Efficacy and safety of mu-opioid antagonists in the treatment of opioid-induced bowel dysfunction: systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
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.


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


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


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


RESULTS
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.
McNicol
Ewan
E
Department of Pharmacy, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA. ewanmcnicol@comcast.net
Boyce
David B
DB
Schumann
Roman
R
Carr
Daniel
D
D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use*; D000818:Animals; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D009292:Narcotic Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000009:adverse effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000502:physiology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu