title: Efficacy of methylnaltrexone for the treatment of opiod-induced constipation: a meta-analysis and systematic review.
abstract: OBJECTIVE
  Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor antagonist, is an effective treatment of opioid induced constipation (OIC) without affecting centrally mediated analgesia. Our objective was to conduct a review and meta-analysis to evaluate the efficacy of methylnaltrexone for treatment of OIC, as well as to provide a clinical discussion regarding newly developed alternatives and provide the current treatment algorithm utilized at our institution.
  
  
  METHODS
  We performed a systematic review and meta-analysis of randomized control trials using Cochrane Collaboration Databases and MEDLINE from 2007-present. Literature related to methylnaltrexone, opioids, opioid receptors, opioid antagonists, opioid-induced constipation were reviewed. A meta-analysis was completed with the primary outcome of rescue-free bowel movement (RFBM) within four hours of administration. All pooled analyses were based on random-effects models.
  
  
  RESULTS
  1239 patients were analyzed; 599 received methylnaltrexone and 640 received placebo. With a 95% CI calculated, the true risk difference is between 0.267 and 0.385, demonstrating a statistically significant difference in RFBM between treatment and placebo groups (p < 0.0001). Both the 0.15 mg/kg, 0.30 mg/kg doses every other day, and 12 mg/day dose were found to have increased risk of RFBM compared to placebo.
  
  
  CONCLUSIONS
  Results support the use of methylnaltrexone. Furthermore, the use of methylnaltrexone to induce laxation may decrease use of health care resources, increase work productivity, and improve cost utilization. New treatments have been made available; however, controlled clinical studies are needed to demonstrate long-term efficacy, safety and cost-effectiveness. Possible limitations of this study include the relatively small number of randomized, placebo-controlled trials investigating the efficacy of methylnaltrexone versus placebo. There is also the possibility of publication bias, which may lead to overestimating the efficacy of methylnaltrexone in treating OIC.
authors.affiliation: a Department of Anesthesiology , Weill Cornell Medical College , New York , USA.
authors.forename: Neel
authors.initials: N
authors.lastname: Mehta
authors.affiliation: a Department of Anesthesiology , Weill Cornell Medical College , New York , USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: O'Connell
authors.affiliation: a Department of Anesthesiology , Weill Cornell Medical College , New York , USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Giambrone
authors.affiliation: b Department of Anesthesiology , Memorial Sloan Kettering Cancer Center , New York , USA.
authors.forename: Aisha
authors.initials: A
authors.lastname: Baqai
authors.affiliation: c Department of Pain Medicine , Lennox Hill Hospital , New York , USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Diwan
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D059350:Chronic Pain / Q000188:drug therapy; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu; C032257:methylnaltrexone; D009271:Naltrexone
keywords: Methylnaltrexone; advanced illness; chronic severe pain; opioid analgesics; opioid-induced bowel dysfunction; opioid-induced constipation; opioids; μ-receptor antagonist