title: Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK [2] Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Ford
authors.forename: Darren M
authors.initials: DM
authors.lastname: Brenner
authors.forename: Philip S
authors.initials: PS
authors.lastname: Schoenfeld
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000009:adverse effects*; D001572:Benzofurans / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000068238:Lubiprostone; D008297:Male; D009270:Naloxone / Q000627:therapeutic use; D009271:Naltrexone / Q000031:analogs & derivatives / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
chemical_list: D000701:Analgesics, Opioid; D001572:Benzofurans; D005765:Gastrointestinal Agents; D009292:Narcotic Antagonists; D010455:Peptides; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu; C406662:prucalopride; C032257:methylnaltrexone; D009270:Naloxone; D009271:Naltrexone; C419502:alvimopan; D000068238:Lubiprostone; D000527:Alprostadil; C523483:linaclotide