Clinical Predictors Could Guide Lithium Dosage in Bipolar Disorder

THURSDAY, May 19, 2022 (HealthDay News) — A model comprising six clinical variables could be used to guide lithium dosage, according to a study published in the June issue of The Lancet Psychiatry.

Vincent Millischer, M.D., from the Karolinska Institutet in Stockholm, and colleagues conducted a population pharmacokinetic study involving two clinical Swedish cohorts with 2,357 patients who received a lithium dose and had clinically relevant plasma concentrations of lithium. The natural logarithm of total body clearance of lithium (CL_Li) associated with clinical variables was examined.

The researchers found that clinical predictors of CL_Li included age, sex, estimated glomerular filtration rate (eGFR), comedication with diuretics, and agents acting on the renin-aldosterone-angiotensin system. There was an association seen between CL_Li and serum lithium, with lower CL_Li associated with higher serum lithium. In a genome-wide association study, one locus (rs583503) was associated with change in CL_Li. Enrichment of the associations with genes expressed in the medulla and cortex of the kidney was also seen, as well as associations with polygenic risk score for eGFR, body mass index, and blood urea nitrogen. A model including six clinical predictors explained 61.4 and 49.8 percent of the variance in CL_Li in cohorts 1 and 2, respectively. No major improvement of the models was seen with addition of genetic markers.

“Replacing the current time-consuming empirical titration with dose prediction models based on individual clinical data might decrease the time needed to reach therapeutic lithium concentrations, increasing patient compliance and therefore improving clinical care for patients with bipolar disorder,” the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.

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