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This led to the development of peripherally acting \u03bc\u2010opioid receptor antagonists (PAMORAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the efficacy of available PAMORAs and other approved or experimental treatments for relieving constipation in patients with opioid\u2010induced constipation, based on a systematic review and meta\u2010analysis of published studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A search of MEDLINE, EMBASE and EBM Reviews Cochrane Central Register of Controlled Trials was completed in July 2019 for randomised trials compared to placebo. FDA approved doses or highest studied dose was evaluated. Efficacy was based on diverse endpoints, including continuous variables (the bowel function index, number of spontaneous bowel movements and stool consistency based on Bristol Stool Form Scale), or responder analysis (combination of &gt;3 spontaneous bowel movements or complete spontaneous bowel movements plus 1 spontaneous bowel movement or complete spontaneous bowel movements, respectively, over baseline [so\u2010called FDA endpoints]). Adverse effects evaluated included central opioid withdrawal, serious adverse events, abdominal pain and diarrhoea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 35 trials at low risk of bias enrolling 13\u00a0566 patients. All PAMORAs demonstrated efficacy on diverse patient response endpoints. There was greater efficacy with approved doses of the PAMORAs (methylnaltrexone, naloxegol and naldemidine), with lower efficacy or lower efficacy and greater adverse effects with combination oxycodone with naloxone, lubiprostone and linaclotide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Therapeutic response in opioid\u2010induced constipation is best achieved with the PAMORAs, methylnaltrexone, naloxegol and naldemidine, which are associated with low risk of serious adverse events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15791","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T03:44:48Z","timestamp":1590637488000},"page":"37-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Systematic review with meta\u2010analysis: efficacy and safety of treatments for opioid\u2010induced constipation"],"prefix":"10.1111","volume":"52","author":[{"given":"Priya","family":"Vijayvargiya","sequence":"first","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-7514","authenticated-orcid":false,"given":"Michael","family":"Camilleri","sequence":"additional","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Vijayvargiya","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Emory University Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Erwin","sequence":"additional","affiliation":[{"name":"Division of Library Services Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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