Nocebo response intensity and influencing factors in the randomized clinical trials of irritable bowel syndrome: A systematic review and meta-analysis

Abstract

Objective: To estimate the magnitude of the nocebo response and explore its influencing factors in irritable bowel syndrome (IBS).

Methods: The PubMed, Embase, and Cochrane Library databases were searched up to March 2021. We performed a random effects meta-analysis of the proportion of adverse events (AEs) in placebo-treated patients with IBS who are involved in parallel-designed, randomized, placebo-controlled trials investigating pharmacological interventions and evaluated the effect of trial characteristics on the magnitude of the nocebo response rate.

Results: A total of 6,107 studies were identified from the databases. After evaluation, 53 met the eligibility criteria and were included. The overall pooled nocebo response rate was 32% (95% CI: 26-38%). The most commonly reported AEs were headache (9%), nasopharyngitis (7%), abdominal pain (4%), and nausea (4%). The nocebo response rate was low compared with that in the treatment group applying probiotics, antispasmodics, and Traditional Chinese medicine, but high compared with that in antibiotic treatment group. The nocebo rate in patients using diaries to record AEs was lower than the average, and was higher in patients recording through checkup.

Discussion: Patients with IBS have significant nocebo response intensity in clinical trials. Based on findings in this study, we recommend the researchers pay attention to the common AEs and carefully analyze the relation to the intervention.

Keywords: adverse event (AE); irritable bowel syndrome; meta-analysis; nocebo response; systematic review.