The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology

Bipolar Disord. 2019 Dec;21(8):741-773. doi: 10.1111/bdi.12847. Epub 2019 Nov 22.


Aims: To systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)-bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI-BP)-and propose treatment recommendations based on a synthesis of the evidence.

Methods: PRISMA-based systematic review of the literature.

Results: The acute antidepressant (AD) efficacy of LT was supported by several open-label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti-manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant activity, conflicting evidence of both antimanic and maintenance efficacy, and support from two case series of improved sleep in both acute and euthymic states. IPSRT monotherapy for bipolar II depression had acute response rates of 41%, 67%, and 67.4% in two open studies and one RCT, respectively; as adjunctive therapy for bipolar depression in one RCT, and efficacy in reducing relapse in two RCTs. Among euthymic BD subjects with insomnia, a single RCT found CBTI-BP effective in delaying manic relapse and improving sleep. Chronotherapies were generally safe and well-tolerated.

Conclusions: The outcome literature on the adjunctive use of chronotherapeutic treatments for BP is variable, with evidence bases that differ in size, study quality, level of evidence, and non-standardized treatment protocols. Evidence-informed practice recommendations are offered.

Keywords: Chronotherapy; bipolar; circadian; cognitive behavioral therapy for insomnia adapted for bipolar disorder; dark therapy; interpersonal social rhythm therapy; light therapy; melatonergic agonist; melatonin; sleep deprivation.

Publication types

  • Systematic Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Antimanic Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Chronotherapy*
  • Cognitive Behavioral Therapy
  • Combined Modality Therapy
  • Drug Chronotherapy*
  • Female
  • Humans
  • Phototherapy
  • Sleep
  • Sleep Deprivation
  • Sleep Initiation and Maintenance Disorders


  • Antidepressive Agents
  • Antimanic Agents