In the 2008 March issue of the Archives, the Tohen commentary “Clinical Trials in Bipolar Mania: Implications in Study Design and Drug Development”1 addressed the merits of the study by Yildiz et al “Protein Kinase C Inhibition in the Treatment of Mania: Double-blind Placebo-Controlled Trial of Tamoxifen”2 that appeared in the same issue. After careful review, we would like to add words of caution to Tohen's conclusion that the report by Yildiz et al