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Osteopathy for primary headache patients: a

systematic review

This article was published in the following Dove Press journal:

Journal of Pain Research
14 March 2017
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Francesco Cerritelli 1–3 Objective: This systematic review aimed to assess the efficacy, effectiveness, safety, and toler-
Eleonora Lacorte 4 ability of osteopathic manipulative treatment (OMT) in patients with headache.
Nuria Ruffini 1 Background: Migraine is one of the most common and disabling medical conditions. It affects
Nicola Vanacore 4 more than 15% of the general population, causing high global socioeconomic costs, and the
currently available treatment options are inadequate.
1
Clinical-based Human Research
Department, Centre for Osteopathic Methods: We systematically reviewed all available studies investigating the use of OMT in
Medicine Collaboration, 2Department patients with migraine and other forms of headache.
of Neuroscience, Imaging and Clinical Results: The search of literature produced six studies, five of which were eligible for review.
Sciences, 3ITAB – Institute for
Advanced Biomedical Technologies, The reviewed papers collectively support the notion that patients with migraine can benefit
G. D’Annunzio University of Chieti, from OMT. OMT could most likely reduce the number of episodes per month as well as drug
Pescara, 4National Centre for
use. None of the included studies, however, was classified as low risk of bias according to the
Epidemiology, Surveillance and Health
Promotion, National Institute of Cochrane Collaboration’s tool for assessing risk of bias.
Health, Rome, Italy Conclusion: The results from this systematic review show a preliminary low level of evi-
dence that OMT is effective in the management of headache. However, studies with more
rigorous designs and methodology are needed to strengthen this evidence. Moreover, this
review suggests that new manual interventions for the treatment of acute migraine are avail-
able and developing.
Keywords: osteopathic manipulative treatment, tension type headache, pain, migraine, disability

Introduction
Description of the condition
Headache is a multicomposite disorder characterized by episodic or recurrent acute
pain in the region of the head. The IHS classifies headache as primary, secondary, or
of other type.1 A recent European study reports a gender-adjusted 1-year prevalence of
78.6% for any type of headache.2 Other forms of headaches include migraine with a
35.3% prevalence, TTH with a 38.2% prevalence, chronic headache (≥15 days/month)
with a 7.2% prevalence, and MOH with a 3.1% prevalence.2 Due to its high prevalence,
headache has a strong impact on health care programs, policies, and economics. It has
also been estimated that 17.7% of males and 28.0% of females lost >10% of days due
to migraine, and that 44.7% of males and 53.7% of females lost >20% of days due
to MOH.2 The economic burden of headache was estimated to be a total annual cost
Correspondence: Francesco Cerritelli
Clinical-based Human Research
of €173 billion among adults aged 18–65 years,3 with a mean annual cost of €1222
Department, Centre for Osteopathic per person for migraine (95% CI: €1055–€1389; indirect costs =93%), €303 for
Medicine Collaboration, Onlus, Via
Vespucci, 188, Pescara 65126, Italy
TTH (95% CI: €230–€376; indirect costs =92%), and €3561 for MOH (95% CI:
Email [email protected] €2487–€4635; indirect costs =92%). Guidelines recommend treating chronic ­headache

