J Int Med Res (1983) 11,42

A Double-Blind Comparison in General Practice of a

Combination Tablet Containing Orphenadrine Citrate and
Paracetamol ('Norgesic') with Paracetamol Alone

B W McGuinness, MD, FRCGP, DObst, DCn, Weaver Vale Practice, Hallwood Health
Centre, East Lane, Runcorn, Cheshire, WA 7 2UT. England

A double-blind trial of a combination tablet containing orphenadrine and

paracetamol, 'Norgesic', was carried out to assess the value of this product
compared with paracetamol alone. All three symptomatic parameters which
were measured: pain, spasm and impaired activity, showed a significantly
quicker recovery when the combination product was used. Further studies are
necessary to evaluate the combination product against orphenadrine citrate
alone.

Introduction Thus, from every angle it is reasonable to

Painful musculo-skeletal conditions comprise a
major portion of the general practitioner's
workload (Fry 1957, Noble 1964), they are
poorly responsive to standard methods of
treatment and cost individual, family and
community dearly in the degrees of
disablement they cause. Although never life-
threatening, a painful back, shoulder, neck or
knee can cause much distress and frustration.
Causes are generally found in the physical
trauma of everyday life and although the
pathological processes are uncertain, it is
reasonable to assume that torn integument is
the basic lesion, with secondary protective
muscle spasm producing stiffness and
limitation of function. Aside from individual
personal distress, the loss of working time
caused by musculo-skeletal traumatic disorder
exceeds that attributable to industrial strife
(Littler 1982).
look for better, quicker and easier methods of
treatment and to assess critically current
therapeutic agents, even if these have been in
use for many years.
The use of combinations of analgesic and
antispasmodic drugs is widespread, yet they
have been inadequately evaluated. Separately,
analgesics like paracetamol and
antispasmodics like orphenadrine citrate have
been shown to be effective (Cailliet 1960,
Lamphier 1962, Moertel et al 1972, Meredith
& Goulding 1980). There has, however, been
no report of a double-blind comparative study
of a combination of these two agents assessed
against one, at least in the literature from
general practice. It was decided, therefore, to
carry out a study to evaluate paracetamol and
orphenadrine given synchronously against
paracetamol alone. The quantity of
paracetamol being the same in each dose.
B W McGuinness 43

Materials and Methods The age, sex and diagnosis details of the
Patients of either sex between the ages of 18 patients are shown in Tables 1 and 2.
and 70 years, suffering from painful musculo-
skeletal disorders, were entered into the study
in random order. The diagnostic catalogue Table 1
included ankle and knee sprains, non-articular
low-back pain, painful shoulder lesions Age-sex characteristics
(rotator cuff syndrome) and a variety of
occupational and sport injuries of the soft 'Norgesic' Paracetamol
tissues. Excluded were patients in whom the
administration .of an anticholinergic drug No. of patients 14 14
might have been undersirable, those who were No. of males 5 9
pregnant, those who have a hypersensitive No. of females 9 5
Mean age 35·7 41·9
history to either component drug and those Age range 19-57 28-70
who were having physiotherapy. A formal
verbal consent was obtained after careful
explanation of the purpose and method to be
used. Table 2
In each case, subjective measures of pain,
stiffness and functional impairment were made Diagnoses
on a 4-point scale of severity, ranging from
normality to severe distress. This evaluation
'Norgesic' Paracetamol
was carried out on the first attendance and
after 5 and 10 days of treatment using a Tennis elbow a.A.
specially designed sheet for the purpose of Back strain a.A. knees
recording. Acute back strain Bicipital myalgia
Lumbago Rotator cuff tear
The allocation of patients to each of the two Lumbago Rhomboid strain
treatment groups was randomized so that Lumbago 'Pulled' muscle
special preference for either was eliminated. In Rotator cuff tear Injured back muscle
all cases, the dose was two tablets three times Acute back strain Low back pain
Rhomboid strain Acute lumbo-sacral strain
daily and the allocation and assessments were Shoulder strain Lumbo-sacral strain
all double-blind so that a further source of Torticollis Lumbar strain
possible bias was excluded. Unsolicited Acute back strain Lumbar strain
comments and possible side-effects were Acute shoulder and Acute back strain
recorded, and these, as well as all other data, elbow strain
were submitted for statistical analysis at the
end of the study.
The two groups are similar, both containing
eight patients with back pain, but there were
Results more males in the paracetamol group as
Of the thirty-two patients who entered the contrasted with more females in the
study, twenty-eight completed the course of combination product group. These differences
treatment. Of the four who did not, one did not are due to random chance.
return, having moved home, and was therefore From Table 3 it may be seen that for all
lost to follow-up, two requested alternative three test parameters: pain, stiffness and
medication to paracetamol which they found functional impairment, there. was significant
too mild an analgesic, and one patient improvement between starting and Day 5 and
receiving the combination product was between starting and Day 10 in the group
troubled by nausea and therefore stopped his treated with 'Norgesic'. By contrast, a
treatment. However, side-effects in general significant relief of pain did not show in the
were mild, transitory and non-specific, and in paracetamol group until Day 10, nor was there
only this one case was treatment discontinued significant improvement in stiffness and
because of them. functional impairment at any. stage of the test
44 The Journal ofInternational Medical Research

