Drugs for Treating Opioid-Induced Constipation: A Mixed Treatment Comparison Network Meta-analysis of Randomized Controlled Clinical Trials.

CONTEXT: Opioid-induced constipation is a common problem associated with chronic use of opioid analgesics.

OBJECTIVES: The objective of this study was to compare available interventions for the treatment of opioid-induced constipation, using principles of network meta-analysis.

METHODS: Electronic 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.

RESULTS: We 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.

CONCLUSION: Subcutaneous methyl naltrexone was found to perform better than other interventions for managing opioid-induced constipation.