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with antidepressants such as amitriptyline, while in case counterbalance the release of proinflammatory molecules
of sporadic headache episodes (up to 10 days per month), and cause subsequent feedback and feedforward effects
pain can be treated with analgesics or NSAIDs.4 Additional on the ANS.17 Consequently, a cascade of biological and
effective, tolerable, and safe intervention approaches would neurological events could be triggered, potentially based on
be extremely useful either in addition to, or as substitutes a rebalance of the abnormal activation of the habituation/
of, drug therapies. sensitization mechanism, resulting in an overall improvement
of clinical outcomes.17
Brief description of the intervention
OM is a nonpharmacological, noninvasive manual medicine, Why is it important to perform this review
regarded by some as CAM. Osteopathic practitioners use a Results from clinical controlled trials on OMT for primary
wide variety of therapeutic manual techniques to improve and secondary forms of headaches are not conclusive. This
physiological function and help restore the homeostasis review is part of a larger project aiming at establishing
altered by any somatic (body framework) dysfunction (ICD- the clinical effectiveness of osteopathy in patients with
10 code: M99.0–99.9).5 The two essential components of headache and other neurological conditions. The primary
OM are 1) the structural assessment for diagnosis and 2) all objective of this systematic review is to assess the efficacy,
the different manipulative techniques for the treatment. effectiveness, safety, and tolerability of OMT in patients
The aim of the structural assessment is to identify specific with headache.
somatic dysfunctions. Diagnostic criteria for somatic dys-
functions focus on the tone and possible abnormalities of Methods
tissue texture. Areas of asymmetry and misalignment of Types of studies
bony landmarks are also evaluated, along with the quality Only RCTs and quasi-RCTs were considered eligible. Studies
of motion, balance, and organization. The term OMT cur- were included if they reported at least one headache-related
rently includes >20 types of manual treatments administered clinical outcome (eg, response, frequency, pain intensity,
by osteopaths.6 headache scores, and use of analgesics). Studies that mea-
sured the effectiveness of OMT using standardized and
How the intervention might work validated PROMs as primary outcome or studies reporting
The possible effect of OMT could be due to two main the number of headache days as a secondary outcome within
mechanisms: increasing of the parasympathetic tone, and a health care program were also included. Descriptive studies
inhibiting the release of proinflammatory substances. and trials reporting only physiological or laboratory param-
Headache has been shown to be associated with impair- eters were excluded.
ment of both the ANS and the specific autonomic nuclei
responsible for pain perception and sustained pain. Patients Types of participants
with chronic headache may show peripheral and central Studies including patients of any gender, ethnicity, and age
sensitization, lack of habituation,7 and other phenomena with a clinical diagnosis of headache according to any cri-
belonging to the so-called pain-matrix.8 Underlying dys- teria were considered eligible. The accuracy and reliability
autonomic symptoms are reported to reduce the release of of the diagnosis and of the diagnostic tools were considered
norepinephrine and to increase the secretion of dopamine as qualitative parameters. Studies including patients with at
and prostaglandins.9 Moreover, studies report that subjects least one of the following clinical conditions were excluded:
having a migraine episode release high levels of proinflam- neurodegenerative, cardiovascular, genetic, respiratory, or
matory agents and serotonin,7,10 thus altering the neural rheumatologic diseases, and/or psychiatric or psychological
autonomic pathways. disorders.
Evidence has shown that application of OMT influences
the ANS, producing a parasympathetic effect,11–13 thus leading Types of interventions
to a trophotropic tuning state.13 Moreover, OMT seems to be We included all studies investigating any type of OMT
associated with a reduction of proinflammatory substances performed by an osteopath. Due to the intrinsic clinical
both in vitro14 and in vivo,15,16 thus bringing up the hypothesis variability of manual techniques in terms of magnitude,
of OMT having an anti-inflammatory role. Therefore, the use frequency, and time, no dosage restrictions (frequency and
of OMT in the treatment of patients with headache could time) were applied.

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Dovepress Osteopathy for primary headache

Types of comparisons available for more than one data point after randomiza-
Sham therapy, standard care/other treatments, or no treatment tion, the following strategies were applied: data closest to 4
were considered as control interventions. We defined as sham weeks were chosen for the first time period, data closest to 8
interventions all interventions mimicking “true” osteopathic weeks were chosen for the second time period, data closest
treatment, but modifying at least one aspect considered relevant to 3 months were chosen for the third time period, and data
by the osteopathic theory, such as the diagnosis of somatic closest to 6 months were chosen for the fourth time period.
dysfunction or the correct location of the area for manual treat-
ment. Standard care or other treatment included pharmacologi- Selection of studies
cal therapies, relaxation, physical therapies, and so on. “No Two reviewers (NR and EL) analyzed the literature retrieved
treatment” required that neither experimental nor standardized through the search strategies and independently selected
treatment could be initiated during the trial period. Trials that the studies pertinent and relevant to the topic of the review.
only compared different forms of OMT were excluded. Studies Disagreements were resolved by consensus or by a third
including combined manual treatments were excluded. OMT reviewer (VN).
interventions and/or sham treatments could be administered The full texts of selected studies were then assessed for
in combination with usual/routine care. inclusion by applying the predefined eligibility criteria.

