To the Editor: We thank Dr. Xiong et al. for their thoughtful response to our article. They make the point that studies on beta blockade have distinguished fatigue from depression, have highlighted that there does not seem to be a temporal association between beta-blocker use and depression (up to 12 months), and that there is no evidence to support a gender difference.

Dr. Xiong et al. state that while we suggested that depression in the setting of beta-blockade use is seen more frequently in women, Crane et al. (1) examined 84 women and found no difference in depression symptoms between women who did and did not use beta-blockers. Although that study suggested that the use of beta-blockade does not cause depression in women, the study had several limitations, including its cross-sectional design, making it difficult to identify causation (even though this is more of an issue when an association is found). We also wish to make the point that very large doses of beta-blockade were used in our case study relative to the doses administered to women in the Crane et al. study, who were post-myocardial infarction and received only conventional doses, thus limiting comparability.

We agree that Van Melle et al. (2) showed no significant difference between groups in the rate of depression at 3, 6, and 12 months. However, the vast majority of these subjects were men (78% in both non-beta-blocker and beta-blocker groups), and thus it is hard to comment on the effect on women.

Beta-blockade is a critical state-of-the-art component of cardiac care, and thus further discussion and research on this topic are of paramount importance, especially given the equivocal nature of the preponderance of evidence to date.