18 Significantly more patients relapsed in the phase-delay protoc

18 Significantly more patients relapsed in the phase-delay protocol

compared with the phase advance protocol (Figure 1). This indicates that the high response rate after SD and phase advance cannot be explained by a placebo phenomenon alone and supports the hypothesis that, in depressed subjects, sleeping at certain phases of the circadian rhythm, ie, especially late in the night and in the morning, has depressogenic effects. Unfortunately, one major issue has been almost completely neglected by researchers: docs SD produce any lasting effects after 4 to 6 weeks, which is the typical period for measuring the effects of antidepressants? There is only one controlled Inhibitors,research,lifescience,medical study using such a design.21 Twenty-four patients Inhibitors,research,lifescience,medical received amitriptylinc without additional SD, whereas 27 patients received amitriptyline plus a series of 6 partial SDs. Observer ratings, but not patient ratings, demonstrated superiority of the combined treatment after 4 weeks. By the standards of evidence -based medicine, there is little evidence to date that SD therapy has lasting effects over the course of several weeks. Figure 1 Antidepressant effects of total sleep

deprivation (TSD) in one night with a consecutive phase advance of the sleep period (blue circles) in comparison with a phase delay of the sleep period (gray circles). Inhibitors,research,lifescience,medical In the phase-advance group, the antidepressant … Neurobiology of SD in Sotrastaurin in vivo Depression There is no generally accepted hypothesis concerning the mechanism of action of SD, nor an explanation for the observation that subsequent sleep after SD leads Inhibitors,research,lifescience,medical to relapses. A variety of neurobiological effects point toward potential mechanisms of action of the procedure (Table III).22-32 Table III. Neurobiological Inhibitors,research,lifescience,medical effects of sleep deprivation. In humans some of the studies were performed in depressed patients, while other studies were in healthy subjects or in depressed patients and healthy subjects. Based on the observations that hyperarousal and a high level of activation

predict a favorable SD response,4 the antidepressant effect was explained using the two-process model of sleep regulation (Figure 2).33 In this model, depressed patients have a deficiency of process S (ie, sleep need) with process C (circadian rhythm) remaining unaffected. Depression is characterized by a deficient build-up of process S (Figure 2) . SD transiently leads to an increase Adenylyl cyclase in process S to normal, whereas relapse occurs after “recovery sleep” due to a return to low levels of S. Figure 2 Two-process mode! of sleep deprivation (SD) and depression . This model can explain the antidepressant effect of SD by assuming that an insufficient build-up of process S (S stands for sleep need), SD transiently increases the level of process S, thus, … Several brain imaging studies have tried to correlate the SD response with metabolic states of certain brain areas.

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