Alexander C Ford1, Nicole C Suares. 1. Leeds Gastroenterology Institute, Room 230, D Floor, Clarendon Wing, Leeds General Infirmary, Great George Street, Leeds LS13EX, UK. alexf12399@yahoo.com
Abstract
BACKGROUND: There has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC). OBJECTIVE: To assess efficacy of these therapies systematically in CIC. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Placebo-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 METHODS: Symptom 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. RESULTS: Twenty-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. LIMITATIONS: Only two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse. CONCLUSIONS: Laxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.
BACKGROUND: There has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC). OBJECTIVE: To assess efficacy of these therapies systematically in CIC. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Placebo-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 METHODS: Symptom 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. RESULTS: Twenty-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. LIMITATIONS: Only two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse. CONCLUSIONS: Laxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.