Pharmacist Dr. Corey Hayes and colleagues found that higher opioid doses did not bring more pain relief—but did increase the risk of harmful side effects. (Photo by Jeff Bowen)

LITTLE ROCK, AR—More isn’t necessarily better when it comes to opioid treatment. That was the somewhat surprising finding of a study focusing on veterans with chronic pain related to arthritis, back pain, neck pain, neuropathic pain or headache/migraine.

A report in the journal Pain noted that VA health system patients had their opioid dosage increased did not have substantial improvements in pain when compared with other patients who continued to take a steady dose.1

Based on those findings, University of Arkansas for Medical Sciences-led authors cautioned that “clinicians should exercise extreme caution when embarking on a path of increasing opioid doses to manage non-cancer pain.”

“What we found … was that the pain relief the provider and the patient are going for really isn’t there when they increase their doses,” explained lead author Corey Hayes, PharmD, MPH. “You don’t see the benefit, but you do see the risk. Our overall message is, when you’re thinking about increasing the dose, you need to realize the risk it brings, too.”

The study team noted that, while prescribers are often confronted with the decision to escalate opioid doses to achieve adequate analgesia, they don’t always have full understanding of the impact of dose escalation on pain intensity.

Researchers used a retrospective cohort study design to focus on more than 50,000 veterans with chronic pain and chronic opioid therapy. The study compared opioid dose escalators—defined as those receiving a 20% increase in average morphine milligram equivalent daily dose—with dose maintainers over two consecutive six-month periods.

The study identified 32,420 dose maintainers and 20,767 dose escalators with 19,358 (93%) matched pairs. The VA patients had been prescribed opioids between 2008 and 2015 for chronic pain related to arthritis, back pain, neck pain, neuropathic pain or headache/migraine.

Results indicate that pain scores were persistently higher among dose escalators at each 90-day period after the index date (0-90 days after index date: dose escalators: 4.68, 95% confidence interval [CI]: 4.64-4.72 dose maintainers: 4.32, 95% CI: 4.28-4.36, P < 0.0001; 91-180 days after index date: dose escalators: 4.53, 95% CI: 4.49-4.57; dose maintainers: 4.25, 95% CI: 4.22-4.29, P < 0.0001) but were not different in the 90 days before the index date (dose escalators: 4.64, 95% CI: 4.61-4.68; dose maintainers: 4.59, 95% CI: 4.55-4.63, P = 0.0551).

“Opioid dose escalation among patients with chronic pain is not associated with improvements in Numeric Rating Scale pain scores,” the authors concluded.

An earlier study hinted at similar results (i.e., that opioid dose escalation does not lead to significantly improved pain scores). A 2016 study by researchers at the VA Portland, OR, Health Care System reported, “This study identified factors associated with improvements in pain intensity in a national cohort of older veterans with chronic pain. We found that older veterans frequently show improvements in pain intensity over time, and that opioid prescriptions, mental health, and certain pain diagnoses are associated with lower likelihood of improvement.”2

In an effort to reduce opioid prescribing in response to the nationwide opioid epidemic, the VA launched the Opioid Safety Initiative in 2013. Subsequently, the number of veterans prescribed opioids each year has dropped by 25% from the rate in 2013.

In fact, as of 2016, only about 16% of VA patients received opioid prescriptions. Past research has shown that the decline is mostly due to less long-term opioid prescribing, as opposed to short-term use for acute pain. The VA also is employing more nonopioid pain therapies, as well as more substance use disorder treatment.

The Center for Care Delivery and Outcomes Research at the Minneapolis VA Healthcare System also participated in the study.

  1. Hayes CJ, Krebs EE, Hudson T, Brown J, Li C, Martin BC. Impact of opioid dose escalation on pain intensity: a retrospective cohort study [published online ahead of print, 2020 Jan 7]. Pain. 2020;10.1097/j.pain.0000000000001784. doi:10.1097/j.pain.0000000000001784
  2. Dobscha SK, Lovejoy TI, Morasco BJ, et al. Predictors of Improvements in Pain Intensity in a National Cohort of Older Veterans With Chronic Pain. J Pain. 2016;17(7):824–835. doi:10.1016/j.jpain.2016.03.006