Clinical Question

What is the most effective drug treatment for chronic idiopathic constipation?

Bottom Line

If nondrug measures are unsuccessful for chronic idiopathic constipation, the choice of a pharmacologic agent should be based on cost, tolerability, and long-term adherence rather than efficacy, because the efficacy is similar among drugs and drug classes. Bisacodyl (Dulcolax) increases the number of spontaneous bowel movements more than other drugs. (Level of Evidence = 1a)

Synopsis

There are many treatment options for patients with chronic idiopathic constipa -tion, including osmotic and stimulant laxatives; 5-hydroxytryptamine receptor 4 agonists, such as prucalopride, tegaserod, and velusetrag (none of which are currently available in the United States); linaclotide (Linzess); lubipros-tone (Amitiza); and elobixibat (not approved in the United States). This study was a network meta-analysis that performed direct comparisons (where possible) and indirect comparisons of trials of different drugs compared with a common control drug or placebo. This was a methodologically rigorous meta-analysis, with a thorough search of multiple databases, data abstraction by two independent investigators, and careful assessment of study quality. The authors identified 21 studies with a total of 9,189 patients that compared nine different drugs with placebo. The primary outcomes that defined a clinical response were having at least three more complete spontaneous bowel movements (CSBMs) per week or an increase from baseline of one or more CSBMs per week. Most studies were set in the United States or Europe, were adequately powered, and enrolled patients with a mean age of late 40s or 50s. Most studies defined constipation as less than two or three CSBMs per week. The overall quality of most included studies was judged to be moderate or high.

The results for several drugs (including bisacodyl, tegaserod, linaclotide, and sodium picosulfate) came from a single trial. In direct comparisons with placebo, the drugs roughly doubled the likelihood of having three or more CSBMs per week, with an average increase overall of slightly more than one CSBM per week. These improvements were statistically significant for bisacodyl, sodium picosulfate, prucalopride, and velusetrag. Although velusetrag had the largest effect, there was a wide confidence interval around the results from its single study, and it was not significantly better than the other drugs. For the secondary outcome of the increase in the number of any (not only complete) spontaneous bowel movements, bisacodyl was more effective, with an increase of 4.9 spontaneous bowel movements compared with 1.9 to 3.2 for the other drugs.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Reference:NelsonADCamilleriMChirapongsathornSet alComparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis. Gut2017;66(9):1611–1622.