Association of lithium use with rate of out-of-hospital cardiac arrest in patients with bipolar disorder

Background: Lithium has been linked with induction of proarrythmic electrocardiographical changes. However, it is unclear whether lithium use is associated with an increased rate of cardiac arrest. We investigated the rate of out-of-hospital cardiac arrest associated with lithium exposure in a nationwide cohort of patients with bipolar disorder. Methods: Data from Danish registries was used to conduct a nationwide nested case-control study assessing the rate of out-of-hospital cardiac arrest associated with lithium exposure among 47,745 bipolar disorder patients from 2001 through 2015. 284 cases with out-of-hospital cardiac arrest were matched on age, sex, and age at first diagnosis of bipolar disorder with 1,386 controls. Rate analyses were performed using Cox regression. Results: Fewer cases than controls were exposed to lithium (24.3% vs. 34.9%, p<.001). In adjusted analyses, lithium monotherapy was not significantly associated with increased rate of out-of-hospital cardiac arrest compared with no mood stabilizing treatment (Hazard ratio [HR] = 0.71 [95% CI, 0.46–1.10]), atypical antipsychotic monotherapy (HR = 0.69 [95% CI, 0.41–1.15]), and anticonvulsant monotherapy (HR = 1.37 [95% confidence interval [CI], 0.65–2.88]). Combination therapy with lithium plus one or more other mood stabilizers was not associated with increased rate of out-of-hospital cardiac arrest compared with combination therapy with two or more non-lithium mood stabilizers (HR = 0.58, [95% CI, 0.31–1.08]). Limitations: Possible residual confounding due to unmeasured variables. Lack of statistical power to detect weak associations. Conclusions: Lithium was not associated with increased rate of out-of-hospital cardiac arrest in bipolar disorder patients compared with other guideline-recommended mood stabilizing pharmacotherapy, nor compared with no mood stabilizer treatment.