Accepted Manuscript

Efficacy of manual therapy on frequency and intensity of pain, anxiety and depression
in patients with tension-type headache. A randomized controlled clinical trial

Gemma Victoria Espí-López, PhD, PT, Laura López-Bueno, PhD, PT, M. Teófila
Vicente-Herrero, PhD MD, Francisco Martínez Arnau, PT, Lucas Monzani, PhD, MSc.

PII: S1746-0689(16)30030-X
DOI: 10.1016/j.ijosm.2016.05.003
Reference: IJOSM 413

To appear in: International Journal of Osteopathic Medicine

Received Date: 16 June 2015

Revised Date: 23 May 2016
Accepted Date: 31 May 2016

Please cite this article as: Espí-López GV, López-Bueno L, Vicente-Herrero MT, Martínez Arnau F,
Monzani L, Efficacy of manual therapy on frequency and intensity of pain, anxiety and depression in
patients with tension-type headache. A randomized controlled clinical trial, International Journal of
Osteopathic Medicine (2016), doi: 10.1016/j.ijosm.2016.05.003.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
 ACCEPTED MANUSCRIPT
Efficacy of manual therapy on frequency and intensity of pain, anxiety and

depression in patients with tension-type headache. A randomized controlled

clinical trial.

Short Title: Manual therapy for tension-type headache

PT
RI
Gemma Victoria Espí-López, PhD, PT, Physiotherapy Department. University of

Valencia. Spain; gemma.espi@uv.es

SC
Laura López-Bueno. PhD, PT, Physiotherapy Department. University of Valencia.

U
Spain; laura.lopez@uv.es
AN
M. Teófila Vicente-Herrero, PhD MD, Occupational Health Service. Correos Group of
M

Valencia, Spain; MTVH@ono.com

D

Francisco Martínez Arnau, PT, Physiotherapy Department. University of Valencia.

Spain; francisco.m.martinez@uv.es
TE

Lucas Monzani, PhD, MSc. Richard Ivey Business School at Western Ontario
EP

University. Ontario, Canada N6G 0N1. lmonzani@ivey.uwo.ca

C
AC

Clinical Trials.gov Identifier: NCT02170259

Funding sources and potential conflict of interest. No funding institution. The authors

declare that there is no conflict of interest.

 ACCEPTED MANUSCRIPT
Keywords: Efficacy, Manual therapy, Tension-type headache, Depression, Anxiety,

Spinal manipulation.

*Correspondence:

Gemma Victoria Espí López

PT
Physiotherapy Department. University of Valencia. Spain

RI
C/ Gascó Oliag, 5

46010 Valencia, Spain

SC
Fax: 34963983852

Tel. 34963983853

gemma.espi@uv.es
U
AN
M
D
TE
C EP
AC
Abstract
ACCEPTED MANUSCRIPT
Introduction. Tension-type headache (TTH) is a highly prevalent disorder with a significant socio-
economic impact and psychological effects for TTH participants. The purpose of this study was to test the
efficacy of three manual therapy TTH treatments with regard to the reduction of TTH-related anxiety and
depression were also addressed.
Subjects and methods. A clinical trial was conducted on 84 participants suffering from tension-type
headache forming 4 groups: the first group received suboccipital soft tissue treatment (ST); the second
group was treated with articulatory techniques (AT); the third group underwent a combination of both

PT
techniques (ST and AT), while the forth group was the control group. Treatment sessions were
administered over four weeks, with post-treatment assessment, and follow-up at one month. We
conducted Repeated measures Analysis of Covariance (RM-MANCOVA) to evaluate the effect of

RI
treatment on between and within-subject conditions and their interaction on reported depression and
anxiety.

SC
Results. While all treatments prove to be effective in reducing its associated psychological symptoms
(depression, anxiety), their efficacy varied between treatments, TTH types and the elapsed time between
measurements.

U
Conclusion. Overall, our findings suggest that treatments including articulatory techniques are more
efficient than soft tissue techniques, or a combination of both, for the reduction of physiological
AN
symptoms in TTH participants and, as a secondary benefit, reduce anxiety and depression levels in these
participants.
M
D
TE
C EP
AC

1
Introduction
ACCEPTED MANUSCRIPT
The International Headache Society (IHS) developed a classification for headache disorders and
their characteristics1, 2, wherein tension-type headache (TTH) is the most common form of primary head-
ache. TTH has a great socio-economic impact3, 4 negatively affecting the quality of participants’ social
and work life.5 In a recent study, 74% of participants suffering from chronic tension-type headache
(CTTH), reported headache frequency as the main cause of their disability.6 CTTH moderately affected
working or social spheres in 60% of the subjects and seriously impaired these areas in 9% thereof; 37%
suffered sleep disorders; 35% experienced changes in energy levels and 33% an alteration of emotional
well-being.