Search methods Data collection and evaluation

All literature published up to April 2016 was retrieved Data extraction was carried out independently by two
through a comprehensive systematic search on the following reviewers. Extracted data included the type of interventions,
databases: Embase, PubMed Central, ScienceDirect, MED- number of patients, study results, and all other descriptive
LINE, Scopus, Web of Science, Google Scholar, the Cochrane characteristics reported in the included trials. Where reported
Library, chiloras/MANTIS, PubMed Europe, WHO ICTRP, details were missing or insufficient, authors were contacted.
OSTMED.DR, and Osteopathic Research Web. Duplicate All data were stored in a specific hard disk, managed only
records were identified using the EndNOTE software and by the two reviewers. Disagreements were discussed and
excluded. Gray literature was also retrieved using the fol- resolved by consensus.
lowing sources: Web searching, conference proceedings,
national trial registers (eg, ClinicalTrials.gov). Details on the Assessment of RoB in the included
search strategy are provided in the Supplementary material. studies
All reviewers independently assessed the methodological
Types of outcomes quality of the included RCTs using two different tools: the
We considered as primary outcome the MD in number of days Jadad score18 and the Cochrane RoB tool.19 Both scores are
with headache per month between study group and control specifically designed to assess the quality of trials and include
group after at least 4 weeks of treatment. specific questions for the identification of potential method-
The secondary outcomes considered herein included the ological issues/biases affecting the following key phases:
following: allocation concealment, comparability of groups at baseline,
blinding of participants and evaluators, and management of
• Safety-related measures, such as number and types of
withdrawals/dropouts.
adverse events in both groups
The Jadad score includes three items: allocation, blind-
• Headache intensity, quantified through any available
ing, and description of withdrawals and dropouts. One
measure
point is assigned for each item if an accurate and detailed
• Frequency of analgesic use, calculated with any continu-
description is provided, while if the item is judged inad-
ous or rank measures available
equate or incomplete, the point is withdrawn. The highest
• Difference from baseline to end of treatment in the dose
possible score is five points, and studies scoring less than
of any pharmacological treatment
three points are usually considered as being of low meth-
• Any PROM
odological quality.
• Any reference to economic impact or cost reduction.
The Cochrane RoB tool includes five domains: sequence
Most of these outcomes rely on patient reports, mainly generation, allocation concealment, blinding to personnel,
collected in headache diaries. In cases wherein data were blinding to outcome analysis, and other bias. RoB is assessed

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for each domain according to a three-point scale: low RoB, Review Manager version 5.2.6, while the remaining statisti-
unclear RoB, and high RoB. cal analyses were performed using the software R. A p-value
The operational definitions adopted to apply the scor- <0.05 was considered as statistically significant.
ing systems will be provided by the authors upon request.
Frequency of agreement and weighted kappa statistics were Results
calculated to measure agreement between the evaluators for A total of 383 records were retrieved through database
both scoring systems. searches and by hand searching of other sources. An exten-
sive search for gray literature was also carried out, though
Measures of treatment effect no additional records were retrieved. After removing dupli-
When available, data for continuous variables were reported cates, 138 articles were excluded. An extensive search for
as MDs, along with their 95% CIs, while dichotomous out- gray literature was also carried out, though no additional
comes were reported as RRs along with their 95% CIs. In the records were retrieved. Out of the 245 records remaining
case of missing data, authors of the studies were contacted after removing duplicates, 239 were excluded based on
for further information. information provided in the titles and/or abstracts. The main
reason for exclusion was that some articles did not report
Assessment of heterogeneity original research, but rather provided general information
Studies were pooled only in case of significant homogeneity, on the management of headache, instructions on the use of
as assessed with the I2 test. The I2 value measures the amount some osteopathic techniques in patients with headache, or
of variation between studies attributable to heterogeneity general information on the possible benefits of OMT. Some
rather than to chance.20 Values ≥75% are usually considered abstracts reporting original research were also excluded as
as reflecting moderate-to-high heterogeneity, but the statis- they did not meet predefined inclusion criteria.
tical significance of I2 also depends on the magnitude and The full texts of the six remaining studies were retrieved
direction of the effect as well as the strength of the evidence. and assessed for inclusion. One further trial was excluded after
Reasons for heterogeneity can be methodological, statistical, reading its full text, as it did not report enough information
or clinical. Clinical heterogeneity was assessed analyzing to be included in the review.24 Therefore, five studies met the
possible differences across studies in the type of enrolled inclusion criteria and were qualitatively assessed25–29 (Figure 1).
patients, the type of intervention under investigation and All included studies were in English. Two trials were car-
how it was administered, the type of intervention chosen as a ried out in Italy,26,28 one was carried out in Germany,29 one in
comparison and how it was administered, the type of outcome Canada,25 and one in the USA.27 All of the included studies
considered, the control event rate/baseline risk, the setting in except for one27 (four out of five included studies, 80%) were
which the trial was carried out, the comparison conditions, published after 2006 and were RCTs with a parallel-group
early stopping rules, if present, and the population risk.21 design. Two studies compared three groups of subjects ran-
Funnel plots were used to test for publication bias,20 and in domized to three arms,26,27 while the other three studies were
case of nonparametric data, the Duval–Tweedie “trim-and- designed to compare two groups of subjects randomized to
fill” test was also used.22 two arms.25,28,29

