A review of treatment interventions in whiplash-associated disorders

Abstract

In recent years, there has been much debate on the treatment of whiplash-associated disorders (WAD). It is not clear if the treatments commonly employed are effective, and concerns have been raised on the available scientific evidence of many of these treatments. The aim of this study was to review the literature systematically to analyze the evidence basis of many commonly used treatments for patients suffering from WAD, both in the acute and the chronic state. A computer-assisted search of the databases Medline (from 1962 to May 2003), CINAHL (1960-2003), Embase (1976-2003), and Psychinfo (1960-2003) was conducted as well as a check of the reference lists of relevant studies. All randomized controlled trials (RCTs) were retrieved and systematically analyzed with three common instruments of measurement of methodological quality. A qualitative analysis ("best-evidence synthesis") was performed. The methodological quality of 26 RCTs was analyzed. The median quality scores for all three instruments were poor. Based on the degrees of evidence and the practical obstacles, the following treatments can be recommended: Early physical activity in acute WAD, radiofrequency neurotomy, combination of cognitive behavioral therapy with physical therapy interventions, and coordination exercise therapy in chronic WAD. High-quality RCTs are not common in the field of WAD. More research is needed, particularly on the treatment of chronic WAD.

Full text

Introduction
From 1989 to 1994, whiplash-associated disorders (WAD)
went from the third most common road traffic injury in
Sweden to the most common [17]. Incidence in Sweden
has been found to be one per 1,000 inhabitants [4]. More-
over, rear-end collisions resulting in reported WAD seem
to have a substantial impact on health complaints in Swe-
den, even long after collision [3, 8].
There has been much confusion with the term whiplash.
It has been used to describe the injury mechanism, the in-
jury itself, and symptoms following injury. The Quebec
Task Force (QTF) redefined WAD in 1995. According to
the QTF, whiplash is an acceleration-deceleration mecha-
nism of energy transfer to the neck, which may result from
rear-end or side-impact motor vehicle collisions but can
also occur during diving or other mishaps. The impact
may result in bony or soft-tissue injuries (whiplash in-
jury), which in turn may lead to a variety of clinical man-
ifestations (WAD) [47].
Neck pain, headache, and reduction of cervical mobil-
ity are cardinal symptoms in the acute phase. WAD can be
classified by five grades of initial severity on the modified
Quebec classification [15, 47] (Table 1). Exposure with-
out initial symptoms is referred to as grade 0. Hartling et
al. have shown that the higher the grade initially, the
greater the risk for WAD at 6, 12, 18, and 24 months [15].
Abstract In recent years, there has
been much debate on the treatment
of whiplash-associated disorders
(WAD). It is not clear if the treat-
ments commonly employed are ef-
fective, and concerns have been
raised on the available scientific evi-
dence of many of these treatments.
The aim of this study was to review
the literature systematically to ana-
lyze the evidence basis of many
commonly used treatments for pa-
tients suffering from WAD, both in
the acute and the chronic state. A com-
puter-
assisted search of the databases
Medline (from 1962 to May 2003),
CINAHL (1960–2003), Embase
(1976–2003), and Psychinfo (1960–
2003) was conducted as well as a
check of the reference lists of rele-
vant studies. All randomized con-
trolled trials (RCTs) were retrieved
and systematically analyzed with
three common instruments of mea-
surement of methodological quality.
A qualitative analysis (“best-evi-
dence synthesis”) was performed.
The methodological quality of
26 RCTs was analyzed. The median
quality scores for all three instru-
ments were poor. Based on the de-
grees of evidence and the practical
obstacles, the following treatments
can be recommended: Early physical
activity in acute WAD, radiofre-
quency neurotomy, combination of
cognitive behavioral therapy with
physical therapy interventions, and
coordination exercise therapy in
chronic WAD. High-quality RCTs
are not common in the field of WAD.
More research is needed, particularly
on the treatment of chronic WAD.
Keywords Whiplash · Treatment ·
Review
REVIEW
Eur Spine J (2004) 13 : 387–397
DOI 10.1007/s00586-004-0709-1
Aris Seferiadis
Mark Rosenfeld
Ronny Gunnarsson
A review of treatment interventions
in whiplash-associated disorders
Received: 24 December 2003
Accepted: 4 March 2004
Published online: 5 May 2004
© Springer-Verlag 2004
A. Seferiadis (✉)
Psychiatric Physiotherapy Unit,
Björkängen, Southern Elfsborg Hospital,
Klinikvägen 40, 501 82 Borås, Sweden
e-mail: aris.seferiadis@vgregion.se
M. Rosenfeld
Institute of Occupational Therapy
and Physiotherapy,
Faculty of Health and Caring Sciences,
The Sahlgrenska Academy
at Göteborg University, Göteborg, Sweden
A. Seferiadis
Department of Primary Health Care,
The Sahlgrenska Academy
at Göteborg University, Göteborg, Sweden
R. Gunnarsson
Research and Development Unit
in Primary Health Care,
Southern Elfsborg County, Sweden

Symptoms cover a wide range, particularly in late whiplash
syndrome defined as persisting symptoms or residual dis-
ability 6 months after the injury [47].
