Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder

TY - JOUR

T1 - Association between lithium treatment and renal, thyroid and parathyroid function

T2 - A cohort study of 6659 patients with bipolar disorder

AU - Wiuff, Anne Christine

AU - Rohde, Christopher

AU - Jensen, Botilla Dalsgaard

AU - Nierenberg, Andrew A

AU - Østergaard, Søren Dinesen

AU - Köhler-Forsberg, Ole

PY - 2024/2

Y1 - 2024/2

N2 - OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up.METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients.RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4).CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

AB - OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up.METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients.RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4).CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

KW - bipolar disorder

KW - drug-related side effects and adverse reactions

KW - kidney diseases

KW - lithium compounds

KW - longitudinal studies

KW - parathyroid diseases

KW - thyroid diseases

KW - Creatinine

KW - Lithium/adverse effects

KW - Calcium

KW - Humans

KW - Male

KW - Parathyroid Diseases/chemically induced

KW - Thyroid Gland

KW - Bipolar Disorder

KW - Biomarkers

KW - Adult

KW - Female

KW - Thyrotropin

KW - Lithium Compounds/adverse effects

KW - Cohort Studies

UR - http://www.scopus.com/inward/record.url?scp=85161707252&partnerID=8YFLogxK

U2 - 10.1111/bdi.13356

DO - 10.1111/bdi.13356

M3 - Journal article

C2 - 37300391

SN - 1399-5618

VL - 26

SP - 71

EP - 83

JO - Bipolar disorders

JF - Bipolar disorders

IS - 1

ER -