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Meta-Analysis
. 2021 Oct;144(4):368-378.
doi: 10.1111/acps.13346. Epub 2021 Jul 16.

Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta-analysis

Chih-Wei Hsu  1   2 , Andre F Carvalho  3 , Shang-Ying Tsai  4   5 , Liang-Jen Wang  6   7 , Ping-Tao Tseng  8   9   10 , Pao-Yen Lin  1   11 , Yu-Kang Tu  12   13 , Eduard Vieta  14 , Marco Solmi  15   16 , Chi-Fa Hung  1 , Hung-Yu Kao  2
Affiliations
Meta-Analysis

Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta-analysis

Chih-Wei Hsu et al. Acta Psychiatr Scand. 2021 Oct.

Abstract

Objective: To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose-response meta-analysis were conducted.

Methods: The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4-0.8, and 0.8-1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random-effects modeling to estimate the dose-response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs.

Results: A total of 1406 participants (cohort: 466; meta-analysis: 940) were included. In the cohort study, the 0.4-0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8-1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose-response meta-analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non-linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L).

Conclusion: Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4-0.8 mmol/L.

Keywords: bipolar disorder; dose-response meta-analysis; lithium; maintenance treatment; serum level.

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Conflict of interest statement

Prof. Vieta has received grants and served as a consultant, advisor, or CME speaker for the following entities: AB‐Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol‐Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo‐Smith‐Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi‐Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the EU Horizon 2020 and the Stanley Medical Research Institute. Other authors declare no financial interests or potential conflicts of interest regarding the authorship and publication of this article.

Figures

FIGURE 1
FIGURE 1
Time to recurrence of any mood episode (Kaplan‐Meier curves). (A) primary analysis of all participants, (B) sensitivity analysis of participants on stable serum levels of lithium for 150 days, and (C) sensitivity analysis of participants on lithium monotherapy
FIGURE 2
FIGURE 2
The linear and non‐linear relationships of lithium serum levels and any recurring major mood episode
See this image and copyright information in PMC

References

    1. Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence‐based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30:495‐553. - PMC - PubMed
    1. Malhi GS, Bell E, Bassett D, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry. 2021;55:7‐117. - PubMed
    1. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97‐170. - PMC - PubMed
    1. Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM. Long‐term lithium therapy for bipolar disorder: systematic review and meta‐analysis of randomized controlled trials. Am J Psychiatry. 2004;161:217‐222. - PubMed
    1. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta‐analysis. BMJ. 2013;346:f3646. - PubMed

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