Although the whiplash mechanism potentially injures
several structures, objective evidence of such injuries has
been scarce. Recent studies have shown that 50% of pa-
tients with chronic WAD suffer from zygapophysial joint
pain [27] and that the brachial plexus is often involved in
the presence of arm symptoms [19, 48]. Instability of the
alar ligaments has also been seen in patients with chronic
WAD [55].
The lack of homogeneity among patients suffering
from WAD has led to many treatment options. The Que-
bec Task Force [47] highlighted the lack of randomized
controlled trials (RCTs) in the field.
The RCT is considered the most reliable method to as-
sess the efficacy of treatments. Systematic review of RCTs
offers a way to cope with the large number of articles pub-
lished. An example of such a review in the field of WAD
is the investigation of Peeters et al. [34] on the efficacy of
conservative treatment.
Assessment of the quality of RCTs included in a re-
view can give an estimate of the likelihood that results are
valid [49]. Trial quality is difficult to define. It has been
defined as “the confidence that the trial design, conduct
and analysis has minimized or avoided biases in its treat-
ment comparisons.” This definition covers internal valid-
ity, although the concept of quality should also encompass
criteria of external validity, statistical analysis and ethics
[11, 29, 46].
Several scales and checklists have been created to as-
sess RCT quality, albeit chiefly in a nonscientific manner
[33]. The three most widely accepted criteria lists are: an
instrument to measure the likelihood of bias in pain re-
search reports (IMLB) by Jadad et al. [20], the Delphi List
(DL) by Verhagen et al. [54], and the criteria list for
methodological quality assessment also known as Maas-
tricht-Amsterdam List (MAL) by the back review group
of the Cochrane Collaboration [51].
The aim of this study was to review the literature sys-
tematically using these three instruments to perform a
qualitative analysis of the evidence basis of many com-
monly used treatment options for patients suffering from
acute and chronic WAD.
388
Table 1 The modified Quebec classification of whiplash-asso-
ciated disorders
Grade Clinical presentation
0No complaint about the neck
No physical sign(s)
INeck complaint of pain, stiffness or tenderness only
No physical sign(s)
IIa Neck complaint and musculoskeletal sign(s):
These include point tenderness but normal cervical
range of motion
IIb Neck complaint and musculoskeletal sign(s):
These include point tenderness and abnormal
cervical range of motion
III Neck complaint and neurological sign(s):
These include decreased or absent deep tendon
reflexes, weakness and sensory deficits
IV Neck complaint and fracture or dislocation
Symptoms and disorders that can appear in all grades include
deafness, dizziness, tinnitus, headache, memory loss, dysphagia,
and temporomandibular joint pain
Table 2 Domains included in
the three methodological qual-
ity lists. IMLB likelihood of
bias in pain research reports,
DL Delphi List, MAL Maas-
tricht-Amsterdam List
Domains of possible interest Methodological quality score
IMLB DL MAL
1 Study question
2 Population x x
3 Sample size and power calculations a priori
4 Treatment allocation x x x
5 Study design x
6 Ethics
7 Intervention x
8 Outcome measures x x
9 Follow-up/withdrawals x x
10 Blinding x x x
11 Cointerventions x
12 Side-effects x
13 Compliance x
14 Prognostic comparability
15 Analysis x x
16 Conclusion
17 Presentation

Materials and methods
Literature search
The Medline database was searched for articles written 1962 through
May 2003. The WebSPIRS 5.02 program was used to search the
databases CINAHL (1960–2003), Embase (1976–2003), and Psych
-
info (1960–2003). The reference lists of relevant RCTs and con-
trolled clinical trials (CCTs) were checked to identify additional
published research not found in the computerized, bibliographic
databases. The search was conducted using the MESH term whiplash
and the word whiplash in the abstract or title of the study. Titles
and abstracts of identified, published articles were initially re-
viewed by one of the authors (AS). All intervention studies dealing
with acute or chronic WAD were retrieved.
Selection for quality assessment
Studies were assessed if they met the following criteria: (1) The in-
tended design was a prospective RCT; (2) the study population in-
cluded patients with WAD; (3) the publication was in English.
