Tricyclic antidepressants and the risk of reflux esophagitis

Incompetence of the lower esophageal sphincter (LES) is a key factor in the pathogenesis of gastroesophageal reflux disease (GERD). Drugs with anticholinergic properties, such as tricyclic antidepressants (TCAs), may facilitate GERD by a relaxing effect on the LES.

To investigate whether the use of TCAs is associated with an increased risk of reflux esophagitis (RE).

A population-based case-control study was conducted within a large Dutch primary care database over the period 1996-2005. Cases with endoscopy-confirmed RE were identified and matched with up to 10 controls on gender, age, GP practice, and calendar time. Exposure to TCAs was assessed in the year prior to diagnosis and categorized as current (last prescription covered or ended within one month prior to the index date), past, and no use. The relative risk of RE was estimated by odds ratios (OR) with 95% confidence intervals (95% CI) using multivariate conditional logistic regression analysis.

During the study period, 1,462 cases with endoscopy-confirmed RE were identified. The risk of RE was increased in current TCA users (OR(adj) 1.61, 95% CI 1.04-2.50). Drug-specific analyses revealed that only clomipramine was associated with an increased risk of RE (OR(adj) 4.6, 95% CI 2.0-10.6) in a duration- and dose-dependent manner (OR(adj) 7.1, 95% CI 2.7-19.2 for use >180 days and OR(adj) 9.2, 95% CI 1.6-51.5 for >1 DDD equivalent/day).

No association was observed between the risk of RE and the use of TCAs other than clomipramine. The association between RE and clomipramine might be drug-related or a result of the underlying indication.