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Monotherapy Best Option for Low Back Pain

November 5, 2015
Acute back pain is best treated with an NSAID like naproxen—even in the emergency department. Adding additional medications does not improve outcomes, and can raise risks.

Every year, millions of Americans enter emergency departments (ED) seeking help for their acute low back pain (LBP). Oftentimes, doctors prescribe a combination therapy: for example, a nonsteroidal anti-inflammatory drug (NSAID) paired with a muscle relaxer or an opioid.1

However, prescribing patients more than one drug does not guarantee better outcomes and increases risks, according to researchers at the Montefiore Medical Center in Bronx, New York.

When patients with nontraumatic, nonradicular LBP were given naproxen, there was no added benefit from also taking a muscle relaxer or an opioid, like cyclobenzaprine or oxycodone/acetaminophen, noted the results of a new study published in JAMA.

The study bares new evidence challenging the supposition that more drugs mean more success when treating acute LBP in the ED setting.2 Even so, physicians often treat the condition through concurrent medications. A substantial fraction of patients even receive all 3 types of drugs at the same time—a NSAID, a muscle relaxant, and an opioid—despite the fact that studies have had conflicting conclusions over the actual clinical efficacy of such a polytherapeutic approach.

“Our results are similar to other studies of NSAIDs combined with cyclobenzaprine3-6 conducted in a variety of settings, including an ED and primary care and specialty clinics. Despite the fact that both NSAIDS and cyclobenzaprine are efficacious when administered as monotherapy,7,8 the bulk of the data, including the findings in this study, suggest combination therapy is not better than monotherapy,” the authors wrote.

The researchers likely chose cyclobenzaprine to represent the general clinical practice, as it is very commonly prescribed as a muscle relaxant. However, according to Jeffrey Fudin, BS, PharmD, DAAPM, FCCP, FASHP, the drug is still a poor choice, which may help explain why there weren’t any added benefits to supplementing it with a naproxen monotherapy regimen.

“There is limited evidence that cyclobenzaprine has any real direct muscle relaxant properties,” said Dr. Fudin, a clinical pharmacy specialist at the Stratton VA Medical Center in Albany, New York, and an editorial board member of Practical Pain Management. Metaxalone or tizanidine could have been a “more reasonable option,” Dr. Fudin said. But even if a cyclobenzaprine dose was efficacious, it should be generally avoided as a concomitant with an opioid.

“(Cyclobenzaprine) clearly has a high side effect profile related to its anticholinergic effects, including sedation and significant constipation. For this reason, as far as I’m concerned, it should almost never be combined with opioids, especially in the opioid naïve patient.”

The Study

In the randomized clinical trial, 323 patients aged 21 to 64 were provided a 10-day supply of medication to treat their acute LBP. Using the Roland-Morris Disability Questionnaire (RMDQ) as the primary measurement of outcomes, all patients started off with a score greater than 5 on the scale, which rates 0 as no functional impairment and 24 as maximum impairment.9 All patients received 20, 500 mg tablets of naproxen, taking 1 tablet every 12 hours as needed. The patients also were randomized to receive 60 tablets of an additional, concurrent medication—5 mg cyclobenzaprine, 5 mg oxycodone/325 mg acetaminophen, or placebo—to be taken as 1 to 2 tablets every 8 hours, if necessary.

After the first week, patients that took naproxen and placebo had significant improvements in their RMDQ by a mean of 9.8 (98.3% CI, 7.9 to 11.7). Interestingly, patients randomized to receive cyclobenzaprine or oxycodone/acetaminophen with their naproxen dose showed little difference from the naproxen/placebo group, with mean RMDQ improvements at 10.1 (98.3% CI, 7.9 to 12.3) and 11.1 (98.3% CI, 9.0 to 13.2), respectively.

Differences in Mean RMDQ

  • Cyclobenzaprine versus placebo: 0.3 (98.3% CI, −2.6 to 3.2; P = 0.77)
  • Oxycodone/acetaminophen versus placebo: 1.3 (98.3% CI, −1.5 to 4.1; P = 0.28)
  • Oxycodone/acetaminophen versus cyclobenzaprine: 0.9 (98.3% CI, −2.1 to 3.9; P = 0.45)

Previous studies have found cyclobenzaprine and various NSAIDs to be effective options as monotherapy for acute LBP.7,8 Indeed, the primary outcome did not differ greatly between the medication types. However, fewer patients used their cyclobenzaprine, oxycodone/acetaminophen, or placebo as often as their naproxen, with as many as 40% reporting use of those medications intermittently, only once, or not at all.

Opioids have not been found to be superior over NSAIDs,8 which contradicts the notion they can function as a competent, concurrent option for as-needed pain relief. There may be some truth to that, though, given patients who took their oxycodone/acetaminophen more than once reported better pain scores than those taking placebo. However, the study authors advised professionals consider those results “cautiously,” given the large amount of analysis and the fact that patients were also at a 19% greater risk of adverse effects.

Persistent Pain

After 1 week, more than 50% of patients still required medication for their LBP, regardless of what medicine they were taking. Three months later, more than 20% of patients were still reporting moderate to severe LBP, and this was despite the fact researchers purposefully assembled a low-risk cohort, excluding those with chronic LBP, radicular symptoms, or chronic use of opioids.

The data did not indicate the opioids helped, as less than 3% of patients reported use with an opioid in the last 72 hours. It’s a distressing finding, given that “there are no additional evidence-based medical therapies” for those patients taking an optimized NSAID regimen, the authors wrote.

Time usually heals the pain, though for those patients still suffering after 3 months, the possibility of other risk factors (smoking, high psychosocial score, neurological distress) could take account.10 This could have been significant, given that the Montefiore ED serves a socioeconomically depressed population, but the study did not cover those prognostic factors. There are other limitations to consider. Methodologically, handing out 60 tablets of concurrent medication at one time is a more liberal opioid regimen than clinical practice guidelines, and it is possible patients’ self-reports may have been influenced by receiving the concurrent medication in the first place.11

According to Dr. Fudin, the study “tells us very little” for such reasons. “You cannot make assumptions on outcomes based on persons that may or may not have taken their (as needed) doses of opioids and/or cyclobenzaprine,” Dr. Fudin said.

A better study design would have been to do away with the pro re nata dosing, splitting patients into 3 monotherapy groups for around the clock regimens of naproxen, cyclobenzaprine, oxycodone, and then having two polytherapy groups—one group taking naproxen and oxycodone and another group taking naproxen, cyclobenzaprine, and oxycodone as dual and triple therapies. However, this would require a far more substantial study population, he noted.

“In my opinion, opioids are overprescribed in the ED setting, and NSAIDs alone are probably at least and indeed, as the authors suggest, more beneficial for nontraumatic, nonradicular LBP as a single agent compared to the other options allowed. I don’t believe this study answered the question that it set out to answer. I also question why combined oxycodone plus acetaminophen was allowed, since this made things even sloppier.”

The Albert Einstein College of Medicine institutional review board provided ethical oversight for the study. All study participants provided written informed consent to participate. None of the study authors reported any conflicts of interest. More info at clinicaltrials.gov.

Last updated on: November 12, 2015
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Acetaminophen Found Ineffective for Treating Low Back Pain
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