March 7, 2018

'Wake-up call': Opioids may be worse than Tylenol for chronic pain. Here's our take.

Daily Briefing

    Read Advisory Board's take on this story.

    Opioid medications are not more effective at relieving certain forms of chronic pain than non-opioid pain medications, according to a study published Tuesday in JAMA.

    Study details

    The study is the first randomized control trial to directly compare opioids and other forms of pain medications, according to the Los Angeles Times' "Science Now." Study author Erin Krebs of the Minneapolis Veterans Administration Health Care System and the University of Minnesota explained previous studies "were short-term studies and mostly compared opioids to placebo medications."

    For the new study, researchers looked at chronic musculoskeletal pain in 240 Veterans Affairs (VA) patients, who were mostly male (87%), mostly white (86%), and had an average age of 58. About two-thirds of the patients had chronic back pain, while about one-third had hip or knee osteoarthritis pain. Patients had experienced such pain for at least six months, and all of them said the level of pain interfered with their day-to-day activities and standard of living.

    The researchers randomly assigned patients to the opioid or non-opioid group. Patients were told whether their group was opioid or non-opioid, which the researchers said could be a limitation on the study. Patients in both groups could receive drugs in three steps, with dosing starting at a lower level and increasing based on patients' individual response.

    For the opioid group:

    • The first step was immediate-release morphine, hydrocodone/acetaminophen, or immediate-release oxycodone;
    • The second step was sustained-action morphine or sustained-action oxycodone; and
    • The third step was transdermal fentanyl.

    For the non-opioid group:

    • The first step was acetaminophen (the generic version of Tylenol) or a nonsteroidal anti-inflammatory drug;
    • The second step was adjuvant oral medications—such as nortriptyline, amitriptyline, or gabapentin—and topical analgesics, such as capsaicin or lidocaine; and
    • The third step was pregabalin, duloxetine, and tramadol.

    From June 2013 through December 2015, patients were asked to rate their pain intensity and function on a scale from zero to 10. Patients returned for monthly visits until the regimen was stabilized, at which point they were asked to return every one to three months. They completed additional follow-up by December 2016.

    Key findings

    After a year of observation, the researchers found no evidence that opioids were better than the non-opioid medications for the treatment of chronic pain.

    According to the researchers, at the start of the study, patients in both the opioid and non-opioid group reported their pain intensity at 5.4 on a scale of zero to 10. By the end of the year, patients in the opioid group reported an average pain severity score of four, while patients in the non-opioid group reported an average score of 3.5. However, the researchers noted that while "non-opioid treatment was associated with significantly better pain intensity, … the clinical importance of this finding is unclear; the magnitude was small."

    Overall, over the 12-month time period, pain severity improved by at least 30% among 41% of patients in the opioid group compared with 54% of patients in the non-opioid group.

    The study also found that patients in both groups reported similar levels of improvement over the course of the study when it came to measures of how pain interfered with daily activities, such as sleep, work, and mood. Scores for patients in the opioid group declined from 5.4 at the start of the study to 3.4 by the end of a year, while the scores for patients in the non-opioid group declined from 5.5 to 3.3 over the same time frame. Overall, 59% of those in the opioid group and 61% of those in the non-opioid group said they experienced at least a 30% improvement for these measures.

    The researchers also did not find significant differences between the two groups on most measures of health-related quality of life, such as fatigue, depressive symptoms, and sexual function. However, patients in the opioid group reported more improvement when it came to anxiety.

    That said, patients in the opioid group reported a significantly higher incidence of medication-related symptoms, such as constipation, fatigue, and nausea, according to Krebs. Hospitalizations, ED visits, and misuse were similar between the two groups.


    The researchers noted that while the study involved a patient population which is not representative of the country as a whole, the findings should lead doctors to reassess use of opioids as first-line treatment for chronic musculoskeletal pain. "This study adds [to] the long-term evidence that shows that opioids really don't have any advantages in terms of pain relief that might outweigh the known harms that they cause," Krebs said, adding, "Medications have some role, but they really shouldn't be the primary way we are treating chronic pain."

    Roger Chou, an internist at Oregon Health & Science University and the co-author CDC's guidelines on opioid use for chronic pain, said the findings were "really pretty astounding" and have the potential "to shake things up" when it comes to prescribing medication for pain relief. "The belief has always been opioids are the most effective pain medicine, certainly for acute pain and even for chronic pain," he said. "This (study) turns that on the head." He added that while he doesn't believe "opioids should necessarily be completely abandoned for chronic pain based on a single study done in the VA system," the findings "should have some impact on how people think about opioids for chronic pain."

    Beth Darnall, a pain psychologist at Stanford University, characterized the study as "rigorous science" but also stressed that certain individuals may still benefit from opioids. She also pointed to the rise of precision medicine for pain treatment. "The future is more precision pain medicine—truly characterizing each individual and having science to inform which treatment works best for each patient. We don't yet know who is the sub-population for whom low-dose opioids may be beneficial" (Krebs et al., JAMA, 3/6; Kaplan, "Science Now," Los Angeles Times, 3/6; Rapaport, Reuters, 3/6; Smith, "Shots," NPR/KCUR, 3/6; Lewis, Medscape, 3/6; Langreth, Bloomberg Technology, 3/6; AP/CBS News, 3/6; Belluz, Vox, 3/6).

    Advisory Board's take

    By Rebecca Tyrrell, Pharmacy Executive Forum, and Gillian Michaelson, Health Care Advisory Board

    Following on the heels of this week’s CDC report of a 30% increase in opioid overdoses from July 2016 to Sept. 2017, this research should serve as a wake-up call to providers that the time has come to critically evaluate whether their current opioid-related policies are firmly grounded in evidence-based medicine.

    This study adds to an important and growing body of work casting doubt on central, decades-old assumptions held by the health care community regarding the optimal medical use of opioids. For instance, a recent study linked opioids to reduced post-operative clinical success, and CDC's 2016 guidelines on prescribing opioids for chronic pain encourage clinicians to evaluate alternative pharmacological and non-pharmacological pain management options before selecting opioids.

    Hospital, health system, and physician practice leaders should use this new information to gain buy-in from clinicians and other clinical care team members to develop new pain management protocols. Physicians can also proactively bring this research to colleagues and leadership to signal interest and commitment to shifting the pain management paradigm.

    Additionally, new research findings should be incorporated into ongoing clinician education to address common misconceptions around pain management and opioid misuse, and to offer concrete evidence on the effectiveness of opioids and opioid alternatives.

    We'll soon be publishing new best-practice research on how health care executives can best support their teams in responding to the opioid crisis. In the meantime, we've compiled all of our top resources on combatting the opioid epidemic here.

    Get the Resources

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