Pain treatment

Does That JAMA Study Really Show That Advil Is Just As Effective As Opioids?

Since responses to pain treatment vary widely, it is hazardous to draw broad conclusions from a single study.


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According to Vox, a JAMA study published this week "finally" provides "proof" that "opioids are no better than other medications for some chronic pain." The results of the study are "devastating," Vox says. To whom or what is not exactly clear, but the author of the article, Julia Belluz, seems to see the study as conclusive evidence against the notion that "opioids help patients with chronic pain in the long run" or that "they are worth all that risk" of "addiction and death." Similarly, NBC News declares that the "jury's in," and its verdict is that "opioids are not better than other medicines for chronic pain." Mother Jones likewise says "a new study shows that opioids are no better than other meds for chronic pain," while Newser agrees that Tylenol and Advil "work just as well as opioids."

The JAMA study—the work of a team led by internist Erin Krebs, a researcher with the Minneapolis Veterans Affairs Health Care System—did not actually demonstrate any of that. But it did highlight journalists' eagerness to believe that no one really needs narcotics for pain relief, which reflects the widespread desire for a simple solution to the "opioid epidemic."

If opioids have no advantage over other analgesics, why prescribe them at all? Why risk "addiction and death" when over-the-counter pain relievers are just as effective? Even if we ignore the fact that the risks for pain patients are actually pretty small (and the fact that opioid-related deaths primarily involve illegally produced drugs), this study does not show what the headlines claim.

Krebs and her colleagues recruited 240 patients with moderate to severe chronic back pain or hip or knee osteoarthritis from V.A. primary care clinics and randomly assigned them to opioid or nonopioid treatment. The opioid group initially received immediate-release morphine, oxycodone, or hydrocodone plus acetaminophen. If those medications proved inadequate, subjects were treated with sustained-action morphine or oxycodone, followed by fentanyl patches if necessary. The nonopioid group initially received acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, followed if necessary by various other medications, including nortriptyline, amitriptyline, gabapentin, topical analgesics, pregabalin, duloxetine, and tramadol.

The main outcome measures were pain-related function (measured by a questionnaire, with higher scores indicating a bigger burden from pain) and pain intensity (also self-reported, on a scale of 0 to 10). After 12 months, both groups were significantly better off by those two measures. The mean pain-related function score fell from 5.4 to 3.4 in the opioid group and from 5.5 to 3.3 in the nonopioid group. Mean pain intensity fell from 5.4 to 4 in the opioid group and from 5.4 to 3.5 in the nonopioid group. The difference between the two groups was statistically significant only for pain intensity, and the researchers note that "the clinical importance of this finding is unclear," since "the magnitude was small."

In short, both groups fared about the same. "Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months," Krebs et al. conclude. "Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain."

People in pain vary widely in how they respond to medication, so the fact that opioids did not have an advantage, on average, for this particular sample with these particular types of pain does not mean they are not a better choice for some patients. The study sample was 87 percent male, and it was drawn from V.A. clinics, which may not be representative of the general patient population. The conditions were limited to chronic back pain and chronic hip or knee pain caused by osteoarthritis, so the study does not speak to opioid treatment for other kinds of pain. The initial pain intensities were middling, so the study may not reflect the experiences of patients with more severe pain.

Notably, the researchers excluded patients who were on long-term opioid therapy, which means they ignored people who had already found they did not get adequate relief from other treatments. It seems reasonable to assume that people who are currently using opioids to treat chronic pain are doing so because they think these drugs work better for them than Advil or Tylenol, and they may even be right to think that. If you exclude those patients from a study of pain treatment, you are excluding precisely the people who are most likely to get more relief from opioids.

The bottom line is that patients should be able to get the medications that work best for them. Many people with severe chronic pain report going through a long list of alternative treatments before finding that opioids were the only thing that kept the agony at bay and gave them a decent quality of life. A study like this one is utterly irrelevant to people in that situation, and to suggest otherwise is illogical as well as cruel.

Addendum: Krebs notes that the study included patients who had tried opioids or who were using them intermittently, provided they were taking fewer than 60 short-acting tablets per month. "To be eligible for the study, we required patients to have moderate-severe pain despite analgesic use," she writes in an email. "All patients in the study had tried and failed other analgesics….We excluded people with more frequent opioid use because they would need tapering/discontinuation of opioids if randomized to the nonopioid arm. Long-term opioid use causes physiological dependence (a phenomenon distinct from addiction), which generates additional clinical complexity."