Naproxen Plus Muscle Relaxants vs. Naproxen Alone for Lower Back Pain

Shanterra Grable, Mercer University College of Pharmacy

In Americans under 45 years old, back pain is the leading cause of disability. It is estimated that anywhere from 60 to 80 % of the United States suffer from low back pain. This can affect flexibility, stability, and strength that can cause pain and discomfort, which can lead to chronic or temporary disability. [1]

While there is moderate evidence to show that a combination of  NSAIDS and muscle relaxants can be beneficial in treating acute back pain, it is not known which medications improve patient perceptions of pain. The mechanism in which muscle relaxants aid in relieving back pain is unknown but is thought to be related to their general analgesic effects in the central nervous system and not directly on skeletal muscles. The two muscle relaxants used in the following study, orphenadrine and methocarbamol, are prescribed in over 250,000 emergency room visits annually; however, there is little evidence to suggest that these two muscle relaxants are effective in treating low back pain.  [2]

A randomized, double-blind, placebo-controlled trial of naproxen with or without orphenadrine or methocarbamol for acute low back pain
Design Randomized, double-blind, comparative effectiveness trial; N=240
Objective To determine if combining orphenadrine or methocarbamol with a nonsteroidal anti-inflammatory drug (NSAID) is more effective than NSAID monotherapy for treating acute, nontraumatic low back pain
Study Groups Orphenadrine 100 mg twice daily (n=80), methocarbamol 750 mg (up to 1,500 mg) three times daily (n=81), or placebo (n= 79)
Methods Patients were selected from emergency department visits for low back pain. Every patient received standard therapy with naproxen 500 mg twice daily and low back pain education. They were then randomized to receive orphenadrine, methocarbamol, or placebo in addition to naproxen for a total duration of seven days.
Inclusion criteria: between ages 18 and 69 years old, presenting to ED for management of low back pain, diagnosis from ED visit of nontraumatic, nonradicular, musculoskeletal low back pain, baseline score of greater than five on RMDQ
Exclusion criteria: radicular pain below gluteal folds, pain duration greater than two weeks, baseline back pain frequency of at least once per month, direct trauma to the back within the previous month, pregnancy or breastfeeding, chronic pain syndrome requiring any daily analgesic, not available for follow up, or allergy, intolerance, or contraindication to study medications
Duration 7 days
Primary Outcome Measure Change in RMDQ score from baseline to week one
Baseline Characteristics Naproxen + placebo (n=79) Naproxen + orphenadrine (n=80) Naproxen + methocarbamol (n=81)
Mean age, years 39 40 38
Male 45 46 40
Female 34 34 41
Work status
Unemployed 8 8 7
Student 0 0 0
<30 hours/week 10 12 13
>30 hours/week 61 60 61
Median RMDQ at ED visit 19 19 19
Median duration of low back pain before ED visit, hours 48 72 48
Previous episodes of low back pain
Never before 21 28 25
A few times before 44 44 47
At least once per year 14 8 9
Depression screen result positive 3 0 1
Results Outcome Naproxen + placebo, no. (%) Naproxen + orphenadrine, no. (%) Naproxen + methocarbamol, no. (%)
Improvement in RMDQ score 10.9 9.4 8.1
Frequency of naproxen use
More than once per day 50 (67) 48 (62) 41 (53)
Once per day 19 (25) 19 (24) 19 (24)
Sometimes 5 (7) 5 (6) 10 (13)
Only once 1 (1) 4 (5) 5 (6)
Never 0 2 (3) 3 (4)
Missing 4 2 3
Frequency of placebo/orphenadrine/ methocarbamol use
More than once per day 38 (51) 36 (46) 34 (44)
Once daily 22 (29) 21 (27) 23 (29)
Sometimes 9 (12) 9 (12) 7 (9)
Only once 4 (5) 4 (5) 6 (8)
Never 2 (3) 8 (10) 8 (10)
Missing 4 2 3
Health care resources used
No visit to any clinician 67 (88) 66 (85) 65 (81)
Subsequent ER visit 1 (1) 2 (3) 5 (6)
Primary care 5 (7) 4 (5) 7 (9)
MD specialist (orthopedist, pain management) 1 (1) 2 (3) 1 (1)
Complementary therapy (chiropractor, massage, physical therapy) 2 (3) 5(6) 6 (8)
Missing 3 2 1
Adverse Events Common Adverse Events: (placebo vs. orphenadrine vs. methocarbamol)

drowsiness: 36% vs.34% vs. 32%

Dizziness: 13% vs. 16% vs. , 13%

Stomach irritation: 15% vs. 8% vs. 8%

Serious Adverse Events: Not disclosed
Percentage that Discontinued due to Adverse Events: Not disclosed
Study Author Conclusions The addition of skeletal muscle relaxants to naproxen does not improve functional or pain outcomes in patients with acute low back pain.

 

There is no universal mechanism of action for muscle relaxants which makes them unique. For instance, both orphenadrine and methocarbamol have unknown mechanism of actions but orphenadrine is likely to provide analgesic effects while methocarbamol has general CNS depression effects. [3,4] Therefore, the results of this study may not reflect the potential effectiveness of the entire class of medications and may not be applicable to all available muscle relaxants. While majority of the patients in each group took naproxen daily, there were variability in frequency of use because patients had the freedom of determining how often to take the medication. This suggests that not all patients may have had the same degree of pain; however, pain is often subjective, and individual tolerability levels are different making it difficult to standardize. Nonetheless, requiring  twice daily naproxen may have been a better approach to evaluate the additional effects of orphenadrine and methocarbamol. It also cannot be ruled out that the lack of scheduled dosing of the skeletal muscle relaxants may have underestimated the benefits of the added therapy. Moreover, methocarbamol had flexible dosing, but the results do not differentiate the different doses, providing limited knowledge on dose effects of methocarbamol.

Regarding study duration, guidelines recommend non-benzodiazepine muscle relaxants for 7-14 days; therefore, although within the range, the study could have lasted up to 14 days to see whether longer duration would lead to different outcomes. [5] One major limitation of this study is the exclusion of patients with chronic or frequent episodes of low back pain leading to a lack of evidence on the role of these medications  in chronic/uncontrolled lower back pain.

This was a single center study where the primary patient population was socioeconomically depressed. As some evidence show that back pain may be associated with socioeconomic status, these results may not be applicable to the general population with different socioeconomic status.  Given the lack of evidence to support additional benefit, orphenadrine and methocarbamol may not be an appropriate add on therapy to NSAIDS in treating acute low back pain.

 

References

[1] University of Maryland Medical Center. (2017). Low back pain. [online] Available at: http://www.umm.edu/health/medical/altmed/condition/low-back-pain Accessed December 8, 2017.

[2] 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. 2017.

 

[3] Robaxin ® [package insert]. Malvern, PA: Endo Pharmaceuticals, Inc. Updated October 2016. Accessed December 17, 2017.

 

[4] Orphenadrine ® citrate injection [package insert]. Schaumburg, IL: Sagent Pharmaceuticals, Inc. Updated December 2009. Accessed December 17, 2017.

 

[5] Casazza, B. (2017). Diagnosis and Treatment of Acute Low Back Pain. [online] Aafp.org. Available at: http://www.aafp.org/afp/2012/0215/p343.html#sec-3. Accessed December 8, 2017.

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