The literature suggests that sleep deprivation can potentiate the effect of antidepressant medication in depressed patients. However, the clinical efficacy of sleep deprivation has not been demonstrated definitively, in part because it is difficult to design an adequate control condition. We conducted a trial of sleep deprivation in 26 depressed patients who remained symptomatic despite 3 months of treatment with antidepressant medication. Since the literature indicates that early sleep deprivation (ESD), carried out in the first half of the night, is a less effective antidepressant than late sleep deprivation (LSD), carried out in the second half of the night, we designed a study that attempted to use ESD as a control condition for LSD. Patients were randomly assigned to ESD or LSD, received a total of 4 nights of sleep deprivation over 2 weeks, and were followed in clinic for the 3 subsequent weeks. ESD proved to be as effective an antidepressant as LSD, with the overall sample showing a mild, but statistically significant, response. There was a significant correlation between patients' acute response at the time of the first course of sleep deprivation treatments and their improvement over the course of the study. There were significant changes in plasma levels of thyroid stimulating hormone, free triiodothyronine, prolactin, and cortisol measured at 8 a.m. before and after sleep deprivation, and in the followup period, but there were no significant correlations between changes in hormonal levels and either acute or chronic response to sleep deprivation.

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