Unformatted text preview: Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
0161-4754/2001/$35.00 + 0 76/1/117090 © 2001 JMPT REVIEWS OF THE LITERATURE
Efﬁcacy of Spinal Manipulation for Chronic Headache: A Systematic Review
Gert Bronfort, DC, PhD,a Willem J.J. Assendelft, MD, PhD,b Roni Evans, DC,a Mitchell Haas,
DC,c and Lex Bouter, PhDd ABSTRACT
Background: Chronic headache is a prevalent condition with substantial socioeconomic impact. Complementary or alternative therapies are increasingly being used
by patients to treat headache pain, and spinal
manipulative therapy (SMT) is among the
most common of these.
Objective: To assess the efﬁcacy/effectiveness of
SMT for chronic headache through a systematic
review of randomized clinical trials.
Study Selection: Randomized clinical trials on chronic headache
(tension, migraine and cervicogenic) were included in the review if
they compared SMT with other interventions or placebo. The trials
had to have at least 1 patient-rated outcome measure such as pain
severity, frequency, duration, improvement, use of analgesics, disability, or quality of life. Studies were identiﬁed through a comprehensive search of MEDLINE (1966-1998) and EMBASE (19741998). Additionally, all available data from the Cumulative Index
of Nursing and Allied Health Literature, the Chiropractic Research
Archives Collection, and the Manual, Alternative, and Natural
Therapies Information System were used, as well as material gathered through the citation tracking, and hand searching of nonindexed chiropractic, osteopathic, and manual medicine journals.
Data Extraction: Information about outcome measures, interventions and effect sizes was used to evaluate treatment efﬁcacy. Levels of evidence were determined by a classiﬁcation system incorporating study validity and statistical significance of
study results. Two authors independently extracted data and
performed methodological scoring of selected trials. a
Department of Research, Wolfe-Harris Center for Clinical
Studies, Northwestern Health Sciences University, Bloomington,
Department of General Practice, Academic Medisch Centrum,
Center for Outcomes Studies, Western States Chiropractic
College, Portland, Ore.
Institute for Research in Extramural Medicine and Department
of Epidemiology and Biostatistics, Vrije Universiteit, The
This study was funded by the Wolfe-Harris Center for Clinical
Studies, Northwestern Health Sciences University, Bloomington, Minn.
Gert Bronfort, DC, PhD, holds the Greenawalt Research Chair,
funded through an unrestricted grant from Foot Levelers, Inc.
Submit reprint requests to: Gert Bronfort, DC, PhD, Department
of Research, Wolfe-Harris Center for Clinical Studies, Northwestern Health Sciences University, 2501 W. 84th St, Bloomington, MN. 55431 E-Mail: [email protected]
Paper submitted June 15, 2000; in revised form August 2, 2000. doi:10.1067/mmt.2001.117090 Data Synthesis: Nine trials involving 683
patients with chronic headache were included. The methodological quality (validity)
scores ranged from 21 to 87 (100-point
scale). The trials were too heterogeneous in
terms of patient clinical characteristic, control groups, and outcome measures to warrant
statistical pooling. Based on predeﬁned criteria,
there is moderate evidence that SMT has shortterm efﬁcacy similar to amitriptyline in the prophylactic treatment of chronic tension-type headache and
migraine. SMT does not appear to improve outcomes when
added to soft-tissue massage for episodic tension-type headache.
There is moderate evidence that SMT is more efﬁcacious than
massage for cervicogenic headache. Sensitivity analyses showed
that the results and the overall study conclusions remained the
same even when substantial changes in the prespeciﬁed assumptions/rules regarding the evidence determination were applied.
