Opioids Show No Benefit, More Risks for Long-term Chronic Pain

Erin E. Krebs, MD, MPH

A new study has found that opioid medication is not more beneficial for long-term treatment of 2 prominent forms of chronic pain than nonopioid medication.

The results of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial — a randomized study comparing the benefits of opioid versus nonopioid therapy in primary care patients with chronic back pain, or hip or knee osteoarthritic pain — has brought more evidence that opioids, even as a therapy for chronic pain patients who have tried other measures, may not be worth the addictive risk.

Led by Erin E. Krebs, MD, MPH, Women’s Health Medical Director, Minneapolis VA Health Care System, and Core Investigator, Minneapolis Veteran’s Affair (VA) Center for Chronic Disease Outcomes Research, researchers conducted the 12-month comparative study under the hypothesis that opioids would lead to better pain-related function and pain intensity, as well as more adverse effects.

Patients were recruited from 62 Minneapolis VA primary care clinicians. They were required to suffer from chronic back pain, or hip or knee osteoarthritic pain, that was moderate-to-severe despite analgesic therapy. Chronic pain was defined as nearly-daily pain for 6 or more months. Patients’ pain was gauged by the 3-item pain intensity, interference with enjoyment of life, and interference with general activity (PEF) scale. The scale ranges from 0 to 10, with 5 or greater indicating moderate or greater severity.

Researchers stratified randomization by primary pain diagnosis, to ensure a balanced rate of patients with back and osteoarthritis pain. The 120 patients assigned opioid therapy were prescribed a 3-step process therapy, with immediate-release morphine, oxycodone, or a hydrocodone/acetaminophen combination.

The 120 patients assigned nonopioid therapy were first prescribed acetaminophen or a nonsteroidal anti-inflammatory drug. Patient response to therapy in either group dictated any dosing adjustments made by physicians.

Patients were measured for pain-related function, as dictated by the Brief Pain Inventory (BPI) interference scale, over 12 months. The primary secondary outcome was pain intensity, as dictated by the BPI severity scale. Both scales range 0 to 10, with greater numbers indicating worse function or pain severity. A 1-point improvement in score was clinically important.

Among the 240 patients, 234 (97.5%) completed the trial. There was no significant difference in mean pain-related function over 12 months between the 2 groups, but nonopioid patients reported a slightly better score (3.4 for opioid; 3.3 for nonopioid; 95% CI; -0.5 — 0.7; P = 0.58).

Pain intensity was also better — this time, significantly so — for the nonopioid group over 12 months. They reported a mean BPI severity of 3.5, compared to the opioid group’s mean 4.0 score (95% CI; 0.0 — 1.0; P = .03).

The opioid group also reported more difficulties with adverse medication-related symptoms than the nonopioid group. Their mean 1.8 medication-related symptoms at 12 months were twice that of the nonopioid group’s 0.9 (95% CI; 0.3 — 1.5; P = .03).

The report of more medication-related symptoms is something that would be more commonly discussed in the era of the opioid crisis, Krebs told MD Magazine. But it’s the limited efficacy reported by opioid patients that differentiates this trial from others.

“A lesser known problem is that we have had very little high-quality scientific evidence about how well opioids work for people with chronic pain,” Krebs said. “This study shows no advantages of opioids that might help outweigh their known serious harms.”

Krebs emphasized that back pain and osteoarthritis pain are 2 of the most common conditions that patients are prescribed long-term opioids for which to treat. The indications of the SPACE trial call for more consideration to non-opioid measures to treat these conditions from the start.

It also calls for reconsideration to opioid treatment on a wider scale of pain conditions. Krebs noted that recent trials have also found similar results when treating patients for acute back pain and acute musculoskeletal injury in the emergency department.

Lastly, the patients who have become addicted to opioids deserve more analysis.

“Most people who take daily opioids for more than a few weeks or months develop physical dependence,” Krebs said. “This means they don’t feel normal unless they take opioids and may have withdrawal symptoms—such as worse pain or flu-like symptoms—if they stop them or decrease their dose.”

Even if the therapy is not as efficacious for pain, the physical dependence can make it too difficult for a patient to stop taking opioids, Krebs said.

The study, "Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain," was published online in JAMA Tuesday morning.

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