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

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.