Quality assessment of studies
The methodological quality of the studies was independently as-
sessed by two reviewers (AS and MR). The assessment was not
performed under masked conditions. All studies received a score
for each of the criteria lists IMLB, DL, and MAL. In case of any
disagreement between the two reviewers (AS and MR), a consen-
sus method was used. If disagreement persisted, a third reviewer
(RG) would make the final decision. A pilot assessment of one
RCT (not included in the study) was conducted to familiarize the
reviewers with the quality assessment lists. Prior to scoring, the re-
viewers discussed the available guidelines to ensure a common in-
terpretation of the lists. After the individual assessment, the re-
viewers then agreed on a final score for each article.
The IMLB consists of three items directly related to the reduc-
tion of bias, treatment allocation, follow-up/withdrawals, and
blinding (Tables 2 and 3). The items were presented as questions to
elicit yes or no answers. One point was awarded for each affirma-
tive answer. Additionally, one point was added or deducted if the
methods used were appropriate or not. This gives a numerical sum
score of 0–5.
The DL consists of nine items concerning study population,
treatment allocation, outcome measures, blinding, and analysis
(Tables 2 and 3). All items have a yes/no/don’t know option. If
bias was unlikely, the item was rated with one point. If information
389
Table 3 Items included in the
three methodological quality
lists and the frequency of an-
swers. IMLB likelihood of bias
in pain research reports,
DL Delphi List, MAL Maas-
tricht-Amsterdam List
a
Domains described in Table 2
b
Number of Yes (1)/No (0)
answers
c
Number of Appropriate
(1)/Nothing (0)/Inappropriate
(–1) answers
d
Number of Yes (1)/No (0)/
Don’t know (0) answers
Domain
a
Items Methodological quality score
IMLB DL
d
MAL
d
2Were the eligibility criteria specified? 20/6/0 8/17/1
4Was the study described as randomized
b
25/1
4Was a method of randomization performed? 25/1/0 10/2/1
4
4Was the method of randomization described
and appropriate?
c
8/17/1
4Was the treatment allocation concealed? 4/5/17 4/5/17
5Were outcome measures relevant? 25/1/0
5Was the timing of the outcome assessment in both
groups comparable?
24/1/1
7Were the experimental and control interventions
explicitly described?
25/1/0
8Were the groups similar at baseline regarding the most
important prognostic indicators?
17/3/6 5/4/17
8Were point estimates and measures of variability
presented for the primary outcome measures?
20/6/0 20/6/0
8Was the sample size of each group described? 20/5/1
9Was there a description of withdrawals and/ dropouts?
b
16/10
9Was the withdrawal / drop-out rate described and
acceptable?
16/9/1
9Was a short-term follow-up measurement performed? 22/4/0
9Was a long-term follow-up measurement performed? 15/11/
0
10 Was the care provider blinded to the intervention? 7/18/1 7/18/1
10 Was the patient blinded to the intervention? 8/18/0 8/18/0
10 Was the outcome assessor blinded to the intervention? 16/2/8 16/2/8
10 Was the study described as double blind?
b
8/18
10 Was the method of blinding described and appropriate?
c
6/19/1
11 Were co-interventions avoided or comparable? 15/8/3
12 Were adverse effects described? 8/18/0
13 Was the compliance acceptable in all groups? 10/0/1
6
15 Did the analysis include an intention-to-treat analysis? 13/7/6 13/8/5

was unavailable or insufficient or if bias was likely, the item was
rated with zero points for an overall numerical sum score of 0–9.
The MAL consists of 19 items related to population, treatment
allocation, study design, intervention, outcome measures, follow-
up/withdrawals, blinding, cointerventions, side-effects, compli-
ance, and analysis (Tables 2 and 3). It includes items similar to the
IMLB and DL and unique items. The response options are similar
to DL, and the overall numerical score is 0–19.
Detailed instructions on using these assessment scales have
been published previously [20, 34, 54]. Differences exist in the as-
sessment guidelines between the DL and MAL in three items.
Thus, in these items, the same item on the two lists can have dif-
ferent scores:
– “Were the eligibility criteria specified?” DL requires inclusion
and exclusion criteria while MAL only requires that the radia-
tion pattern of back pain and duration of the disorder be de-
scribed to score a “Yes”
– “Was a method of randomization performed?” DL requires that
words such as random and randomization are used. MAL also
requires that the randomization procedure is appropriate. This
means that articles receiving a “Yes” on DL could score “Don’t
know” on MAL when a description of the randomization proce-
dure was lacking.
– “Were the groups similar at baseline regarding the most impor-
tant prognostic indicators?” DL requires the reviewer to deter-
mine this item, while MAL specifically requests adequate de-
scriptions of age, duration of complaints, percentage of patients
with radiating pain, and main outcome measures to evaluate
similarity. Also this item could elicit differing scores, though it
exists on both lists.