Data synthesis Interventions and comparisons

Data from the review were reported according to the PRISMA All trials considered OMT as their primary intervention. One
statement.23 study considered OMT in association with usual care.26 The
A meta-analysis of either dichotomous outcomes or osteopathic techniques and approaches varied highly across
continuous outcomes was carried out whenever possible; studies, as well as the number of sessions per patient, which
where a meta-analysis was not possible, results were pre- ranged from one to eight. The dose, frequency, and length of
sented using summary and descriptive statistics. Weighted treatment were also heterogeneous. Details on the profession-
MDs as well as effect sizes were calculated. When feasible, als administering the treatment (ie, background, experience,
subgroup analyses were carried out, stratifying for age classes and number of professionals recruited) were reported only
(adolescent, adult, and elderly), type of headache (chronic in two studies.26,29
vs acute; primary vs secondary), gender, as well as type and The characteristics of the control groups also widely
frequency of OMT. Meta-analyses were carried out using varied across studies. Two studies26,28 used sham therapy, a

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Dovepress Osteopathy for primary headache

323 Records identified 60 Additional

through database records identified
searching through other sources

245 Records after

duplicates removed

245 Records screened 239 Records excluded

6 Full-text articles 1 Full-text article

assessed for eligibility excluded, with reasons

5 Studies included in
qualitative synthesis

Figure 1 Flowchart of study selection.

treatment mimicking the primary intervention but without One of the two trials including three groups26 showed that
applying any technique; one study25 used progressive mus- OMT was effective in reducing migraine episodes during 6
cular relaxation; one study27 administered either palpatory months of treatment. It also reported a decrease from eight
examination or supine rest sessions; and the last study29 to six units in the HIT-6 score in the treated group when
used a questionnaire. Osteopathic interventions and control compared to both the control group and the sham group, in
procedures were administered in different settings, ranging addition to a decrease in migraine episodes, use of drugs, as
from private clinics to public hospitals. well as pain and disability scores.
Voigt et al29 reported OMT to be effective in significantly
Sample size and length of study improving pain scores, HRQoL, and working disability in
Overall, included trials enrolled a total of 265 participants female patients with migraine, but not in reducing days of
(mean: 53, range: 22–105). All included patients were adults migraine.
(age range: 18–65 years). All trials reported the length of Rolle et al28 reported a significantly lower frequency of
follow-up, which ranged from 9 to 20 months. Rolle et al28 headache in the OMT group compared to the control group
conducted the only study that considered a further follow-up and proved OMT to be effective in reducing the use of medica-
at 3 months. tions over time. No adverse effects were reported in this trial.
Anderson and Seniscal25 reported a significant increase
Outcomes reported in the number of headache-free days per week in the treated
Four out of five trials reported data on the frequency of group. No statistically significant differences were observed
headache, which was the outcome we considered as primary in the headache degree of improvement and the headache
for this review. diary rating between groups.

