ColumnsSubtypes of Major Depressive Disorder Based on Pharmacological ResponsivenessPreskorn, Sheldon H. MD Author Information PRESKORN: Kansas University School of Medicine—Wichita, Wichita, KS Over his 40-year career, S.H.P. has worked with over 140 pharmaceutical and biotech companies in the United States and throughout the world. Over the past year, he has received grants/research support from or has served as a consultant, on the advisory board, or on the speakers bureau for Alkermes, BioXcel, Eisai, Janssen, Otsuka, Sunovion, and Usona Institute. All clinical trial and study contracts were with and payments made to the Kansas University Medical Center Research Institute, a research institute affiliated with Kansas University School of Medicine-Wichita. Please send correspondence to: Sheldon H. Preskorn, MD, Kansas University School of Medicine-Wichita, 1010 North Kansas Street, Wichita, KS 67214. Journal of Psychiatric Practice: November 2021 - Volume 27 - Issue 6 - p 448-452 doi: 10.1097/PRA.0000000000000591 Buy Metrics Abstract Major depressive disorder (MDD) is a descriptive, syndromic diagnosis which will likely be discovered to be more than a single disorder when understood from a pathobiological or pathoetiological perspective. To date, attempts to divide this disorder into more homogenous phenotypes on the basis of signs and symptoms have not yielded more information on the pathobiological or pathoetiological factors that can cause a major depressive episode. This column proposes a new way of dividing MDD into 3 subtypes based on responsiveness to pharmacological treatments that are pharmacologically quite different from each other: type 1, which is responsive to treatment with biogenic amine antidepressants; type 2, which is not responsive to treatment with biogenic amine antidepressants but is responsive to antidepressants that work on the glutamine neurotransmitter system via the N-methyl-D-aspartate receptor; and type 3, which is not responsive to either of these 2 types of antidepressants. The goal of this formulation is to develop biologically meaningful subtypes that can be further studied to understand the pathobiology underlying these 3 types of MDD with the goal of developing newer treatments and earlier ways of diagnosing these conditions. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.