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Adverse effects of opioids for non-cancer pain

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Despite a lack of evidence that opioids are more effective than other drugs used for chronic non-cancer pain (CNCP) there has been a large increase in the use of opioids for CNCP and concerns expressed over the risks associated with long-term use.1 An overview of Cochrane systematic reviews has assessed the occurrence and nature of adverse events associated with opioids.2 The review assessed any opioid agent (any dose, frequency or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults. The overview included 16 reviews (61 studies, 18,679 participants), of which 14 presented unique quantitative data on 14 different opioid agents that were administered for periods of 2 weeks or longer. The longest study lasted 13 months, with most in the 6- to 16-week range. The reviews included 61 studies with a total of 18,679 randomised participants.

In the study’s main findings, opioids significantly increased the risk of any adverse event compared with placebo (risk ratio [RR] 1.42, 95% CI 1.22 to 1.66) or with a non-opioid active pharmacological comparator (RR 1.21, 95% CI 1.10 to 1.33). Opioids also significantly increased the risk of a serious adverse event (RR 2.75, 95% CI 2.06 to 3.67). Opioids were associated with significantly increased risk ratios for the following adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus and vomiting. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event.

The Cochrane authors note that the studies and reviews reported a limited range of specific adverse events. In particular, the studies did not provide information on some significant harms including addiction, cognitive dysfunction, respiratory depression, sleep apnoea or sleep-disordered breathing.

Comment: The lack of data on some important adverse effects is of concern. The review’s authors suggest that “reliance on earlier studies with less robust methodology may have contributed to the current opioid use epidemic and opioid overdoses and deaths.” A letter published in 1980 has been inappropriately cited as evidence that addiction with long-term opioid therapy is rare.1 Recently updated guidelines on the management of CNCP have highlighted the risks associated with opioids and encouraged use of non-opioid drugs and nonpharmacologic therapy, rather than a trial of opioids.3,4


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