Best-evidence synthesis
A qualitative analysis (“best-evidence synthesis”) was conducted
using a rating system utilized by the Cochrane Collaboration Back
Group [52]. It consists of the following degrees of evidence:
1. Strong evidence: generally consistent findings in multiple
high quality RCTs
2. Moderate evidence: generally consistent findings in multiple
low quality RCTs and/or one high quality RCT
3a. Limited evidence: only one low quality RCT
3b. Conflicting evidence: inconsistent findings in multiple RCTs
4. No evidence: no RCTs and no double-blind trials.
A study was arbitrarily judged to be of high quality if the sum
score in all three scales (IMLB, DL, and MAL) was at least 50%
of the total score.
Statistical methods
The outcome of quality assessment and best-evidence synthesis is
presented. Kappa is calculated to estimate interobserver reliability
of quality assessment.
390
Table 4 Scores received on
the instrument for measurement
of likelihood of bias (IMLB)
stratified after type of study
a
In each column studies focus-
ing on acute/chronic whiplash-
associated disorders (WAD)
b
Instrument for measuring the
likelihood of bias
c
Combination of physical ther-
apy and psychological support
IMLB
b
Type of study
a
scoring
Chiropractic Drug Orthopedic Physical Multimodal
intervention therapy surgery therapy intervention
c
0–25% 0/2 0/1 0/0 3/2 0/1
26–50% 0/0 0/1 0/0 5/1 0/1
51–75% 0/0 0/1 0/0 2/0 0/0
76–100% 0/0 1/1 0/3 1/0 0/0
Total 0/2 1/4 0/3 11/3 0/2
Table 5 Scores received on
the Delphi List (DL) stratified
after type of study
a
In each column studies focus-
ing on acute/chronic whiplash-
associated disorders (WAD)
b
Delphi List
c
Combination of physical ther-
apy and psychological support
DL
b
scoring Type of study
a
Chiropractic Drug Orthopedic Physical Multimodal
intervention therapy surgery therapy intervention
c
0–25% 0/0 0/0 0/0 1/0 0/1
26–50% 0/1 0/1 0/0 3/2 0/0
51–75% 0/1 0/2 0/1 5/1 0/1
76–100% 0/0 1/1 0/2 2/0 0/0
Total 0/2 1/4 0/3 11/3 0/2
Table 6 Scores received on
the Maastricht-Amsterdam List
(MAL) stratified after type of
study
a
In each column studies focus-
ing on acute/chronic whiplash-
associated disorders (WAD)
b
Combination of physical ther-
apy and psychological support
MAL
b
scoring Type of study
a
Chiropractic Drug Orthopedic Physical Multimodal
intervention therapy surgery therapy intervention
b
0–25% 0/0 0/0 0/0 0/0 0/0
26–50% 0/1 0/1 0/0 6/3 0/2
51–75% 0/1 0/3 0/1 4/0 0/0
76–100% 0/0 1/0 0/2 1/0 0/0
Total 0/2 1/4 0/3 11/3 0/2

Results
In the literature search, 1,726 studies were found. 56 were
intervention studies and 33 were CCTs. Seven CCTs did
not use randomization, while 26 studies were RCTs that
subsequently were quality assessed. The interobserver re-
liability in quality assessment between the two indepen-
dent reviewers was very good (κ=1) for IMLB and good
for DL (κ=0.76) and MAL (κ=0.74). There was no need
for the third reviewer to arbitrate. Median scores (in-
terquartile range) were for IMLB 2 (1–3), for DL 5 (4–6),
and for MAL 9.5 (8–12). Studies evaluating orthopedic
surgery were often scored higher than studies investigat-
ing effects of chiropractic, drug therapy, physical therapy,
or multimodal interventions (Tables 4, 5, and 6). The three
most prevalent shortcomings were lack of information on
patient and/or care provider blinding, lack of information
on concealment of treatment allocation, and lack of de-
scription of adverse effects (Table 3).
Evaluated therapeutic interventions and their degree of
evidence according to the Cochrane Collaboration Back
Group system [52] are presented in Table 7. An overview
of all references is presented in Table 8.
