• Kannan Sridharan and Gowri Sivaramakrishnan.
• School of Health Sciences, College of Medicine, Nursing and Health Sciences, Fiji National University, Suva, Fiji. Electronic address: skannandr@gmail.com.
• J Pain Symptom Manage. 2018 Feb 1; 55 (2): 468-479.e1.

ContextOpioid-induced constipation is a common problem associated with chronic use of opioid analgesics.ObjectivesThe objective of this study was to compare available interventions for the treatment of opioid-induced constipation, using principles of network meta-analysis.MethodsElectronic databases were searched for randomized controlled clinical trials evaluating drugs used in opioid-induced constipation. Number of patients with rescue-free bowel movements (RFBM) was the primary outcome, and time for achieving RFBM, adverse events, and changes in the analgesic activity of the opioid analgesics were the secondary outcomes. Inverse variance heterogeneity model was used for direct and mixed treatment comparison analysis. Odds ratio for categorical outcomes and weighted mean difference for numerical outcomes were the effect estimates.ResultsWe included a total of 23 studies in the systematic review and 21 in the network meta-analysis. Lubriprostone, prucalopride, naldemedine, naloxegol, alvimopan, subcutaneous, and oral methyl naltrexone were observed to perform better than placebo in terms of RFBM. Additionally, subcutaneous methyl naltrexone was significantly better than lubiprostone, naloxegol, oral methyl naltrexone, and prucalopride. Lubiprostone and naldemedine were associated with increased risks of adverse events. Subcutaneous methyl naltrexone did not significantly affect the analgesia due to background opioid use. Quality of evidence for the comparisons is either low or very low.ConclusionSubcutaneous methyl naltrexone was found to perform better than other interventions for managing opioid-induced constipation.Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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