PT
Some studies reported that TTH participants suffer an increased tenderness in pericranial
myofascial tissues and several trigger points (TrPs), which suggests that tension in the craniocervical

RI
muscles may be a possible physiological cause of TTH,7 physiotherapy and muscle relaxation therapies
being efficient treatments for such muscular tension.8 The latter include manual therapy as a non-invasive
alternative to medication-based treatments; spinal manipulation shows positive results in reducing

SC
headache frequency, duration and intensity.9 For example, manual therapy aimed at the active TrPs of the
sternocleidomastoid muscle is an efficient technique to reduce cervicogenic headaches and to improve
overall cervical movement.10 In addition, articulatory mobility (articulatory normalization) and muscular

U
relaxation treatments, when applied to the craniocervical soft tissues and joints of the suboccipital region,
AN
not only improve TTH, as certain evidence suggests, but also efficiently reduce adverse TTH-related
psychological states, such as anxiety and depression.11
However, in view of the poor methodological quality of previous trials (e.g., single blind studies
M

or no control group), a better understanding of the efficacy of these manual treatments is needed.12 Spinal
manipulation in former studies was applied according to participants’ joint mobility dysfunction;
D

therefore, the manipulation level differed for each patient,13 which made it impossible to establish if these
techniques would render similar results if applied separately. Furthermore, while only one study
TE

combined treatment of the craniocervical region with other techniques (e.g., inhibition of soft tissues with
muscle-energy techniques),13,14 we found no studies applying a joint manipulation in this region for TTH
participants (e.g., combining suboccipital soft tissue treatment with other techniques). While a joint
EP

manipulation may have two advantages (e.g. increased muscular relaxation and balance between the
suboccipital and pericranial regions), the efficacy of combined manual treatments on TTH frequency and
intensity of pain, and in consequence on anxiety and depression, is still unknown.
C

On the other hand, existing TTH literature is unclear in terms of the causal direction between
AC

TTH and depression and anxiety. Early studies considered anxiety and depression as psychogenic causes
of TTH. A study of 25 TTH participants reported that anxiety affected their headache frequency, pain,
vitality and social functioning. In turn, other authors established that anxiety and depression are
associated with an increased burden of accompanying symptoms, such as intestinal or sleep disorders.15
Finally, it appears that that TTH is one possible cause and not an effect of negative emotional states such
as depression and anxiety.16, 17
For example, Holroyd (2000)6 reported that participants with Chronic
Tensional Type Headache (CTTH) suffer higher levels of anxiety and depression, but did not compare
these values with those found in subjects suffering episodic Tensional Type Headache (ETTH).
The present study proposes that focusing treatment on the suboccipital region can neutralize
pain, and reduce both TTH-related physiological and psychological symptoms. It is to be noted that this

2
 ACCEPTED MANUSCRIPT
study is framed within a larger project that includes recently published studies. This study extends former
findings by exploring the secondary benefits of manual therapy on TTH participants’ negative emotional
states (e.g., Anxiety and depression). These psychosocial criteria require a separate study due to their
impact on the emotional tone of TTH participants and their well-being.18 Therefore, the goals are first, to
evaluate the relative efficacy and temporal stability of treating TTH participants with (1) a suboccipital
soft tissue (ST) technique, (2) an articulatory technique (AT), and (3) combining both techniques (ST +
AT), in terms of their weekly THH pain frequency and intensity. The second goal is to establish if these
treatments lead to an overall reduction in negative emotional states associated with TTH, namely,

PT
depression and anxiety. Thirdly, we shall determine if the efficacy of the above-mentioned treatments also
vary depending on the TTH type (episodic vs. chronic) and the elapsed time.

RI
Subjects and methods
Participants
Participants participating in this study were recruited from two primary healthcare centers in

SC
Spain over a period from January 2010 to December 2011. All participants had been previously diagnosed
by a neurologist with frequent episodic tension-type headache (ETTH) or chronic tension-type headache
(CTTH) as described by the International Headache Society (IHS).1,2 Before starting the test a clinical

U
interview is done to confirm the diagnosis according to IHS. Participants further presented TTH evolving
AN
over a period greater than six months and all were pharmacologically stable.

Prior to our study, a vertebral artery test was performed bilaterally for all potential participants.
Although there is some controversy about the efficacy of this test for the purpose of ensuring the absence
M

of vascular injury,19,20 we included the latter in this study as a main exclusion criterion. Therefore,
participants with vertebrobasilar insufficiency symptoms were excluded. Other exclusion criteria covered
D

participants with secondary headaches suffering from photophobia or phonophobia, nausea or vomiting,
cases of headache aggravated by head movements, rheumatoid arthritis, previous neck trauma, vertigo,
TE

dizziness, arterial hypertension, arthritis or advanced degenerative osteoarthritis, participants with heart
devices, excessive emotional stress, neurological disorders, radiological alterations and pregnancy.
EP

Study design

Prior to data collection, the design and method of this study was supervised and approved by the
C

research committee of the first author’s university. Informed consent of all participants was obtained, and
all procedures were conducted according to the Declaration of Helsinki and the study was approved by
AC

the institutional ethics committee. Moreover, the present clinical trial is registered on ClinicalTrials.gov
(NLM identifier NCT02170259).
This study was a pragmatic, randomized, double-blind, controlled trial, with blinding of
participants and examiners. Participants were randomly divided into 4 groups (3 treatment groups and 1
control group): Group 1 received the ST treatment; group 2 was applied the AT treatment and group 3
received the combined ST+AT treatment. The required number of subjects in each group was estimated
using nQuery Advisor (Statistical Solutions, Boston, MA). For an ANOVA with one inter-subject factor,
with 4 groups, and aiming to detect medium (0.5-0.8) to large (> 0.8)21 effects with a p < .05, at least 19
subjects in each group are required.

