Lithium Long Term Risks

Peter ForsterBipolar Treatment

Elsewhere we have talked about accumulating evidence that suggests that lithium may have significant long-term beneficial effects for brain function and health in people with bipolar. A recent article in the British journal the Lancet reminds us that lithium remains a medication that requires close monitoring and which has the potential to cause rare but significant adverse effects on kidney, thyroid and parathyroid function.

The authors of this study looked at clinical laboratory data for a large group of patients in Oxfordshire, England. The fact that their study included so much data over the course of roughly 30 years is a strength of the study, but there was no other clinical data available so the doses of lithium, the reason for lithium being prescribed, the presence or absence of other health problems, etc. is all unknown.

After controlling for the presence or absence of diabetes, lithium treatment, which was defined as having had at least two blood levels for lithium performed, was associated with an increased risk of hypothyroidism, an elevated serum calcium (which may or may not have been associated with hyperparathyroidism), and chronic renal disease.

Hypothyroidism is the most common of these potential adverse effects and is easily managed by taking a small dose of thyroid medication.

An elevated serum calcium is not that unusual in patients with lithium, but the potentially serious problem of hyperparathyroidism is much rarer and so the significance of the finding in this study is unclear. The vast majority of the patients in our clinic with an elevated serum calcium do not have evidence of hyperparathyroidism.

A large meta-analysis published in the same journal in 2012 concluded that the risk of chronic renal disease was elevated in those taking lithium long-term, but that the risk was quite low (0.5% of patients). Other studies have come to similar conclusions that the risk of chronic renal disease with long-term lithium is less than 1%, and that the increased risk attributable to lithium is less than 0.5% (since about 0.5% of people would develop chronic renal disease without lithium treatment).

This study suggested that the risk was primarily in younger women and occurred early on in the course of treatment, highlighting the importance of close monitoring of kidney function early in treatment.


Shine B, McKnight RF, Leaver L, Geddes JR. Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data. Lancet. 2015 May 20. pii: S0140-6736(14)61842-0. doi: 10.1016/S0140-6736(14)61842-0. [Epub ahead of print] PubMed PMID: 26003379.

McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012 Feb 25;379(9817):721-8. doi: 10.1016/S0140-6736(11)61516-X. Epub 2012 Jan 20. Review. PubMed PMID: 22265699.