Conclusions: SMT appears to have a better effect than massage for cervicogenic headache. It also appears that SMT has
an effect comparable to commonly used ﬁrst-line prophylactic
prescription medications for tension-type headache and
migraine headache. This conclusion rests upon a few trials of
adequate methodological quality. Before any firm conclusions
can be drawn, further testing should be done in rigorously
designed, executed, and analyzed trials with follow-up periods
of sufficient length. (J Manipulative Physiol Ther 2001;24:
Key Indexing Terms: Headache; Orthopedic Manipulation; Chiropractic Manipulation; Osteopathy; Systematic Review INTRODUCTION
Headaches vary widely in terms of severity, frequency,
and disability—from rare episodes of minor discomfort to
daily, incapacitating headaches. By far the most common
type of headache is tension-type headache, with a 1-year
prevalence ranging from 40 to 80%.1,2 The cost, in terms of
work loss and decreased quality of life, is high among those
who experience tension-type headache, with 10% reporting
lost workdays and almost half reporting decreased effectiveness at work, home, or school.2
Although less common than tension-type headaches,
migraines affect a sizable proportion of individuals and tend
to be more severe and disabling.1,3 Recent population-based
studies which use International Headache Society (IHS)
criteria estimate that 10 to 12% of adults have experienced
a migraine in the previous year,1,3 with 2 to 4 times more
women affected than men. In one study, almost all mi- 457 458 Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al graineurs reported that headache pain affected their ability
to work and perform daily activities, and 43% missed work
because of their headaches.1
The financial cost of headaches is great, with billions of
dollars spent annually for lost productivity and treatment.4
Although persons affected with headaches are commonly
treated by traditional medical practitioners, they are
increasingly turning to non-medical or alternative therapies for relief. A recent study by Eisenberg et al5 reported
that one of the most common alternative practitioners
sought out for the treatment of headaches was the chiropractor—the most common provider of spinal manipulation in the United States. For the purpose of this study,
spinal manipulative therapy (SMT) is defined as the application of high-velocity, low-amplitude manual thrusts to
the spinal joints slightly beyond the passive range of joint
A systematic review of cervical SMT for neck pain and
headache published in 1996 concluded that SMT might be
beneﬁcial for tension-type headaches, but further studies of
higher methodological quality were needed in order to
reach firmer conclusions.7 Further studies have been performed since that time. The purpose of this article is to
assess the clinical efficacy of cervical SMT for chronic
headache based on the results of the existing randomized
clinical trials (RCTs). METHODS effect sizes was used to evaluate treatment efficacy. Two of
us (GB and WJJA) independently extracted and recorded
relevant data from each article. All original data on outcomes were standardized into percentage-point scores
whenever possible. Contrary to meta-analysis, studies for
which effect sizes cannot be computed are retained as primary evidence in a best-evidence synthesis.8-11 Statistical
pooling of effect sizes was considered to be an adjunct to the
systematic review and not the primary goal. Effect Size Computations
The effect size (ES) differences between the SMT and
comparison groups were calculated at the end of the treatment intervention phase and at the main post-treatment follow-up and were adjusted for baseline differences in main
outcome measures. Effect sizes were computed as described
by Glass et al12 and Cohen13 (difference in treatment and
control group means divided by the pooled standard deviation). In the absence of these statistics, effect sizes were calculated from T-scores, F-values, and confidence intervals,
provided sample sizes were given.12,14 Effect sizes for differences in proportions were estimated by using probit
transformation.14 Correction for ES estimate bias associated
with small sample sizes (n < 50) was accomplished by using
the method described by Hedges and Olkin.15 If conﬁdence
intervals could not be directly calculated for effect sizes,
they were estimated by using p-values and sample sizes. Study Selection Assessment of Methodological Quality of RCTs Randomized clinical trials on chronic headache were
included in this review if they compared SMT with a placebo
or other interventions, and if they had at least 10 subjects in
the SMT arm of the trial. The trials also had to have at least one
patient-rated outcome measure such as headache pain severity,
frequency, duration, improvement, analgesic use, disability, or
quality of life. “Chronic headache” included, but was not limited to, tension-type, cervicogenic, and migraine headaches classiﬁed according to the International Headache Society (IHS)
criteria (some studies were anticipated to predate or not adhere
to the 1988 IHS classiﬁcation system). Studies were identiﬁed
by a comprehensive search of MEDLINE (1966-11/1998)
and EMBASE (1974-11/1998). The primary MeSH headings
and keywords were: headache, manipulation/orthopedic, randomized controlled trials, comparative study, review literature, chiropractic, and osteopathy medicine. Studies were
further identified through the Cumulative Index of Nursing
and Allied Health Literature, the Chiropractic Research Archives Collection, and the Manual, Alternative, and Natural
Therapies Information System (MANTIS), and by citation
tracking and hand searching of the non-indexed chiropractic,
osteopathic, and manual medicine journals. References found
in relevant publications were also examined. Abstracts from
proceedings and unpublished studies were not included. A critical evaluation list of 20 methodological items and
their operational deﬁnitions was used to assess methodological quality. This list represents a modiﬁcation of previously