Discussion
The main finding of this review was the large number of
physical therapy articles on the subject. Apparently, this
profession is often called upon to treat patients with
WAD. The interventions for acute WAD that have the
strongest scientific support are: early physical activity [5,
6, 14, 31, 32, 35, 39, 40, 45] (degree 2), electromagnetic-
field therapy [13, 50] (degree 2), and high-dose methyl-
391
Table 7 Treatment interventions and the degrees of evidence in their support. WAD whiplash-associated disorders
Degree of
evidence
a
Claim References
b
1Radiofrequency neurotomy reduces pain and psychological distress
in patients with chronic WAD and zygapophysial joint pain
Lord 1996 [27], Wallis 1997 [55]
2Melatonin therapy advances melatonin onset and sleep-wake
rhythm in patients with chronic WAD and delayed melatonin onset
van Wieringen 2001 [52]
2High-dose methylprednisolone therapy administered within 8 h
of injury reduces sick leave
Pettersson 1998 [36]
2Intra-articular corticosteroid therapy lacks effect in patients
with chronic WAD and zygapophysial joint pain
Barnsley 1994 [1]
2Electromagnetic Field therapy reduces pain and increases cervical
range of motion in patients with acute WAD
Foley-Nolan 1992 [13], Thuile 2002 [50]
c
2Early physical activity reduces pain, increases cervical range of
motion and reduces sick leave in patients with acute WAD
Bonk 2000 [5], Borchgrevink 1998 [6],
Gennis 1996 [14}
d
, McKinney 1989 [30],
Mealy 1986 [32], Pennie 1990 [35], Söderlund
2000 [45], Rosenfeld 2000 [39]
e
, Rosenfeld
2003 [40]
e
2Cognitive behavioural therapy combined with Physical therapy
reduce pain and sick leave in patients with chronic WAD
Johansson 1998 [21}, Provinciali 1996 [37],
Söderlund 2001 [44]
2Coordination exercise therapy reduces pain in patients with chronic
WAD
Fitz-Ritson 1995 [12]
f
, Humphreys 2002 [18]
3a Ultra-reiz current therapy combined with physical therapy reduces
pain and cervical range of motion in patients with acute WAD
Hendriks 1996 [16]
3a Spinal manipulation therapy reduces pain and increases cervical
range of motion in patients with neck pain with radiation to the
trapezius muscle
f
Cassidy 1992 [10]
3a Fluoxetine therapy provides similar pain reduction to that
of Amitriptyline therapy in patients with chronic WAD
Schreiber 2001 [43]
3b Subcutaneous sterile water injection therapy reduces pain and
increases cervical range of motion in patients with chronic WAD
Byrn 1993 [9], Sand 1992[41]
h
a
Rating system derived from the system utilized by the Cochrane
Collaboration Back Group [52] (See “Methods”-section)
b
Studies presented by first author in alphabetical order where ap-
propriate. Bold references denote studies defined as high quality
c
It was unclear if patients in this randomized controlled trial
(RCT) suffered from acute or chronic whiplash-associated disor-
ders (WAD)
d
The results of this RCT conflict with the claim
e
The two articles by Rosenfeld are based on the same data and
should therefore be regarded as one RCT
f
The groups in this RCT were different at baseline
g
The claim refers to effects immediate following treatment. Long-
term effects have not been studied
h
This RCT conflicts with the claim, and the study population is
heterogeneous

392
Table 8 Overview of all evaluated randomized controlled trials (RCTs). T Timing when intervention is initiated, IMLB instrument
for measuring the likelihood of bias, DL Delphi List, MAL Maastricht-Amsterdam List.
Articles sorted after first author TScales
IMLB DL MAL
Barnsley et al. [1] C5
816
Double-blind comparison of intraarticular corticosteroid (Betamethasone) injection therapy with local
anesthetic (bupivacaine) injection therapy. Neither treatment provided lasting pain-relief. The median
time for return to 50% preinjection level of pain was 3 days in the betamethasone group and 3.5 days in
the bupivacaine group
Bonk et al. [5] A2
3 8
Comparison of active therapy (3 weeks of active and passive mobilization, postural exercises and
advice) with collar therapy (3 weeks wearing collar). Patients receiving active therapy were signif-
icantly improved in pain intensity and cervical range of motion and comparable to a control group of
unexposed individuals at 6 weeks. At 12 weeks, the collar-therapy group did not differ from the control
group of unexposed individuals either. Outcome assessors were not blinded
Borchgrevink et al. [6] A2
611
Single-blind comparison. All patients received instructions for self-training of the neck beginning on the
first day of treatment and a 5-day prescription of NSAIDs before being randomized to “act-as-usual”
group (advice to act as usual, no sick-leave, no collar) or immobilized group (14 days sick-leave, soft
neck collar). Patients in the “act-as-usual” group had greater improvements in subjective symptoms,
including pain localization, pain during daily activities, neck stiffness, memory and concentration,
and pain and headache intensity
Byrn et al. [9] C1
511
Double-blind comparison of subcutaneous sterile water injection therapy with saline injection therapy.
Patients receiving active treatment improved in minimum and maximum pain intensity, neck mobility,
and self-assessment of improvement. Therapist blinding failed because sterile water injection therapy
was painful to the patient. The eligibility criteria for inclusion were not specified
Cassidy et al. [10] C1
513
Single-blind comparison of manipulation with mobilization of the neck. Patients receiving manipula-
tion had greater improvements in pain intensity and cervical range of motion. Evaluation was conducted
immediately posttreatment without long-term follow-up
Fitz-Ritson [12] C1
3 9
Comparison of chiropractic therapy plus either standard exercise program or “phasic” exercise program.
