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J Affect Disord. 2013 Jan 10;144(1-2):28-33. doi: 10.1016/j.jad.2012.06.022. Epub 2012 Jul 24.

Total sleep deprivation followed by sleep phase advance and bright light therapy in drug-resistant mood disorders.

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Department of Neuropsychiatry, Bioregulatory Medicine, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita-City 010-8543, Japan.



Drug-resistant depression is a major therapeutic issue in psychiatry and the development of non-drug therapies that treat drug-resistant depression is required. Sleep deprivation (SD) is a non-drug treatment classified as a form of chronotherapy in addition to bright light therapy (BLT) and sleep phase advance (SPA). Combined chronotherapy is hypothesized to improve drug-resistant depression. In this study, we investigated the benefits of total sleep deprivation (TSD) followed by SPA and BLT in drug-resistant depression alongside ongoing antidepressant medication and observed the added effectiveness of the combined chronotherapy.


Thirteen drug-resistant inpatients affected by a major depressive episode were studied. They were treated by TSD followed by SPA (three days) and BLT (five days) with ongoing drug treatment. Effectiveness was rated using the Hamilton Rating Scale for Depression (HAM-D), the Zung Self-Rating Depression Scale (SDS), and the Visual Analogue Scale (VAS) over 3 weeks.


Significant improvements of depressive symptoms were observed in both objective mood ratings (HAM-D) and subjective mood ratings (SDS and VAS). Eight out of 13 patients maintained this responsiveness (50% or greater changes in HAM-D) across the study period. Moreover, no patients dropped out of the combined chronotherapy procedure.


The study did not have a placebo group, and more subjects may be needed.


The trial of combined chronotherapy successfully induced rapid improvement in depressive symptoms in drug-resistant patients without early relapse or obvious side effects.

[Indexed for MEDLINE]

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