Welcome to PsychEd, the psychiatry podcast for medical learners, by medical learners. This episode covers ketamine for treatment-resistant depression (TRD) with Dr. Sandhya Prashad, a psychiatrist and the founder and medical director of Houston Ketamine Therapeutics. She has extensive expertise using ketamine and is one of the most experienced ketamine psychiatrists in the United States, with her clinical practice focusing on TRD and incorporating transcranial magnetic stimulation (TMS), sometimes in conjunction with ketamine. Dr. Prashad is also a founding member and current president of the American Society of Ketamine Physicians (ASKP), a non-profit organization created to advocate for the safe use of ketamine for mental illness and pain disorders and to expand access to ketamine therapy.   We’re also experimenting with something new for this episode — providing a transcript of the entire interview! The transcript can be found at psychedpodcast.org/transcripts/ketamine. We’d love to hear your feedback as listeners on this as a feature, including whether it’s something you’d be interested in seeing for other episodes moving forward!   The learning objectives for this episode are as follows:   By the end of this episode, you should be able to… Describe ketamine and how it came to be used in the field of psychiatry. Develop an appreciation for benefits and potential harms associated with ketamine and how this compares to other treatments for depression. Understand how ketamine fits into the treatment of depression and suicidality, patient characteristics to consider before initiation, potential mechanisms of action, different models of administration, and incorporation of psychotherapy.   Guest expert: Dr. Sandhya Prashad   Hosts: Jimmy Qian (MS2), Dr. Nikhita Singhal (PGY2), Dr. Chase Thompson (PGY3)   Audio editing by: Dr. Chase Thompson   Show notes by: Gray Meckling (MS4)   Interview transcript by: Gray Meckling   00:00 – Introduction 03:00 – Learning objectives 03:30 – History of ketamine 06:20 – Recreational use of ketamine, phenomenology of the ketamine experience 09:45 – Where does ketamine fall in the algorithm for treatment of depression? 11:50 – Ketamine’s use in acute suicidality 13:40 – Ketamine contraindications 14:40 – Ketamine efficacy 19:00 – Combining ketamine with rTMS 21:15 – Limitations to ketamine 24:35 – Ketamine mechanism of action 26:05 – Ketamine formulations, and integrating ketamine into psychotherapy 33:10 – Combining ketamine with traditional antidepressant treatment 37:30 – Practicalities of administering ketamine 39:40 – Ketamine as treatment for OCD and PTSD 41:40 – Closing remarks   Resources: American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP) Sandhya Prashad, MD (Website) NEJM interview with Dr. Roy Perlis: Esketamine for Treatment-Resistant Depression — First FDA-Approved Antidepressant in a New Class   References: Berman, R., Cappiello, A., Anand, A., Oren, D., Heninger, G., Charney, D.. (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47: 351–354. Daly, E. J., Trivedi, M. H., Janik, A., Li, H., Zhang, Y., Li, X., ... & Thase, M. E. (2019). Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA psychiatry, 76(9), 893-903. J.W. Murrough, D.V. Iosifescu, L.C. Chang, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two site randomized controlled trial. Am. J. Psychiatry, 2013 (170) (2013), pp. 1134-1142 Kim, J., Farchione, T., Potter, A., Chen, Q., & Temple, R. (2019). Esketamine for treatment-resistant depression-first FDA-approved antidepressant in a new class. N Engl J Med, 381(1), 1-4. McIntyre, R. S., Rosenblat, J. D., Nemeroff, C. B., Sanacora, G., Murrough, J. W., Berk, M., ... & Stahl, S. (2021). Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. American Journal of Psychiatry, appi-ajp. Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJA, Curran HV. Journey through the K-hole: Phenomenological aspects of ketamine use. Drug and Alcohol Dependence [Internet]. 2008 Jun 1;95(3):219–29. Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, Summergrad P, Nemeroff CB. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA psychiatry. 2017 Apr 1;74(4):399-405. Williams NR, Heifets BD, Blasey C, Sudheimer K, Pannu J, Pankow H, Hawkins J, Birnbaum J, Lyons DM, Rodriguez CI, Schatzberg AF. Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. American Journal of Psychiatry. 2018 Dec 1;175(12):1205-15. Williams NR, Heifets BD, Bentzley BS, Blasey C, Sudheimer KD, Hawkins J, Lyons DM, Schatzberg AF. Attenuation of antidepressant and anti suicidal effects of ketamine by opioid receptor antagonism. Molecular psychiatry. 2019 Dec;24(12):1779-86. Zarate, C., Singh, J., Carlson, P., Brutsche, N., Ameli, R., Luckenbaugh, D.. (2006a) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63: 856–864.   CPA Note: The views expressed in this podcast do not necessarily reflect those of the Canadian Psychiatric Association (CPA). For more PsychEd, follow us on Twitter (@psychedpodcast), Facebook (PsychEd Podcast), and Instagram (@psyched.podcast). You can provide feedback by email at psychedpodcast@gmail.com. For more information, visit our website at psychedpodcast.org.