Peripherally acting μ-opioid antagonist for the treatment of opioid-induced constipation: Systematic review and meta-analysis
Corresponding Author
Kenichi Nishie
Department of Respiratory Medicine, Iida Municipal Hospital, Iida, Nagano, Japan
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
Correspondence
Kenichi Nishie, Department of Respiratory Medicine, Iida Municipal Hospital, 438 Yawatamachi, Iida, Nagano 395-0814, Japan.
Email: [email protected]
Search for more papers by this authorShuhei Yamamoto
Department of Rehabilitation, Shinshu University Hospital, Matsumoto, Japan
Search for more papers by this authorTakayoshi Yamaga
Department of Occupational Therapy, Health Science University, Fujikawaguchikomachi, Yamanashi, Japan
Search for more papers by this authorNaoto Horigome
Department of Digestive Surgery, Iida Municipal Hospital, Iida, Nagano, Japan
Search for more papers by this authorMasayuki Hanaoka
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
Search for more papers by this authorCorresponding Author
Kenichi Nishie
Department of Respiratory Medicine, Iida Municipal Hospital, Iida, Nagano, Japan
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
Correspondence
Kenichi Nishie, Department of Respiratory Medicine, Iida Municipal Hospital, 438 Yawatamachi, Iida, Nagano 395-0814, Japan.
Email: [email protected]
Search for more papers by this authorShuhei Yamamoto
Department of Rehabilitation, Shinshu University Hospital, Matsumoto, Japan
Search for more papers by this authorTakayoshi Yamaga
Department of Occupational Therapy, Health Science University, Fujikawaguchikomachi, Yamanashi, Japan
Search for more papers by this authorNaoto Horigome
Department of Digestive Surgery, Iida Municipal Hospital, Iida, Nagano, Japan
Search for more papers by this authorMasayuki Hanaoka
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
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| jgh14586-sup-0001_F1.epsPS document, 169.4 KB |
Figure S1. Funnel plot. |
| jgh14586-sup-0002_F2a.epsPS document, 1.2 MB |
Figure S2. (a) Adverse events in diarrhea. |
| jgh14586-sup-0003_F2b.epsPS document, 1.2 MB |
Figure S2. (b) Adverse events in abdominal pain. |
| jgh14586-sup-0004_F2c.epsPS document, 1.2 MB |
Figure S2. (c) Adverse events in vomiting. |
| jgh14586-sup-0005_F2d.epsPS document, 1.1 MB |
Figure S2. (d) Adverse events in flatulence. |
| jgh14586-sup-0006_F2e.epsPS document, 1.2 MB |
Figure S2. (e) Adverse events in nausea. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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