Risk of Depression Related to Use of Proton Pump Inhibitors and Tegoprazan: A Nationwide Cohort Study

Background: There are potential concerns of depression associated with the use of gastric acid suppressants.This study compared associations of potassium competitive acid blockers (PCABs) and proton pump inhibitors (PPIs) with the development of depressive disorder.Methods: Patients newly prescribed five PPIs (omeprazole, pantoprazole, lansoprazole, rabeprazole, and esomeprazole) and one PCAB (tegoprazan) from January 2020 to April 2022 were identified by Health Insurance Review and Assessment Service.Primary outcome was diagnosis of depression with more than 60 prescription days of antidepressants.Multivariable logistic regression and survival curve analysis with Kaplan-Maier method were performed with two models to calculate the risk of depression with all PPIs (model 1) or each individual PPIs (model 2) compared to tegoprazan.Sensitivity analyses using propensity score matching (PSM) and subgroup analyses stratified by treatment duration were followed.Results: A total of 6,104,743 patients aged 18-80 years were included.The occurrence of depression was higher in all PPI groups (adjusted odds ratio for all PPIs, 1.34; 95% confidence interval, 1.24-1.44;lansoprazole, 1.80; pantoprazole, 1.42; esomeprazole, 1.32; rabeprazole, 1.22; omeprazole, 1.15) than in the PCAB group.Cumulative incidence of depression up to 1200 days after beginning prescription was significantly higher in PPI groups (all P < 0.001) than in the PCAB group.Sensitivity and subgroup analyses using PSM replicated significance except for esomeprazole.Conclusion: In this national longitudinal study, PCAB users had a lower likelihood of developing depression than PPI users.Additional studies on the biological mechanism for the risk of depression and gastric acid suppressants are needed.