Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

BACKGROUND: In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium’s effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. METHOD: We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. RESULTS: During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment. CONCLUSIONS: This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.