Side Effects of Lithium Prescribed to Bipolar Patients May Increase Risks of Thyroid, Kidney Problems: Study

Researchers recommend establishing cutoff levels for healthy doses of lithium, to prevent severe side effects.

New research suggests that commonly prescribed lithium doses may pose greater risks of thyroid and kidney problems for bipolar disorder patients than previously thought.

Lithium-based antipsychotic medications, such as Lithane and Lithobid, have been widely used since the 1970s to treat schizophrenia, bipolar disorder and other psychiatric illnesses. According to the National Alliance on Mental Illness (NAMI), approximately three percent of the U.S. population has schizophrenia or bipolar disorder, which are conditions that often require antipsychotic treatment.

While lithium is effective, prolonged use has been associated with hypothyroidism, which can cause fatigue, weight gain and other metabolic issues, as well as kidney damage, potentially leading to chronic kidney disease or kidney failure.

Now, a study published in JAMA Network Open on February 11 suggests that these risks can develop at even lower lithium levels than previously believed. Researchers caution that current dosage guidelines may not fully account for these risks, urging doctors and patients to carefully evaluate lithium therapy to minimize potential long-term harm.

The study, which was led by Joe Kwun Nam Chan of the University of Hong Kong, looked at data maintained by the Hong Kong Hospital Authority, for patients who were older than 15 years of age and first diagnosed with bipolar disorder between 2002 and 2018.

Among this cohort, researchers compared data on thyroid and kidney illnesses for individuals who had filled at least one lithium prescription, and those who did not.

The researchers found 4,752 incidents of hypothyroidism among patients with a mean age of 39 years old, 4,500 incidents of hyperthyroidism for patients with a mean age of 39, and 7,029 incidents of chronic kidney disease for patients with a mean age of 37 years old. Among all illnesses, approximately 60 percent of those who reported the illness were women.

Per 1,000 person-years, there were 25.7 incidents of hypothyroidism, 12.9 incidents of hyperthyroidism and 10.8 incidents of stage 3 chronic kidney disease (CKD) or higher. Compared with other mood stabilizers, lithium did not appear to increase the risk of more severe forms of CKD.

In addition, symptoms began appearing at lithium levels of 0.50 to 0.58 milliequivalents per liter (mEq/L), which is lower than the recommended clinical guidelines of 0.60 to 0.80 mEq/L for lithium maintenance treatment.

However, since the study was composed of an entirely Asian population, the researchers were not sure if their results would hold across all ethnicities.

“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 (bipolar disorder), particularly in Asian populations,” the researchers concluded.

Lithium use has previously been linked to higher risks of acute kidney injuries. In a study from July 2023, Swedish researchers determined that patients on high lithium doses for longer than one year had up to a 30% higher risk of chronic kidney disease progression than patients taking similar amounts of Depakote, a mood stabilizer that can be prescribed for bipolar disorder in place of lithium.

A Danish study from 2018 indicated that lithium side effects could increase the risk of birth defects as well. The researchers found that there was a 71% increased risk of major malformations among children of women who took lithium during their first trimester of pregnancy.