Chronic Pain Relief: CMAJ Study Evaluates Predictors of Fatal and Non-Fatal Overdoses Interview with:
Li Wang, PhD
Associate professor
Department of Anesthesia
Michael G. DeGroote Institute of Pain Research and Care
McMaster University
Ontario, Canada What is the background for this study? What are the main findings?

Response: Chronic pain affects one in five people globally and is commonly treated with opioids. Unfortunately, opioid use may lead to serious harms including fatal and nonfatal overdose. Identifying predictors of opioid overdose may improve the shared decision-making for clinicians and patients when considering a trial of opioids for chronic pain. Although there have been previous reviews looking at predictors of opioid overdose following prescription for chronic pain, they have important limitations.

Our systematic review included 28 studies and 23,963,716 patients prescribed opioids for chronic pain that reported the associations of 103 predictors with opioid overdose. The baseline risk of non-fatal overdose was 1 in 500, and the risk of fatal overdose was 1 in 1000.

We identified 10 predictors, supported by moderate-to-high certainty evidence, that increased the risk of opioid overdose by 2-fold or more, including prescription of high-dose opioids (≥90mg morphine equivalent/day), fentanyl prescription, multiple opioid prescribers, use of multiple pharmacies, history of overdose, current substance use disorder, depression, bipolar disorder, other mental illness, or pancreatitis. The absolute risks of development of opioid overdose in patients with the predictor range from 4-12 per 1000 for non-fatal overdose and 2-6 per 1000 for fatal overdose, respectively. What should readers take away from your report?

Response: Our previous work has found opioids may provide modest benefits to a minority of people living with chronic pain, but they are also associated with several harms. Overdose following prescription of opioids for chronic pain is an infrequent, but critical harm. Identification of patients at higher risk of fatal or nonfatal opioid overdose can support shared decision-making between patients and clinicians regarding whether or not to pursue a trial of opioids for chronic pain.

In particular, some patients may place higher value on the possible benefits of opioids, while others may place greater value on the possible harms. Our findings will support these discussions by informing the absolute risk that an individual has of a non-fatal or fatal overdose following prescription of opioids. Our risk factors are independent, and so can be summed to produce the aggregate risk among individuals that present with multiple factors.

For example, our findings support that a patient with depression and an active substance use disorder would have an absolute risk of 9.6/1000 (1%) of a non-fatal overdose and an absolute risk of 4.8/1000 (0.5%) of a fatal overdose. What recommendations do you have for future research as a result of this study?

Response: We found preliminary evidence that different opioid tapering or discontinuation strategies, as well as traumatic brain injury, may be linked to opioid overdose. These factors should be further investigated. For example, emerging evidence suggests that forced opioid tapering is harmful and may increase the risk of overdose – particularly if patients replace prescription opioids with illicit sources, while consensual and supported tapering appears to be effective and safe. Opioid overdose is a serious public health issue, and there is urgency to reduce these events; however, caution is warranted to ensure that well-intended strategies, such as tapering patients prescribed high doses of opioids, do not result in net harm. Therefore, high-quality evidence on the effective opioid harm-reduction strategies or intervention is urgently needed. In addition, a valid and reliable predictive model or screening tool for opioid overdose should be developed.  

Disclosures: Our review was funded by Health Canada, and we received no industry funding. This work is part of a larger initiative to update our previous opioid guideline.


Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies

Li Wang, Patrick J. Hong, Wenjun Jiang, Yasir Rehman, Brian Y. Hong, Rachel J. Couban, Chunming Wang, Corey J. Hayes, David N. Juurlink, Jason W. Busse

CMAJ Oct 2023, 195 (41) E1399-E1411; DOI: 10.1503/cmaj.230459

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Last Updated on October 26, 2023 by