Martin M. Katz: Depression and Drugs


Martin Katz’s reply to Donald F. Klein’s 8th comment 


I believe that I have replied to the substance of D. Klein’s last comment in earlier notes as he so indicates. In this comment, he again finds it difficult to accept the accuracy of the prediction that change in one of the clinical dimensions within the first  week to ten days of the treatment period, is highly associated with a full positive clinical response at outcome of a 6 week course of treatment. I can understand the skepticism but I was quoting from the logistic regression analysis in our paper in Katz et al 2004 (pg. 574), which showed for the desipramine-treated patients, a combination of sensitivity and specificity of 0.90 and 0.88, respectively, with only the depressive mood-motor retardation dimension as the independent change variable.

We acknowledge that this result was from a study having a modestly sized sample and the dimensional concept warrants re-testing using a larger sample and diverse drugs, but consider the 2004 study sound evidence for the likelihood that that prediction is a valid one. The result is supported by the fact that large sample studies which only utilized early improvement on the Hamilton Depression Scale, e.g., the Stassen et al  and Szegedi et al studies, found similarly high associations between improvement at two weeks and positive clinical response at outcome. These studies had in common the finding of near certainty (>90%) that the treatment would fail if the patient showed no sign of improvement during this two weeks period.

All of these studies provide strong evidence that the two to three week trial is a more than viable option. My colleagues and I make a more detailed case for “shortening the trial” in the recently published Katz et al 2015 article.


Katz MM, Tekell J, Bowden CL Brannan S, Houston JP, Berman N, Frazer A. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology 2004; 29: 566-79.

Katz MM, Berman N, Bowden CL, Frazer A. Evidence for Shortening the Duration of Clinical Trials of Antidepressants and a Proposed Paradigm for Such Studies’, J Clin Psychopharmacology 2015, 35:329-332.


Martin M. Katz

April 28, 2016