A large population-based cohort study found that lithium use in bipolar disorder patients was associated with an increased risk of hypothyroidism and chronic kidney disease stage 3 or higher, compared to other mood stabilizers.
Published in JAMA Network Open, study investigators analyzed data from February to May 2024, examining three distinct patient cohorts: 4752 for hypothyroidism analysis, 4500 for hyperthyroidism analysis, and 7029 for chronic kidney disease (CKD) outcomes. The study population had a mean age of 39.5 years, was approximately 60% female, and had a mean follow-up period of 8.4 years.
Researchers examined the incidence of hypothyroidism, hyperthyroidism, and CKD outcomes based on lithium use, contrasting findings with patients receiving alternative mood stabilizers like valproate, olanzapine, quetiapine, and risperidone. Cox proportional hazards regression models were employed, adjusting for multiple covariates, including demographics and comorbidities.
Key findings indicated that lithium users had twice the risk of developing hypothyroidism and a 35% higher risk of CKD stage 3 or higher. However, lithium was not linked to more advanced kidney dysfunction or end-stage kidney disease.
Serum lithium levels played a critical role. Thresholds greater than 0.50 mEq/L were associated with hypothyroidism, levels above 0.50 mEq/L with hyperthyroidism, and levels exceeding 0.59 mEq/L with CKD stage 3 or higher.
Longer lithium exposure correlated with lower thyroid and kidney risks. A greater number of lithium toxicity episodes was associated with elevated CKD risk.
Alternative treatments demonstrated a reduced risk profile. Valproate, olanzapine, quetiapine, and risperidone users generally exhibited a lower likelihood of thyroid dysfunction and CKD compared to lithium users. For instance, olanzapine use was associated with a 70% reduced risk of hypothyroidism.
The findings provide empirical evidence to inform clinical guidelines on determining optimal lithium serum levels, balancing treatment efficacy and safety. The identified thresholds of lithium serum levels associated with thyroid and kidney abnormalities provide evidence to inform treatment guidelines, potentially facilitating more personalized care and equity in the treatment of BD, particularly in Asian populations.
The study acknowledged several important limitations, including its observational nature, which precluded random assignment of medication treatment. Additionally, researchers noted the lack of data on lifestyle variables such as physical activity, dietary patterns, smoking, and body mass index. The varying frequency of lithium monitoring in clinical practice also affected the consistency of serum level measurements.
Full disclosures can be found in the study.
