Date: May 13th, 2022
Reference: Abril et al. The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies. J Emerg Med 2022
Guest Skeptic: Dr. Sergey Motov is an Emergency Physician in the Department of Emergency Medicine, Maimonides Medical Center in New York City. He is also one of the world’s leading researchers on pain management in the emergency department and specifically the use of ketamine. His twitter handle is @PainFreeED.
Case: A 45-year-old man without a significant past medical history presents to your emergency department (ED) with two days of severe lower back pain after shoveling some dirt. The pain is 10/10 in intensity, gets worse with bending, turning, and prolonged walking. He denies numbness or paresthesia in both lower extremities, as well as bowel or bladder dysfunctions. A heating pad and acetaminophen has not helped with the pain. On examination, he is in moderate distress and has prominent tenderness to palpation at the bilateral paralumbar region and intact neurovascular examination. You diagnose him with a lumbar muscle strain and plan to prescribe him a non-steroidal anti-inflammatory (NSAID) while setting expectations. However, the patient wonders if you can give him something that can relax his back muscles and take his pain away.
Background: Low back pain (LBP) is one of the most encountered ailments in clinical practice and is responsible for 2.6 million visits to U.S. EDs annually (1). Many patients with acute LBP experience substantial improvement in the first month, but up to one third report persistent back pain, and 1 in 5 report some limitations in activity. These persistent symptoms are associated with high costs, including those related to health care, and indirect costs from missed work or reduced productivity (2).
Many pharmaceutical treatments besides opioids have been tried to address acute LBP pain with limited success (SGEM#87 and SGEM#173). These include: acetaminophen (Williams et al Lancet 2014), steroids (Balakrishnamoorthy et al Emerg Med J 2014) and benzodiazepines (Friedman et al Ann Emerg Med 2017). Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medication therapy for patients with LBP despite a lack of evidence of efficacy (Machado et al Ann Rheum Dis 2017),
There are several non-pharmaceutical treatments that have also been tried to treat LBP. They include: CBT and mindfulness (Cherkin et al JAMA 2016), chiropractic (Paige et al JAMA 2017), physical therapy (Paolucci et al J Pain Research 2018) and acupuncture (Colquhoun and Novella Anesthesia and Analgesia 2013). Unfortunately, none of these other treatment modalities has high-quality evidence supporting their use.
Skeletal muscle relaxants (SMRs) are a frequently used in the ED and at discharge for acute back pain management and include methocarbamol, cyclobenzaprine, orphenadrine, carisoprodol, tizanidine, metaxalone, and baclofen. Estimates suggest up to 35% of patients with nonspecific low back pain are prescribed SMRs, with orphenadrine, and methocarbamol being used in more than 250,000 U.S. ED visits for low back pain annually (3-5). Despite their branding as muscle relaxants, the anti-spasmodic and analgesic effects of SMRs are predominantly due to unknown mechanism of action.
Clinical Question: What is the efficacy of skeletal muscle relaxant administration in addition to an NSAID in treating acute low back pain?
Reference: Abril et al. The Relative Efficacy of Seven Skeletal Muscle Relaxants. An Analysis of Data From Randomized Studies. J Emerg Med 2022
- Population: Patients were considered for inclusion if they were 18– 69 years of age and presented to the ED primarily for management of acute LBP. This was defined as pain of two weeks’ duration or less originating between the lower border of the scapulae and the upper gluteal folds, and received a diagnosis consistent with nontraumatic, non-radicular, musculoskeletal LBP, as determined by the attending emergency physician. All patients had already received a dose of an NSAID.
- Exclusions: Radicular pain, pain duration for greater than two weeks, direct trauma to the back within the previous month, or a history of experiencing LBP on average more than several times per year, pregnancy, breastfeeding, allergy to study medications.
- Intervention: One of seven skeletal muscle relaxants (metaxalone, tizanidine, baclofen, diazepam, orphenadrine, methocarbamol, or cyclobenzaprine)
- Comparison: Placebo
- Primary Outcome: Improvement in the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and the 1-week follow-up. The RMDQ goes from 0 to 24 with a 5-point improvement on this scale generally considered clinically significant.
- Secondary Outcomes: Moderate or severe LBP 1 week after the ED visit and medication adverse effects, assessed by asking patients to report any symptoms from the medications and dichotomizing their responses (yes/no).
