Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis

BackgroundThere has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC).ObjectiveTo assess efficacy of these therapies systematically in CIC.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs).Data sourcesMEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010).Eligibility criteria for selecting studiesPlacebo-controlled trials of laxatives or pharmacological therapies in adult CIC patients were eligible. Minimum duration of therapy was 1 week. Trials had to report either a dichotomous assessment of overall response to therapy at last point of follow-up in the trial, or mean number of stools per week during therapy.Study appraisal and synthesis methodsSymptom data were pooled using a random effects model. Effect of laxatives or pharmacological therapies compared to placebo was reported as RR of failure to respond to therapy, or a weighted mean difference (WMD) in mean number of stools per week, with 95% CIs.ResultsTwenty-one eligible RCTs were identified. Laxatives (seven RCTs, 1411 patients, RR=0.52; 95% CI 0.46 to 0.60), prucalopride (seven trials, 2639 patients, RR=0.82; 95% CI 0.76 to 0.88), lubiprostone (three RCTs, 610 patients, RR=0.67; 95% CI 0.56 to 0.80), and linaclotide (three trials, 1582 patients, RR=0.84; 95% CI 0.80 to 0.87) were all superior to placebo in terms of a reduction in risk of failure with therapy. Treatment effect remained similar when only RCTs at low risk of bias were included in the analysis. Diarrhoea was significantly more common with all therapies.LimitationsOnly two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse.ConclusionsLaxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.