Efficacy and safety of lansoprazole combined with flupentixol-melitracen for functional dyspepsia: A randomized, double-blinded, placebo-controlled clinical trial

Abstract

BACKGROUND

Psychosocial factors play a major role in the pathogenesis of functional dyspepsia (FD); however, there is a paucity of evidence from randomized controlled trials supporting the use of neuromodulators in FD.

AIM

To evaluate the efficacy and safety of lansoprazole (LPZ) combined with flupentixol-melitracen (FM) in FD.

METHODS

This was a single-center, double-blind, randomized, placebo-controlled trial enrolling patients aged 18-80 years who met the Rome IV diagnostic criteria for FD. Patients with a positive Helicobacter pylori test or abnormal upper gastrointestinal endoscopy/abdominal ultrasound were excluded. Participants completed the Leuven Postprandial Distress Scale, Short Form Nepean Dyspepsia Index (SF-NDI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorders-7, and Pittsburgh Sleep Quality Index. Patients were randomized 1:1 to receive LPZ (30 mg once daily) combined with FM (flupentixol 0.5 mg + melitracen 10 mg) or matched placebo for 2 weeks, followed by a 4-week follow-up. The primary endpoint was clinical response rate in the intention-to-treat population, defined as a reduction of at least 0.7 in the postprandial discomfort syndrome (PDS) score at the end of treatment among patients with a baseline PDS score of ≥ 1.

RESULTS

Between March 5 and August 10, 2025, 183 patients were randomized to receive LPZ + FM (n = 92) or LPZ + placebo (n = 91). At week 2, the clinical response rate was higher in the LPZ + FM group than in the placebo group (63.0% vs 46.2%; relative risk = 1.42, 95% confidence interval: 1.04-1.93). LPZ + FM resulted in greater reductions in PDS, SF-NDI, PHQ-9, Generalized Anxiety Disorders-7, and Pittsburgh Sleep Quality Index scores. Improvements in PDS, SF-NDI, and PHQ-9 persisted through follow-up. Adverse events were mild and occurred in 32.6% of patients receiving LPZ + FM and 23.1% receiving placebo, with no serious adverse events reported.

CONCLUSION

Short-term, low-dose FM combined with LPZ is an effective and safe treatment for FD.

Keywords: Flupentixol-melitracen; Functional dyspepsia; Lansoprazole; Anxiety; Deanxit

Core Tip: This randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of flupentixol-melitracen combined with lansoprazole for functional dyspepsia (FD). Our study demonstrated that this low-dose short-term regimen not only improved FD symptoms and quality of life within two weeks but also sustained efficacy for four weeks post-treatment. Future long-term follow-up and multicenter studies are warranted to verify its lasting benefits and health economic value, potentially advancing FD management from a “stepwise sequential” approach to a “brain-gut co-management” therapy.