The easiest way to avoid getting hooked on opioids may be to never take them in the first place. After all, an initial prescription of just a few days' worth of pills can trap patients into using the highly addictive, often deadly drugs for a year or more. But despite the dangers, many patients don’t have the luxury of passing on potent pain killers—for instance, those stumbling into a hospital emergency room with a broken or badly bloodied limb.

At least, that’s what doctors assumed.

In a randomized, double-blind clinical trial —the gold standard of trials—a combination of ibuprofen (Advil) and acetaminophen (Tylenol) was just as effective at treating patients with acute pain in an extremity as three other pain-killer combinations containing opioids. The authors of the study, which was published Tuesday in JAMA, suggest that emergency room doctors may be able to simply skip the opioids during and after urgent treatment.

“This change in prescribing habit,” they write, “could potentially help mitigate the ongoing opioid epidemic by reducing the number of people initially exposed to opioids and the subsequent risk of addiction.”

Beyond that, the study flings into light the poor data backing current opioid prescription practices and the dwindling scenarios in which the dangerous drugs are firmly warranted. The implications are staggering given the current epidemic of opioid abuse and addiction gripping the country. In 2015, more than 30,000 people died of opioid overdoses, and currently an estimated 91 people die each day from the drugs.

Precarious prescriptions

The authors of the new trial, led by Andrew Chang of Albany Medical College in New York, note that common medical practice and guidelines, including those championed by the World Health Organization, suggest that opioids are simply more effective at treating acute pain than non-opioid medications—or combinations of them. Yet, the data backing that is shaky.

Ibuprofen and acetaminophen have completely different molecular activities in the central nervous system and brain—offering a one-two punch to pain when used in combination. Researchers haven’t done the work to show that the duo are knocked out by opioids in terms of treating extreme pain in a limb. But a handful of studies on dental and post-operative patients clearly indicated that non-opioid drug pairs were just as effective. The studies compared a combination of ibuprofen and acetaminophen to a combo of codeine and acetaminophen and found that no codeine-containing treatment—regardless of the dose—beat out the non-opioid blend.

Likewise, when researchers and health experts recently reassessed the common practice of using opioids for chronic pain, they also found a dearth of data backing the prescriptions. What they did find was a heap of evidence that long-term opioid use led to tolerance, dependence, addiction, and, in many cases, overdoses. As such, the Centers for Disease Control and Prevention updated their prescribing guidelines last year, urging doctors to avoid using opioids to help patients manage chronic pain

“Plainly stated, the risks of opioids are addiction and death, and the benefits for chronic pain are often transient and generally unproven,” then-CDC Director Tom Frieden said at the time.

Painful results

In the new trial, Chang and colleagues enrolled 411 patients who arrived in one of two Bronx, New York, emergency rooms with acute pain in a limb. The enrolled patients were all between 18 and 64 years old, cleared of complicating health conditions, had no history of allergies or signs of opioid addiction, and were on no medications that might interact with the pain treatments. When they arrived, the patients had a mean pain score of 8.7 on a standard 11-point scale.

Researchers then randomly assigned the patients to get one of four pain-pill combinations: 400mg of ibuprofen and 1,000mg of acetaminophen; 5mg of oxycodone and 325mg of acetaminophen; 5mg of hydrocodone and 300mg of acetaminophen; or 30mg of codeine and 300mg of acetaminophen. Each of the pill combinations looked identical to the patients—three opaque capsules.

Two hours later, the patients scored their pain again. There were no statistically significant differences in pain reduction across the four groups. Mean scores dropped by 4.3 with ibuprofen and acetaminophen; 4.4 with oxycodone and acetaminophen; 3.5 with hydrocodone and acetaminophen; and 3.9 with codeine and acetaminophen. The biggest difference between any two of the groups was 0.9—oxycodone and acetaminophen vs hydrocodone and acetaminophen—which is not a clinically significant difference in pain level.

Patients who needed more pain medication than the given treatment—which was determined at the discretion of the treating physician—could get a rescue dose of 5mg of oxycodone. Seventy-three of the 411 patients (~18 percent) got a rescue dose. But they were generally evenly distributed among the four treatment groups. In other words, there were no significant differences in the fraction of patients in each group getting a rescue dose.

Chang and colleagues note the main limitation of the study, which is that it only looked at pain treatment in a two-hour window. But, they note, “the goal was to determine if a single dose of an analgesic [pain reliever] would provide superior pain relief for patients while in the ED.” It’s possible that one combination could wear off faster, but they all have similar half-lives of three to four hours, they note.

“The trial by Chang et al provides important evidence that nonopioid analgesia can provide similar pain reduction as opioid analgesia for selected patients in the [emergency department] setting,” emergency medicine physician Demetrios Kyriacou of Northwestern University concluded in an accompanying editorial. Still, researchers will need more data to know if pain patients in other clinical settings can skip the opioids.

JAMA, 2017. DOI: 10.1001/jama.2017.16190 (About DOIs).