Anxiety Severity and Proton Pump Inhibitor Nonresponse Association Across Gastroesophageal Reflux Disease Phenotypes Defined by the Lyon 2.0 Classification.

BACKGROUND & AIMS: Persistent symptoms, despite proton pump inhibitor therapy, are common in patients with gastroesophageal reflux disease. The Lyon Consensus 2.0 provides an objective diagnostic framework, but factors associated with proton pump inhibitor nonresponse across gastroesophageal reflux disease phenotypes remain incompletely defined. The aim of this study was to assess the association between anxiety severity and proton pump inhibitor response across gastroesophageal reflux disease phenotypes defined by the Lyon 2.0 classification.

METHODS

We analyzed 204 consecutive patients undergoing off-therapy pH impedance monitoring and anxiety assessment using the Hamilton Anxiety Rating Scale. Patients were classified according to Lyon 2.0 criteria. Multivariable logistic regression and receiver operating characteristic analyses were performed.

RESULTS

Proton pump inhibitor response rates progressively declined from conclusive gastroesophageal reflux disease (70.2%) to inconclusive gastroesophageal reflux disease with supportive evidence (53.3%), inconclusive gastroesophageal reflux disease without supportive evidence (31.6%), and no gastroesophageal reflux disease (30.8%) (P < .001). Nonresponders showed significantly higher anxiety scores than responders (20.9 ± 9.8 vs 13.4 ± 6.3; P < .001). Anxiety was significantly associated with proton pump inhibitor nonresponse in patients with inconclusive gastroesophageal reflux disease with supportive evidence (odds ratio, 1.14 per 1-point Hamilton Anxiety Rating Scale increase; P = .004) and in patients with no gastroesophageal reflux disease (odds ratio, 1.22; P < .001), but not in patients with conclusive gastroesophageal reflux disease. Increasing anxiety severity was associated with a marked reduction in response rates (59.0% mild, 20.5% moderate, 7.7% severe; P < .001). The Hamilton Anxiety Rating Scale demonstrated good discrimination for proton pump inhibitor nonresponse (area under the curve = 0.73 overall), with highest performance observed in patients with no gastroesophageal reflux disease (area under the curve = 0.78).

CONCLUSIONS

Anxiety is significantly associated with proton pump inhibitor refractoriness, particularly in patients with no gastroesophageal reflux disease. Integrating anxiety evaluation into the diagnostic framework may contribute in both optimizing therapeutic strategies and reducing inappropriate proton pump inhibitor use, although its role in managing treatment strategies requires confirmation in prospective studies.