VA/DoD CLINICAL PRACTICE GUIDELINE FOR OPIOID THERAPY FOR CHRONIC PAIN

VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain
Table 3. Incidence Rate Ratios for Opioid Overdose Deaths, by Average Milligrams Morphine
Equivalent Daily Dose[135]
MEDD
(mg)
Deaths Person-Years Sample Size IRR 95% CI
Unexposed 151 3,554,850 7,377,860 0.57 0.44, 0.73
>0 - 39.9 98 1,305,835 1,305,969 1
40 - 59.9 90 457,227 457,322 2.6 2.0, 3.5
60 - 79.9 47 213,816 213,868 2.9 2.1, 4.1
80 - 99.9 34 72,448 72,483 6.2 4.2, 9.2
100 - 119.9 23 45,536 45,559 6.7 4.3, 10.6
120 - 139.9 22 20,699 20,721 14.1 8.9, 22.5
140 - 159.9 14 14,586 14,599 12.8 7.3, 22.4
160 - 179.9 15 6,769 6,784 29.5 17.1, 50.7
180 – 199.9 11 9,604 9,615 15.2 8.2, 28.4
200 – 249.9 24 11,653 11,678 27.4 17.5, 42.8
250 – 299.9 20 7,406 7,425 35.9 22.2, 58.0
300 – 349.9 17 4,495 4,512 50.2 30.0, 84.0
350 – 399.9 17 3,563 3,580 63.2 37.8, 105.7
400 – 499.9 14 3,527 3,541 52.7 30.1, 92.2
500 – 5000 32 4,684 4,718 90.4 60.7, 134.6
Total 629 5,736,696 9,560,234 -- --
Abbreviations: CI: confidence interval, IRR: incidence rate ratios; MEDD: morphine equivalent daily dose; mg:
milligram(s)
Achieving an improved understanding of the factors contributing to prescription opioid-related overdose is
an essential step toward addressing this epidemic problem. Although it is widely accepted that
progressively higher doses of prescribed opioids result in correspondingly higher risks of opioid overdose,
patients using any dose of opioids can still experience life-threatening respiratory or CNS depression,
especially when opioid naïve. This risk begins to increase with MEDD as low as 20-50 mg. Risk is further
increased when certain concomitant demographic factors, co-occurring medical or psychiatric conditions,
or interacting medications or substances exist.
Recognizing the lack of evidence of long-term benefit associated with LOT used alone and the risks of
harms with use of opioids without risk mitigation, dosing determinations should be individualized based
upon patient characteristics and preferences, with the goal of using the lowest dose of opioids for the
shortest period of time to achieve well-defined functional treatment goals. Understandably, there will be
greater mortality, co-occurring medical conditions, and other adverse events in patients who require
higher doses of opioids, even in those who benefit from such therapy. When closer follow-up is needed,
healthcare resources and patient adherence should be considered.
Subgroups at higher risk
Risk of prescription opioid overdose is elevated across MEDD dosage levels in patients with co-occurring
depression (moderate-quality evidence).[66,133] Following an elevated baseline adjusted risk ratio (ARR)
of 3.96, depressed patients taking 1-19 mg, 20 to