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Hoyt et al27 showed a reduction of headache severity in Selective bias

the treated group, but no changes in EMG parameters. As protocols were not accessible for any of the included
studies, selective bias could not be assessed.
Description of quality
Mean interrater reliability in the qualitative assessment using Other bias
the Jadad score resulted in a kappa value of 0.74, while the The quality of included studies was further evaluated by con-
kappa value for the qualitative assessment using the Cochrane sidering the presence/absence and adequacy of other reported
RoB tool was 0.68. information such as informed consent, ethical approval, trial
registration, data collection, data management, data moni-
Allocation toring committee, access to data, reporting funding source,
Two studies26,28 used a computer-based random-generated conflict and declaration of interests, and confidentiality. Two
list26 and coin tossing28 as methods of randomization, and studies reported having requested and obtained informed
both methods were considered at low RoB. Another study consent from enrolled participants,25,28 while three were rated
used a random-generated table but did not report any further as unclear, as no details were reported.26,27,29 Three out of five
detail.25 The remaining studies27,29 did not specify the method studies reported having obtained ethical approval,25,26,29 while
for randomization. only one study reported having registered the trial, and only
As for the method used for allocation concealment, one one study provided information on data collection.26 Only
study was considered at high RoB,28 as the treating physi- two studies reported information on the source of funding,26,27
cian also performed randomization, while another26 was and the majority of included studies reported statements from
considered at low RoB, as the process for randomization authors declaring to have no conflicts of interests.25,26,28,29
was performed by an external subject. All other trials did None of the included studies reported information on
not report enough information to allow for assessment.25,27,29 confidentiality, data management, data monitoring commit-
tee, and access to data.
Blinding of participants and personnel
In three studies, the osteopathic therapists were unblinded Description of adverse events
to the allocation of participants.26–28 Two studies reported no Two studies out of five (40%) collected data on adverse
information on the topic.25,29 events,26,28 stating that none of the participants reported any
Participants were blinded to treatment in two out of the five adverse event/effect attributable to the treatment.
included trials. One trial compared OMT with home-based
relaxation exercises, thus keeping participants unblinded to Description of heterogeneity
the treatment.25 One trial explicitly stated that participants A high level of clinical heterogeneity was observed among
were not blinded to the treatment they were receiving,29 and included studies, with wide variation across studies in the
another trial did not report details on blinding.27 Only one type of considered participants, interventions, and outcomes,
study kept participants blinded to the treatment they were as shown in Table 1. Enrolled participants differed in terms
receiving, with only a one-question posttreatment telephone of age, disease severity at baseline, and comorbidities. The
survey administered by a neurologist.26 type of OMT used, its dose and frequency of administration,
Two studies reported no information on who enrolled the length of treatment, the type of therapist performing the
participants.26,27 One study reported that participants were treatment, and the setting in which it was administered widely
enrolled by the treating practitioner,25 while another study did varied across studies. A wide variability was also observed in
not provide any further information.28 The last study reported the type of comparisons used (manual vs ­non-manual), the
having used newspaper advertisements and flyers to recruit way the control intervention was administered (light touch, no
patients but did not provide any further details.29 intervention, and relaxation exercises), the type of therapist
who administered it, as well as the dose and setting. More-
Blinding of outcome assessors over, none of the included studies reported any information
Two studies reported that the investigators who assessed the on concomitant treatments.
outcome were blinded to the allocation of participants.25,26 High heterogeneity was also observed in the type of
The remaining studies did not provide information on the outcomes considered and in the length of follow-up, which
topic.27–29 ranged from immediately after treatment up to 6 months. Only

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Dovepress Osteopathy for primary headache

