Six predictors could 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. The study, published in the journal The Lancet Psychiatry , also points to genetic markers that appear to influence how quickly the body eliminates lithium from its system.
“Our model could already be used to predict how much lithium a patient with bipolar disorder will need. This could reduce valuable time spent finding the right dose for each patient, which could have a life-saving impact,” says Martin Schalling, professor at the Department of Molecular Medicine and Surgery at 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. The amount needed varies greatly between individuals and finding the correct dosage for each patient is key, as too much can be toxic, while too little is ineffective.
To minimize the risk of side effects, doctors tend to start treatment at low doses that increase over time, meaning it can take months before the treatment takes effect.
To overcome this, researchers have long sought a model that could predict dose response in individual patients. Previous studies have identified markers such as age, sex, and kidney function as possible predictors of how quickly the body removes lithium from your system (lithium clearance), which can be used to determine the amount needed daily. However, most studies have been limited by small sample sizes.
In the current study, researchers examined electronic medical records and registry data from a total of 2,357 patients with bipolar disorder, which may represent the largest sample size for this type of study to date. Both men and women ranging in age from 17 to 89 years, primarily of European ancestry, were included.
| The study found associations between lithium elimination rate and age, sex, kidney function (measured as eGFR), serum lithium concentrations, and medication with diuretics and substances targeting the renin-angiotensin-aldosterone system (RAAS). , which could be used to treat hypertension 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 lithium concentrations in the blood do not appear to be completely proportional, which goes somewhat against current thinking. “Our model based on these predictors explained about 50-60 percent of the variation in lithium clearance, which is better than previous models and could be used to inform treatment decision,” says first author Vincent Millischer, postdoctoral researcher. in the Department of Molecular Medicine. and Surgery, Karolinska Institute, and resident in psychiatry at the Medical University of Vienna.
The study also found associations between lower lithium clearance and a genetic locus on chromosome 11 and could also show that genetic variants affecting BMI and kidney function were associated with lithium clearance. Although adding the genetic markers only marginally improved the model’s predictive ability, the researchers say it opens up the opportunity for 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 result is positive, we will develop a digital application that psychiatrists could use in the future to help assess lithium dosing 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, the Bror Gadelius Minnesfond, the Swedish Mental Health Fund, the Karolinska Institute and Karolinska University Hospital. . Some of the authors have disclosed receipt of consulting and speaking fees from various pharmaceutical companies, while others have disclosed no competing interests.
Conclusions
Our predictor model could be used clinically to better guide lithium dosing, shortening the time to reach therapeutic concentrations and thus improving care. Identification of the first genomic locus and PRS associated with CLLi presents the opportunity for individualized medicine in lithium treatment.
