Rethinking Lithium Monitoring: Insights from a Comparative Analysis of Saliva, Plasma, and Erythrocytes
Darko Vlahović1,2, Vivian Andrea Badžim1, Ivan Ljoka1
1Clinical Department of Psychiatry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.
Neuropsychobiology
|August 28, 2025
Summary
Erythrocyte lithium levels reliably predict plasma lithium, offering a robust biomarker for monitoring mood disorder treatment. Salivary lithium shows potential as a non-invasive, though less consistent, alternative for therapeutic drug monitoring.
Area of Science:
- Pharmacology
- Psychiatry
- Analytical Chemistry
Background:
- Lithium carbonate is crucial for mood disorder treatment, particularly bipolar disorder.
- Its narrow therapeutic window requires precise blood lithium monitoring.
- Reliability of non-plasma lithium measurements (salivary, erythrocyte) is not well-established.
Purpose of the Study:
- To evaluate predictive relationships between lithium concentrations in saliva, plasma, and erythrocytes.
- To assess temporal dynamics and utility of these matrices for therapeutic monitoring.
- To consider advantages of non-invasive sampling methods.
Main Methods:
- Recruited 77 patients with psychiatric conditions receiving lithium carbonate treatment.
- Measured lithium levels in saliva, erythrocytes, and plasma at six daily time points.
- Utilized spectrophotometry for lithium concentration determination.
Main Results:
- Erythrocyte lithium concentration consistently predicted plasma levels across most time points.
- Salivary lithium showed weaker, time-dependent associations with plasma levels.
- The strongest model fit (r² = 0.665) occurred at 3:00 PM, driven by erythrocyte lithium.
Conclusions:
- Erythrocyte lithium serves as a reliable biomarker for estimating plasma levels, especially in complex cases.
- Salivary lithium offers conditional clinical value as a non-invasive option in specific settings.
- Findings support erythrocyte lithium for robust therapeutic drug monitoring.
