Real-world Lithium Intake

Bipolar disorder is a severe mental disorder1 and lithium represents the first-line pharmacological treatment1-5. The individual lithium dose is based on monitoring of clinical effect and lithium blood levels6,7 (i.e., plasma lithium (P-Li) levels), which can be measured easily and accurately via blood sampling. Treatment guidelines recommend measuring P-Li levels during up-titration, but also regularly (2-4x/year) when patients have reached a stable dose6-8. P-Li levels are also measured to avoid high blood levels that are associated with side effects. Specifically, it is well-known that lithium can have adverse effects on the kidneys9-11 and the thyroid gland11, and that the therapeutic window is relatively narrow6.

P-Li levels reach a peak concentration after 2-4 hours, following which the concentration steadily decreases, as lithium is excreted entirely through the kidneys6. Treatment guidelines have for >50 years recommended that P-Li levels should be measured 12 hours after the patient has taken the most recent lithium dose in order to evaluate the target P-Li and lithium dose for each individual patient6,7,12, allowing a time window from 10 to 14 hours after lithium intake6,7,13,14. Typically, patients take the lithium dose in the evening and the blood sample is collected the following morning before a potential morning dose of lithium is taken. As the vast majority of lithium-treated patients are outpatients, this 12-hour timing depends entirely on the patient, meaning that the patient is responsible to get the blood test 12 hours after the most recent lithium intake. However, patients may have difficulties to get the lithium blood test taken 12 hours after the lithium dose15, blood sampling may be delayed for logistic reasons, and/or patients forget about the specific timing. Hence, P-Li levels may not necessarily reflect the actual 12-hour P-Li level and this complicates clinical decision-making. Indeed, initial data from Central Denmark Region have indicated that 50-75% of lithium-treated patients may not comply with the 12-hour lithium blood test requirement16. This has a potential high impact as e.g., a P-Li level measured 16 hours after the last lithium dose, but interpreted as a 12-hour P-Li level, may lead to an unwarranted increase of the lithium dose, potentially increasing the risk for side effects.

We have developed a new method to estimate the 12-hour P-Li level, termed eLi12 (estimated lithium level at 12 hours). eLi12 is a mathematical equation that can estimate the 12-hour P-Li when the lithium blood test is taken at a different time point, e.g., 8 or 16 hours. This method would represent a solution for the abovementioned clinical challenge but depends on the patient-reported time for lithium intake. As the time point of the lithium blood test always is registered, eLi12 depends on that the patient takes the prescribed lithium dose and correctly reports the time for intake of the most recent lithium intake before the lithium blood test. However, despite that the self-reported time for lithium intake has been used for >50 years in everyday clinical treatment, no study has investigated the pattern on lithium intake in a real-world clinical setting.