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Meta-Analysis
. 2022 May:58:20-29.
doi: 10.1016/j.euroneuro.2022.01.112. Epub 2022 Feb 11.

Differences in the prophylactic effect of serum lithium levels on depression and mania in bipolar disorder: A dose-response meta-analysis

Chih-Wei Hsu  1 , Shang-Ying Tsai  2 , Ping-Tao Tseng  3 , Chih-Sung Liang  4 , Eduard Vieta  5 , Andre F Carvalho  6 , Brendon Stubbs  7 , Hung-Yu Kao  8 , Yu-Kang Tu  9 , Pao-Yen Lin  10
Affiliations
Meta-Analysis

Differences in the prophylactic effect of serum lithium levels on depression and mania in bipolar disorder: A dose-response meta-analysis

Chih-Wei Hsu et al. Eur Neuropsychopharmacol. 2022 May.

Abstract

The optimal serum lithium levels for preventing the recurrence of mood episodes in bipolar disorder are controversial, especially when polarity is considered. The present study aimed to comprehensively examine the dose-response relationship between lithium concentration and risk of recurrence of mood episodes. We conducted a systematic search of major databases before January 2021 (PROSPERO: CRD42021235812). A one-stage, random-effects, restricted cubic splines model was used to estimate the dose-response relationship between lithium concentration and risk of recurrence of any or specific mood episodes (depression or mania). The effect size is shown as odds ratio (OR). Our meta-analysis included six randomised controlled trials with a total of 975 participants. The dose-response curve showed that increased serum concentrations were associated with a gradual decrease in the risk of any mood episodes (OR 0.50 at 0.60 mmol/l, OR 0.15 at 1.20 mmol/l). The risk of depression decreased slightly with a concentration of 0.60 mmol/l (OR 0.83) but dropped rapidly as the concentration increased to 1.20 mmol/l (OR 0.39). By contrast, the risk for mania initially decreased steadily (OR 0.44), but decreased only marginally (OR 0.30) as the concentration increased. To reduce the recurrence risk to 56%, prevention of depression required a higher concentration than that required for mania (1.13 mmol/l vs. 0.60 mmol/l). Our results suggest a negative dose-response relationship between serum lithium levels and risk of recurrence. In particular, the different preventive effects of serum concentration on depression and mania will be an important clinical reference.

Keywords: Bipolar disorder; Dose-response meta-analysis; Lithium; Maintenance; Polarity; Serum level.

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Conflict of interest statement

Declaration of competing interest Prof. Vieta has received grants and serves 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.

Comment in

  • As in cooking, so in medicine: Doses do matter.
    De Prisco M, Oliva V. De Prisco M, et al. Eur Neuropsychopharmacol. 2023 Apr;69:24-25. doi: 10.1016/j.euroneuro.2022.10.013. Epub 2023 Jan 15. Eur Neuropsychopharmacol. 2023. PMID: 36645957 No abstract available.

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