Nocebo response intensity and influencing factors in the randomized clinical trials of functional dyspepsia: A systematic review and meta‐analysis

Abstract

ObjectiveThe nocebo effect, a phenomenon that pertains to the negative impacts experienced by patients due to their negative expectations, is not connected to the physiological mechanism of the treatment in question. Our article aims to evaluate the degree of the nocebo response in patients with functional dyspepsia and explore its influencing factors.MethodsThe researchers searched Embase, Pubmed and Cochrane Library databases through March 2021, including randomized, parallel‐designed, placebo‐controlled trials examining pharmacological interventions for patients with functional dyspepsia. Our study involved conducting a meta‐analysis that utilized random effects to analyze the proportion of adverse events among participants who were administered placebos. We aimed to investigate the correlation between trial characteristics and the magnitude of the nocebo effect response rate.ResultsUpon thorough research and scrutiny of various databases, a staggering 8,076 studies were identified for further analysis. After an assessment, 27 studies were deemed eligible and included in our analysis. The total nocebo response rate was 27% (95% CI: 18–37%). The most frequently reported adverse events were nasopharyngitis (9%), constipation (6%), headache (5%) and diarrhoea (3%). The nocebo response rate in the international combination trials was higher than that in the Asian trials, higher in the twice‐daily than that in the three‐time‐daily dose and higher in the anti‐vomit drugs than that in the acid inhibitors.DiscussionPatients with functional dyspepsia exhibit notable nocebo response strength in clinical trials. Therefore, we propose researchers adopt a more careful approach when analyzing the relationships between everyday adverse events and interventions administered in such trials.This article is protected by copyright. All rights reserved.