Study: 6 Predictors Help Determine Amount of Lithium for Patients With Bipolar Disorder

There are 6 predictors that help determine the amount of lithium that is needed to treat individuals with bipolar disorder, according to the results of a study conducted by the Karolinska Institutet in Sweden.

The results of the study, published in The Lancer Psychiatry, also identify genetic markers that seem to influence how quickly the body eliminates lithium from its system.

“Our model could already now be used to predict how much lithium a patient with bipolar disorder will need. This could cut valuable time spent on finding the right dose for each patient, potentially with life-saving impact,” Martin Schalling, MD, PhD, professor at the Department of Molecular Medicine and Surgery at the Karolinska Institutet, said in a statement.

Lithium is a common and important treatment for individuals with bipolar disorder, a condition that has been linked to an increased risk of suicide. The substance works as a mood stabilizer and reduces episodes of depression and mania.

However, the amount of lithium needed varies among individuals, and finding the right dosage is key, as too little can be effective and too much can be toxic.

Physicians often start treatment at low dosages and increase them over time to minimize the risk of adverse events, but this could take months before the treatment has an effect.

Investigators have tried to find a model that could predict dose responses in individuals, and previous studies have identified markers, such as age, kidney function, and sex, as possible predictors of how quickly the body eliminates lithium from its system. This can be used to determine the amount needed daily. However, most studies are limited because of small sample sizes.

In this study, investigators examined electronic health records and registry data from a total of 2357 individuals with bipolar disorder, 1 of the largest sample sizes for this kind of study to date.

The study found associations between the speed of lithium clearance and age, sex, kidney function, which was measured as eGFR, serum lithium concentrations, and medication with diuretics and substances targeting the renin-angiotensin-aldosterone system.

“Our findings suggest that older patients, women, patients with reduced kidney function, and those taking certain medications require lower doses of lithium,” Vincent Millischer, a postdoctoral researcher at the Department of Molecular Medicine and Surgery at the Karolinska Institutet and resident in psychiatry at the Medical University of Vienna, said in the statement. “Our model based on these predictors explained around 50% to 60% of the variance in lithium clearance, which is better than previous models and could be used to inform treatment decision,”.

Investigators also said that they discovered that the amount of lithium taken and lithium concentration in the blood do not appear entirely proportional.

The results also demonstrated an association between a lower lithium clearance and 1 genetic locus on chromosome 11, which could also show that genetic variants affecting body mass index and kidney function were associated with lithium clearance.

Even though adding the genetic marker slightly improves the model’s predictive capability, investigators said it opens up the opportunity for personalized medicine in lithium treatment.

Investigators also say they will evaluate the model in a clinical trial to see if it can reduce the time it takes to find the right amount of lithium for each individual.

If the outcome is positive, investigators plan to develop an application that could be used by psychiatrists to assess lithium doses for individuals with bipolar disorder.

Reference

Six lithium dose predictors for patients with bipolar disorder. EurekAlert. News release. May 12, 2022. Accessed May 13, 2022. https://www.eurekalert.org/news-releases/952346