Subject Category: Clinical and Systematic Review

Continuing Medical Education Am J Gastroenterol 2013; 108:1566–1574; doi:10.1038/ajg.2013.169; published online 11 June 2013

Efficacy of Pharmacological Therapies for the Treatment of Opioid-Induced Constipation: Systematic Review and Meta-Analysis

Alexander C Ford MBChB, MD, FRCP1,2, Darren M Brenner MD3 and Philip S Schoenfeld MD, MSEd, MSc (Epi)4

  1. 1Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK
  2. 2Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
  3. 3Northwestern Memorial Hospital, Chicago, Illinois, USA
  4. 4Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA

Correspondence: Dr Alexander C. Ford, MBChB, MD, FRCP, Leeds Gastroenterology Institute, Bexley Wing, St James's University Hospital, Room 125, 4th Floor, Beckett Street, Leeds LS9 7TF, UK. E-mail:

Received 13 January 2013; Accepted 4 May 2013
Advance online publication 11 June 2013

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There has been no definitive synthesis of the evidence for any benefit of available pharmacological therapies in opioid-induced constipation (OIC). We conducted a systematic review and meta-analysis to address this deficit.



We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials through to December 2012 to identify placebo-controlled trials of μ-opioid receptor antagonists, prucalopride, lubiprostone, and linaclotide in the treatment of adults with OIC. No minimum duration of therapy was required. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Effect of pharmacological therapies was reported as relative risk (RR) of failure to respond to therapy, with 95% confidence intervals (CIs).



Fourteen eligible randomized controlled trials (RCTs) of μ-opioid receptor antagonists, containing 4,101 patients, were identified. These were superior to placebo for the treatment of OIC (RR of failure to respond to therapy=0.69; 95% CI 0.63–0.75). Methylnaltrexone (six RCTs, 1,610 patients, RR=0.66; 95% CI 0.54–0.84), naloxone (four trials, 798 patients, RR=0.64; 95% CI 0.56–0.72), and alvimopan (four RCTs, 1,693 patients, RR=0.71; 95% CI 0.65–0.78) were all superior to placebo. Total numbers of adverse events, diarrhea, and abdominal pain were significantly commoner when data from all RCTs were pooled. Reversal of analgesia did not occur more frequently with active therapy. Only one trial of prucalopride was identified, with a nonsignificant trend toward higher responder rates with active therapy. Two RCTs of lubiprostone were found, with significantly higher responder rates with lubiprostone in both, but reporting of data precluded meta-analysis.



μ-Opioid receptor antagonists are safe and effective for the treatment of OIC. More data are required before the role of prucalopride or lubiprostone in the treatment of OIC are clear.