Becker, G., Galandi, D., & Blum, H.E. (2007). Peripherally acting opioid antagonists in the treatment of opiate-related constipation: A systematic review. Journal of Pain and Symptom Management, 34, 547-565.
To evaluate evidence on the effectiveness of the peripherally acting mu-receptor antagonists alvimopan and methylnaltrexone in the management of opioid-induced constipation.
Databases searched were Ovid MEDLINE, Biological Abstracts, BIOSIS Previews, CINAHL, Evidence-Based Medicine Reviews (EBMR) (Cochrane Database of Systematic Reviews, ACP [American College of Physicians] Journal Club, Database of Abstracts of Reviews of Effectiveness [DARE], and the Cochrane Central Register of Controlled Trials [1966-May 2005]), PubMed (1996-May 2005), CancerLit (1963-June 2005), and Embase (1980-May 2002). A hand search also was conducted on bibliographies of books about palliative care. From that hand search, reference citations concerning constipation were identified to find additional clinical trials to include in the review.
Search keywords were constipation, intestinal obstruction, opioid bowel dysfunction, opioid related constipation, opioid-related disorders, peripherally acting opioid antagonist, opioid antagonist, opioid mu receptors, narcotic antagonists/naltrexone, methylnaltrexone, and alvimopan.
Studies were included in the review if
Studies were excluded if they had a small sample size (fewer than 10 participants) or used the Rome Diagnostic Criteria to define constipation.
Ten studies were appropriate for this review. However, four of the 10 had two or three parts performed in different populations or using different dosing regimens. The differing parts were treated as different studies and assessed individually, yielding 15 studies (10 randomized controlled trials and five phase II studies addressing dose and toxicity).
This systematic review looked mainly at the efficacy of using the peripherally acting opioid antagonists methylnaltrexone (nine studies) and alvimopan (six studies) in managing opioid-induced constipation. Internal validity of the studies was high, indicating methylnaltrexone and alvimopan may be effective in relieving opioid-induced constipation. However, most study participants were healthy volunteers or members of methadone programs.