3
 ACCEPTED MANUSCRIPT
Both participants and physicians were blinded to treatment group allocation. For this purpose,
participants were randomly assigned to either one of the treatment groups or to the control group using a
computer-generated sequence after an initial clinical interview. Therapists were unaware of the type of
study in which they were participating, or its objectives. This was achieved through a research assistant
who provided the therapists with a patient number, a treatment protocol and evaluation criteria in a
closed, previously coded, envelope at the beginning of each session. Confidentiality provisions were
fulfilled following the Spanish legislation on personal data protection (Act 15/1999 of December 13th,
1999). All participants were assessed under the same conditions before treatment, after treatment (at 4

PT
weeks), and at follow-up (after 8 weeks) in the same location where treatment was conducted. The study
ended when the required number of subjects was obtained.

RI
Experimental intervention
The whole intervention lasted one month, over which period each patient received one treatment

SC
session per week, adding up to a total of 4 sessions within each group. Each treatment session lasted
approximately 20 minutes. After the treatment, all participants stayed in supine resting position for five
minutes. The control group did not receive any treatment and merely rested in supine position for 10

U
minutes.22
The suboccipital technique (ST) aims to relieve affected muscle spasm of the in tension-type
AN
headaches and suboccipital soft tissues in general, as they are responsible for the mobility dysfunction of
the occiput-atlas-axis joint; releasing the facial restriction of this region.17 As mentioned, participants lay
on a stretcher, in supine position, with their occiput resting against the physiotherapist’s hands. Fingertips
M

slid until contacting the posterior arch of atlas so that it “hung” from the fingers. A deep and progressive
pressure was applied, perpendicularly to muscle fibers, until the therapist perceived a decrease in
D

muscular tone. The duration of ST was 10 minutes and it was performed with participants’ eyes closed
due to the connection between craniocervical muscle tone and eye movements.14, 18, 23
TE

The articulatory technique (AT) was administered to correct and restore the mobility of joints
between occiput, atlas and axis – correcting a global joint dysfunction. This technique was conducted in
the same position as the ST technique (supine position), bilaterally and in two phases that lasted 5
EP

minutes in all. First, gentle head decompression was applied, followed by small circumduction searching
for the joint barrier in rotation through selective tension. Second, a high-velocity manipulation was
C

conducted, performing a cranially directed rotation towards the same side as the circumduction and
around a vertical axis passing through the axis, without cervical flexion or extension and very little side-
AC

bending.18,23,24
After the administration of each experimental group treatment, all participants stayed in supine
position for 5 minutes, with neutral ranges of head flexion, extension, lateral flexion and rotation, to allow
the tissues to adapt to the changes undergone after the treatment.
Combined treatment (ST and AT). Combined treatment consisted of the application of the two
preceding treatments in the same sequence: first, treatment with ST (10 minutes) and subsequently AT (5
minutes), thereafter maintaining the resting position for five minutes.18,23
Control intervention. The control group was applied no treatment technique; however, this group
attended the same sessions and was evaluated in a similar way as the treatment groups. In each session,

4
 ACCEPTED MANUSCRIPT
after the evaluation, instead of receiving treatment, participants just stayed in a resting position for 10
minutes.18,23
Assessment
Prior to commencing the trial, but after the randomization of participant was conducted, a
clinical interview was carried out by a research assistant, who was blind to the study objectives, and
participants’ treatment groups. The clinical interview collected socio-demographic data and inquiring
about their headaches in the four weeks prior to treatment. Further, the same assistant administered two
psychometric scales, measuring anxiety and depression. Further, the physicians who applied the

PT
respective treatments were not present neither in the clinical interview, nor when these scales were
administered.

RI
Anxiety was assessed with the State-Trait Anxiety Inventory (STAI-SA and STAI-TA).25,26 This
questionnaire is designed for the self-assessment of anxiety, both as a temporary state and a latent

SC
permanent trait, with 20 questions and 4-item Likert scale ranging from 0 = “not at all” to 3 = “very
much”. Overall scores range from 0 to a maximum of 60 points; scoring above the 50th percentile
indicates the presence of anxiety. For males, this percentile correlates with a score of 19 points, both for

U
STAI-state and STAI-trait. For females, scores over 21 for STAI-state and 24 for STAI-trait determine this
level. Cronbach’s α for this scale ranges from .83 to .92).27
AN
Depression was assessed with the Beck Depression Inventory (BDI),28 which consists of 21
items, assessing depressive symptoms on a Likert scale of 0-3, ranging from 0 = “rarely or not at all” to 3
M