Table 3
Mean 'scores'

'Norgesic' Paracetamol

Pain

Day 0 Day 5 Day 10 Day 0 Day 5 DayJO

2·3 0·9 0·2 2·1 1·4 1·3

(p < 0·001) (p < 0·001) (N/S) (p < 0·02)

Stiffness

Day 0 Day 5 Day 10 Day 0 Day 5 Day 10

2·1 0·7 0·3 2·1 1·7 1·5

(p < 0·001) (p < 0·001) (N/S) (N/S)

Function
Day 0 Day 5 Day 10 Day 0 Day 5 Day 10

2·1 1·0 0·1 2·1 1·6 1·1

(p < 0·001) (p < 0·001) (N/S) (N/S)

N/S = Not significant

period in this group. At the fifth and tenth day,
the combination preparation scored higher
than paracetamol alone in all three respects
(p < 0·05).
Discussion
Muscle spasm in response to injury is the
result of protective reflexes evolved to limit
movement and facilitate tissue repair. This is
well seen in long bone fractures, where spasm
may accentuate deformity and, unless
overcome, makes accurate well-aligned healing
impossible. All skeletal muscle responds in this
way and although inherently protective,
muscle spasm can be disadvantageous by
slowing the recovery of function.
General principles of injury management in
the acute phase are to limit mobility, give
support, and relieve pain. Within a short time,
re-mobilization is essential and unless this is
achieved reasonably quickly muscular
weakness through atrophy is likely. In the
treatment of strains, painful muscular
conditions and most soft tissue injuries, early
physiotherapy is desirable. However,
limitation of the number of physiotherapists
for the forseeable future makes this an ideal
unlikely to be attained. For this
reason, alternative approaches are necessary.
The logic of combining analgesic and
antispasmodic drugs has appealed to those
responsible for treating soft tissue and
especially muscle injury for many years. The
analgesic is given to limit distress due to pain
and the antispasmodic to facilitate early
mobility by overcoming excessive muscle
spasm. 'Norgesic' is a combination of
paracetamol 450 mg and orphenadrine 35 mg
which has been available for many years but
which has not been tested in general practice
on a double-blind basis against each of its
components alone. Proof of the muscle
B W McGuinness
relaxant properties of orphenadrine in skeletal
muscle was shown as long ago as 1959 by
Finch and by Benedig. It is also effective in
relieving rigidity in Parkinson's Syndrome
(Doshay & Constable 1957, Rosenfeld,
Nayampalli & Goldner 1959). These authors
commented that the more rapid resolution of
symptoms in patients receiving combinations
of orphenadrine and analgesic was attributable
to the relief of skeletal muscle spasm.
In an open study conducted in general
practice by Cohen in 1967, the only criterion
used to assess improvement was relief of pain.
The current investigation, however, took also
into account relief of muscle stiffness and
change in impairment of function. Analysis of
the results indicates that there was a significant
difference between equipotent tablets:
paracetamol alone and a combination of
orphenadrine and paracetamol. Thus,
confirmation of the effectiveness of the
product in treating relatively minor soft tissue
injuries, including strains, back pain, and torn
integumental tissues commonly encountered in
general practice was shown. In situations
where physiotherapy is not freely available to
general practitioners this product is, therefore,
particularly useful. It may, of course, be
valuable also where physiotherapy can be
provided.
Acknowledgements
The assistance of Mr N W Marshall in
arranging statistical analysis of results is
45
gratefully acknowledged. Riker Laboratories
provided identical matching tablets of
'Norgesic' and paracetamol.
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