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

Anne Christine Wiuff*, Christopher Rohde, Botilla Dalsgaard Jensen, Andrew A Nierenberg, Søren Dinesen Østergaard, Ole Köhler-Forsberg

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


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.

Original languageEnglish
JournalBipolar disorders
Pages (from-to)71-83
Number of pages13
Publication statusPublished - Feb 2024


  • bipolar disorder
  • drug-related side effects and adverse reactions
  • kidney diseases
  • lithium compounds
  • longitudinal studies
  • parathyroid diseases
  • thyroid diseases
  • Creatinine
  • Lithium/adverse effects
  • Calcium
  • Humans
  • Male
  • Parathyroid Diseases/chemically induced
  • Thyroid Gland
  • Bipolar Disorder
  • Biomarkers
  • Adult
  • Female
  • Thyrotropin
  • Lithium Compounds/adverse effects
  • Cohort Studies


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