What is the clinical evidence from this study?

Study design: Cohort. Population: Gastric acid-related diseases (n=6104743). Intervention: Proton pump inhibitors (PPIs) vs. Tegoprazan (PCAB). Primary outcome: Diagnosis of depression with more than 60 prescription days of antidepressants (aOR 1.34, 95% CI 1.24-1.44, p=<0.001).

January 1, 2026Journal of Korean Medical Science1 citationsOpen Access

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

Q: What are the key findings of this study?

Proton pump inhibitors were associated with a 34% higher risk of developing depression compared to the potassium competitive acid blocker tegoprazan (aOR 1.34).

SKSunghwan KimSt. Mary's Hospital JKJoon Sung KimIncheon St. Mary's Hospital

Key Result

Proton pump inhibitors were associated with a 34% higher risk of developing depression compared to the potassium competitive acid blocker tegoprazan (aOR 1.34).

Study Design

Type

Cohort (n=6,104,743)

Structured PICO

Does the use of proton pump inhibitors increase the risk of depression compared to tegoprazan in adult patients?

Population

6,104,743 adult patients aged 18-80 years newly prescribed proton pump inhibitors or tegoprazan from January 2020 to April 2022, excluding those taking multiple acid suppressants, diagnosed with psychiatric diseases within 1 year prior, or with severe comorbidities.

Intervention

Proton pump inhibitors (omeprazole, pantoprazole, lansoprazole, rabeprazole, and esomeprazole)

Comparator

Tegoprazan (a potassium competitive acid blocker)

Outcome

Diagnosis of depression with more than 60 prescription days of antidepressantssafety

In a large nationwide cohort, the use of the potassium competitive acid blocker tegoprazan was associated with a significantly lower risk of developing depression compared to proton pump inhibitors.

Main Result

Effect estimate: aOR 1.34 (95% CI 1.24-1.44)

p-value: p=<0.001

Limitations

Dosage information for each drug was not considered.
Associations between PPI or PCAB use and depression were relatively modest, with all aORs below 2.
Multiple comparison correction was not performed, leaving a possibility of false-positive findings.
Database did not provide information about baseline depressive status, predisposing factors, lifestyle, psychosocial factors, or endoscopic findings.
Exclusion of individuals with psychiatric disorders diagnosed within one year prior may have introduced selection bias.
The observation period was relatively short.
Only one PCAB, tegoprazan, was included, making it difficult to generalize results to the entire class.

Abstract

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.

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