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Efficacy and Safety of Mu-Opioid Antagonists in the Treatment of Opioid-Induced Bowel Dysfunction: Systematic Review and Meta-analysis of Randomized Controlled Trials


Ewan McNicol, MS, Departments of Pharmacy and Anesthesia, Tufts-New England Medical Center, 750 Washington Street, Box 420, Boston, MA 02111, USA. Tel: 617-636-5389; Fax: 617-636-4633; E-mail:


Context.  Opioid-induced bowel dysfunction (OBD) is characterized by constipation, incomplete evacuation, bloating, and increased gastric reflux. OBD occurs both acutely and chronically, in multiple disease states, resulting in increased morbidity and reduced quality of life.

Objective.  To compare the efficacy and safety of traditional and peripherally active opioid antagonists vs conventional interventions for OBD.

Design.  We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE. Additional reports were identified from the reference lists of retrieved articles.

Study Selection.  Studies were included if they were randomized controlled trials that investigated the efficacy of mu-opioid antagonists for OBD.

Data Extraction.  Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse events.

Results of Data Synthesis.  Twenty-two articles met inclusion criteria and provided data on 2,352 opioid antagonist-treated patients. The opioid antagonist investigated was alvimopan (eight studies), methylnaltrexone (six), naloxone (seven), and nalbuphine (one). Meta-analysis demonstrated that methylnaltrexone and alvimopan are efficacious in reversing opioid-induced increased gastrointestinal transit time and constipation, and that alvimopan is safe and efficacious in treating postoperative ileus. The incidence of adverse events with opioid antagonists was similar to placebo and generally reported as mild-to-moderate.

Conclusions.  Insufficient evidence exists for the safety or efficacy of naloxone or nalbuphine in the treatment of OBD. Long-term efficacy and safety of any of the opioid antagonists is unknown, as is the incidence or nature of rare adverse events. Alvimopan and methylnaltrexone both show promise in treating OBD, but further data will be required to fully assess their place in therapy.