Chronotherapeutics in Bipolar and Major Depressive Disorders: Implications for Novel Therapeutics

  • Wallace C. DuncanJr.Email author
Part of the Milestones in Drug Therapy book series (MDT)


Chronotherapeutic interventions (CTs) produce rapid antidepressant effects and, when applied sequentially, maintain an enduring antidepressant response following the initial CT intervention or in association with traditional drug therapies. Rapid antidepressant effects associated with CTs (sleep deprivation (SD), partial sleep deprivation (PSD), sleep phase advance (SPA)) and with the novel therapeutic ketamine are present in both major depressive disorder (MDD) and bipolar disorder (BD). The effects of the N-methyl-d-aspartate (NMDA) antagonist ketamine and CTs on sleep slow waves (SWS), brain-derived neurotrophic factor (BDNF), cortical excitability, and neuronal plasticity are present in MDD. Whether slow wave effects are also present in drug-free BD or healthy controls requires further investigation. The existing literature suggests that there are important differences in MDD versus BD patients in the regulation of SWS that may underlie diagnostic differences in slow wave response to ketamine. These differences further suggest that mood stabilizers may affect the expression of slow waves and moderation of mood cycles in BD.


Bipolar disorder Sleep deprivation Chronotherapeutics Ketamine BDNF 



This work was funded by the Intramural Research Program, National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH).


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© Springer International Publishing Switzerland (outside the USA)  2016

Authors and Affiliations

  1. 1.Experimental Therapeutics & Pathophysiology Branch, Intramural Research ProgramNational Institute of Mental Health, National Institutes of HealthBethesdaUSA

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