Patients doing “phasic” exercises improved in measures of Neck Disability Index. The groups were
dissimilar in age, gender distribution, and previous injuries. Blinding of the outcome assessor inadequate
Foley-Nolan et al. [13] A4
715
Placebo-controlled double-blind trial of high-frequency pulsed electromagnetic therapy. Patients
receiving active treatment improved in measures of pain intensity at 2 and 4 weeks but not at 12. Cervical
range of motion was initially worse in the active treatment group but became significantly better than
that of the placebo treatment group at 12 weeks. Patients in the active treatment group used significantly
less analgesics at 2, 4, and 12 weeks
Gennis et al. [14] A1
3 6
Trial of the effect of soft cervical collars. Patients were assigned to either soft cervical collar or no
collar groups. Both groups were advised to rest. The groups showed no difference in pain scores at
6 months. The randomization procedure was flawed, and blinding of the outcome assessor unknown
Hendriks et al. [16] A1
4 8
Comparison of ice treatment, neck exercises, and advice on neck care, posture and use of collar with/
without ultrareiz current therapy. Patients receiving ultrareiz current therapy significantly improved
in pain intensity and cervical range of motion at 6 weeks. Blinding of outcome assessor unknown
Humphreys et al. [18] C1
4 8
Trial of the effect of coordination exercises. Four groups: chronic neck pain or asymptomatic individuals
assigned to coordination exercises or nonexercise group. Individuals with chronic neck pain assigned to
coordination exercise group experienced reduction in pain intensity. Both coordination exercise groups
exhibited an increase in head-repositioning accuracy. Blinding of outcome assessor unknown
Johansson et al. [21] C2
2 8
Trial of the effect of a 4-week cognitive behavioral pain management program. Patients were randomized
to treatment group or waiting list control group. Patients participating in the program had decreased
catastrophizing and pain behaviors and greater activity level in the spare time post-treatment. At the
1-month follow-up, they still had greater activity level in the spare time and were more often in occu-
pational training. Not reported whether the outcome assessors were blinded and whether the groups
were similar at baseline

393
Table 8 (continued)
Articles sorted after first author TScales
IMLB DL MA
L
Lord et al. [28] C5
817
Placebo-controlled double-blind trial of percutaneous radiofrequency neurotomy. Patients receiving
active treatment improved in measures of McGill Neck Pain Questionnaire and pain intensity
McKinney et al. [30] A3
510
Single-blind comparison of outpatient physiotherapy (treatment could include heat, cold, short-wave
diathermy, hydrotherapy, traction, McKenzie assessment and treatment, Maitland mobilization,
postural correction and home exercises) with standard therapy (rest and analgesia, general advice on
mobilization after 10–14 days), and home mobilization (instructions on postural correction, use of
analgesia and collar, use of heat sources and muscle relaxation, mobilizing exercises). Both patients
receiving outpatient physiotherapy and patients receiving home mobilization improved in cervical
range of motion and pain intensity more than patients with standard therapy. There was no difference
in effectiveness between outpatient physiotherapy and home mobilization
Mealy et al. [32] A2
5 8
Single-blind comparison of standard treatment (rest, initial immobilization with soft cervical collar for
2 weeks, gradual mobilization) with early active mobilization (ice in the first 24 h, Maitland mobiliza-
tion, daily neck exercises every hour). Patients in the early active mobilization group had greater
improvements in pain intensity and cervical range of motion at 8 weeks
Pennie et al. [35] A1
1 6
Comparison of standard treatment (2 weeks of rest in soft collar, then exercise therapy) with active
treatment (traction, advice on neck care and sleeping posture, neck and shoulder exercises). No differ-
ences were found between the two treatments at 6–8 weeks or 5 months in pain intensity, neck mobility,
or time off work. The randomization procedure was flawed and blinding of the outcome assessor
unknown
Pettersson et al. [36] A4
816
Placebo-controlled double-blind trial of high-dose methylprednisolone therapy administered within 8 h
of injury. Patients receiving active treatment exhibited reduction in sick leave at the 6-month follow-up
Provinciali et al. [37] C1
5 8
Single-blind comparison of multimodal treatment (postural training, manual technique, psychological
support) with control treatment (physical agents only, such as electrical or sonic modalities). Patients
receiving multimodal treatment had greater improvement in pain levels, return to work delay, and self-
rating scores of treatment efficacy. Neck mobility increased equally in both groups
Rosenfeld et al. [39] A2
5 8
Single-blind comparison of standard intervention (initial rest, recommended use of soft collar, gradual
mobilization) with active intervention (frequent active cervical rotation, McKenzie assessment and
treatment) either within 96 h or after 14 days. Patients receiving active intervention had a greater
reduction in pain intensity at the 6-month follow-up. There were no differences in cervical range of
motion. Active intervention gave better results when administered within 96 h. Standard intervention
gave better results when administered after 14 days
Rosenfeld et al. [40] A3
712
Single-blind comparison of standard intervention (initial rest, recommended use of soft collar, gradual
mobilization) with active intervention (frequent active cervical rotation, McKenzie assessment, and
treatment) either within 96 h or after 14 days. Pain intensity, cervical range of motion, and sick leave
were significantly lower for patients receiving active intervention at the 6-month and 3-year follow-up.
