Low-dose methotrexate and serious adverse events among older adults with chronic kidney disease
Muanda FT, Blake PG, Weir MA, Ahmadi F, McArthur E, Sontrop JM, Urquhart BL, Kim RB, Garg AX. JAMA Netw Open. 2023; 6(11):e2345132. Epub 2023 Nov 27.
The use of opioids for chronic noncancer pain has increased dramatically over the past 25 years in North America and has been accompanied by a major increase in opioid addiction and overdose deaths. The increase in opioid prescribing is multifactorial and partly reflects concerns about the effectiveness and safety of alternative medications, particularly the nonsteroidal anti-inflammatory drugs. However, much of the rise in opioid prescribing reflects the assertion, widely communicated to physicians in the 1990s, that the risks of dependence and addiction during chronic opioid therapy were low, predictable, and could be minimized by the use of controlled-release opioid formulations. In this narrative review, the researchers offer a critical appraisal of the publications most frequently cited as evidence that the risk of addiction during chronic opioid therapy is low. The researchers conclude that very few well-designed studies support the notion that opioid addiction is rare during chronic opioid therapy and that none can be readily generalized to present-day practice. Despite serious methodological limitations, these studies have been repeatedly mischaracterized as showing that the risk of addiction during chronic opioid therapy is rare. These studies are countered by a larger, more rigorous and contemporary body of evidence demonstrating that dependence and addiction are relatively common consequences of chronic opioid therapy, occurring in up to one-third of patients in some series.
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