Six lithium dose predictors for patients with bipolar disorder


Six predictors may help determine the amount of lithium needed to treat patients with bipolar disorder, according to a large study led by researchers at Karolinska Institutet in Sweden. This study published in the journal The Lancet PsychiatryIt also indicates genetic markers that affect how quickly the body removes lithium from its system.

“Our model can now be used to predict how much lithium a patient with bipolar disorder will need. This could potentially result in life-saving implications, with valuable time spent on finding the right dosage for each patient.” could reduce the risk of cancer,” says Professor Martin Scholing of the Department of Molecular Medicine and Surgery, Karolinska Institutet and senior author of the study.

Lithium is one of the most important treatments for patients with bipolar disorder, a condition that has been linked to an increased risk of suicide. The chemical works as a mood stabilizer and reduces episodes of depression and mania. How much is needed varies between individuals and it is important to find the right dosage for each patient because too much can be toxic while too little is ineffective. To reduce the risk of side-effects, physicians start treatment at a low dose that increases over time, which means it can take months for the treatment to be effective.

To overcome this, researchers have long sought to find a model that can predict dose response in individual patients. Previous studies have identified markers such as age, gender and kidney function as potential predictors of how quickly the body removes lithium from its system (lithium clearance), which have been used to determine the amount needed on a daily basis. can go. However, most studies have been limited by small sample sizes.

In the current study, researchers examined electronic health records and registry data from a total of 2,357 patients with bipolar disorder, which may represent the largest sample size ever recorded for such a study. Both men and women aged 17 to 89 years were included, mainly of European descent.

The study found an association between the speed of lithium clearance and age, sex, kidney function (measured as eGFR), serum lithium concentrations and drugs with diuretics and substances that target the renin-angiotensin-aldosterone system (RAAS). Gaya, which can be used for treatment. High blood pressure and other conditions.

“Our findings suggest that older patients, women, patients with reduced kidney function and those taking certain medications require lower doses of lithium. Interestingly, we also found that the amount of lithium taken and the amount of lithium in the blood increased.” does not seem to be completely proportional, which is contrary to current thinking. Based on these predictions, our model explained approximately 50–60 percent variation in lithium clearance, which is superior to previous models and informed treatment decisions. can be used to do this,” says first author Vincent Militcher, a postdoctoral researcher in the Department of Molecular Medicine. and Surgery, Karolinska Institutet, and resident in psychiatry at the Medical University of Vienna.

The study also found an association between low lithium clearance and a genetic locus on chromosome 11 and may also show that genetic variants affecting BMI and kidney function were associated with lithium withdrawal. Even though adding genetic markers marginally improved the model’s predictive ability, the researchers say it opens up the opportunity for personalized medicine in future lithium treatments.

“Next we will test our model in a clinical trial to see if it can reduce the time it takes to find the right amount of lithium for each patient,” says Martin Scholing. “If the result is positive, we will develop a digital app that can be used in the future by psychiatrists to help assess lithium dosage for patients with bipolar disorder.”

The study was funded by the Stanley Medical Research Institute, the Swedish Research Council, the Swedish Foundation for Strategic Research, the Swedish Brain Foundation, the Söderström Königska Foundation, Bror Gadelius Minesfond, the Swedish Mental Health Fund, Karolinska Institutet and Karolinska University Hospital. , Some authors have declared to have received consulting and lecture fees from various pharmaceutical companies, while others have declared no competing interests.

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Material provided by Karolinska Institute, Note: Content can be edited for style and length.

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