= “most of the time or always”, with overall scores ranging from 0 to a maximum of 63 points. 15 of the
21 items measured cognitive or psychological symptoms while the other 6 measure physiological or
D

somatic symptoms. A total score of 0-13 indicates no depression; 14-19 mild depression; 20-28 moderate
depression and ≥29 severe depression. The BDI was adapted to Spanish and validated by Conde and
TE

Useros, showing very good psychometric properties (Cronbach’s α was .86).29-31

Statistical Analysis
EP

We performed a Repeated measures Analyses of Covariance (RM-ANCOVA) using pre, post and
follow-up measurements as data-points as within-subject factors, and treatment type and TTH type
(dummy coded 0 = Episodic TTH / 1 = Chronic TTH) as between-subject factors, taking p. < .05 as
C

significance level and rating effect sizes as small (0.2-0.5), medium (0.5-0.8) or large (> 0.8).21
AC

In terms of overall treatment efficacy, significant mean differences in the expected direction
between pre-test, post-test or follow-up measures would indicate that a specific treatment had the
intended effect. Furthermore, non-significant differences between post-test and the follow-up
measurements would indicate that this effect remained stable in time, while significant differences would
evidence a time-lagged effect of TTH treatment. In turn, to compare the efficacy of different TTH
treatments on depression or anxiety, we explored mean differences over our control group, using pairwise
estimated marginal mean differences (I-J) adjusted using Bonferroni’s method. A main effect would
suggest differences in TTH treatment efficacy, only if they significantly differed from the control group.
Instead, significant two-way or three-way between-within subject interactions would indicate that TTH
treatment efficacy varies across data points, TTH types, or both.

5
 ACCEPTED MANUSCRIPT
To ensure the validity of our conclusions, before interpreting our results we checked that all
assumptions of linear models were met. First, we tested the normality assumption by calculating the
Skewness and Kurtosis levels of our dependent variables (which was in all cases between the accepted -1
to 1 range) .32 Furthermore, we verified the homogeneity of the variance assumption using Levene’s test
(which was not significant in all between-subject analyses); and lastly, due to the repeated measures
design, we used Mauchly’s33 statistic to test for violations of the assumption of Sphericity. Following
Girden,34 we applied Huynh-Feldt’s correction if ε > .75 in both Greenhouse-Geisser35 and Huynh-Feldt36
tests whenever the assumption of Sphericity was violated.

PT
Results
Eighty-four subjects participated in this study: 68 women (81%) and 16 men (19%). Mean age

RI
was 39.7 years (SD 11.38), while the age range was from 18 to 65 years. 54.8% of the subjects suffered
from ETTH and 45.2% from CTTH. According to headache characteristics, 97.6% had bilateral pain, and
non-pulsating pain in 81% cases. 92% of the subjects perceived pain intensity as mild and 8% as

SC
moderate. Once the headache was established, for 71.4% of the subjects, the performance of physical
activity did not increase pain intensity. Trigger factors were assessed through a multiple choice

U
questionnaire: stress was the most important trigger factor for 70.2% of the sample, followed by work-
related factors (48.8%), emotional factors (34.5%) and family-related factors (19%) and those related to
AN
academic matters (8.3%). Four participants dropped out of the study: Two participants dropped out of the
AT group during the treatment period, (one due to slight physical discomfort after starting treatment and
one due to personal reasons). Similarly, two participants dropped out of the control group (one due to a
M

transient ordinary disease during the treatment period and one during the follow-up period in the absence
of pain relief). Our final sample consisted of 80 participants who completed the trial in full (see Figure 1).
D

Table 1 shows estimated marginal means, standard errors and 95% CI for our RM-ANCOVAS having
TE

anxiety-state, anxiety-trait and depression as dependent variables and table 1 for depression and anxiety.

Anxiety-Trait
EP

With regard to anxiety-trait, our multivariate analyses show that the three-way interaction
between Treatment type, TTH type and time was only marginally significant (Wilks’ Λ = .86; F (6, 136) =
1.84† η² = .07). However, a two-way interaction between TTH treatment types and elapsed time (F (6,
C

144) = 2.25* η² = .09), suggested that the efficacy of our treatments varied across treatment sessions, but
not across TTH types. As compared to the control group, ST is initially more efficient than AT treatment,
AC

but the latter eventually has a slightly stronger effect, independently of the participants’ TTH type (see
Figure 2).

Anxiety-State
For Anxiety-state multivariate analyses were non-significant. However, between-subject analyses
show an interaction effect between treatment types and TTH types (F (3, 68) = 2.90* η² = .11), indicating
that mean differences across treatment types vary according TTH type. More precisely, Figure 2 shows
that for participants suffering CTTH, as compared to the control group, the AT treatment group report the
lower scores in Anxiety-state, but ETTH participants report a lower anxiety state in the ST group.

