Lithium Doubles Risk of Thyroid and Kidney Dysfunction

In a new study, researchers found that even short-term lithium use doubled the risk of hypothyroidism, hyperthyroidism, and chronic kidney disease. The study focused on patients with a bipolar disorder diagnosis in Hong Kong.

Higher lithium levels were associated with a higher risk for thyroid and kidney problems, but the increased risk still showed up at serum lithium levels lower than those recommended by treatment guidelines. According to the researchers, guidelines suggest lithium levels of 0.60 to 0.80 mEq/L. However, the increased risk for hypothyroidism, hyperthyroidism, and chronic kidney disease showed up at 0.50 to 0.58 mEq/L.

“These data can provide important empirical evidence that can inform clinical guidelines on determining optimal range of lithium serum levels, balancing treatment efficacy and safety, and promoting personalized treatment for BD, particularly in Asian populations,” the researchers write.

The study was led by Joe Kwun Nam Chan and Wing Chung Chang at the University of Hong Kong. It was published in JAMA Network Open.

The current study was a population-based cohort study with data from electronic health records in Hong Kong. The researchers included all patients at least 15 years old who received their first bipolar diagnosis between 2002 and 2018. The researchers then compared those who were prescribed lithium to those who were not. The researchers also stratified the lithium level, when possible, so they could analyze whether those taking higher doses were at increased risk.

The outcomes of interest were hypothyroidism, hyperthyroidism, chronic kidney disease (CKD; stratified into CKD3+ and the more severe CKD4+), and end-stage kidney disease (ESKD). In total, 4752 patients were assessed for hypothyroidism, 4500 for hyperthyroidism, and 7029 for CKD.

The researchers found that those taking lithium were at twice the risk of hypothyroidism (adjusted hazard ratio [aHR] 2.00) and 35% increased risk of CKD (aHR 1.35).

Those with higher serum lithium levels were at higher risk: aHR 2.08 for hypothyroidism, aHR 1.81 for hyperthyroidism, and aHR 2.11 for CKD.

Those who experienced more episodes of lithium toxicity were also at increased risk of developing CKD.

The researchers accounted for a variety of possible confounding factors: “A comprehensive array of covariates was included in the analyses, comprising patient demographics, pre-existing physical comorbidities, substance and alcohol use disorders, use of other psychotropics, and use of medications with nephrotoxic risk when interacting with lithium,” they write.

The researchers compared those taking lithium to those taking specific other drugs, and write that “valproate, olanzapine, quetiapine, and risperidone generally exhibited reduced likelihood of thyroid dysfunction and CKD3+ compared with lithium, without any difference in advanced CKD.” However, these drugs have their own list of harmful effects.

They did not find an association between lithium use and more severe kidney problems (CKD4+ and ESKD). However, they note that the relatively short duration of use they found in the study (on average, about 8.5 years) may not have been long enough for them to see the kidney problems to progress to this stage. They write that it may be 10 to 20 years before kidney disease progresses to this level of severity.

Another odd finding: the researchers did not find longer-term use of lithium to be associated with increased risk for thyroid or kidney problems, despite previous research finding that longer-term use increases the risk. One explanation, according to the researchers, is that their finding is due to reverse causality—those who had early signs of these health problems might have stopped taking lithium. After all, more than half of those who start taking lithium discontinue it due to adverse effects.

Lithium is considered one of the most dangerous drugs in psychiatry’s armamentarium, with a range for toxicity that overlaps the supposed therapeutic range. Patients must be carefully monitored, as lithium toxicity can also cause permanent brain damage.

Previous studies have found a high risk of chronic kidney disease and other ailments after lithium use. For instance, one study found that lithium use was associated with a sixfold increase in hypothyroidism. Other researchers have noted that 20% of patients develop nephrogenic diabetes insipidus, and that the kidney damage can be irreversible even if patients stop taking the drug.

Still, some psychiatrists, such as Nassir Ghaemi, tout its mental health benefits, even while acknowledging that other psychiatric drugs fail to live up to expectations. And some researchers have even called for adding lithium to drinking water, arguing that it will reduce suicide rates at a population level.

But trials of lithium don’t support its anti-suicidal properties. In 2021, a study on veterans was terminated early because the drug didn’t improve suicide-related events compared with a placebo. Similarly, a 2022 meta-analysis also found no evidence that lithium prevented suicide-related events.

Moreover, lithium in drinking water also has dangerous properties. A 2023 study in JAMA Pediatrics found that mothers who were exposed to high levels of lithium in drinking water while pregnant were 46% more likely to have a baby with an autism diagnosis. High lithium levels during pregnancy have also been associated with an increased risk of spontaneous abortion, congenital anomalies, and cardiovascular problems in offspring.

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Chan, J. K. N., Solmi, M., Correll, C. U., Wong, C. S. M., Lo, H. K. Y., Lai, F. T. T., & Chang, W. C. (2025). Lithium for bipolar disorder and risk of thyroid dysfunction and chronic kidney disease. JAMA Network Open, 8(2), e2458608. doi:10.1001/jamanetworkopen.2024.58608 (Link)