Lithium-associated bradycardia: A systematic review of 121 case reports

Lithium can induce various side effects, including bradycardia. Although numerous case reports have described bradycardia associated with lithium treatment, the condition is not widely recognized. This study aimed to conduct a systematic review of case reports on lithium-associated bradycardia. A systematic literature search was conducted in MEDLINE and Embase on June 20, 2025, using the keywords "lithium AND (sinus OR bradycardia OR bradyarrhythmia)." Case reports of bradycardia after lithium treatment were included. A total of 135 cases from 121 reports were identified. Information on patient clinico-demographics, lithium treatment, bradycardia characteristics, interventions, and lithium re-challenge was extracted. The cases included patients ranging in age from infancy to 87 years (mean 56.7 ± 16.3 years) and no apparent sex difference observed. Excluding cases with intentional overdoses, the mean lithium dose at bradycardia onset was 1090 mg/day, with a median of 900 mg/day. Among cases with reported lithium blood concentrations, the median level was 1.9 mmol/L, with 32.1% falling within the therapeutic range (0.6-1.2 mmol/L). Sinus bradycardia was the most common presentation, occurring in 64.4% of cases. Regarding bradycardia outcomes, 121 cases showed improvement, 2 remained asymptomatic, and 5 resulted in death. Re-challenge trials were conducted in 27 cases, with 51.9% experiencing recurrent bradycardia. Lithium-associated bradycardia can occur at any age, dose, and duration, even within the therapeutic range, with a high recurrence rate upon lithium re-challenge. This underscores the need for routine and careful monitoring of heart rate during lithium treatment.