Introduction Opioids are increasingly prescribed in the West, and have deleterious gastrointestinal consequences. Pharmacological therapies to treat opioid-induced constipation (OIC) are available, but their relative efficacy is unclear. We performed a systematic review and network meta-analysis to address this deficit in current knowledge.
Methods We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through to December 2017 to identify randomised controlled trials (RCTs) of pharmacological therapies in the treatment of adults with OIC. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of pharmacological therapies was reported as a pooled relative risk (RR) with 95% confidence intervals (CIs) to summarise the effect of each comparison tested, and ranked treatments according to their P-score.
Results Twenty-seven eligible RCTs of pharmacological therapies, containing 9149 patients, were identified. In our primary analysis, using failure to achieve an average of ≥3 bowel movements (BMs) per week with an increase of ≥1 BM per week over baseline, or an average of ≥3 BMs per week, to define non-response the network meta-analysis ranked naloxone first in terms of efficacy (RR=0.65; 95% CI 0.52 to 0.80, P-score 0.84), and it was also the safest drug. When non-response to therapy was defined using failure to achieve an average of ≥3 bowel movements (BMs) per week, with an increase of ≥1 BM per week over baseline, naldemidine was ranked first (RR=0.66; 95% CI 0.56 to 0.77, P-score 0.91).
Conclusion In network meta-analysis, naloxone and naldemidine appear to be the most efficacious treatments for OIC. Naloxone was the safest of these agents.
League Table of Results for Failure to Achieve an Average of ≥3 BMs per Week with an Increase of ≥1 BM per Week Over Baseline or an Average of ≥3 BMs per Week.
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