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Observational Study
. 2025 Jul 1;25(1):655.
doi: 10.1186/s12888-025-07111-9.

Sex differences in lithium concentrations among bipolar patients with different episodes based on real-world therapeutic monitoring data

Yuanhan Bai #  1 , Haichen Yang #  1   2 , Jindong Chen  3 , Lina Wang  4 , Zuowei Wang  5 , Xinhua Shen  6 , Jing Sun  7 , Tiebang Liu  1
Affiliations
Observational Study

Sex differences in lithium concentrations among bipolar patients with different episodes based on real-world therapeutic monitoring data

Yuanhan Bai et al. BMC Psychiatry. .

Abstract

Background: Sex differences in lithium-associated efficacy and adverse events have been well studied in bipolar disorder. Exploring variations in lithium concentrations between sexes may offer potential explanations.

Methods: This multicenter, real-world, observational study, which was based on therapeutic monitoring data, was conducted at six Chinese hospitals. Sex differences in lithium concentrations and potential affecting factors were explored using the generalized estimating equation and multiple linear regression analysis, respectively.

Results: A total of 525 bipolar patients were included, comprising 328 patients diagnosed with mania or mania with depressive features and 197 with bipolar depression. There were 398 females and 127 males, including 79 patients aged 13-17 years. The median final lithium dosage of all the subjects was 0.9 g per day, with an average final concentration of 0.68 mmol/L. The lithium concentration was relatively stable in the context of a fixed dosage. In patients with mania or mixed features, lithium concentrations in females were significantly higher than those in males when a fixed lithium dosage was administered. This phenomenon was not observed in patients with bipolar depression. The number of factors influencing lithium concentrations was greater for males with mania or mixed features than for females, which was not observed between males and females with bipolar depression.

Conclusions: The therapeutic lithium concentrations of bipolar male and female patients in real-world clinical practice were lower than the guideline-recommended ranges. In patients with manic or mixed features, females have a greater propensity for lithium accumulation than males do, and lithium concentrations are more likely to be affected by internal and external changes in males than in females. Therefore, the potential risk of toxicity and the stability of lithium concentrations are key points in females and males on lithium therapy, respectively.

Keywords: Bipolar disorder; Concentration; Lithium; Sex.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Ethics Committees of all the participating centers reviewed and approved the study protocol, including Shenzhen Kangning Hospital (leading research center, approval no. 2020-K025-01-1, 2020-K025-02); The Second Xiangya Hospital of Central South University (approval no. 2020-144); Nanjing Brain Hospital (approval no. 2020-KY210-01); Tianjin Anding Hospital (approval no. 2021-01); Huzhou Third Municipal Hospital (approval no. 2020-108); and Shanghai Hongkou Mental Health Center (deceleration of ethics approval: study can be started upon the leading research center passing ethics approval). Written informed consent was required for participation in the study. Consent for publication: All authors agreed on the publication of this work and are accountable for all aspects of the work. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
Sex differences in lithium concentrations across different lithium dosages in all bipolar patients. (a) Patients with mania or mixed features. (b) Patients with bipolar depression. * Statistically significant difference between male and female patients
See this image and copyright information in PMC

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