Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews.
Level 1 - systematic review of randomized trials
Overview of Cochrane systematic reviews of randomized controlled trials
PubMed 29084357 · doi:10.1002/14651858.CD012509.pub2
What was done
This overview evaluated Cochrane systematic reviews (searched through March 2017) examining adverse events from medium- or long-term opioid therapy (two weeks or longer) across any dose, frequency, or route for chronic non-cancer pain in adults. Review quality was evaluated using AMSTAR, and evidence certainty was graded using the GRADE system. Quantitative data were synthesized across 14 Cochrane reviews covering 14 distinct opioid agents, encompassing 61 randomized studies (including 12 cross-over trials) and 18,679 participants, with most study durations ranging from 6 to 16 weeks (maximum 13 months).
What was found
In placebo-controlled trials, the absolute event rate among opioid users was 78% for any adverse event and 7.5% for serious adverse events. Opioid use significantly increased the risk of experiencing any adverse event compared to placebo (RR 1.42, 95% CI 1.22 to 1.66) and compared to active non-opioid controls (RR 1.21, 95% CI 1.10 to 1.33). Serious adverse events were also significantly increased versus placebo (RR 2.75, 95% CI 2.06 to 3.67). Significantly elevated risks were observed for constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting. None of the included reviews contained data on addiction, cognitive dysfunction, mood disturbances, endocrine dysfunction/hypogonadism, respiratory depression, sexual dysfunction, sleep apnea, or outcomes stratified by sex or ethnicity.
Why it matters
Given the high incidence of generic and serious adverse events, substantial and demonstrated clinical benefit is required to justify medium- to long-term opioid therapy for chronic non-cancer pain in clinical practice.
Limits
Study durations were relatively short for evaluating chronic therapy (mostly 6 to 16 weeks), leaving long-term or latent harms unmeasured. Critical opioid-related safety outcomes—including addiction, cognitive decline, and respiratory depression—were entirely absent from the included trial literature. The overall certainty of evidence for adverse events was downgraded to moderate, low, or very low due to risk of bias, indirectness, and imprecision.
Cited by
- supports Clinical trials for opioid approval in pain management are typically 9 to 12 weeks in duration.