Comparative Efficacy of Drugs for the Treatment of Chronic Constipation: Quantitative Information for Medication Guidelines.

BACKGROUND: Quantitative information is scarce with regard to guidelines for currently prescribed medications for constipation. Furthermore, these guidelines do not reflect the differences in the number of bowel movements caused by each drug.

GOALS: In this study, we used a model-based meta-analysis to quantitatively estimate the deviations from the baseline number of spontaneous bowel movements (SBMs) and complete spontaneous bowel movements (CSBMs) associated with pharmacotherapy for chronic constipation to bridge the knowledge gap in the guidelines for current medications.

STUDY: A comprehensive survey was conducted using literature databases. In this study, we also included randomized placebo-controlled trials on chronic constipation. Pharmacodynamic models were established to describe the time course of the numbers of SBMs and CSBMs produced by each drug.

RESULTS: Data from 20 studies (comprising 9998 participants and 8 drugs) were used to build this model. The results showed that bisacodyl had the greatest effect on increasing the frequency of bowel movements, whereas plecanatide yielded the lowest increase in the number of SBMs and CSBMs. After eliminating the placebo effect, the maximal increase in bowel movement frequency associated with bisacodyl was 6.8 for SBMs (95% confidence interval: 6.1-7.6) and 4.7 for CSBMs (95% confidence interval: 4.3-5.1) per week. These numbers are ∼4 times higher than the number of bowel movements produced by plecanatide. The change in the frequency of SBMs and CSBMs for other drugs, such as sodium picosulfate, velusetrag, linaclotide, elobixibat, lubiprostone, and prucalopride, was similar. The highest increases in the frequency of SBM and CSBM were 2.5 to 4 and 1 to 2.1 per week, respectively. Bisacodyl had the most noticeable loss of efficacy between week 1 and week 4; it reduced the frequencies of SBMs and CSBMs by 2.3 and 2.2, respectively. By contrast, the changes in the frequencies of SBMs and CSBMs were not as great with other drugs.

CONCLUSIONS: The data provided in this study may be a valuable supplement to the medication guidelines for the treatment of chronic constipation.