High Vasopressin Levels Common With Long-Term Lithium

Blue capsules on white background
The prospective single-center observational study involved 217 individuals aged 18 and or over treated with lithium.

Over half of patients taking lithium for bipolar disorder in a recent study experienced elevated vasopressin levels, which is a symptom of nephrogenic diabetes insipidus (NDI). Results of the study were recently published in Kidney International Reports.

Lithium therapy can lead to NDI, which causes excessive thirst and polyuria. No consensus intervention exists, and the mechanism of lithium-induced NDI is only partly known. The researchers evaluated patterns of urine concentration to better inform treatment.

The prospective single-center observational study involved 217 individuals aged 18 and over treated with lithium. Participants collected urine samples for 24 hours and fasted from 8 PM the evening before each study visit. A subset of patients also received kidney MRIs. The researchers measured urine and plasma osmolality, natremia, plasma copeptin level, plasma vasopressin level, urine output, ionogram, urea, and creatine.

The researchers found 21% of the patients experienced polyuria (urine output of more than 3 liters per day). Median fasting plasma copeptin and vasopressin levels were 13 [8-23] pmol/l and 5.8 [3.9-10.3] pg/ml respectively. Participants who had taken lithium the longest, and who happened to take lower doses, had the lowest mean urine osmolality, as well as higher urine output, and higher free water clearance. More than half (55%) of all participants had elevated vasopressin levels. The researchers found no association between galenic formulation of lithium therapy and diuresis.

Limitations of the study include the cross-sectional and observational design, as well as missing data on plasma lithium levels.

“Lowering lithium daily dose might decrease 24-hour urine output, and that it should be considered in individuals affected by the disorder,” the researchers concluded.

“Controlling salt and protein intake might also help decreasing 24-hour urine volume as it affects 24-hour urine osmolar output. We also found an early increase in vasopressin level in a majority of individuals probably even before the development of polyuria, suggesting an early resistance to the action of vasopressin, hence the development of NDI, that might have potential deleterious role in the pathophysiology of CKD associated with chronic lithium treatment.”


Tabibzadeh N, Vidal-Petiot E, Cheddani L. Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria. Kidney Int Rep. Published online April 15, 2022. doi:10.1016/j.ekir.2022.04.008.