used instruments.16,17 Fourteen of the items addressed validity issues, yielding a validity score. An additional 6 items concerned descriptive information. For example, we awarded
points for the following: a statistical analysis that included a
power calculation based on a predetermined clinically important difference between treatment and control groups; an
adjustment made for baseline differences between treatment
and control groups (eg, analysis of covariance); an adjustment
of significance levels to account for multiple comparisons,
primary outcomes, and follow-up time; and an appropriate
analysis of dropouts, compliance, and missing data. The
study conclusions also had to be supported by the design and
data analyses. A detailed list of the individual items and operational deﬁnitions is described in the Appendix. The methodological scoring of the RCTs was performed by 2 reviewers
independently (WJJA and GB). Differences in scores were
resolved through consensus by the 2 reviewers. The validity
scores of the individual RCTs were used as part of the evidence determination. Two of us (GB and RE) performed a
supplementary methodological scoring of the studies by
using the short checklist developed by Jadad et al.18 Data Extraction Assessment of the Level of Evidence of Efﬁcacy A best-evidence synthesis method incorporating explicit
information about outcome measures, interventions, and The criteria for determining the level of evidence of efﬁcacy has been adapted from the Agency for Health Care Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al Table 1. Deﬁnition of levels of evidence modiﬁed from the U.S. and British low back pain clinical guidelines19,71
Level of evidence
of efﬁcacy or
D. Inconclusive Number of
≥50 Number of
=21-49 Number of
signiﬁcant results ≥2
Minimal standards for classiﬁcation as limited evidence were not met or
the evidence from eligible RCTs was conﬂicting Policy and Research panel that evaluated the efﬁcacy of various treatments for acute low back pain.19 Our system evaluates the evidence taking into account: (1) the type of comparison intervention (established efficacious treatment,
commonly used therapy, or placebo); (2) methodological
quality (validity scores); (3) the number of studies; and (4)
statistical significance of study findings. Four categories
were used to describe evidence levels: strong, moderate,
limited, and inconclusive. All eligible RCTs were considered regardless of their results. Statistical pooling of 2 or
more trials was considered if they were homogeneous in
terms of headache type, subjects, treatments, outcomes, and
For determination of the outcome of each RCT, we prioritized patient-rated pain severity, frequency, and duration,
unless otherwise speciﬁed.
The assessment of efﬁcacy depended on the type of comparison intervention. If the study showed that SMT had at
least a similar magnitude of effect compared with an established efﬁcacious treatment or was superior to a placebo or a
commonly used therapy, it was considered to be evidence of
efficacy. If the study showed that SMT was inferior to an
established efficacious treatment, commonly used therapy
or placebo, or showed an effect similar to a placebo intervention, it was considered evidence of inefficacy. We prespecified that SMT was considered superior/inferior to a
comparison therapy or placebo if the ES was equal to ± 0.5.
Methodological quality and statistical significance were
then considered to determine the evidence level, as defined
in Table 1. RESULTS
Our literature search identified 22 original studies that
assessed the effect of SMT in the treatment of headache. We
excluded 13 papers because one was a case study20 and 12
were prospective or retrospective clinical series without
comparison groups.21-32 The reports of 9 RCTs involving
683 patients were retained in our review. The main features
of these trials are summarized in Table 2.
A total of 386 patients received spinal manipulation. Age
inclusion criteria ranged from 15 to 70 years of age. The
number of SMT treatments ranged from 1 to 12 (average of
6) over a period of 1 day to 8 weeks (average of 4 weeks). In
3 studies, SMT was combined with other therapies (massage,33 azapropazone,34 and deep friction massage with Yes
No placebo).35 In 5 of the studies, SMT was performed by chiropractors35-39; in 3 studies, by medical doctors34,40,41; in 1
study, by medical doctors or physical therapists;38 and in
another study, by osteopaths.33
Comparison groups included amitriptyline,36,39 deep friction with placebo,35,37 mobilization,38,41 palpation and rest,33
cold packs,40 azapropazone,34 and waiting list.41 None of
the studies compared spinal manipulation directly with a
sham or placebo spinal manipulation procedure. Outcome
measures varied greatly across studies. The main outcomes
abstracted from the 9 trials were pain intensity and frequency of headaches, medication use, and general health
The methodological quality (validity) scores of the trials
ranged from 21 to 87 on a 100-point scale. Detailed results
of the methodological quality assessment of the trials are
noted in Table 3. The 2 methodological quality assessors
initially agreed on 74% of the 20 quality items for the 9
RCTs; all disagreement was resolved through joint review
by the assessors.
The ES differences including 95% confidence intervals
for the 9 trials are depicted in Figure 1. Description of the Individual Trials
Tension-Type Headache. The trial by Boline et al36 included a
mix of patients with chronic headache and patients with
episodic tension-type headache. The primary research goal
was to assess the sustained treatment effect (4 weeks after
treatment) of 6 weeks of SMT when compared with 6 weeks
of amitriptyline (an efﬁcacious prescription medication). At
the 4-week post-treatment follow-up, the results showed an
advantage for SMT in headache pain, use of non-prescription
analgesics, and general health status (P < .05). Conversely,
at the end of the 6-week treatment period the amitriptyline
group fared slightly better than the SMT group in terms of
headache pain (P = .05). Amitriptyline patients reported
more side effects than those receiving SMT.
