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.

Conclusion: 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.

KEYWORDS:

• Methylnaltrexone
• opioids
• opioid-induced constipation
• opioid-induced bowel dysfunction
• opioid analgesics
• chronic severe pain
• advanced illness
• μ-receptor antagonist

Acknowledgments

All co-authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Mehata, Diwan, and Baqai designed the study protocol. Miss O’Connell and Mr. Giambrone managed the literature searches and summaries of previous related work and wrote the first draft of the manuscript. Drs. Mehta, Diwan, and Baqai provided revision for intellectual content and final approval of the manuscript.

Financial and competing interests disclosure

Departmental funds of Weill Cornell Medical Center Division of Pain Medicine and Department of Anesthesiology were utilized to conduct the reported study. No external funding was provided. N Mehta is a paid speaker for Salix Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.