We read with interest the letter by Drs Kruszewski and Paczynski regarding our study of tamoxifen in acute mania. The letter first points to the 3-week duration, single-site nature, provision of “individualized” food and recreation, and worsening with placebo as weaknesses of our study. We respectfully disagree with this characterization for the following reasons. First, a duration of 3 weeks is in fact typical for acute mania trials (31 of 34 placebo-controlled monotherapy trials in acute mania conducted to date are of 3 weeks' duration) (A.Y., E. Vieta, MD, PhD, and R. J. Baldessarini, MD, unpublished data, August 15, 2008). Because of drug-placebo separation between days 7 and 21, 3 weeks has been suggested as an optimum duration for acute mania trials.1 Second, there is little literature on the impact of single-site designs in acute mania clinical trials. In a recently conducted analysis (of 48 comparisons between 15 active drugs and placebo in 34 trials with 9135 total patients with mania), we found that site number is associated with placebo, but not drug, responses (A.Y., E. Vieta, MD, PhD, and R. J. Baldessarini, MD, unpublished data, August 15, 2008). Therefore, we view the single-site nature of our study not as a weakness but as one factor that may have reduced the placebo response rate.