Table 1 Main characteristics of the included studies

Author Outcome measures Description of Time to Population Type of Relevant outcome
(year) interventions outcome headache results
measurement
Cerritelli Effectiveness of OMT in OMT (n=35): Description: 6 mo N=105; age Migraine Decrease of HIT-6
et al, 201526 terms of the following: NBT, 8 sessions (4 weekly, =38.7±9.3 years; (according score for OMT vs
1) HIT-6 score, 2) days/mo 2 bimonthly, 2 monthly, male =34% to ICHD-II) controls (p<0.001)
with migraine, 3) severity 30 min) Decrease in days of
of pain, 4) amount of Concomitant treatments: migraine for OMT vs
rescue medication, 5) Y, triptans at need controls (p<0.001)
functional disability, and Control 1 (n=35): sham Decrease in pain
6) adverse effects of OMT OMT intensity for OMT vs
Description: sham OMT, controls (p<0.001)
8 sessions (4 weekly, 2 Decrease in drug
bimonthly, 2 monthly, consumption for OMT
30 min) vs controls (p<0.001)
Concomitant treatments: Adverse events: none
Y, triptans at need
Control 2 (n=35): usual
care
Description: triptans at need
Rolle et al, Efficacy of OMT in terms OMT (n=21): 4 w; follow-up N=40; age Frequent Headache frequency:
201428 of the following: Description: NBT, 4 sessions at 1 and 3 mo =34.5±12 years; episodic TTH
OMT vs control: 33%
1) headache frequency, 2) (weekly) male =14% (according to
decrease (p<0.001)
headache pain intensity, 3) Concomitant treatments: ICHD-III) Pain intensity: 20%
over-the-counter Y, not specified reduction within OMT
medication use, and 4) HDI Control (n=19): sham OMT group compared to
Description: sham OMT, 4 baseline (p<0.001)
sessions (4 weekly) Drug consumption: 45%
Concomitant treatments: reduction within OMT
Y, not specified group compared to
baseline (p<0.001)
Adverse events: none
Voigt et al, Effectiveness of OMT in OMT (n=21): 6 mo N=42; age Migraine Decrease in pain
201129 terms of the following: Description: NBT, 5 sessions =45±11 years; (according intensity (within group):
1) HRQoL, 2) pain (bimonthly, 50 min) male =0% to ICD-10) OMT (p<0.05), control
intensity, 3) days of Concomitant treatments: (p=0.87)
migraine headache, Y, not specified Decrease in days of
4) working disability, Control (n=21): no migraine (within group):
5) German ‘‘Pain intervention OMT (p=0.31); control
Questionnaire”, and 6) Description: not specified (p=0.89)
MIDAS, and 7) SF-36 Decrease in working
disability (within group):
OMT (p=0.06); control
(p=0.47)
Decrease in MIDAS
(within group): OMT
(p=0.04); control
(p=0.76)
Anderson Effects of OMT in terms of OMT (n=14): 6w N=26; age = Any type Decrease in headache
and Seniscal, the following: Description: protocol, 3 NA; male = NA of TTH frequency (free days/w):
200625 1) headache frequency, 2) sessions (weekly) (according OMT vs control
headache intensity, 3) HD, Concomitant treatments: to IHS 2004) (p=0.016)
and 4) HI Y, PMR
Control (n=12): PMR
Description: relaxation
exercise (1/day, 20 min)
(Continued)

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Table 1 (Continued)
First author, Outcome measures Description of Time to Population Type of Relevant outcome
year interventions outcome headache results
measurement
Hoyt et al, Effects of OMT in terms of OMT (n=10): IAT N=22; age = Chronic Decrease in headache
197927 the following: Description: protocol, NA; male = NA muscle intensity (worst
1) headache pain intensity 1 session (same day, tension headache
and 2) EMG 10 min) headache improvement): OMT
Concomitant treatments: NA vs control (p=0.07)
Control 1 (n=6): OE Pain intensity: among
Description: protocol, 3 groups: F=17.16
1 session (same day, 10 min) (p<0.001); reduction
Concomitant treatments: NA within OMT group
Control 2 (n=6): rest compared to baseline
Description: supine (p<0.001)
Concomitant treatments: NA
Abbreviations: OMT, osteopathic manipulative treatment; HIT-6, headache impact test-6; NBT, need-based treatment; PMR, progressive muscular relaxation exercises;
OE, osteopathic evaluation; HD, headache diary; HDI, headache disability index; HI, headache index; EMG, electromyography; IAT, immediately after treatment; NA, not
available; TTH, tension type headache; ICHD, International Classification of Headache Disorders; ICD, International Classification of Diseases; IHS, International Headache
Society; Y, yes; mo, months; w, weeks; min, minutes; MIDAS, Migraine Disability Assessment questionnaire; SF-36, Short Form-36.

