To systematically review evidence on the efficacy and safety of sleep deprivation (SD) as a treatment option for patients with unipolar or bipolar depression.
A systematic review according to PRISMA-guidelines was conducted. The certainty of evidence was assessed using the GRADE approach. Controlled trials were included in efficacy analysis, case-series for evaluating complications and qualitative studies for patients’ experiences.
Eight controlled studies (368 patients), one qualitative study, and seven case-series (825 patients) were included. One week after treatment start, SD combined with standard treatment did not reduce depressive symptoms compared to standard treatment (standardised mean difference, SMD =-0.29, [95%-confidence interval, CI: – 0.84 to 0.25], P=0.29). When excluding a study in elderly patients in a post-hoc analysis, the difference was statistically significant (SMD = -0.54 ([95%-CI: -0.86 to -0.22], P<0.001)) but it diminished two weeks after treatment start. No superiority of SD was found compared to antidepressants, but SD may be superior to exercise in certain settings. It is uncertain whether SD affects quality of sleep, quality of life, everyday functioning or length of stay. Apart from switch to mania (ranging between 2.7%-10.7%), no other serious complications were reported.
Sleep deprivation has been studied in a wide range of settings resulting in divergent results for the short-term efficacy on depressive symptoms. Post hoc analyses indicated that there may be a significant but transient effect in certain populations. Further studies should focus on identifying subgroups of responders as well as examining feasibility in routine clinical care.

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