Authors’ Conclusions: “Among patients in the ED with acute LBP treated with a nonsteroidal anti-inflammatory drug, SMRs do not improve outcomes more than placebo. Neither age, sex, nor baseline impairment impacts these results.”
Quality Checklist for Non-Systematic Review:
- The clinical question is sensible and answerable. Yes
- The primary studies were of high methodological quality. Yes
- The assessment of studies were reproducible. Yes
- The outcomes were clinically relevant. Yes
- There was low statistical heterogeneity for the primary outcomes. Yes
6.The treatment effect was large enough and precise enough to be clinically significant. No
Results: There were four RCTs conducted between 2012 and 2018 by the same research group with a combined total of 887 patients. The mean age was 39 years, 56% were male, median RMDQ score was 18 and 67% had a history of LBP.
Key Result: All treatments including placebo had a clinically significant decrease in their RMDQ score without a statistical difference between groups.
- Primary Outcome: The seven SMRs and placebo group reported a decrease in their RMDQ score by about 10 points. The between-group differences were not statistically significantly different. We will put a table in the show notes with the point estimates and the 95% confidence intervals.
Results were similar regardless of age, sex, and baseline severity. Higher baseline RMDQ was associated with greater clinical improvement (B coefficient 5.7 < 0.01).
- Secondary Outcomes: Regarding pain intensity at 1 week, there was also no statistically significant differences among the groups (p = 0.93). Adverse medication effects were more common with cyclobenzaprine than with placebo (p < 0.01).
1. Not a SRMA – This publication was a planned analysis of four RCTs looking at seven different SMRs with a total of 887 patients. All four of the RCTs had the same principal investigator, Dr. Friedman, and he was the senior author on this manuscript. Dr. Friedman has contributed greatly to the area of pain management.
The analysis was not a SRMA nor was it claimed to be one. The team presented the results of their four RCTs. A more comprehensive study would been to conduct a systematic review using the PRISMA guidelines. This would have included an exhaustive search of the world’s literature without language restrictions and of the grey literature. Some of these RCTs may have been captured in the search depending on the inclusion and exclusion criteria.
2. Statistical Analysis – They performed a reasonably robust statistical analysis of their data. This was beyond the baseline characteristics of age, sex, RMDQ score and type of SMR recorded as a mean with a standard deviation, median with interquartile range or frequency with a precent when appropriate.
Their analysis included an ANOVA to determine if the between group differences measured on the RMDQ were statistically significant. There was no statistical or clinical (5-point change) difference between the seven SMR or placebo. They conducted a linear regression model to determine if there was an association of age, sex, baseline RMDQ severity, and history of back pain with the primary outcome. They also performed two logistic regression models with detailed explanation of variables.
3. Age Restriction – None of the four RCTs included patients over the age of 69 years. This is important to remember because this older cohort of patients is generally at greater risk of adverse events from medications with sedative side effects.
Any potential benefit from the treatment, which was not demonstrated in this publication, would need to be weighed against the potential harms. The harms in a geriatric age group could be more serious. As an example, SMR could lead to more falls. Falls are the most common cause of traumatic injury resulting in older adults presenting to the ED . Approximately 20% of falls result in injuries, and falls are the leading cause of traumatic mortality in this age group [7-9].
4. Placebo Effect – This study provides more evidence that the placebo effect is real and can be clinically significant. The mean improvement on the RMDQ score was 10.5 which is more than double what is considered clinically important. It demonstrates how easily it could patients can be fooled and how we can fool ourselves thinking the treatment provided “works”. SMR were just as effective in lowing RMDQ scores as a placebo. We also need to consider the ethical considerations of knowingly prescribing a placebo in clinical practice (10).
5. Nihilism – It is hard not to become nihilistic when reviewing the evidence for LBP. There is a serious lack of high-quality evidence demonstrating clinical improvement to inform our care. This includes both pharmacologic (steroids, NSAIDS, and acetaminophen), and non-pharmacologic therapies (chiropractic, acupuncture, message therapy and physical therapy).
Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion that combination of an NSAID and a SMR does not improve acute LBP outcomes more than an NSAID plus placebo, regardless of age, sex, baseline functional impairment, or history of LBP.