6
Depression
ACCEPTED MANUSCRIPT
Finally, our multivariate analyses (Wilks’ Λ = .80; F (6, 138) = 2.74*, η² = .11) show a three-way
interaction between TTH treatment types, TTH types and elapsed time. In addition, between-subject
analyses show significant main effects between TTH types and TTH treatment groups. On the one hand,
participants with ETTH (I) reported significantly lower headache pain frequency that those suffering
chronic TTH (J; I-J = -5.49***, 95% CI [-7.95; -3.03]). Depression levels in the AT (I) group were
significantly lower than in the control group (J; I-J = -4.58*, 95% CI [-8.44; -.72]). Taken as a whole,
Table 1 and figure 3 show that while participants of ETTH in the AT group report lower absolute scores in

PT
depression, mean differences between the AT group and the control group are higher for CTTH
participants.

RI
Discussion
Our result show that in general, vertebral manipulative techniques (AT) in this study were more
efficient than inhibitory techniques (ST) due to the global bilateral effect that an articulatory release may

SC
have on the peripheral cervicocranial muscles. In other words, articulatory techniques enable a more
efficient muscular relaxation in this region than that achieved with direct muscular work only. As

U
suggested by some scholars, our results show mixed findings regarding the secondary benefit of manual
therapies on negative psychosocial symptoms associated with TTH.37 On the one hand, for anxiety-state,
AN
a more situational form of anxiety, we found that CTTH participants in the AT group report lower anxiety
(state) than those in the ST group. The opposite occurs for ETTH participants; ETTH participants in the
ST treatment group report lower anxiety-state than those in the AT group. We believe this may be due to
M

the fact that manual techniques in participants with chronic headache pain, such as CTTH, may break the
existing tensional sensitivity, bringing the articulatory complex back to normal, reducing the weekly
D

frequency and intensity of headache pain, showing an improvement whereby participants’ TTH-related
anxiety levels are reduced. Because ETTH is not chronic, as in CTTH, a ST seems to suffice to reduce
TE

anxiety. We believe that this is because this type of TTH does not affect the articulatory complex, but the
muscular level instead.
We found that for anxiety trait, understood as a natural disposition to feel anxious, the beneficial
EP

effects of TTH treatments did not vary between TTH types, however the duration of effects differed.
While as compared to the control group, participants in the ST treatment group showed lower initial
C

scores of anxiety trait, these scores did not change after the treatment, nor at follow-up sessions.
However, participants in the AT treatment group showed an important improvement during the treatment,
AC

and its scores for Anxiety-trait remained the lowest of all groups at the follow-up evaluation. We believe
that this may be due to the fact that the AT treatment has stronger impact on articulatory movement and
especially on the muscles of an area which may naturally accumulate tension in those individuals with a
tendency towards anxiety.
Finally, we found that the beneficial effect of TTH treatments on depression is contingent on
both the TTH type and the treatment received. This suggests that when physicians detect a patient with
visible symptoms of depression, the chosen treatment should be adjusted according to the patient’s TTH
type. Our results suggest that AT treatment participants report significantly lower scores on depression
than the control group, and this difference was even larger for ETTH participants.
In short, manual therapy treatments can positively impact the health of TTH participants,

7
 ACCEPTED MANUSCRIPT
relieving TTH episodes in the various affected areas. Our research helps to provide evidence regarding
the maximum scope of efficacy of manual therapy in headache treatment. More specifically, treatments
focusing on the suboccipital area efficiently reduce TTH-related physiological symptoms (e.g., headache
pain frequency and intensity) and as a secondary benefit, reduce depression and anxiety in participants
suffering from different TTH types. This study compared manual techniques that focused on the
suboccipital region, using suboccipital soft tissue and manipulative treatments. ST was chosen with the
aim of reducing craniocervical muscle tension, a possible cause of headache onset, while we chose AT for
its releasing and normalizing effect on movement and soft tissues. Taken as a whole, our findings suggest

PT
that AT is the technique which shows better results.
According to other authors,38 the clinical treatment of TTH participants should go above and
beyond localized treatment of the point at which the pain is located, and therapeutic strategies should be

RI
aimed at normalizing the overall sensibility of the central nervous system, which may be responsible for
extending pain in time. Besides the techniques used in this study, we recommend other techniques such as

SC
TrPs therapy, other specific exercises or cognitive focusing of pain.

Strengths and Limitations

U
An essential strength of this study is its robust design employing a randomized, double-
blinded, controlled clinical trial, investigating both individual and combined therapeutic approaches.
AN
Furthermore, the characteristics of TTH in our sample are consistent with the 2004 IHS classification1,2.
Finally, physiotherapists who administered the treatments in our study had more than 10 years of clinical
experience. Therefore, our study represents a valuable contribution to existing research on the treatment
M

of physiological symptoms of different TTH types and secondary benefits on associated psychosocial
symptoms.
D

However, our work entails certain limitations that future research should address. First of all, a
more extended evaluation of the positive effects of our treatments is required. Even though we conducted
TE

a short-term follow-up, a longer monitoring period would be desirable to better establish the temporal
stability of our TTH treatment effects. This seems particularly relevant when evaluating the positive effect
of TTH treatment on negative psychological states of TTH participants (e.g., anxiety and depression),
EP

because other environmental factors not considered in this study, such as risk factors in the patient’s
workplace, may foster stress-related tension in craniocervical muscles, which may lead to a relapse in
C

anxiety and depression (e.g. a poor ergonomic design in a patient’s workstation). In this line, future
research should explore the role played by TTH in work-related symptoms such as distress or burnout.
AC

Furthermore, the effect of treatment on physical measures was not assessed, as it exceeded the scope of
this study; accordingly, this would be another subject to be explored in future studies.