one study reported results during the follow-up period.28 Two criteria adopted for the selection of participants; moreover,
studies did not report information on included subjects.25,27 the inadequate and inaccurate description of interventions
The type of headache was also heterogeneous across and comparisons affected the reproducibility and reliability
studies. Included trials enrolled patients with different con- of results. The majority of trials did not report adverse events
ditions, such as chronic migraine, episodic TTH or episodic with a structured methodology, and unreported details were
migraine, chronic muscle-tension headache, and any type of pointed out.
TTH. This is further confirmed by the different classification
codes adopted (ICHD-II, ICHD-III, ICD-1030). A consistent Study limitations
variability was also observed in the pathophysiological con- Every attempt was made to include all relevant studies, though
siderations used across the included studies. the risk of having missed some other pertinent or relevant pub-
Only one study calculated the sample size before enrolling lication cannot be ruled out. We used strict eligibility criteria
participants.26 Included studies can, therefore, be considered to increase the external validity of results and their generaliz-
as having substantial heterogeneity in terms of study design ability to different settings. Several studies investigated the
and characteristics and, subsequently, in their overall RoB. comparative effectiveness of different preventive strategies
and therapeutic programs, but results from these studies
Discussion should be cautiously considered when planning interven-
Results showed that several different types of OMT have been tions aimed at the prevention and management of headache.
used with the objective of preventing and treating primary A further limitation of included studies is their consideration
headache. This systematic review showed that the evidence of heterogeneous populations. This limits the generalizability
supporting the effectiveness of OMT in decreasing pain of results and affects the interpretation of results. Moreover,
intensity and frequency, as well as in reducing disability in selection bias cannot be ruled out, as no behavioral or neuro-
patients with headache, is still preliminary and of low meth- psychological assessment was performed at baseline and/or
odological quality. The overall quality of included evidence at enrollment, thus leaving the possibility of having missed
is also too low to draw conclusions on the effectiveness of some psychological and/or psychiatric conditions.
OMT in improving any other considered outcome. Quality Specific types of headaches are likely to respond in dif-
assessment showed that the majority of studies were at high ferent ways and extents to the same treatment and should
or unclear RoB, with most of the studies having several meth- therefore be studied individually. The heterogeneity of
odological limitations in the management of confounding included studies, along with the high RoB and the impreci-
factors, the random sequence generation, and having a high sion of results, made it impossible to perform a quantitative
risk of incomplete reporting of outcome data. The compara- analysis and/or meta-analysis of the results for any of the
bility of results was also affected by the heterogeneity in the predefined outcomes.

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Dovepress Osteopathy for primary headache

Consideration (or recommendation) for PROM, patient-reported outcome measure; WHO ICTRP, World
future research Health Organization’s International Clinical Trial Registry Plat-
Future studies should be carefully designed and include proper form; RoB, risk of bias; MD, mean difference; RR, r­ elative risk;
control intervention and randomization strategies. Partici- PRISMA, Preferred Reporting Items for Systematic Reviews
pants should be enrolled based on the ICHD to ensure proper and Meta-Analyses; HIT-6, headache impact test-6; HRQoL,
comparability of samples across studies. An intention-to-treat Health-related quality of life; EMG, electromyography. ICHD,
analysis should be performed, and appropriate strategies for International Classification of Headache Disorders; ICD, Inter-
the management of missing data should be considered. Atten- national Classification of Diseases; IHS, International Headache
tion should be paid to the accuracy and precision of results, Society; RCTs, randomized controlled trials
as both were relevant issues affecting results in several of the
included studies that did not provide data as mean values along Disclosure
with CIs. The sample size should also be calculated, to ensure The authors report no conflicts of interest in this work.
that the study had adequate statistical power. A complete and
adequate reporting of results should also be guaranteed. References
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Dovepress Osteopathy for primary headache

Supplementary material
Search strategy: keywords used
(((((((((((((osteopath* AND manipulat* AND (treatment OR therapy))) OR Manipulation, Osteopathic[MeSH]) OR ((osteo-
path* AND medicine))) OR ((manual* AND treatment*))) OR ((spinal AND manipulat*))) OR Manipulation, Spinal[MeSH])
OR ((visceral AND manipulat*))) OR (((crani* OR crani* AND sacral OR cranio *sacral) AND osteopat* AND (manipulat*
OR manual OR treatment)))) OR (((craniosacral OR cranio-sacral OR cranio sacral)))) OR ((osteopath* AND diagnosis)))
OR ((osteopath* AND palpat*))) OR ((osteopath* AND principle* AND practice*)) AND ((headache AND (disease* OR
disorder*)))))

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