A Review of Potential Adverse Effects of Long-Term Opioid Therapy

OBJECTIVE: Review, synthesize, and summarize recent evidence on adverse effects of long-term opioid treatment for noncancer pain and present an organ system-based guide for primary care physicians in initiating and monitoring patients receiving chronic opioid therapy. DATA SOURCES: A search for studies published in peer-reviewed journals from 2005 to 2011 was conducted using MEDLINE, Agency for Healthcare Research and Quality Clinical Guidelines and Evidence Reports, and the Cochrane Database of Systematic Reviews. Related citations and expert recommendations were included. DATA EXTRACTION: Studies were selected if the search terms opioid and the organ system of interest were in the article's title, abstract, or text. Systems considered were gastrointestinal, respiratory, cardiovascular, central nervous, musculoskeletal, endocrine, and immune. Of 1,974 initially reviewed articles, 74 were selected for evidence regarding effects of chronic opioid use on that organ system. Of these articles, 43 were included on the basis of direct relevance to opioid prescriptions in the primary care setting. DATA SYNTHESIS: A qualitative review was performed because the number of articles pertaining to specific adverse effects of opioids was typically small, and the diversity of adverse effects across systems precluded a quantitative analysis. RESULTS: Through a variety of mechanisms, opioids cause adverse events in several organ systems. Evidence shows that chronic opioid therapy is associated with constipation, sleep-disordered breathing, fractures, hypothalamic-pituitary-adrenal dysregulation, and overdose. However, significant gaps remain regarding the spectrum of potentially opioid-related adverse effects. Opioid-related adverse effects can cause significant declines in health-related quality of life and increased health care costs. CONCLUSIONS: The diverse adverse effects potentially caused by chronic opioid therapy support recommendations for judicious and selective opioid prescribing for chronic noncancer pain by primary care physicians. Additional research clarifying the risks and management of potential adverse effects of chronic opioid therapy is needed to guide clinical practice.