Peripherally acting opioid antagonists in the treatment of opiate-related constipation: a systematic review

Many patients treated with opioids suffer from constipation. Opiate- or opioid-related constipation is not only a frequent but also a distressing symptom and difficult to treat. There is emerging evidence regarding a novel approach to the management of opiate-related constipation. The aim of this paper is to collect, critically appraise, and summarize the evidence on the effectiveness of recently developed peripherally acting micro-receptor antagonists in the treatment of opiate-related constipation. A comprehensive search of 11 computerized databases was conducted and efforts were made to identify unpublished and ongoing research. Twenty studies were identified; 13 were randomized controlled trials (RCTs) and 7 were Phase II studies assessing toxicity. Studies were mainly executed in healthy volunteers or members of methadone programs with opioid-induced constipation as a model to mimic the condition of patients on opioids. Two RCTs were conducted in hospice patients. Quality of study design and validity of the findings was assessed in all studies. Data show proof of concept but do not allow a definitive answer concerning the effectiveness of the peripherally acting micro-opioid antagonists methylnaltrexone and alvimopan in managing opiate-related constipation. Further research is needed. If future Phase III trials provide supportive data, opioid antagonists may become a standard therapeutic option for the treatment of opiate-related constipation in patients with advanced cancer.