The trial by Bove and Nilsson35 assessed whether the
addition of SMT to soft tissue massage would improve outcomes for episodic tension-type headache. There were 2
treatment groups: deep friction massage with SMT and deep
friction massage with placebo laser treatment. All participants received 8 treatments over a 4-week period. Outcomes
were assessed at the end of treatment and 3 months after
treatment. Both groups improved at similar rates during the 459 460 Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al Table 2. Randomized controlled trials of spinal manipulation for headaches (arranged in order of methodological quality [validity
First author, reference,
year, validity score
type Study groups (n) Results of abstracted data Nelson
(VS = 87) Chronic
migraine G1: SMT-DC (77)
G2: SMT-DC+ Amitriptyline (70)
G3: Amitriptyline (71) Boline36
(VS = 75)
(VS = 67)
1978 and 1980
(Re-analyzed by New
(VS = 67)
(VS = 56) Chronic and
cervicogenic G1: SMT-DC (75)
G2: Amitriptyline (75) Hoyt33
(VS = 45)
(VS = 34)
(VS = 32)
(VS = 21) Chronic
muscle-tension Small group difference in headache pain index
(pain × frequency) and medication use at the end
of 2 months of treatment (NS)
G1 had greater reduction in headache pain index
at 1-month follow-up (NS)
G2 had greater pain reduction after 6 weeks of tx (SS)
G1 had greater reduction in pain, frequency, and medication use 4 weeks after tx (SS)
G1 had greater reduction in headache intensity and
hours of headache per day at the end of 3 weeks of
G1 had greater pain reduction than G3 after 2 months
of tx (NS) G1: SMT-DC (28)
G2: Deep friction massage +
placebo laser (25)
G1: SMT-DC (30)
G2: SMT-PT/MD (27)
G3: Cervical mobilization-PT/MD (28) Chronic
tension-type G1: SMT-DC + friction
G2: friction massage +
placebo laser (37)
G1: Massage + SMT-DO (10)
G2: Palpation (6)
G3: Rest 10 min (6)
G1: SMT-MD (11)
G2: Cold Packs (12)
G1: NSAID (Azapropazone) +
G2: NSAID (13)
G1: SMT-MD (10)
G2: Mobilization-MD (10)
G3: 3 week waiting list, then
SMT-MD (10) Post-traumatic Neck pain
Cervicogenic-like Relatively small group difference in headache pain
severity, duration, and medication use at the end of 2
months of treatment and at 1- and 3-month
Immediately after one tx G1 had much greater pain
reduction than G2 and G3 (SS) After one and only tx G1 had higher % of patients
showing improvement immediately (NS)
No group difference 3 weeks after tx (NS)
G1 had greater pain reduction than G2, and much
higher than G3 after 3 weeks of tx (NS) G1 had much greater pain reduction after 3 weeks of
tx (SS) VS, Validity score; MD, medical doctor; DO, osteopathic doctor; PT, physiotherapist; DC, chiropractor; G1, group 1; G2, group 2; G3, group 3; tx,
treatment; SMT, spinal manipulative therapy; MOB, spinal mobilization; NSAID, nonsteroidal anti-inﬂammatory drug; SS, statistically signiﬁcant (P ≤
.05); NS, not statistically signiﬁcant. Table 3. Methodological quality scores of randomized clinical trials evaluating spinal manipulation for chronic headache.
Validity items* First author,
reference, year B C D E F G J L M N P Q R Nelson (39) 1998
Boline (36) 1995
Nilsson (37) 1997
Parker (38,42) 1978+80
Bove (35) 1998
Hoyt (33) 1979
Jensen (40) 1990
Howe (34) 1983
Bitterli (41) 1977 +
– Study information items* S Validity
% score A H I K O T +
p +, Yes; –, no; p, unclear/partly; na, not applicable.
*The critical evaluation list contains 20 items (A-T) of which 14 (B-G, J, L-N, P-S) have been classiﬁed as (internal) validity items and six (A, H, I, K,
O and T) as information items. The Appendix contains a description of each item as worded in the list (italicized), accompanied by operationalization
where needed. Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al Fig 1. Effect size (ES) differences for randomized trials on the role of spinal manipulation (SMT) for chronic headache. Line with box,
ES difference with 95% confidence interval; 0.2, small ES difference; 0.5, medium ES difference; 0.8, large ES difference; VS, validity
score; DC, chiropractor; MD, medical doctor; PT, physical therapist; MOB, spinal mobilization. treatment and follow-up period. There were no important
differences between the groups in either daily headache
hours, pain intensity per episode, or daily analgesic use.
