Martin M. Katz: Clinical Trials of Antidepressants: How Changing the Model Can Uncover New, More Effective Molecules

Martin M. Katz’s reply to Walter Brown’s comment

Walter Brown, a highly experienced figure in the clinical trials field, provides a detailed analysis of the book and a sharp, well thought through review of its contents. He points to the failure of the drug industry to come up with novel drugs and the slow pace in uncovering the "little-known specific brain abnormalities" that underlie depression. The monograph he states is persuasive in citing that even if new effects of a trial drug were present, the current model trial is expensive and wasteful and not designed to uncover them. Confining assessment to one depression scale prevents possible specific effects on particular symptoms, like anxiety, or anything novel in the drug's effects, in other words, from being detected. He understands that such studies if they applied a componential approach, would provide a "spectrum of drug actions" not available in the current model. He cites the new model’s strengths in clarifying onset of clinical action, in predicting outcome from early reactions to drugs and the potential for shortening such trials. Regarding limitations, although impressed with the early results reported utilizing the video approach, he is somewhat reluctant to see it applied generally before further data on validity is produced. Also, believing that the "validity of the monoamine hypothesis of drug efficacy is slowly vanishing", he suggests the author stick to psychopathology until there is more clarity concerning neurochemical mechanisms in this area. In summary, the author agrees that results linking behavioral and neurochemical factors are only starting to be uncovered but believes that this area of research is farther along than Brown acknowledges. Nevertheless, Walter Brown sees much to gain by the field attending seriously to the book's proposed changes in the clinical trials model, and provides an excellent overview of its content

Martin M. Katz

July 21, 2016