Systematic review and practical guideline for the prevention and management of the renal side effects of lithium therapy

Eur Neuropsychopharmacol. 2020 Feb:31:16-32. doi: 10.1016/j.euroneuro.2019.11.006. Epub 2019 Dec 11.


Lithium is the first line therapy of bipolar mood disorder. Lithium-induced nephrogenic diabetes insipidus (Li-NDI) and lithium nephropathy (Li-NP, i.e., renal insufficiency) are prevalent side effects of lithium therapy, with significant morbidity. The objective of this systematic review is to provide an overview of preventive and management strategies for Li-NDI and Li-NP. For this, the PRISMA guideline for systematic reviews was used. Papers on the prevention and/or treatment of Li-NDI or Li-NP, and (influenceable) risk factors for development of Li-NDI or Li-NP were included. We found that the amount of evidence on prevention and treatment of Li-NDI and Li-NP is scarce. To prevent Li-NDI and Li-NP we advise to use a once-daily dosing schedule, target the lowest serum lithium level that is effective and prevent lithium intoxication. We emphasize the importance of monitoring for Li-NDI and Li-NP, as early diagnosis and treatment can prevent further progression and permanent damage. Collaboration between psychiatrist, nephrologist and patients themselves is essential. In patients with Li-NDI and/or Li-NP cessation of lithium therapy and/or switch to another mood stabilizer should be considered. In patients with Li-NDI, off label therapy with amiloride can be useful.

Keywords: Chronic renal insufficiency; Lithium; Nephrogenic diabetes insipidus.

Publication types

  • Systematic Review

MeSH terms

  • Antimanic Agents / administration & dosage
  • Antimanic Agents / adverse effects
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Diabetes Insipidus, Nephrogenic / chemically induced*
  • Diabetes Insipidus, Nephrogenic / diagnosis
  • Diabetes Insipidus, Nephrogenic / prevention & control
  • Humans
  • Lithium Compounds / administration & dosage
  • Lithium Compounds / adverse effects*
  • Practice Guidelines as Topic / standards*
  • Withholding Treatment / standards*


  • Antimanic Agents
  • Lithium Compounds