Headache pain intensity per episode showed no important
change during the trial in either of the groups.
Migraine. In the RCT by Parker et al,38,42 chiropractic SMT
showed an advantage in pain intensity, disability score,
duration, and frequency of attacks after 8 weeks of treatment when compared with SMT and mobilization delivered
by medical physicians and physical therapists. There was also a slight advantage in headache frequency in patients
receiving chiropractic SMT at 20 months’ follow-up. However, there was uncertainty regarding the appropriateness
of the original statistical analyses and subsequent reanalyses.42
In a recently published trial on chronic migraine by
Nelson et al,39 patients were randomized into 3 groups:
SMT, amitriptyline, or a combination of the 2 therapies.
Patients were treated for 8 weeks and were evaluated at the
end of treatment and 4 weeks after treatment. In the follow- 461 462 Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al up period, there was a reduction in headache index score for
the SMT group compared with the other 2 groups, which
was of borderline statistical significance. There was no
advantage to combining amitriptyline and SMT. During the
treatment phase, the SMT group experienced a clinical
effect of similar magnitude to the amitriptyline group, but
reported fewer side effects.
Cervicogenic Headache. The trial by Nilsson et al37 on cervicogenic headache compared 3 weeks of SMT with 3 weeks of
deep friction massage with placebo laser therapy with no
follow-up period. The study was performed in 2 stages. The
first stage, reported in 1995,43 was unable to detect a clinically important difference between the 2 treatment arms.
The trial was continued after a pause in recruitment; an
additional 14 patients added to the original sample, resulting
in a total sample of 53 patients. The results of the extended
trial showed a decrease of 69% in headache hours in the
SMT group compared with a 47% decrease in the massage
group (P < .05). Patients receiving SMT also reported
approximately twice as much reduction in headache intensity per episode than the massage group (P < .05).
Other Types of Chronic Headache. The remainder of the trials
either predated the IHS classiﬁcation system or did not adequately adhere to it. They were also of lower methodological quality. Jensen et al40 compared 2 sessions of SMT with
2 sessions of cold packs for patients with post-traumatic
chronic headaches. The cold pack group did not improve
over the 8-week study duration, and the advantage of SMT
was evident at both 3 (P = .03) and 8 weeks (P > .05). The
trial by Howe et al34 on headache-related neck pain showed
that the addition of 1 SMT session to nonsteroidal antiinflammatory drug therapy compared with nonsteroidal
anti-inﬂammatory drug therapy alone was superior immediately following treatment, but this difference was lost at 3
weeks after treatment (P > .05). Bitterly et al41 showed a
clinically important advantage for SMT compared with
mobilization and waiting list control (P > .05) after 3 weeks
of treatment for cervicogenic-like headache. The trial by
Hoyt et al33 showed a large advantage for SMT over the 2
controls (palpation and rest) for muscle-tension headache (P
= .0001). However, the investigators tested the effect of only
1 SMT session immediately following treatment; no followup was included.
Evidence of Efficacy. Statistical pooling was not justified due
to study differences in chronic headache type, main outcome measures, baseline clinical characteristics, assessment
time points, and number and type of SMT interventions.
Assessing the preponderance of the evidence based on our
predefined criteria, and factoring in the magnitude and
direction of effect size differences, we conclude that there is
moderate evidence that SMT has short-term efﬁcacy comparable with amitriptyline in the prophylactic treatment of
chronic tension-type headache and migraine. SMT does not
appear to improve outcomes when added to soft-tissue massage for episodic tension-type headache. There is moderate
evidence that SMT is more efﬁcacious than massage for cervicogenic headache. Several sensitivity analyses were performed to test the
robustness of the assumptions behind the weighting of the
evidence by using headache pain as the main outcome measure. An increase of 33% or any amount of decrease of the
prespeciﬁed cut-off point for adequate methodological quality (validity) did not change the weight of the evidence or
the overall conclusions. Neither a decrease of the prespecified cut-point for what constituted a minimal clinically
important effect size difference from 0.5 to 0.1 nor an
increase to 0.6 changed the weight of the evidence or the
overall conclusions. The effect size cut-point had to be set to
0.7 or above (corresponding to a near large effect size difference) to invalidate the conclusions regarding the effect of
SMT for cervicogenic headache.
