Dec
2018
39
F
Feature
Internal Validity
Are the results valid?
Randomised patient assignment?
Yes. A research pharmacist performed the
randomisation.
Groups similar at the start?
Yes. The groups were similar. 2
Groups treated equally apart from
assigned treatment?
Yes, but both clinician and patient would
have been able to guess whether they
were in the placebo vs orphenadrine, or
placebo vs methocarbamol groups. It is
reasonable to assume that this did not have
an important effect on the outcome.
All patients accounted for?
Yes. Relatively few participants dropped
out and the analysis was conducted on an
intention-to-treat basis.
Measures objective? Or patients and
clinicians kept blinded?
Yes. The authors undertook an
assessment of blinding, and thus
it seems that participants were
successfully kept blinded. 2
Critical appraisal
I will use the randomised controlled trial
appraisal sheet from the Centre for Evidence-
Based Medicine. 3
Comparator: “placebo”, Outcomes: blank).
The search identified a new key randomised
trial from 2017 as the first hit. 2 This trial
compared orphenadrine and another
muscle relaxant (methocarbamol, which
is not available in Australia). The study
assessed the effect of the muscle relaxants
given with an NSAID, compared with
NSAID therapy alone. I did a quick search
through PubMed, and this appeared to
be the most appropriate piece of evidence
to review.
Let’s look at Friedman et al. (2017),
published in the Annals of Emergency
Medicine, in more detail.
PICO
Participants: who was studied?
The study included 240 adults (aged between
18 and 69), recruited from two academic EDs in
New York, US, presenting with acute low back
pain. The patient was required to have received
a diagnosis consistent with non-traumatic,
non-radicular, musculoskeletal low back pain,
and was to be discharged home.
Important exclusions: radicular pain below
the gluteal folds, pain duration longer than two
weeks, a baseline back pain frequency of at least
once a month, direct trauma to the back within
the previous month, pregnancy, breastfeeding,
and use of any analgesic medication daily or
near-daily. The mean age of participants was 39,
55% were male, and the median duration of low
back pain was two to three days.
Intervention: what was the exposure?
Orphenadrine group: naproxen 500mg/bd +
orphenadrine 100mg/bd × 7 days.
Methocarbamol group: naproxen 500mg/bd +
methocarbamol 750mg 1-2 tabs/tds PRN × 7 days.
Comparator: what was the control/
alternative?
Placebo group 1: naproxen 500mg/bd + placebo
1 cap/bd.
Placebo group 2: naproxen 500mg/bd + placebo
1-2 cap/tds PRN.
Outcomes: what was measured?
Primary outcome: improvement in low back
pain at one week, and three months after an
ED visit, as measured by the Roland-Morris
Disability Questionnaire (RMDQ). Note: this
is a validated 24-item low back pain functional
scale (0 = no low back pain-related functional
impairment, and 24 = maximum impairment).
What were the results?
Primary outcome: the difference in low back
pain-related impairment between the placebo
group and orphenadrine group at one week was:
• 1. 5 RMDQ points (95% confidence interval
— 1.4 to 4.3) (result favouring placebo).
• Note: the “minimal clinically important
difference” (see Stat Facts) for the RMDQ is
estimated to be 4 or 5 points. 4
Discussion and conclusion
This was a well-conducted effectiveness trial
undertaken in the American ED setting. It is
likely informative, and probably externally valid
in Australian general practice.
Although the aforementioned
Cochrane systematic review identified that
non-benzodiazepine skeletal muscle relaxants
(and potentially oral orphenadrine) may have a
beneficial effect for acute low back pain when
used alone compared to placebo therapy, it was
not at all certain how these agents compared
to other known effective pharmacotherapy for
acute low back pain. 1
This study demonstrated no meaningful
benefits to adding orphenadrine to naproxen.
The point estimate is close to zero, and the
extent of the 95% confidence interval most
favouring benefit is still well within the minimal
clinically significant difference for RMDQ
scores. There was similarly no benefit from the
other agent, methocarbamol.
Currently, acute low back pain guidelines
recommend against the routine use of
pharmacotherapy and, notably, the median time
to recovery with no medicines is approximately
2.5 weeks. 5 When pharmacotherapy is used,
NSAIDs might be reasonable, though side-
effects need to be considered. 6
For Harry, I provided reassurance that
he will recover and recommended he try to
maintain usual activities, to use heat packs,
and to avoid bed rest. I did not recommend
orphenadrine.
Dr Michael Tam
BSc(Med), MBBS, MMH(GP), FRACGP
Senior Lecturer, Discipline of GP, USyd;
Staff Specialist, SWSLHD & Ingham Inst.
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