SGEM#366: Relax, Don’t Do It – Skeletal Muscle Relaxants for Low Back Pain

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 Outcome: 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 [6]. 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,