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Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis
  1. Pavit Luthra1,2,
  2. Nicholas E Burr1,2,
  3. Darren M Brenner3,
  4. Alexander C Ford1,2
  1. 1 Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds, UK
  2. 2 Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
  3. 3 Division of Gastroenterology and Hepatology, Northwestern University – Feinberg School of Medicine, Chicago, Illinois, USA
  1. Correspondence to Professor Alexander C Ford, Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds LS9 7TF, UK; alexf12399{at}


Objective Opioids are increasingly prescribed in the West and have deleterious GI 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.

Design 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% 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 BMs per week, with an increase of ≥1 BM per week over baseline, naldemedinewas ranked first (RR=0.66; 95% CI 0.56 to 0.77, P score=0.91) and alvimopan second (RR=0.74; 95% CI 0.57 to 0.94, P-score=0.71).

Conclusion In network meta-analysis, naloxone and naldemedine appear to be the most efficacious treatments for OIC. Naloxone was the safest of these agents.

  • constipation
  • meta-analysis

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  • PL and NEB are joint first authors

  • Contributors PL, NEB, DMB and ACF conceived and drafted the study. ACF and PL collected all data. ACF and NEB analysed and interpreted the data. ACF, PL and NEB drafted the manuscript. ACF is guarantor. All authors commented on drafts of the paper. All authors have approved the final draft of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests PL, NEB and ACF: none declared. DMB has acted as a consultant, advisor and speaker for Synergy, Allergan, Ironwood, AstraZeneca, Daiichi Sankyo, Shionogi, Salix Pharmaceuticals, Medscape LLC, Medtronic and GI Health Foundation.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. The joint author statement has been added.