BIPOLAR DISORDERS: A lithium dosing model

Lead author Dr. Martin Schalling, Professor of Molecular Medicine and Surgery at Karolinska Institutet, explains the work: “Our model can already be used to predict how much lithium a patient with bipolar disorder will need. It will reduce the time spent searching for the right dose for each patient, which in concrete terms will save lives.”

Lithium is one of the basic treatments for bipolar disorder,

a condition associated with an increased risk of suicide. The chemical acts as a mood stabilizer and reduces episodes of depression and excitement. The amount needed varies greatly from patient to patient and it is essential to find the correct dose for each patient as too much can be toxic and too little can be ineffective. To minimize the risk of side effects, doctors tend to start treatment at low doses and gradually increase them, which means it can take months for treatment to take effect.

Towards a dose-response model for each patient: this is the goal of many research teams, and previous studies have already identified markers such as age, gender, and kidney function as potential predictors of how quickly the body eliminates lithium (clearance). These criteria can help determine the amount needed daily, however they do not. they have the same influence on all patients.

The study: Analysis of electronic medical records and registry data from a total of 2,357 participants with bipolar disorder, aged 17 to 89 years, identified associations between lithium clearance rate and age, gender, renal function (measured in eGFR), serum lithium concentrations, and drugs containing diuretics. and substances that target the renin-angiotensin-aldosterone system that are used to treat high blood pressure and other conditions. Finally, the analysis suggests that:

  • the elderly, women, patients with reduced kidney function, and those taking certain medications require lower doses of lithium;
  • the amount of lithium collected and lithium concentrations in the blood do not appear to be completely proportional, which goes against generally accepted ideas;
  • These different data allow the development of a model that integrates approximately 50 to 60% of the variance in lithium clearance, that is, a more efficient model than the previous tools and that allows clarifying the treatment decision, summarizes the researcher Vincent Millischer, trainee in psychiatry at the Medical University of Vienna.
  • There are associations between decreased lithium clearance and a genetic locus on chromosome 11;
  • Genetic variants that affect BMI and renal function appear to be associated with lithium clearance;
  • Although the addition of genetic markers to the model only marginally improves its predictive capacity, a step has been taken in terms of personalized treatment with lithium.

The model should soon be validated by a clinical trial. If the result is positive, the researchers will develop a user-friendly digital application for psychiatrists.

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