Conclusions
Overall, all treatments applied in this study have shown to have a positive effect in reducing headache
pain intensity. In our study, AT treatment seems to be the most efficient approach to TTH, also showing a
positive secondary effect on TTH-related psychosocial variables, such as depression and anxiety.
Treatments including AT, understood as vertebral high-speed manual techniques applied to the
suboccipital region, have shown to be more efficient than ST in reducing the weekly frequency of
headache pain. However, AT in participants suffering from TTH-related negative emotional states, such as

8
 ACCEPTED MANUSCRIPT
anxiety state, is more efficient for CTTH participants than for ETTH participants. Conversely, even
though failing to reach statistical significance at the p. < 0.5 level, ETTH participants show an
improvement with ST techniques. Finally, for TTH-related depression symptoms, both the AT treatment
alone, or combined with an ST treatment, is more efficient for participants suffering from ETTH.
Among all TTH treatments explored in this study, AT shows to be the treatment requiring less time and
obtaining better overall results. It should be noted that all treatments used in this study seem to have an
enhanced effect on ETTH and on CTTH. Therefore, we recommend using AT treatment due to its effect in
reducing the weekly frequency and intensity of headaches in TTH participants, and its positive effects on

PT
associated negative emotional states (anxiety and depression).

RI
U SC
AN
M
D
TE
C EP
AC

9
 ACCEPTED MANUSCRIPT

References

1. The International Headache Society. The International Classification of Headache Disorders, 2nd
edition. Cephalalgia 2004; 24(1):9-160. doi:10.1111/j.1468-2982.2003.00824.x
2. Headache Classification Committee of the International Headache Society (HIS). The international

PT
classification of headache disorders, (beta version). Cephalalgia 2013;33(9),629-808.
doi: 10.1177/0333102413485658

RI
3. Lenssinck MLB, Damen L, Verhagen AP, Berber MY, Passchier J, Koes BW. The effectiveness of
physiotherapy and manipulation in patients with tension-type headache: a systematic review. Pain
2004;112:381-387.

SC
4. Volcy-Gómez M. The impact of migraine and other primary headaches on the health system and in
social and economic terms. Rev Neurol 2006;43(4):228-227. doi:10.1111/j.1526-4610.2009.01369.x
5. Felício AC, Bichuetti DB, Celso dos Santos WA, Godeiro CO, Marin LF, Carvalho DS.

U
Epidemiology of primary and secondary headaches in a Brazilian tertiary-care center. Arq Neuro-
AN
Psiquiatr 2006;64(1):41-44.
6. Holroyd KA, Stensland M, Lipchik GL, Hill KR, O'Donnell FS, Cordingley G: Psychosocial
correlates and impact of chronic tension-type headaches. Headache 2000;40(1):3-16.
M

doi: 10.1046/j.1526-4610.2000.00001.x
7. Fernández-de-Las-Peñas C, Cuadrado ML, Arendt-Nielsen L, Ge HY, Pareja JA: Association of
D

cross-sectional area of the rectus capitis posterior minor muscle with active trigger points in chronic
tension-type headache: a pilot study. Am J Phys Med Rehabil 2008;87(3):197-203.
TE

doi:10.1097/PHM.0b013e3181619766
8. Bendtsen L, Fernández-de-la-Peñas C: The Role of Muscles in Tension-Type Headache. Curr Pain
Headache Rep 2011;15:451-458. doi:10.1007/s11916-011-0216-0
EP

9. Fernández-de-las-Peñas C, Alonso-Blanco C, Cuadrado ML, Gerwin RD, Pareja JA. Trigger Points
in the Suboccipital Muscles and Forward Head Posture in Tension-Type Headache. Headache
2006;46:454-460. doi:10.1111/j.1526-4610.2006.00288.x
C

10. Bodes-Pardo G, Pecos-Martín D, Gallego-Izquierdo T, Salom-Moreno J, Fernández-de-Las-Peñas,

AC

Ortega-Santiago R. Manual treatment for cervicogenic headache and active trigger point in the
sternocleidomastoid muscle: a pilot randomized clinical trial. J Manipulative Physjol Ther
2013;36(7):403-11. doi: 10.1016/j.jmpt.2013.05.022
11. Sánchez MC, Comeche MI, Vallejo MA. El biofeedback EMG en el tratamiento de pacientes de
ansiedad y depresión con cefalea tensional. Rev. Soc. Esp. Dolor 1999;6:17-23.
12. Espí GV, Gómez A. Eficacia del tratamiento en la cefalea tensional. Revisión sistemática. Fisiotera-
pia 2010;32(1):33-40. doi:10.1016/j.ft.2009.07.001
13. Castien RF, van der Windt DA, Grooten A, Dekker J: Effectiveness of manual therapy for chronic
tension-type headache: a pragmatic, randomised, clinical trial. Cephalalgia 2011;31(2):133-143.
doi:10.1177/0333102410377362

