Friedman, B. W., Dym, A. A., Davitt, M., Holden, L., Solorzano, C., Esses, D., … & Gallagher, E. J. (2015). Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain: a randomized clinical trial. Jama, 314(15), 1572-1580.the

Clinical Question:

Does adding either muscle relaxants or opioids to NSAIDs improve functional outcomes and pain in patients with acute lower back pain (LBP)?

Bottom Line: 

Adding Cyclobenzaprine or Oxycodone/Acetaminophen to Naproxen did not improve functional outcomes or pain at 1-week or 3-month follow-up. The use of these additional medications is not supported by this study.

Study Design:

–Study Type: randomized, double-blind, 3-group clinical trial

–Population: ED patients aged 21-64 with nontraumatic, nonradicular LBP of 2 weeks or less duration. 

–Intervention:  Discharge home with Naproxen + Cyclobenzaprine, or Naproxen + Oxycodone/acetaminophen. 

–Control: Discharge home with Naproxen + Placebo

–Outcome (Primary): Improvement in RMDQ score (a score used to assess functional outcome) between the initial ED visit and 1-week telephone follow-up.

–Outcome (Secondary): Actual RMDQ scores at 1-week telephone follow-up and 3-month telephone follow-up, and specific exploratory outcomes as listed below.

• 1-week outcomes:
  • severity and frequency of LBP in the previous 24 hours
  • use of medications for LBP in the previous 24 hours
  • desire to use same medications for future episodes of LBP
  • number of days before return to normal function or work
• 3-month outcomes:
  • severity and frequency of LBP during previous 72 hours
  • use of medications for LBP in the previous 72 hours

Results:

Primary Outcome:

There was no statistically significant difference in mean RMDQ improvement between groups at 1-week follow-up.

Exploratory Outcomes:

-Adverse effects were more likely in the Oxycodone/Acetaminophen group (NNH 5.3) compared to placebo (NNH 7.8)

-None of the other exploratory outcomes revealed a statistically significant difference between groups.

Strengths:

-Clinically relevant question

-Double-blinded

-Decent follow-up in all groups (>90%)

-Results match up with prior studies exploring these same questions

Criticisms:

-Single center study 

-Small study (only 323 patients)

-Lack of standardized doses or dose frequencies (However, this could also be considered a strength of the study as this more accurately reflects clinical practice)

-Low compliance to assigned regimen

-Outcome measures were subjective so there may be biases

-Did not evaluate the adequacy of patient blinding

-Did not determine whether participants were using NSAIDs at the time of enrollment, which significantly limits generalizability

-The study was conducted in an urban ED setting serving a socioeconomically depressed population which limits its generalizability to all populations

-Large number of exclusion criteria

Discussion:

This study suggests that Naproxen monotherapy for acute LBP is sufficient, and that adding muscle relaxers or opiates to NSAIDs could potentially increase adverse effects without providing any functional or analgesic benefits. If applied to clinical practice in the correct patient population, this could reduce polypharmacy and prevent unnecessary adverse medication effects. However, this study has limited generalizability and cannot be appropriately applied to many clinical encounters, especially those in which the patient has already taken NSAIDs or other medications prior to ED 

arrival.