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

Martin M. Katz’s reply to Malcolm Lader’s comment

Malcolm Lader is well known in British and European psychiatry and psychopharmacology having contributed substantially to the literature on clinical trials. He is in accord with the author's criticisms of the FDA model for evaluating antidepressants and broadens that critique to include the wasteful aspects and the "limited conclusions that can be drawn" from such trials. He is in agreement that although the Hamilton Depression Rating Scale has turned out to be a very important instrument for standardizing the measurement of efficacy, he turns to his personal experience with Professor Hamilton and the method to cite his reservations about its methodologic inadequacies. Dr. Lader also takes the opportunity to identify other problems to which the FDA presumably has not attended, e.g., allowing trials with ineffective drugs to go on too long, thus, further jeopardizing patient health, not following up with sufficient time to detect potentially serious withdrawal effects, etc. He is also critical of the author's evidence on correlations between clinical and biochemical effects, accepting some of these results, not others. Lader has a point that the correlational evidence is far from overwhelming but at the same time is, within its limitations, sound, and in my view, a highly useful step toward uncovering the complex interactive relationships between behavior and chemistry that characterize this neurobehavioral syndrome and that underlie the efficacy of the antidepressant agents. M. Lader, although supportive of the general approach and the new models proposed by the author, is not convinced through his cursory analysis of their background, that we know enough about these methods as vehicles for finding new antidepressants. He is, however, prepared, to await further developments in clinical trials research. One direct way in which that can be accomplished is for investigators to begin to apply these proposed, well researched alternative methods in more studies

Marin M. Katz

July 28, 2016