Placebo Response in Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis

Abstract

OBJECTIVES: Chronic idiopathic constipation (CIC), like other functional gastrointestinal disorders, has been associated with a high placebo response rate. However, the placebo response in randomized controlled trials has not been described. METHODS: We conducted a search of the medical literature following the protocol outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement using MEDLINE, EMBASE and EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials for all drugs used for the treatment of CIC. Two independent reviewers performed eligibility assessment and data extraction. The mean response rate was examined for the following 2 responder endpoints: (i) greater than or equal to 3 complete spontaneous bowel movements (CSBMs)/wk (≥3 CSBMs/wk responders) and (ii) mean increase of ≥1 CSBM/wk compared with baseline (increase in ≥1 CSBM/wk responders). RESULTS: A total of 23 placebo-controlled trials met our inclusion criteria and were included in this meta-analysis. The placebo response in CIC trials ranged from 4% to 44%. The magnitude of the placebo response was 13% (95% confidence interval 11%–16%) with the ≥3 CSBM/wk responder endpoint and 28% (95% confidence interval 21%–30%) with the increase of ≥1 in the CSBM responder endpoint. Higher baseline CSBM, older age, and trials with more male participants were significantly associated with a stronger placebo response for both the ≥3 CSBMs/wk endpoint and increase in the ≥1 CSBM/wk endpoint. Trial characteristics such as location (Europe vs Asia/United States) and laxative class (prokinetic vs secretagogue) revealed key differences in the placebo response for both endpoints. The placebo response was not significantly affected by the number of study visits, study duration, year of publication, number of drop outs, or likelihood of receiving active drug. DISCUSSION: The placebo response in CIC trials ranges from 4% to 44% depending on the endpoint. Modifying factors of the placebo response include multiple subject and trial characteristics.

Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomised, double-blind, placebo-controlled, multicenter trial

“…The homogeneous result of intergroup difference in the mean PAC-QoL total score and significant reduction of intragroup difference in both questionnaires reflected a strong placebo effect in both treatments. The placebo effect has been systematically described in clinical trials of CIC, with a range from 4 to 44%, 26 which is consistent with results in other functional gastrointestinal diseases. 7 Psychological comorbidity was caused by repeated consultations, unnecessary investigations and impaired health-related quality of life in patients with FC.…”

Do synbiotics really enhance beneficial synbiotics effect on defecation symptoms in healthy adults?

“…It tended, however, to be time-dependently increased in the control group as well as in the probiotics group. Meta-analysis indicated that a placebo increased bowel movement in patients with chronic idiopathic constipation [23] . Another clinical trial also indicated that a placebo increased bowel movement in healthy adults with constipation tendency [19] .…”

“…Meta-analysis indicated that a placebo increased bowel movement in patients with chronic idiopathic constipation. [23] Another clinical trial also indicated that a placebo increased bowel movement in healthy adults with constipation tendency. [19] The time-dependent increase of bowel movement frequency may therefore be associated with placebo effects.…”

Exploring Pharmacological Treatments for Chronic Idiopathic Constipation in Adults: A Look Back to the Future

“…In conclusion, a thorough literature search has shown that there might be a rethink on the use of a few old, relatively inexpensive and effective drugs for CIC patients, such as some magnesium salts, while many others need more accurate and modern investigations before they can be proposed for this purpose. There is little doubt that the pharmacologic approach to the treatment of CIC, despite important advances in drug development [ 11 , 12 ], is still far from an ideal goal [ 8 , 63 ]. Furthermore, patients’ knowledge on this issue is hampered by the poor quality and readability of online information [ 64 ].…”