthetic medication that was discovered in the 1960s. It is classified as a dissociative anesthetic and is primarily used in anesthetic medicine. It is believed that ketamine works by disrupting the transmission of glutamate, an excitatory neurotransmitter. Specifically, ketamine acts as an antagonist of the NMDA receptor in the CNS. In recent years, ketamine has been shown to have a robust and rapid-acting but temporary antidepressant effect that begins to work within hours of administration. The antidepressant effect of ketamine varies in its duration but clinical studies have shown that it often lasts for 1 to 2 weeks, and its effect can be extended by multiple administrations. However, ketamine is a controversial treatment because it induces a temporary dissociative or altered state in recipients. This aspect of ketamine treatment does not bother most patients, especially if they are prepared for it. However, the medical community has traditionally been strongly biased using agents that create psychedelic experiences. This study reviewed the existing literature on using ketamine to treat patients with severe and refractory depression, bipolar disorder, and suicidal ideation as well as other aspects of what is currently known about ketamine. Specific roles and responsibilities of the clinical psychologist regarding therapeutic ketamine i treatment were discussed. Gaps in the current literature on ketamine were explored at length and suggestions for several new directions for research were made. ii Copyright © 2014 Raquel G. Bennett All rights reserved iii ACKNOWLEDGMENTS I wish to express my heartfelt gratitude to my mentor and clinical research project chair, Polly Lytle, for her guidance and support over many years. I also wish to thank my reader, Nikki Wolfe, for her help with this project. In addition, I want to acknowledge some of my other teachers and guides, including Elisabeth Targ, Francoise Bourzat, and Diana Fuery for their extraordinary compassion and wisdom. Finally, I wish to dedicate this study to my parents, Rachelle “Shelley” Bennett and Ralph Bennett, who taught me the value of service, creativity, courage, and determination. iv TABLE OF CONTENTS Page ABSTRACT ......................................................................................................................... i COPYRIGHT PAGE ......................................................................................................... iii ACKNOWLEDGMENTS ................................................................................................. iv CHAPTER I: INTRODUCTION ........................................................................................ 1 Problem Statement .............................................................................................................. 1 Purpose Statement ............................................................................................................... 2 Significance Statement ........................................................................................................ 2 Definitions of Key Terms ................................................................................................... 2 CHAPTER II: LITERATURE REVIEW ........................................................................... 6 Ketamine’s Discovery ......................................................................................................... 7 Ketamine in Anesthesia ...................................................................................................... 8 Ketamine’s Chemistry ...................................................................................................... 10 Ketamine’s Mechanism of Action .................................................................................... 11 Metabolism of Ketamine ................................................................................................... 14 Effects of Ketamine .......................................................................................................... 15 Ketamine As a Street Drug and Its Abuse ........................................................................ 19 Side Effects and Risks of Ketamine Use .......................................................................... 22 Ketamine’s Legal Status ................................................................................................... 26 Routes of Administration .................................................................................................. 28 Ketamine-Assisted Psychotherapy .................................................................................... 31 Clinical Research on Ketamine ......................................................................................... 34 MDD ..................................................................................................................... 34 Ketamine for Depressed Patients .......................................................................... 36 Bipolar Disorder .................................................................................................... 45 Ketamine for Bipolar Patients ............................................................................... 46 Suicidality ............................................................................................................. 49 Ketamine for Suicidal Patients .............................................................................. 50 Other Therapeutic Uses of Ketamine ................................................................................ 54 Ketamine Versus ECT ...................................................................................................... 55 Psychedelic Psychotherapy ............................................................................................... 57 Summary ........................................................................................................................... 61 CHAPTER III: METHODS .............................................................................................. 63 Overview of Methodology ................................................................................................ 63 Objectives ......................................................................................................................... 63 Data Sources ..................................................................................................................... 63 v Analysis............................................................................................................................. 64 Limitations ........................................................................................................................ 65 Delimitations ..................................................................................................................... 65 CHAPTER IV: RESULTS ................................................................................................ 66 Chapter Objective ............................................................................................................. 66 Role of the Psychologist in Ketamine Treatment ..............................................................67 CHAPTER V: DISCUSSION .......................................................................................... 73 Optimal Dose .................................................................................................................... 73 Routes of Administration .................................................................................................. 74 Optimal Window for Treatment ........................................................................................ 76 Multiple Treatments .......................................................................................................... 77 Using Ketamine Over Time .............................................................................................. 78 Concerns About Addiction ............................................................................................... 80 Interactions With Other Medications ................................................................................ 81 Different Kinds of Depression .......................................................................................... 82 Suicidal Patients ................................................................................................................ 84 The Psychedelic Experience and the Antidepressant Effect ............................................. 85 The Ketamine Experience ................................................................................................