BIPOLAR DISORDERS: A Lithium Dosing Model

First author Dr. Martin Schalling, Professor of Molecular Medicine and Surgery at Karolinska Institutet, explains the work: “Our model can already predict how much lithium a patient with bipolar disorder will need. It will reduce the time it takes to find the right dose for each patient, which will actually 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, reducing episodes of depression and excitement. The amount needed varies greatly from patient to patient and finding the right dose for each patient is important as too much can be toxic while too little can be ineffective. To minimize the risk of side effects, doctors tend to start treatment with low doses and increase them gradually, meaning it can take months for the treatment to work.

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 possible predictors of how quickly the body eliminates lithium (clearance). These criteria can help determine the amount needed each day, but do not have the same impact 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 identifies associations between lithium clearance rate and age, gender, renal function (measured in eGFR), serum lithium concentrations and medicinal products containing diuretics and agents that target the renin-angiotensin-aldosterone system and are used to treat hypertension and other disorders. In conclusion, the analysis suggests that:

  • elderly patients, women, patients with impaired kidney function and people taking certain medications require lower doses of lithium;
  • the amount of lithium collected and blood lithium concentrations do not appear to be fully proportional, contrary to commonly accepted notions;
  • these different data make it possible to develop a model that integrates about 50 to 60% of the variance in lithium clearance, i.e. a more efficient model than the previous tools, and that allows clarification of the treatment decision, summarizes researcher Vincent Millischer, resident in Psychiatry at the Medical University of Vienna.
  • There are associations between lower lithium clearance and a genetic locus on chromosome 11;
  • genetic variants affecting BMI and renal function appear to be associated with lithium clearance;
  • Although the addition of genetic markers to the model improves its predictive power only slightly, a step towards personalized treatment with lithium is taken.

The model must soon be validated by a clinical study. If the result is positive, the researchers will develop a digital application that psychiatrists can easily use.

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