Opioid Dose Escalation Among Veterans

The findings from 2 recent studies published in the journals Pain and Addiction indicated that increasing opioid doses does not appear to improve pain symptoms in patients with chronic pain and can lead to an increased risk of adverse effects.

In the first study of veterans with chronic pain1, the researchers compared 32,420 dose maintainers (±20% change in average morphine milligram equivalent [MME] daily dose) and 20,767 dose escalators (>20% increase in average MME daily dose). All participants were assessed over 2 consecutive 6-month windows of time.

Overall, pain scores were higher among dose escalators at each 90-day time period following the index date but were not different in the 90 days prior to the index date.

In a companion study by the same team,2 the researchers examined the potential adverse effects of dose escalation among the same groups of dose maintainers and dose escalators. Overall, composite adverse outcomes and individual subsequent substance use disorder and adverse outcome subtypes (except for opioid-related accidents and overdoses and violence-related injuries) were higher in dose escalators than in dose maintainers.

Consultant360 reached out to lead author Bradley C. Martin, PharmD, PhD, who is professor of pharmaceutical evaluation and policy at the University of Arkansas for Medical Sciences, about these findings.

Consultant360: For your studies, you evaluated the effects of opioid dose escalation among veterans with chronic, non‐cancer pain; this is a very specific patient population. Can you talk about why this population was chosen?

Bradley Martin: Veterans were chosen because they frequently experience chronic painful conditions, are disproportionately treated with chronic opioid therapy, and (importantly for this study) have their pain levels regularly recorded as part of their usual care, which is recorded in a national data warehouse that permits studies like these.
C360: The results of your analyses showed that escalating opioid doses increased the risk of substance use disorder and opioid-related adverse outcomes, as well as that pain scores were not affected by escalating opioid doses. What do these findings mean for clinical practice and how opioids are prescribed to this patient population?

BCM: We hope that this is a cautionary tale for prescribers who have patients on chronic opioid therapy. Prescribers are frequently confronted with the temptation to increase opioid doses, often at the behest of patients, but our data do not point to improved self-reported pain measures. It is possible that escalating doses may confer benefits such as improving functioning, but right now the evidence are lacking.

Readers of this work should also be aware that this was an observational study and not a clinical trial, and therefore, we cannot rule out the possibility that increasing doses among chronic opioid users may improve self-reported pain. However, until trials are conducted, there does not appear to be a discernible benefit on pain associated with escalating opioid doses.
C360: Suicide and mental health disorders (such as post-traumatic stress disorder [PTSD] and major depression) are common among veterans. Do you think opioid use negatively affects this population in different ways than it does the general population?

BCM: I can only speculate there. You are correct that veterans do experience mental health disorders more often, including having higher rates of suicide and PTSD. It is possible that escalating opioid doses may elevate the risks of suicide and mental health disorder more in veterans, but we would need data that compared opioid dose escalation in veterans with the general population to know this.
C360: In your opinion, do you think that chronic, non-cancer pain should be managed differently among this population? Why or why not?

BM: This relates to the previous question. Until we know that veterans are more or less vulnerable to the adverse effects of escalating opioid doses, we cannot really say veterans should be managed differently and believe caution is warranted when considering escalating anyone’s chronic opioid dose by more than 20%.

—Michael Potts

1. Hayes CJ, Krebs EE, Hudson T, Brown J, Li C, Martin BC. Impact of opioid dose escalation on pain intensity [published online January 7, 2020]. Pain. https://doi.org/10.1097/j.pain.0000000000001784.
2. Hayes CJ, Krebs EE, Hudson T, Brown J, Li C, Martin BC. Impact of opioid dose escalation on the development of substance use disorders, accidents, self‐inflicted injuries, opioid overdoses and alcohol and non‐opioid drug‐related overdoses: a retrospective cohort study [published online January 15, 2020]. Addiction. https://doi.org/10.1111/add.14940.