On the relationship between systematic reviews and clinical guidelines, we are understandably very pleased that Dr. Hirschfeld et al. have already noticed our review, and we look forward to the next update of the APA guideline for bipolar disorder. We agree that developing treatment guidelines requires the updating and integration of all available data. When this leads to different conclusions by different consensus groups, it means—in the absence of obvious cultural or legal constraints—either that the evidence has been selectively evaluated or there is simply too little evidence to make better than an opinion-led summary. For example, lamotrigine was recommended for the acute treatment of bipolar depression by the APA bipolar disorder guideline on the basis, at that time, of just one available study in which lamotrigine was more effective than placebo on a secondary—not the primary—outcome measure. Since then, the results of two other acute studies have also become available, and they were both negative (3).