Cervical range of motion at the 3-year follow-up was similar to that of a control group of unexposed
individuals if active intervention was received within 96 h
Sand et al. [41] C2
3 8
Double-blind comparison of subcutaneous sterile water injection therapy with saline injection therapy
in patients with cervicogenic headache. No benefit was observed for either treatment on either pain or
neck mobility. Not all patients in the sample suffered from whiplash-associated disorders
Schreiber et al. [43] C3
511
Single-blind comparison of fluoxetine therapy with amitriptyline therapy. Both groups decreased in
pain intensity. The between-group differences were not significant. Not all patients in the sample suffered
from whiplash-associated disorders. No long-term follow-up
Söderlund et al. [45] A2
511
Single-blind comparison of coordination exercise therapy. Patients were randomized to regular treatment
(advice on posture and being active, neck and shoulder exercises) or additional treatment group (as pre-
vious plus a coordination exercise). Patients in the additional treatment group had not improved more
than patients with regular treatment at 6 months

prednisolone therapy [36] (degree 2). Interventions for
chronic WAD with the strongest scientific support are: ra-
diofrequency neurotomy [28, 56] (degree 1), combined
cognitive behavioral therapy with physical therapy inter-
ventions [21, 37, 44] (degree 2), melatonin therapy [53]
(degree 2), and coordination exercise therapy [12, 18] (de-
gree 2).
Methodological aspects
The inherent risk of bias must be considered in this re-
view. The selection process was limited to articles pub-
lished in the English language. Therefore, it is possible
that relevant articles published in other languages have been
missed. Trials with positive outcomes are more likely to
be published; however, it was noted that articles both in
favor and in disfavor of interventions were identified.
It is the purpose of systematic reviews to pool, if pos-
sible, the results of trials. This can provide valuable infor-
mation on size of treatment effect and clinical relevance.
Nevertheless, intervention trials on WAD display hetero-
geneity of patient populations. This is, in part, due to dif-
ferences in the definition of WAD, making pooling of re-
sults, in practice, impossible.
Scientific shortcomings with some types of interventions
The lists commonly used for measuring methodological
quality of RCTs have been developed for drug therapy
rather than health sciences. This could lead to bias towards
interventions of health sciences. In this review, physical
therapy RCTs achieved consistently lower methodologi-
cal scores compared to drug therapy and orthopedic sur-
gery RCTs (Tables 4, 5, and 6). Interventions used by sev-
eral health professions often cannot be administered in a
double-blind fashion. Therefore, they can never achieve
full score.
Acute and chronic WAD
Patients suffering from acute WAD differ from those suf-
fering from chronic WAD. It is currently not possible to
identify the injured structures in the acute stage. The avail-
able
data [6, 23, 25, 45] lead to the suggestion that the
combination of the injury with psychological factors such
as coping style [7] and explanatory style [24] may lead to
chronic WAD. With this in mind and the evidence avail-
able, this review recommends that patients suffering from
acute WAD be prescribed advice to “act as usual” and
early, controlled, physical activity to tolerance level.
394
Table 8 (continued)
Articles sorted after first author TScales
IMLB DL MA
L
Söderlund et al. [44] C2
5 9
Single-blind comparison of individualized physiotherapy management (treatment could include
stabilization exercises, coordination exercises, muscle stretching, body posture training, strengthening
exercises, relaxation training, TENS, acupuncture, heat) with individualized physiotherapy manage-
ment integrating cognitive behavioral components (learning, application and generalization of basic
skills in everyday activities). Basic skills could include muscle stabilization techniques, relaxation
training, reeducation of humeroscapular rhythm, and exercises aimed to increase neck range of motion,
coordination, and endurance of neck muscles. Patients whose physiotherapy included cognitive
behavioral components reported less pain and better performance of daily activities at 3 months
Thuile et al. [50] C? 1
4 7
Comparison of low-energy, low-frequency magnetic-field treatment. Patients received standard
treatment (diclofenac and tizanidine therapy) with or without magnetic field treatment. Patients
receiving magnetic-field treatment improved in pain intensity and neck mobility. Blinding of outcome
assessor unknown. Uncertain whether the patients suffered from acute or chronic whiplash-associated
disorder (WAD)
Van Wieringen et al. [53] C5
814
Placebo-controlled double-blind trial of melatonin treatment. Patients with delayed melatonin onset
receiving active treatment exhibited advances in melatonin onset and sleep-wake rhythm. Other sleep
parameters, pain, quality of life, cognitive processing speed, and vigilance were not influenced by
1 month of treatment
Wallis et al. [56] C4
612
Double-blind placebo-controlled trial of percutaneous radiofrequency neurotomy. Patients receiving
active treatment improved in measures of pain intensity and exhibited resolution of their preoperative
allpsychological distress. No report on whether the groups were similar at baseline
A = Acute (whiplash-associated disorder persisting <3 months)
C = Chronic (whiplash-associated disorders persisting ≥3 months)

Treatment of acute WAD
Early physical activity reduces pain, increases cervical range
of motion, and reduces sick leave in patients with acute
WAD. This is supported by one high-quality study [40]
and several low-quality studies [5, 6, 30, 32, 35, 39, 45].
