The Use of Antidepressants in Patients With Depression Is Associated With Gastroesophageal Reflux Disease and Disease Severity

Introduction: A few studies have demonstrated an association between gastroesophageal reflux disease (GERD) and depression, with some reporting that antidepressants may affect lower esophageal sphincter tone, thus exacerbating reflux. Here, we study the impact of antidepressants in patients with depression on GERD and its complications. Methods: The TriNetX electronic health records network, which involves 70 healthcare organizations in the United States was utilized for this study. Data from patients between January 2015 and January 2025 was used. Patients with depression on tricyclic antidepressant (TCA) only, on selective serotonin reuptake inhibitors (SSRI) only, or on serotonin and norepinephrine reuptake inhibitors (SNRI) only were evaluated. The prevalence of developing a new diagnosis of GERD, erosive esophagitis (EE), esophageal stricture, or Barrett's esophagus (BE) was assessed in each group and compared to a control group of patients with depression on no antidepressants. Adjusted odds ratios (aOR) were used after a 1:1 propensity score matching for age, obesity, male sex, Caucasian race, alcohol use, and tobacco use between comparison groups. A sensitivity analysis evaluating the odds of developing GERD, EE, BE, or esophageal stricture within 1 month, 6 months, 1 year, 3 years, 5 years, and 10 years after initiation of antidepressant was also conducted. Results: A total of 2,775,955 patients with depression started on an antidepressant. The use of TCA was associated with increased odds of developing GERD (aOR = 1.52, p < 0.01), EE (aOR = 1.47, p < 0.01), and esophageal stricture (aOR = 2.29, p < 0.01). There was no significance with BE (aOR = 1.18, p = 0.226). The use of SSRI was associated with increased odds of GERD (aOR = 1.48, p < 0.01), EE (aOR = 1.46, p < 0.01), BE (aOR = 1.21, p < 0.01), and esophageal stricture (aOR = 1.35, p < 0.01). The use of SNRI was associated with increased risk of GERD (OR = 1.53, p < 0.01), EE (OR = 1.53, p < 0.01), BE (OR = 1.30, p < 0.01), and esophageal stricture (OR = 1.60, p < 0.01). Conclusion: There is an increased association in developing GERD, EE, BE, and esophageal stricture with TCA, SSRI, and SNRI use. This association increased with prolonged use of medication over 10 years. Further prospective studies are needed to confirm our findings.