Martin M. Katz’s reply to Donald F. Klein’s 5th comment (“Atypical depression”) on his monograph Depression and Drugs.
I will follow up Don Klein’s added comments to my last reply regarding linkage between neurotransmitter effects and behavior changes, in a separate text. Here I respond to his fifth comment citing “atypical depression” as a special case that he believes undermines the value of the scheme of relationships I have described, and leaves open the question of how one explains the positive and specialized actions of monoamine oxidase inhibitors in its treatment. The “atypical” is a contrary form of depression, its symptoms very unlike the classic melancholia. The monoamine oxidase (MAO) inhibitor drugs, demonstrated to be effective for this category, specifically phenelzine, inhibit the catabolism of many neurotransmitters. How would these actions fit into my scheme? A simple answer is that it requires examination of the neurochemical and behavioral mechanisms operating in this framework. The pattern of associations between neurotransmitter actions and behavior is different in “atypical” depression, e.g., the dopaminergic system apparently plays a different role, than that found with typical depressions. Only new research could provide the entire answer. The new research would be a challenge and an investigator with the necessary resources might find this study worth doing. In sum, there is as yet no evidence that the syndromes or diagnoses are in themselves, associated with specific dysfunctional patterns in neurotransmitter systems, no “biological markers” of these clinical concepts. The evidence so far indicates that such associations if they exist, are still outside of our research grasp.
If I read between the lines from Klein’s critique it appears that he is disturbed with the putting aside of traditional, tried and tested clinical concepts of syndrome and diagnosis, when seeking to uncover the mechanisms of effective drug action in the treatment of depression. I can assure him from my side of the problem that I respect these concepts and the efforts over these many years to increase their reliability and validity for application in clinical practice. But I am suggesting that the complexity of their nature and their resistance to quantification indicates that they are not yet suitable to insert into a research framework that is aimed at uncovering how the established drugs bring about their therapeutic actions. The scheme I set forth in my book generates a conceptual approach to the understanding of the neurobiologic dynamics of the depressed state drawn from this type of analysis that identifies conflicting affective and motoric dimensions, the conflict between the “aroused” anxiety-agitated neurobehavioral and “depressed mood- motorically retarded” neurobehavioral states, as the basis of the inner turmoil and suffering associated with an acute episode of depression. This approach has already resulted in new evidence on drug action mechanisms and I believe that this “conflicting dimensions” conception of the depressed state will continue to provide a proper guideline for future advances in understanding depression and in uncovering the bases of drug efficacy.
Martin M. Katz
February 12, 2015