Peripherally acting μ‐opioid antagonist for the treatment of opioid‐induced constipation: Systematic review and meta‐analysis

• Published in: Journal of gastroenterology and hepatology 2019-05, Vol.34 (5), p.818-829
• Main Authors: Nishie, Kenichi, Yamamoto, Shuhei, Yamaga, Takayoshi, Horigome, Naoto, Hanaoka, Masayuki
• Format: Article
• Language: English
• Subjects: Clinical trials; Constipation; Gastrointestinal diseases; Intestine; Meta-analysis; Narcotics; Opioid receptors; opioid‐induced constipation; peripherally acting μ‐opioid antagonist; Quality of life
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.14586

Background and Aim Opioid‐induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting μ‐opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated. Methods We conducted a quantitative meta‐analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases. Results We included 31 RCTs with 7849 patients. A meta‐analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18–1.68; n = 5622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55–2.12; n = 4821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, −0.22; 95% CI, −0.28 to −0.17; n = 2884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06–1.15; n = 7715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85–1.28; n = 5890). Conclusion Peripherally acting μ‐opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta‐analysis. The possibility of publication bias was the limitation of this study.