Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials

INTRODUCTION: Opioid-induced constipation (OIC) is a distressing side effect during opioid analgesia and is mainly mediated by gastrointestinal μ-opioid receptors. Methylnaltrexone, a peripheral μ-opioid receptor antagonist with restricted ability to cross the blood–brain barrier, may alleviate OIC without reversing analgesia. We performed a meta-analysis to assess the efficacy and safety of methylnaltrexone for the treatment of OIC. METHODS: This meta-analysis was registered in PROSPERO (CRD42020187290). We searched PubMed, Embase, and Cochrane Library for randomized controlled trials that compared methylnaltrexone with placebo for the treatment of OIC. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model. We used the GRADE approach to assess the certainty of the evidence. RESULTS: Eight trials with 2034 participants were included. Compared with placebo, methylnaltrexone significantly increased rescue-free bowel movement (RFBM) within 4 h after the first dose (eight trials; 1833 participants; RR 3.74, 95% CI 3.02–4.62; high-certainty evidence), RFBM within 24 h after the first dose (two trials; 614 participants; RR 1.98, 95% CI 1.52–2.58; moderate-certainty evidence), and RFBM ≥ 3 times per week (three trials; 1,396 participants; RR 1.33, 95% CI 1.17–1.52; moderate-certainty evidence) and decreased need to take rescue laxatives (three trials; 807 participants; RR 0.73, 95% CI 0.63–0.85; moderate-certainty evidence). For safety outcomes, there was no difference in any adverse events between the two groups (eight trials; 2034 participants; RR 1.11, 95% CI 0.99–1.23; moderate-certainty evidence), including diarrhea, nausea, vomiting, and flatulence; but for the most commonly reported adverse events, the abdominal pain was higher in methylnaltrexone group than that in placebo group (six trials; 1813 participants; RR 2.30, 95% CI 1.29–4.08; moderate-certainty evidence). CONCLUSION: Methylnaltrexone is an effective and safe drug for the treatment of OIC, but the safety of abdominal pain should be considered.