Six predictors may help determine the amount of lithium needed to treat a patient bipolar disorderaccording to a large study led by researchers at the Karolinska Institutet in Sweden.
The study, published in the journal The Lancet Psychiatry, also pinpointed genetic markers that appear to affect how quickly the body clears lithium from its system.
“Our model can now be used to predict how much lithium a patient with bipolar disorder will need. This can cut valuable time spent figuring out the right dose for each patient, potentially having a life-saving impact,” he said. Martin Schallingprofessor at Department of Molecular Medicine and SurgeryKarolinska Institutet, and lead author of the study.
Lithium is one of the most important treatments for patients with bipolar disorder, a condition that is associated with an increased risk of suicide. The chemical acts as a mood stabilizer and relieves depressive and manic episodes.
The dosage needed varies widely among individuals and finding the right dose for each patient is key as too much can be toxic while too little will be ineffective. To minimize the risk of side effects, clinicians tend to start treatment at a low dose and increase it over time, meaning it can take many months before treatment takes effect.
To overcome this, researchers have long been trying to find a model that can predict dose response in individual patients. Previous studies have identified markers such as age, sex, and kidney function as predictors of how quickly the body clears lithium from the system (lithium clearance), which can be used. to determine the required daily amount. However, most studies are limited by small sample sizes.
Studied over 2,300 patients
In the current study, the researchers examined electronic health records and registry data from a total of 2,357 patients with bipolar disorder, possibly representing the largest sample size for the type of study. this so far. Both men and women between the ages of 17 and 89 were included, mostly of European descent.
The study found an association between the lithium clearance rate and age, sex, renal function (as measured by eGFR), serum lithium levels, diuretics, and substances that target the renin-angiotensin system. -aldosterone (RAAS), which can be used to treat hypertension and other conditions.
“Our findings suggest that older patients, women, patients with impaired renal function and those taking certain medications need lower doses of lithium. Interestingly, we also found that lithium intake and blood levels of lithium do not appear to be completely commensurate, which is somewhat contrary to current thinking. Our model based on these predictors explained about 50-60 percent of the variance in lithium clearance, better than previous models and can be used to inform decisions. intention to treat,” said the first author Vincent Millischera postdoctoral researcher in the Department of Molecular Medicine and Surgery, Karolinska Institutet, and a resident in psychiatry at the Medical University of Vienna.
Genetic link
The study also found an association between lower lithium clearance and a genetic site on chromosome 11 and may also indicate that genetic variants affecting BMI and kidney function are involved. to lithium clearance. While adding genetic markers only slightly improves the model’s predictive ability, the researchers say it opens the door to personalized medicine in lithium treatment in the future.
“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 Schalling. “If the results are positive, we will develop a digital app that could be used by psychiatrists in the future to help assess lithium dosage for patients with bipolar disorder.”
The source: Karolinska Institutet
