Analytical Imprecision and Therapeutic Intervals for Lithium – Are There Implications for Old Age Patients with Bipolar Disorder?

BACKGROUND: Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4-0.8 mmol/L and 0.4-0.7 mmol/L for adults aged 60-79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic intervals been confirmed with real-world patient data. METHODS: Serum samples spiked with various concentrations of lithium ranging from 0 to 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the therapeutic intervals recommended by the ISBD task force. RESULTS: Routinely employed colorimetric methods for lithium measurements have sufficient precision within the recommended therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults. CONCLUSION: Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows recommended by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.