One high-quality RCT suggests that high-dose methyl-
prednisolone therapy within 8 h of injury should be pre-
scribed [36]. In the authors’ view, however, the practical
difficulties of this treatment (8-h limitation, 23-h infusion,
need for hospitalization, cost) only warrant its use on pa-
tients that run higher risk of developing chronic WAD.
Findings associated with increased risk are neurological
signs, initially reduced cervical range of motion [15], and
brachial plexus tension signs [19].
The use of magnetic fields is not recommended by this
review on the basis that the equipment used in the high-
quality RCT by Foley-Nolan [13] was collar-mounted,
thus conflicting with the advice on early activity, and neg-
ative effects of collars. It is possible that magnetic-field
therapy administered by other equipment is equally effi-
cient, but the authors did not locate any RCTs on the sub-
ject.
Treatment of chronic WAD
Knowledge of the origin of symptoms in the late stage is
increasing. Thus, treatment interventions can be directed
or developed in a purposeful manner. The identification of
cervical zygapophysial joints as the symptom-giving struc-
ture in approximately 50% of patients suffering from chronic
WAD [2, 27] is an example. Interventions were evaluated
on this condition, and intraarticular corticosteroid injec-
tion therapy was discarded [1] in favor of radiofrequency
neurotomy. This review recommends that patients suffer-
ing from chronic WAD be examined for cervical zyg-
apophysial joint pain. In cases of such findings, radiofre-
quency neurotomy could be considered on the basis of
two high-quality RCTs [28, 56]. However, the technique
is difficult, even for experienced personnel [26].
The prescription of combined, cognitive, behavioral ther-
apy
and physical therapy interventions in chronic WAD
could be recommended on the basis of three low-quality
RCTs [21, 37, 44]. These interventions have respectively
strong and moderate evidence of significant reductions in
neck pain and sick leave.
Abnormalities in sleep quality have been reported in
patients suffering from chronic WAD [42]. Melatonin ther-
apy
could be considered to improve melatonin onset and
sleep/wake rhythm in patients exhibiting delayed mela-
tonin onset and chronic WAD. This recommendation is
based on one high-quality RCT [53], although 1 month of
treatment did not influence other sleep parameters, pain,
quality of life, cognitive processing speed, or vigilance.
This review also cautiously recommends including co-
ordination exercises in physical therapy interventions on
the basis of two low-quality RCTs. There is moderate ev-
idence that coordination exercises significantly reduce
neck pain in patients suffering from chronic WAD.
Need for future research
Since the consequences of WAD may be great for the pa-
tient and the economical costs for society large, WAD pre-
vention should be exhaustively researched. Moreover, re-
finement of the acute care of WAD is needed to reduce the
amount of patients developing chronic symptoms. Future
RCTs should focus on evaluating treatment interventions
that lack evidence such as surgical stabilization and dis-
cectomy.
Since positive brachial plexus tension signs indicate
poor prognosis [19, 22, 38, 48], the evaluation of inter-
ventions on adverse peripheral nerve tension is urgent.
This dysfunction may explain the continuing suffering of
patients with chronic WAD that do not suffer from zyg-
apophysial joint pain.
Conclusions
Based on the degrees of evidence and the practical obsta-
cles, the following treatments can be recommended: Early
physical activity in acute WAD, radiofrequency neuro-
tomy, combination of cognitive behavioral therapy with
physical therapy interventions, and coordination exercise
therapy in chronic WAD. High-quality RCTs are not com-
mon in the field of WAD. More research is needed, par-
ticularly on the treatment of chronic WAD.
395
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Whiplash-Associated Disorders in
Vancouver, British Columbia, Canada,
February 1999. J Musculoskel Pain 8:
123–132
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