Side Effects. In the studies comparing SMT with amitriptyline,36,39 more than half the patients taking amitriptyline
reported side effects such as drowsiness, dry mouth, and
weight gain, and approximately 10% were withdrawn from
the studies due to drug intolerance. In comparison, only 5%
of the patients receiving SMT reported side effects, the most
frequent being muscle soreness and neck stiffness. These
effects are common and considered normal reactions to
spinal manipulation.44 No serious complications (ie, vertebrobasilar accidents) were reported in any of the studies
included in this review. The risk of serious complications
from SMT is considered low. Estimates of vertebrobasilar
accidents range from 1 per 20,000 patients to 1 per 1 million
cervical manipulations;45 however, large prospective studies
are needed to provide more reliable estimates. DISCUSSION
A previous systematic review assessing the effect of SMT
on chronic headaches has suggested that SMT may be a
worthwhile therapy for tension-type headache7. The ﬁndings
of our review, which includes 3 additional relatively highquality RCTs, provide a basis for considering SMT in the
therapeutic management of migraine, chronic tension-type
and cervicogenic headaches. Although migraine, cervicogenic headache and tension-type headache generally are
considered to be separate conditions, there is some support
in the literature for the notion that they represent a continuum with several common underlying mechanisms, including
cervical spine dysfunction.46,47 One possible explanation of
the apparent effect of SMT in chronic headache comes from
the results of several studies that have demonstrated that
headache can be induced experimentally by noxiously stimulating tissues, including joint capsules, ligaments, and
paraspinal muscles, enervated by the cervical nerve roots
(C1-C3).48 Headache pain caused by such stimulation may
be possible because of the common neurological pathways
shared by the trigeminal nucleus and the C1-C3 nerves.48 Methodological Limitations
Different methodologies have been advocated for the systematic review of studies addressing therapeutic efficacy.15,18,49-52 Given the nature of RCTs available for this
review, we chose to evaluate the strength of the evidence Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al based on the best-evidence synthesis method rather than a
formal meta-analysis.9,53 A number of meta-analytical methods
have been advocated for combining results of RCTs.15,54 It
is recognized by international experts that one of the most
important limitations of published meta-analyses is inadequate control for clinical heterogeneity among synthesized
studies.8,55,56 There is currently little consensus on decision
rules regarding statistical pooling of study results.57 The
clinical heterogeneity of the trials, in terms of headache
type, patient characteristics, interventions, comparison therapies, and outcome measure prevented statistical pooling in
A possible limitation of the current review is publication
bias, of which there are several potential sources.58 No effort
was made to identify unpublished research,59 which is more
likely to have negative outcomes.60 However, it is recognized that attempts to retrieve unpublished trial data may
also bias studies.60 The search strategy may have missed
important studies not currently indexed, but by including
citation tracking of non-indexed journals it is unlikely that
many were overlooked. Optimally, reviews should include
all trials regardless of language.61-63 However, this review
was initially restricted to the languages we spoke: English,
German, French, Dutch, and the Scandinavian languages.
Although an attempt was made to identify trials in other languages, this approach was not fully systematic; the possibility that some relevant trials may have been overlooked must
The evidence for efﬁcacy or inefﬁcacy rests primarily on
the results of a small number of RCTs of acceptable methodological quality. A few additional high-quality RCTs in
the future could easily change the conclusions of our
review.62,64 Little research has been done to determine what
constitutes a minimal clinically-important difference in
headache outcomes. The chosen cut-point of a medium
effect-size (0.5) difference to determine inferiority/superiority of an intervention is somewhat arbitrary but similar to
other reported estimates.65,66 Also, sensitivity analyses
showed that the results and the overall study conclusions
remained the same even when substantial changes in the prespeciﬁed assumptions/rules regarding the evidence determination were applied.
The reliability with which different reviewers use similar
methodological scoring systems is a source of uncertainty.67
Conclusions regarding the weight of evidence are largely
dependent on the exact deﬁnition of the evidence classiﬁcation system used.64 An additional methodological assessment of the studies included in this review was performed
by using a 5-point scoring system developed by Jadad et
al.18 This scale addresses 3 areas—randomization, double
blinding, and description of dropouts—which, if not
addressed adequately, may be important sources of bias.
