A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain

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Clinical Question

In adult patients with acute low back pain, does the addition of metaxalone, tizanidine, or baclofen to ibuprofen improve pain and functional outcomes?

Bottom Line

The purpose of the study was to determine if adding muscle relaxants (metaxalone, tizanidine, or baclofen) to a nonsteroidal antiinflammatory drug, NSAID, (ibuprofen) would improve pain and functional outcomes. There was no statistical significance of adding a muscle relaxant to an NSAID in the treatment of acute back pain.

Major Points

Many people within the US every year experience low back pain that makes them visit their physician. About 1 in every 4 US citizens reports having lower back pain in the past 3 months. There is also a global prevalence of 18%. According to the American College of Physicians (ACP) first line pharmacologic treatment for acute low back pain is the use of NSAIDs. The use of NSAIDs alone is often not enough to completely manage the symptoms in patients being treated that way, thus leaving them with reduced functional outcomes.

In “A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain”, three hundred twenty patients of two urban emergency departments (EDs) of Montefiore Medical Center (Bronx, NY) were randomized into 4 arms. There was a control arm with ibuprofen plus placebo, and arms with ibuprofen plus tizanidine, ibuprofen plus baclofen, and ibuprofen plus metaxalone. The primary outcome was measuring the level of functional impairment after a one week follow-up based on the Roland-Morris Disability Questionnaire (RMDQ). After a week it was shown that the addition of a skeletal muscle relaxer to ibuprofen showed no benefit to the primary outcome with a mean improvement in the RMDQ score of 10.8 (95% CI 9.8 to 11.8). There are limitations for the trial due to the population and location lacking the ability to be generalized.

Guidelines

ACP (2017) Inconsistent findings for a decrease in pain intensity with skeletal muscle relaxants (SMRs) + NSAIDs compared to NSAIDs alone

Design

  • Randomized, double-blind, parallel-group, comparative-effectiveness study
  • N = 320 participants
  • Experimental arms
    • Metaxalone + ibuprofen: n = 80 participants
    • Tizanidine + ibuprofen: n = 80 participants
    • Baclofen + ibuprofen: n = 80 participants
  • Standard arm
    • Placebo + ibuprofen: n = 80 participants
  • Setting: Two academic emergency departments of Montefiore Medical Center (Bronx, NY)
  • Enrollment: May 2017 - July 2018
  • Mean follow-up: 1 week
  • Mean Improvement in Roland-Morris Disability Questionnaire: Out of 24 points, higher indicating maximum functional impairment
  • Analysis: intention-to-treat
  • Primary outcome: Improvement on the Roland-Morris Disability Questionnaire between ED discharge and 1 week later


Population

Inclusion Criteria

  • Adults aged 18 to 64 years presenting to ED for management of acute, nonradicular, nontraumatic, musculoskeletal low back pain
  • Low back pain no longer than 2 weeks
  • Previous episodes of low back pain no more frequent than once per month
  • Functional impairment (baseline score >5 on Roland-Morris Disability Questionnaire)

Exclusion Criteria

  • Unavailable for follow-up
  • Pregnant or breastfeeding
  • Currently receiving medication for a chronic pain syndrome (use of any analgesic medication daily or near daily)
  • Allergy to, intolerance of, or contraindication to any of the investigational medications

Baseline Characteristics

  • All study arms
    • Demographics: mean age 37-40 years
    • Median RMDQ at ED visit: 18-20
    • Median duration of low back pain before presentation to ED: 48-72h
    • Previous episodes of low back pain: never 19-28%, few 56-65%, at least once/year 14-18%
    • There were no significant differences between the groups at the beginning of the study.

Interventions

Patients were randomized in a 1:1:1:1 ratio to 1 of 4 medication regimens:

  • Control arm: ibuprofen 600 mg + placebo orally every 8 hours as needed
  • Baclofen arm: ibuprofen 600 mg + baclofen 10 to 20 mg orally every 8 hours as needed
  • Metaxalone arm: ibuprofen 600 mg + metaxalone 400 to 800 mg orally every 8 hours as needed
  • Tizanidine arm: ibuprofen 600 mg + tizanidine 2 to 4 mg orally every 8 hours as needed

Patients were instructed to take 1 ibuprofen plus 1 to 2 muscle relaxant capsules. If the patient did not see sufficient relief with one capsule in 60 minutes, they were instructed to take a second.


Outcomes

Primary Outcomes

Mean Improvement in RMDQ Ibuprofen + placebo: 11.1 (95% CI 9.0 to 13.3) Ibuprofen + baclofen: 10.6 (95% CI 8.6 to 12.7) Ibuprofen + metaxalone: 10.1 (95% CI 8.0 to 12.3) Ibuprofen + tizanidine: 11.2 (95% CI 9.2 to 13.2)

None of the study arms had statistically significant results.

Secondary Outcomes

Moderate to severe pain 48 hours after ED discharge Out of 312 participants 53% (95%; CI 48% to 59%)

Moderate to severe pain 1 week after ED discharge Out of 312 participants 33% (95%; CI 28% to 39%)

Use of medication for low back pain 48 hours after ED discharge Out of 312 participants 91 % (95%; CI 88% to 94%)

Use of medication for low back pain 1 week after ED discharge Out of 312 participants 63% (95%; CI 58% to 68%)

Additional health care resources one week after ED discharge Out of 304 participants 11% (95%; CI 8% to 15%)

Adverse Effects reported Out of 283 participants 8% (95%; CI 6% to 12%)

Subgroup Analysis

Subgroups were analyzed based on their age, sex, work status, RMDQ score, duration of current episode of low back pain, frequency of previous episodes, and diagnosis of depression. There were no clinically important or statistically significant differences among the study arms.

Adverse Events

The most common adverse events reported were drowsiness, headache, nausea, and dizziness. The adverse events were not serious and did not differ between study arms.

Criticisms

  • Doses were not based on previous dose-findings because there are no guidelines that include dosing.
    • Patients may have been underdosed because there are no guidelines to support what dose is needed for different patient characteristics.
  • The study was done in 2 urban EDs in New York, making this data inapplicable to a generalized population.
  • If patients do not have adequate access to care their outcomes for low back pain could be different than those included in this study.

Funding

The study was funded by the National Institutes of Health/National Center for Advancing Translational Science Einstein-Montefiore CTSA grant.

Further Reading

  • Deyo, R. A., Mirza, S. K., & Martin, B. I. (2006). Back Pain Prevalence and Visit Rates. Spine, 31(23), 2724–2727. doi: 10.1097/01.brs.0000244618.06877.cd
  • Hoy D, Bain C, Williams G, et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012;64:2028-2037.
  • Qaseem, A., Wilt, T. J., Mclean, R. M., & Forciea, M. A. (2017). Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine, 166(7), 514. doi: 10.7326/m16-2367
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