Letter: Clinical Trial: Treatment of Functional Dyspepsia According to Subtype Compared With Empirical Proton Pump Inhibitor: Authors' Reply

Abstract

We thank Dr. Miyahara et al. for their interest in our paper [1] and for their constructive comments [2]. We agree that certain aspects of the study design could be improved to enhance its robustness.

Placebo-controlled studies are widely regarded as the gold standard for evaluating the efficacy and safety of drugs. However, in the context of functional dyspepsia (FD), numerous placebo-controlled trials have already been conducted. Additionally, well-conducted meta-analyses have pooled these studies to report on treatment outcomes [3].

The unique design of our study aimed to address the utility of treatment strategies for FD according to subtypes, compared to empirical proton pump inhibitor (PPI) therapy [1]. The Rome IV consensus recommends subdividing FD into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) subtypes. This symptom-based subdivision reflects the putative differences in pathophysiology and may inform tailored treatment approaches [4]. The first Asian consensus on FD has also adopted this subtype-based approach to treatment [5]. In contrast, American and Canadian guidelines suggested empiric PPI therapy for all patients with FD [6]. However, it is unclear which treatment strategy is superior. Our findings provide a valuable alternative to PPI in FD, specifically the use of prokinetics. While PPIs are generally considered safe, widespread overuse has raised concerns about potential adverse effects [7].

Our study was underpowered to provide definitive conclusions on treatment efficacy for individual FD subtypes. However, randomized controlled trials have demonstrated that prokinetics perform better than placebo in FD [8]. Our study included a representative distribution of FD subtypes, with most patients presenting with PDS or PDS-EPS overlap, reflecting global subtype trends. Our findings suggest that a prokinetic is at least as effective as PPIs for these subtypes. However, our study was not designed to determine the optimal treatment for the EPS subtype independently [1].

Miyahara and colleagues expressed concern that we did not exclude “mild” psychological disorders, which may have influenced our study findings. However, the significance of mild psychological disorders in FD and DGBI remains uncertain. In a cross-sectional study of patients with FD, we demonstrated that only higher anxiety scores, as assessed by the Hospital Anxiety and Depression Scale (HADS), were associated with more severe dyspepsia symptoms; lower HADS scores showed no significant correlation [9]. Furthermore, in a longitudinal study of patients with DGBI in secondary care, we found that poorer symptom improvement at follow-up was associated with clinically diagnosed anxiety and depression [10]. Based on these findings, it is reasonable to assume that mild psychological disorders (not severe enough for clinical diagnosis) in patients with DGBI did not significantly impact their gastrointestinal symptoms over time.

In conclusion, our study indicated that subtype-specific treatment—prokinetic for PDS and PPI for EPS—demonstrated efficacy and safety comparable to empirical PPI therapy. These findings reinforce existing guideline recommendations while providing clinicians with additional therapeutic options. We hope our study will contribute to the development of future guidelines and stimulate further research in this field.

Kee Huat Chuah: conceptualization, writing – original draft, writing – review and editing. Sanjiv Mahadeva: conceptualization, writing – review and editing.

Guarantor of article: Professor Chuah Kee Huat.

This article is linked to Chuah et al. papers. To view these articles, visit https://doi.org/10.1111/apt.18418 and https://doi.org/10.1111/apt.70011.