They ask whether total sleep deprivation and other sleep-wake manipulations trigger remissions from the depressive episode or cause only transient mood fluctuations. According to our knowledge, our clinical experience, and the literature (R1558281F), total sleep deprivation itself only very rarely leads to a full remission from major depression. The main purpose of our study had been to confirm findings from our earlier pilot study (R1558282F) that the positive effects of total sleep deprivation were preserved by a succeeding phase advance of the sleep period lasting for 7 days. We have to mention that our previous study did not include further psychopathological measurements beyond that time period. In addition, the unmedicated patients who participated and responded well to our sleep-wake manipulation all were given antidepressant medication after termination of the study, in order to prevent relapses. We considered this necessary for ethical reasons because we were unsure how long-lasting the effects of our therapy might be. In order to properly answer the issue raised by Dr. Smeraldi and his colleagues, it would be necessary to conduct a longitudinal study of unmedicated patients and to monitor their clinical outcomes after the end of the study.