Mu-opioid antagonists in the treatment of bowel dysfunction as a result of previous treatment by opioids

There is insufficient evidence to show that new opioid antagonists are effective in treating constipation due to strong analgesics. Opioids (morphine-like drugs) are substances used to treat severe pain. They cause many side effects, and frequently affect the stomach and bowels. Opioid-induced bowel dysfunction (OBD) is a recently coined term used to describe constipation, incomplete evacuation of the bowels, bloating, and increased reflux of stomach contents. OBD occurs both with short and long term use of opioids, in patients with many types of diseases, and causes increased disease and reduced quality of life. Traditional opioid antagonists (drugs that block the receptors which opioids bind to) can be used to reverse many of the side effects of opioids, including constipation, but because they block opioid receptors in the brain, they may also reverse reduction of pain. The search for opioid antagonists that act only in the gut ("peripherally active" antagonists), therefore not reversing reduction of pain, has produced two new drugs, methylnaltrexone and alvimopan, which are at an advanced phase of development. There is not enough information to make firm conclusions about the safety or effectiveness of traditional opioid antagonists in the treatment of OBD. Alvimopan and methylnaltrexone both show promise in treating OBD, but further data will be required to fully assess their effectiveness.

Authors' 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.

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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.

Objectives: 

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

Search strategy: 

We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in January 2007. Additional reports were identified from the reference lists of retrieved papers.

Selection criteria: 

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

Data collection and analysis: 

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

Main results: 

Twenty-three studies met inclusion criteria and provided data on 2871 opioid antagonist-treated patients. The opioid antagonists investigated were alvimopan (nine studies), methylnaltrexone (six), naloxone (seven), and nalbuphine (one). Meta-analysis demonstrated that methylnaltrexone and alvimopan were better than placebo in reversing opioid-induced increased gastrointestinal transit time and constipation, and that alvimopan appears to be 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.

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