Constipation: opioid antagonists in people prescribed opioids
Constipation is a common, debilitating, and sometimes dose-limiting side effect from opioids when prescribed for pain control. Opioids cause constipation because they act on peripheral opioid receptors in the gastrointestinal (GI) tract, as well as in the nervous system where their desired analgesic benefits arise. These gastrointestinal opioid receptors are involved in the normal regulation of bowel motility and fluid absorption by the endogenous opioid system. These functions are disturbed when pharmacological doses of therapeutic opioids are presented to the bowel lumen. It, therefore, makes good sense to try to block the action of opioids on these peripheral GI receptors.
Focus of the review
This overview focuses on the use of opioid antagonists for managing constipation in people prescribed opioids. Traditionally, laxatives have been used to try and manage constipation when it occurs as a side effect of opioid therapy. These act by relieving the symptoms and effects of opioid-induced constipation (i.e., palliation) by stimulating bowel movement or softening the stools. They do not address the cause of opioid-induced constipation, and the evidence base for their efficacy is poor (see previous version of this topic). The relatively new use of opioid antagonists, on the other hand, represents a targeted approach to stopping the cause of opioid-induced constipation at the bowel opioid receptor level.
Comments on evidence
So far, the new peripherally-acting opioid antagonists have only been compared with placebo. There was considerable variation in terms of the characteristics of participants, indications for opioid therapy (e.g., cancer versus non-cancer pain), and type of setting (primary, secondary, and tertiary care). Further RCTs comparing these preparations with each other and with conventional laxative therapies are needed.
Search and appraisal summary
The updated literature search for this overview was carried out from the date of the last search, July 2009, to May 2014. A back search from 1966 was performed for the new options added to the scope at this update. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 162 studies. After deduplication and removal of conference abstracts, 84 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 37 full publications. Of the 37 full articles evaluated, two systematic reviews and one RCT were included at this update.
Substantive changes at this update
Alvimopan Restructured to form new option. One systematic review added. Categorised as 'likely to be beneficial'.
Methylnaltrexone Restructured to form new option. One systematic review added. Categorised as 'beneficial'.
INTRODUCTION: Constipation is a common adverse effect of opioids. As an example, constipation is reported in 52% of people with advanced malignancy, and this figure rises to 87% in people who are terminally ill and taking opioids. There is no reason to believe that people with chronic non-malignant disease who are prescribed opioids will be any less troubled by this adverse effect. METHODS AND OUTCOMES: We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of opioid antagonists for constipation in people prescribed opioids? The population we studied included people with any condition, although most studies were in people with cancer pain. We searched Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). RESULTS: At this update, searching of electronic databases retrieved 162 studies. After deduplication and removal of conference abstracts, 84 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 37 full publications. Of the 37 full articles evaluated, two systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for three PICO combinations. CONCLUSIONS: In this systematic overview we categorised the efficacy for three interventions based on information relating to the effectiveness of alvimopan, methylnaltrexone, and naloxone.
Laxatives for the management of constipation in palliative care patients. ( 25 November 2015 )
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