10
 ACCEPTED MANUSCRIPT
14. Toro-Velasco C, Arroyo-Morales M, Fernandez-de-las-Peñas C, Cleland JA, Barrero-Hernández FJ.
Short-term effects of manual therapy on heart rate variability, mood state, and pressure pain
sensitivity in patients with chronic tension-type headache: a pilot study. J Man Physiol Ther
2009;32(7):527-535. doi:10.1016/j.jmpt.2009.08.011
15. Mongini F, Rota E, Deregibus A, Ferrero L, Migliaretti G, Cavallo F, Mongini T, Novello A.
Accompanying symptoms and psychiatric co-morbidity in migraine and tension type headache
patients. J Psychosom Res 2006;61:447-451.
16. Hackett GI, Boddie HG Harrison P. Chronic Muscle Contraction Headache: the importance of

PT
depression and anxiety. J R Soc Med 1987;80:689-691.
17. Kowacs F, Socal MP, Ziomkowski SC, Borges-Neto VF, Toniolo DP, Francesconi CRM, Chaves
MLF. Symptoms of depression and anxiety, and screening for mental disorders in migrainous

RI
patients. Cephalalgia 2003;23:79-89. doi:10.1046/j.1468-2982.2003.00461.x
18. Espí-López GV, Gómez-Conesa A. Efficacy of manual and manipulative therapy in the perception of

SC
pain and cervical motion in patients with tension-type headache: a randomized, controlled clinical
trial. J Chirop Med 2014;13(1): 4-13. doi:10.1016/j.jcm.2014.01.004
19. Thiel H, Rix G: Is it time to stop functional pre-manipulation testing of the cervical spine?. Man Ther

U
2005;10(2):154-158. doi.org/10.1002/14651858.CD008112
20. Johnson EG, Landel R, Kusunose RS, Appel TD: Positive patient outcome after manual cervical
AN
spine management despite a positive vertebral artery test. Man Ther 2008;13(4):367-364. doi:
10.1016/j.math.2007.12.001.
M

21. Cohen J. A power primer. Psychological bulletin 1992;112(1):155. doi.org/10.1037/0033-

2909.112.1.155
22. Hanten WP, Olson S L, Hodson JL, Imler VL, Knab VM, Magee JL. The effectiveness of CV-4 and
D

resting position techniques on subjects with tension-type headaches. J Man Manip Ther 1999;7(2),
64-70.
TE

23. Espí-López GV, Gómez-Conesa A, Arnal A, Benítez J, Oliva A, Rodríguez C. Treatment of tension-
type headache with articulatory and suboccipital soft tissue therapy: A double-blind, randomized,
EP

placebo-controlled clinical trial. J Bodywork Mov Ther 2014;18(4),576-585.

doi:10.1016/j.jbmt.2014.01.001
24. Fryette HH. Occiput-Atlas-Axis. J Am Osteopath Assoc 1936;35:353-4.
C

25. Spielberger CD. STAI manual for the state-trait anxiety inventory. Self-Evaluation Questionnaire, 1-
24.
AC

26. Spielberger CD, Gorsuch RL, Lushene RE. STAI. Cuestionario de Ansiedad Estado/Rasgo. Madrid:
TEA, Ediciones, 1999.
27. Speilberger CD Vagg PR. Psychometric properties of the STAI: a reply to Ramanaiah, Franzen, and
Schill. J Pers Assess 1984;48(1):95-97.
28. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch
Gen Psychiatr 1961;4:561-571. doi:10.1001/archpsyc.1961.01710120031004.
29. Conde V, Useros E. Adaptación castellana de la Escala de Evaluación Conductual para la Depresión
de Beck. Rev Psiquiatr Psicol Med Eur Am Lat 1975;12:217-219.

11
 ACCEPTED MANUSCRIPT
30. Beck AT, Steer RA, Brown GK. Beck: Depression Inventory–Second. San Antonio (TX): Psycholog-
ical Corporation, 1996.
31. Storch EA, Roberti JW, Roth DA: Factor structure, concurrent validity, and internal consistency of
the beck depression inventory-second edition in a sample of college students. Depres-
sion and anxiety 2004;19(3):187-189. doi: 10.1002/da.20002
32. Groeneveld RA, Meeden G. Measuring Skewness and Kurtosis. The Statistician 1984;33(4):391-399.
doi:10.2307/2987742
33. Mauchly J: Significance test for Sphericity of a normal n-variate distribution. Ann Inst Stat Math

PT
1940;11:201-209.
34. Girden E. ANOVA: Repeated measures. Newbury Park, CA: Sage, 1992.

RI
35. Greenhouse SW, Geisser, S. On methods in the analysis of profile data. Psychometrika 1959;24:95-
112.

