Abstract

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Highlights

  • Background & AimsRebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI)

  • Si evaluamos la proporción acumulada entre las semanas 8 y 12 de pacientes con síntomas relevantes la diferencia es 44% vs 15%, respectivamente; es decir, el riesgo de inducir síntomas de Reflujo gastroesofágico (RGE) al suspender inhibidores de la bomba de protones (IBP) versus el no usar terapia prácticamente se triplica

  • El presente artículo corresponde a un estudio bien diseñado que muestra datos clínicos y fisiopatológicos que sugieren la generación de síntomas asociados a secreción ácida tras la suspensión de drogas diseñadas para lo contrario

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Summary

Introduction

Background & AimsRebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). Si consideramos que el objetivo del estudio es evaluar un efecto adverso, para poder concluir fehacientemente que la aparición de los síntomas es secundaria al uso previo de IBP los autores deben estar absolutamente seguros que los pacientes consumieron la droga en forma apropiada, por lo tanto, el análisis por protocolo es el indicado en esta situación.

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