Subtypes of Major Depressive Disorder Based on Pharmacological Responsiveness

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.