Studies that scored highly with our system also scored relatively high with the Jadad scale (correlation coefficient of
.62). It is important to note that none of the studies could
achieve higher than a 3-point score with the Jadad scale
because none of them were double-blinded. Another possible limitation of this review is that we who
performed the methodological scoring were not blinded to
the authors and results of the individual RCTs because of
our familiarity with the SMT literature. Some maintain that
blinding yields signiﬁcantly lower methodological scores,18
whereas others contend that it does not make a difference.68
Berlin et al69 have demonstrated that the overall results of
meta-analyses are uninﬂuenced by blinding. Limitations of the Individual Trials
Most of the headache trials, including those of acceptable
quality, have substantial methodological limitations. In the
trials by Boline et al36 and Nelson et al,39 withdrawal of
amitriptyline at the end of treatment is inconsistent with normal clinical practice. The return of these patients to near baseline values could be largely due to a medication rebound
effect, making the apparent advantage of the SMT group less
impressive. Longer periods of observation after treatment are
necessary to adequately judge the value of SMT as a potential
ﬁrst line of therapy for tension-type headache.
In the trial by Nelson et al,39 it appears that SMT has a
magnitude of effect similar to the commonly used prophylactic medication amitriptyline. However, the trial was not
designed to assess equivalence and did not have sufficient
power to do so. Thus, whether the 2 therapies are equivalent is still unknown. Another concern regarding this
study is the substantial loss of patients to follow up
(28%). Although the study investigators performed missing data analyses, these can never fully compensate for
the loss of data.
The authors of the trials by Bove and Nilsson35 conclude
that, as an isolated intervention, SMT does not have a positive effect on episodic tension-type headache. However, by
its design the Bove and Nilsson trial did not assess the isolated effect of SMT; rather it looked at the combined effect
of SMT with soft tissue massage. Whether there is an interaction that results from combining SMT with soft tissue
massage is unknown. A more appropriate conclusion would
have been that SMT, when combined with soft tissue massage, is no better than soft tissue therapy alone for episodic
tension-type headache. This conclusion neither supports
nor refutes the efﬁcacy of SMT as a separate therapy.
In the trial by Parker et al,38,42 there is no description of
the dropouts, increasing the likelihood of bias. The extended
trial by Nilsson et al37 on cervicogenic headache is somewhat unorthodox in that the decision to recruit more patients
was made after the original analyses of the data. No prespeciﬁcations were made regarding separate analyses of the
data, and one must be concerned about the possibility of a
Type I error.
The results of the remainder of the trials, which were of
lower methodological quality, all tend to suggest that SMT
was better than the comparison therapies. This is consistent
with studies in other fields that have shown that those of
lower methodological quality tend to have positive outcomes.52,64,70 Thus, one must interpret the results of these
trials with caution. 463 464 Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al None of the studies reviewed evaluated the cost-effectiveness
of SMT for chronic headaches. Trials are needed to establish SMT’s relative cost-effectiveness to other commonly
used therapies, and are particularly needed to address the
potential for long-term effects. Finally, caution should be
exercised when extrapolating from studies of SMT, because
there is substantial diversity in terms of training and technique among providers. CONCLUSION
SMT appears to have a better effect than massage for cervicogenic headache. It also appears that SMT has an effect
comparable with commonly used ﬁrst-line prophylactic prescription medications for tension-type headache and
migraine headache. This conclusion rests on a few trials of
adequate methodological quality. Before any firm conclusions can be drawn, further testing should be done in rigorously designed, executed, and analyzed trials with followup periods of sufﬁcient length. REFERENCES
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Royal College of General Practitioners, 1996:1-35. APPENDIX
Evaluation list for scoring: descriptions
Scoring: A YES score (+) is only used when all described
individual item criteria are met. A NO score (-) is only used
when it is clear from the article that none of the described
individual item criteria are met. UNCLEAR/PARTLY (p) is
used when the documentation or description is insufficient
to answer yes or no to whether any or all of the described
individual item criteria are met. The validity score (VS) is
the percentage score of the applicable validity items (maximum of 14). (+) = 1, (p) = 1⁄2, and (-) = 0.
A. Are the inclusion and exclusion criteria clearly
defined? They must be stated explicitly. If a more detailed
description was needed, or only inclusion or exclusion criteria were clearly deﬁned, the score is UNCLEAR/PARTLY.
B. Is it established that the groups are comparable at baseline? If different, are appropriate adjustments made during
the statistical analysis? Comparability should be present
especially for main outcomes, but also for important clinical
and demographic variables, such as age, gender, duration
and severity of condition, and known prognostic indicators.
C. Is the randomization procedure adequately described
and appropriate? If it was only noted that randomization
was used, the score is NO. To receive a YES score, the randomization process must be described (ie, randomly generated list, opaque envelopes), the method used (simple,
block, stratiﬁcation, minimization) must be appropriate, and
the concealment of randomization must be described explicitly. If only one or two of these criteria are met, a score of
UNCLEAR/PARTLY is the highest possible.
