Lithium toxicity following co-prescription of lithium and ACEI/ARBs: A population-based cohort study
Abstract
Guidelines caution against co-prescribing angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) together with lithium, as this may increase lithium levels leading to toxicity. We conducted a population-based retrospective cohort study using administrative health data in Ontario, Canada, to evaluate the 90-day risk of any hospital encounter with lithium toxicity, all-cause mortality, and all-cause hospitalization in chronic lithium users newly prescribed an ACEI or ARB between 2002 and 2021. Modified Poisson regression was used to estimate risk ratios (RR). ACEI/ARB use versus non-use was not associated with a higher 90-day risk of lithium toxicity (2.20% vs. 1.75%, risk ratio [RR] 1.25, 95% confidence interval [CI] 0.86-1.84), and was associated with a lower risk of 90-day all-cause mortality (0.75% vs. 2.05%, RR 0.36, 95% CI 0.22-0.61). While there are potential concerns about confounding in this analysis, these findings suggest that warnings in guidelines and drug monographs against using ACEIs and ARBs with lithium may be unwarranted.