Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Aug;23(5):445-453.
doi: 10.1111/bdi.13070. Epub 2021 Mar 16.

Effect of lithium on circadian rhythm in bipolar disorder: A systematic review and meta-analysis

Ni Xu  1 , Kiyomi Shinohara  2 , Kate E A Saunders  1   3 , John R Geddes  1   3 , Andrea Cipriani  1   3
Affiliations
Meta-Analysis

Effect of lithium on circadian rhythm in bipolar disorder: A systematic review and meta-analysis

Ni Xu et al. Bipolar Disord. 2021 Aug.

Abstract

Objectives: Circadian rhythm disruption is commonly reported in patients with bipolar disorder. Lithium has been suggested to have effects on the circadian clock, the biological basis of the circadian rhythm. The objective of the current review was to review systematically the existing studies on the effect of lithium on circadian rhythm in patients with bipolar disorder.

Methods: We systematically searched the scientific literature up to September 2020 for experimental or observational studies which measured circadian rhythm in bipolar patients taking lithium (in comparison with placebo or other active treatments) and carried out a meta-analysis. Circadian rest-activity was our primary outcome, but we also collected data about sleep quality and chronotype (Morningness-Eveningness). The protocol was registered in PROSPERO (CRD42018109790).

Results: Four observational studies (n = 668) and one experimental study (n = 29) were included. Results from the meta-analysis suggest a potential association between lithium and shifts towards morningness (standardized mean difference [SMD]: 0.42, 95% confidence interval [CI]: -0.05 to 0.90). One cohort study with 21 days of follow-up found that patients treated with lithium had significantly larger amplitude (0.68, 0.01 to 1.36) when compared to anticonvulsants.

Conclusion: This review highlights the insufficient evidence to inform us about the effect of lithium on circadian rhythm. However, we found that chronotype can be a potential target for further exploration of biomarkers or biosignatures of lithium treatment in patients with bipolar disorder. Further studies with prospective and longitudinal study design, adopting actigraphy to monitor daily circadian rest-activity changes are needed.

Keywords: bipolar disorder; circadian rhythm; lithium.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Grandin LD, Alloy LB, Abramson LY. The social zeitgeber theory, circadian rhythms, and mood disorders: review and evaluation. Clin Psychol Rev. 2006;26(6):679-694.
    1. Hofstra WA, de Weerd AW. How to assess circadian rhythm in humans: a review of literature. Epilepsy Behav. 2008;13(3):438-444.
    1. Melo MCA, Abreu RLC, Linhares Neto VB, de Bruin PFC, de Bruin VMS. Chronotype and circadian rhythm in bipolar disorder: a systematic review. Sleep Med Rev. 2017;34:46-58.
    1. Faedda GL, Ohashi K, Hernandez M, et al. Actigraph measures discriminate pediatric bipolar disorder from attention-deficit/hyperactivity disorder and typically developing controls. J Child Psychol Psychiatry. 2016;57(6):706-716.
    1. Jones SH, Hare DJ, Evershed K. Actigraphic assessment of circadian activity and sleep patterns in bipolar disorder. Bipolar Disord. 2005;7(2):176-186.