D. Is it established that at least one main outcome measure was relevant to the condition under study, and were the
reliability and validity documented? This must be explicitly 465 466 Journal of Manipulative and Physiological Therapeutics
Volume 24 • Number 7 • September 2001
Headache and Spinal Manipulation • Bronfort et al established by investigation, appropriately referenced, or
generally accepted (eg, VAS scales, Oswestry, or RolandMorris disability scales). If all of the above conditions are
not met the score is NO.
E. Are patients blinded to the degree possible, and did the
blinding procedure work? This may not apply to study (na)
(eg, a comparison of a drug and physical therapy) and is therefore not included in % scores. If the presence of either “optimal blinding” or “effectiveness of blinding” is not documented, a score of UNCLEAR/PARTLY is the highest attainable. If
at least one study involves a “blindable” intervention, then the
effectiveness of the blinding must be documented; otherwise a
score of UNCLEAR/PARTLY is the highest attainable.
F. Is it established that treatment providers were blinded
to the degree possible, and did the blinding procedure work?
This may not apply to study (na) and is therefore not included in % scores.
G. Is it established that assessment of the primary outcomes was unbiased? If assessment of outcomes could be
blinded, was it done? Was the effectiveness of blinding documented? Was there documentation that patients were not
inﬂuenced by providers or investigators on how they scored
their own outcomes?
H. Is the postintervention follow-up period adequate and
consistent with the nature of the condition under study? This
may not apply to study (na) (eg, crossover designs) and is
therefore not included in % scores. This minimum followup period is 1 month for acute conditions and 3 months for
chronic conditions in order to receive a YES score. A minimum of 2 weeks for acute conditions and 1 month for
chronic conditions must be met for an UNCLEAR/PARTLY
I. Are the interventions described adequately? Did all
interventions follow a defined protocol? Is it possible from
the description in the article or reference to prescribe or
apply the same treatment in a clinical setting? If not, YES is
not an appropriate score.
J. Were differences in attention bias between groups controlled for and explicitly described? Were time, provider
enthusiasm, and number of intervention sessions equivalent
among study groups?
K. Is comparison made to existing efficacious or commonly practiced treatment option(s)? If a placebo controlled
study, has a comparison to existing efficacious standard
therapy been made previously?
L. Is the primary study objective (hypothesis) clearly
deﬁned in terms of group contrasts, outcomes, and time points a priori? (Many studies present biased posthoc conclusions.)
M. Is the choice of statistical test(s) of the main results
appropriate? Is the main analysis consistent with the design
and the type of the outcome variables?
N. Was it established at randomization that there was adequate statistical power (β = 0.2 with α = 0.05) to detect an a
priori determined clinically important between-group difference of the primary outcome(s) including adjustment for
multiple tests and/or outcome measures?
O. Are conﬁdence intervals (CI), or data allowing CI to be
P. Are all dropouts described for each study group separately
and accounted for in the analysis of the main outcomes? Look
for analysis of impact of dropouts or worst/best case analysis.
Almost all studies with appropriate follow-up periods that evaluated the effects of therapeutic management of a condition will
have some attrition (>5%). If no dropouts, this item does not
apply to study (eg, studies with one intervention and outcomes
collected in same session) and is not included in % scores.
Q. Are all missing data described for each study group
separately and accounted for in the analysis of the main outcomes? Look for analysis of impact of missing data. Almost
all studies that evaluated the effects of therapeutic management of a condition will have missing data (>5%). If no
missing data, this item will not apply to study (na) and is not
included in % scores.
R. If indicated, was an intention-to-treat analysis used? In
studies with documented full compliance with allocated
treatments, and no differential co-intervention between
groups, a YES score can apply. In single session studies (eg,
studies with one intervention and outcomes collected in
same session) this item does not apply (na) and is therefore
not included in % scores.
S. Were adjustments made for the number of statistical
tests (2 or more) when establishing cut-off point of P-level
for each test? If applicable (avoidance of increasing risk of
Type I errors), was it documented that this was an issue that
could have influenced the outcome of the study, and were
adjustments made (eg, Bonferonni’s or similar type of
adjustment)? If indicated adjustment(s) were incapable of
changing main result/outcome of study, or if study involved
only one test at one point in time, a score of ‘na’ applies.
T. Are the conclusions directly related to the primary
objectives of the study, and are they valid? Were the a priori
testable hypotheses tested and prioritized appropriately in
the conclusions (see also item L)? ...
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- Randomized controlled trial, Evidence-based medicine, Headache, Chronic headache, Spinal manipulation