Ketamine and Mind-Altering Drugs in Treating Anxiety and Depression: Potential Roles and Pitfalls
Friday, March 29, 3:15 pm to 4:45 pm
This year’s Ross Symposium brings together a group of experts with extensive experience in the clinical use of ketamine and psilocybin, their psychopharmacology, and potential substance abuse. These invited speakers will each provide brief presentations followed by an interactive discussion among themselves and with the audience.
The risk:benefit profile of these approaches, and roles in clinical practice will be discussed, as well as examination of the role of concurrent psychotherapies in prolonging their transient benefit. Ethical and medico-legal issues will also be explored. Click here for the full session description.
Adriana Feder, MD
Director, Trauma and Resilience Program
Associate Director for Research, WTC Mental Health Program
Associate Professor of Psychiatry
Icahn School of Medicine at Mount Sinai
Roland Griffiths, PhD
Professor in the Departments of Psychiatry and
Neurosciences at the Johns Hopkins School of Medicine
Alan Schatzberg, MD
Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences
Stanford University School of Medicine
Carlos A. Zarate, MD
Chief of the Experimental & Therapeutics Branch and of the Section on Neurobiology and Treatment of Mood and Anxiety Disorders
National Institute of Mental Health
Sanjay Mathew, MD
Professor of Psychiatry and Behavioral Sciences
Baylor College of Medicine
The past decade has witnessed growing scientific and clinical interest in the therapeutic potential of ketamine, an FDA-approved dissociative anesthetic, for multiple psychiatric indications, including treatment-resistant depression (TRD) and disorders with limited available pharmacotherapies. It is a high-affinity antagonist of the NMDA glutamate receptor, originally developed in the 1960s as a more tolerable anesthetic than PCP (“angel dust’). Recent randomized, placebo-controlled trials have found that a low (subanesthetic) dose of ketamine has rapid-acting benefit for depressive symptoms, suicidal ideation and behavior, PTSD, anxiety, and OCD. In parallel, industry-supported studies have led to a recent FDA New Drug Application of intranasal esketamine (the S-enantiomer of ketamine) for TRD in adults. While there is little systematic data on the “off-label” use of ketamine for psychiatric disorders, numerous clinics now provide a variety of treatment protocols, often at considerable out-of-pocket cost.
Despite enthusiasm among some clinicians and patient advocates, serious concerns about ketamine’s long-term safety have been raised. As a DEA Schedule III drug, ketamine has well-known abuse liability; less appreciated are the cognitive, urological, and hepatic toxicities associated with longer term abuse. A recent study reported that ketamine’s antidepressant activity appears to be mediated by opioid receptor activity, raising important questions regarding its mechanism of action, and whether unrestricted off-label use could have the unintended consequence of further fueling the U.S. opioid crisis.
Beyond ketamine, other “mind-altering” agents under investigation include psilocybin, MDMA, LSD, and ayahuasca. Psilocybin in single doses has shown prolonged benefit for cancer-associated anxiety and depression, and studies have progressed to late-stage testing in TRD. The FDA has granted Breakthrough Therapy Designation for MDMA-assisted psychotherapy for PTSD.
Interested in sponsoring the Jerilyn Ross Lecture? Email Gabby Oved for more information.
Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry, 2014 Adriana Feder, MD
Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD), Molecular Psychiatry, September 2018