SGEM Bottom Line: We cannot recommend the routine use of SMR in adult patients presenting to the ED with acute, non-traumatic, non-radicular low back pain who have already received an NSAID.
Case Resolution: You recommend an oral dose of ibuprofen 400mg as a first line agent and try to set reasonable expectations.
Clinical Application: There still appears to be no great treatment options for patients presenting with acute low back pain. Evidence for individual pharmaceutical therapies is limited and this trial provides evidence that a combination therapy of SMR and NSAIDs is not better than NSAIDs alone.
One final thing that is important is to discuss expectations with the patient. They need to know that their pain might not be completely relieved in the ED. It is about limiting suffering not eliminating pain. Most patients will have persistent symptoms a week after presentation and many will have continued pain and functional impairment months after symptom onset [11-13]. We need to be supportive and realistic when discussing the natural history of acute low back pain with patients.
What Do I Tell My Patient? You have a muscle strain in your back. This is a very common problem and can be very painful. Ibuprofen may help lower your pain, but it is unlikely get rid of your pain completely. Adding medications like a muscle relaxant has not shown to be more effective. In addition, muscle relaxants can cause some very bothersome and potentially dangerous side effects, such as dizziness, drowsiness that may lead to loss of balance and/or coordination and falls. Unfortunately, you may have pain over the next few weeks or months. Try to stay active and if your pain is getting worse, you can’t function or are otherwise worried please return to the ED for re-assessment.
Keener Kontest: Last weeks’ winner was Dr. Daniel McCollum who is the Associate Residency Director AUMC / MCG Dept of Emergency Medicine. He knew the bones of the fingers were thought to resemble a row of Greek warriors ready for battle, so Aristotle called them “phalanges” (Greek for “closely knit row”).
Listen to the podcast to hear this weeks’ question. Send your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.
Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.
- Friedman BW, Chilstrom M, Bijur PE, Gallagher EJ. Diagnostic testing and treatment of low back pain in United States emergency departments: a national perspective. Spine 2010;35:E1406–11.
- Qaseem A, Wilt TJ, McLean RM, Forciea MA. Clinical Guidelines Committee of the American College of Physicians. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2017;166:514–30.
- Witenko C, Moorman-Li R, Motycka C, et al. Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain. P T. 2014;39:427-435.
- Cherkin DC, Wheeler KJ, Barlow W, Deyo RA. Medication use for low back pain in primary care. Spine (Phila Pa 1976). 1998;23:607-614.
- Friedman BW, Cisewski D, Irizarry E, et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain. Ann Emerg Med. 2018;71:348-56 e5.
- Albert A, McCaig LF, Ashman JJ. Emergency department visits by persons aged 65 and over: United States, 2009–2010. NCHS Data Brief2013;130:1–8.
- Masud T, Morris RO. Epidemiology of falls. Age Ageing2001;30:3–7.
- Yildiz M, Bozdemir MN, Kilicaslan I, et al. Elderly trauma: the two years experience of a university-affiliated emergency department. Eur Rev Med Pharmacol Sci2012;16(Suppl 1):62–7.
- Centers for Disease Control and Prevention. Fatalities and injuries from falls among older adults–United States, 1993–2003 and 2001–2005. MMWR Morb Mortal Wkly Rep2006;55:1221–4.
- Lichtenberg P, Heresco-Levy U, Nitzan U. The ethics of the placebo in clinical practice. Journal of Medical Ethics 2004;30:551-554.
- Itz CJ, Geurts JW, van Kleef M, Nelemans P. Clinical course of non-specific low back pain: a systematic review of prospective cohort studies set in primary care. Eur J Pain. 2013 Jan;17(1):5-15. doi: 10.1002/j.1532-2149.2012.00170.x. Epub 2012 May 28. PMID: 22641374.
- Donelson R, McIntosh G, Hall H. Is it time to rethink the typical course of low back pain? PM R. 2012 Jun;4(6):394-401; quiz 400. doi: 10.1016/j.pmrj.2011.10.015. Epub 2012 Mar 3. PMID: 22381638.
- da C Menezes Costa, L., Maher, C. G., Hancock, M. J., McAuley, J. H., Herbert, R. D., & Costa, L. O. (2012). The prognosis of acute and persistent low-back pain: a meta-analysis. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne, 184(11), E613–E624. https://doi.org/10.1503/cmaj.111271