SC
36. Huynh H, Feldt LS. Estimation of the Box correction for degrees of freedom from sample data in
randomised block and split-plot designs. J Educ Stat 1976;1:69-82.

37. Bryans R, Descarreaux M, Duranleau M, Marcoux H, Potter B, Ruegg R, Shaw L, Watkin R, White

U
EJ. Evidence-based guidelines for the chiropractic treatment of adults with headache.
AN
J Manipulative Physiol Ther 2011;34(5):274-89. doi: 10.1016/j.jmpt.2011.04.008
38. Fernández-de-las-Peñas C, Courtney CA. Clinical reasoning for manual therapy management of
tension type and cervicogenic headache. J Man Manip Ther 2014;22(1):45-51.
M

doi.org/10.1179/2042618613Y.0000000050
D
TE
C EP
AC

12
 ACCEPTED MANUSCRIPT

Table 1. Mean differences between estimated marginal means of headache pain intensity
and frequency by TTH treatment type, TTH type and data Point.

PT
RI
U SC
AN
M
D
TE
C EP
AC

13
 ACCEPTED MANUSCRIPT

Table 2. Mean differences between estimated marginal means of depression and anxiety
by TTH treatment type, TTH type and data Point.

PT
RI
U SC
AN
M
D
TE
C EP
AC

14
 ACCEPTED MANUSCRIPT
Figure 1. Flowchart according to CONSORT Statement for the Report of randomized
trials.

PT
RI
U SC
AN
M
D
TE
C EP
AC

15
 ACCEPTED MANUSCRIPT
Figure 2. Effect of different TTH Treatments on Anxiety (trait and state) by
patientsparticipants with episodic (ETTH) and chronic TTH (CTTH) or data point.

PT
RI
U SC
AN
M
D
TE
C EP
AC

16
 ACCEPTED MANUSCRIPT
Figure 3. Effect of different TTH Treatments on Depression for participants with
episodic and chronic TTH.

PT
RI
U SC
AN
M
D
TE
C EP
AC

17
 ACCEPTED MANUSCRIPT
Table 1. Mean differences between estimated marginal means of depression and anxiety
by TTH treatment type, TTH type and data Point.

Treatment TTH Est. Marginal 95% 95%

Measure Data Point SE
Type Type Means LLCI ULCI
Depression Control ETTH Pre-test 6.24 1.45 3.35 9.13
Post-test 4.67 1.27 2.12 7.18
Follow-up 3.67 1.25 1.18 6.16
CTHH Pre-test 15.98 1.99 12.01 19.96
Post-test 14.23 1.74 10.75 17.70

PT
Follow-up 12.53 1.72 9.10 15.95
AT ETTH Pre-test 4.93 1.53 1.87 7.99
Post-test 3.34 1.34 .67 6.01

RI
Follow-up 2.02 1.32 -.61 4.66
CTHH Pre-test 7.70 2.02 3.69 11.73
Post-test 5.23 1.76 1.71 8.75

SC
Follow-up 6.57 1.74 3.10 10.04
ST ETTH Pre-test 9.34 1.81 5.74 12.94
Post-test 7.19 1.58 4.05 10.33
Follow-up 7.22 1.55 4.12 10.32

U
CTHH Pre-test 13.36 1.63 10.10 16.61
Post-test 13.39 1.43 10.55 16.24
AN
Follow-up 9.32 1.41 6.52 12.13
AT+ST ETTH Pre-test 8.28 1.57 5.14 11.42
Post-test 5.48 1.37 2.74 8.22
M

Follow-up 4.05 1.35 1.35 6.76

CTHH Pre-test 11.87 1.82 8.24 15.50
Post-test 11.51 1.59 8.34 14.68
Follow-up 10.57 1.57 7.45 13.70
D

Anxiety State Control ETTH - 23.95 1.72 20.52 27.39

CTHH - 22.52 2.45 17.63 27.40
TE

AT ETTH - 24.53 1.83 20.87 28.19

CTHH - 18.79 2.32 14.16 23.43
ST ETTH - 16.81 2.09 12.64 20.98
EP

CTHH - 22.10 1.92 18.27 25.94

AT+ST ETTH - 19.39 1.80 15.80 22.98
CTHH - 21.18 2.15 16.89 25.47
Anxiety Trait Control - Pre-test 22.39 2.02 18.37 26.41
C

- Post-test 24.64 2.00 20.65 28.64

- Follow-up 23.46 1.77 19.92 26.99
AC

AT - Pre-test 23.75 2.05 19.65 27.84

- Post-test 21.04 2.04 16.98 25.11
- Follow-up 21.17 1.80 17.57 24.77
ST - Pre-test 21.55 1.93 17.69 25.41
- Post-test 21.73 1.92 17.89 25.56
- Follow-up 21.29 1.70 17.90 24.68
AT+ST - Pre-test 27.90 1.95 24.02 31.79
- Post-test 24.96 1.93 21.10 28.82
- Follow-up 21.95 1.71 18.53 25.36

Note: A Bonferroni’s correction has been applied for multiple comparisons. AT = Articulatory technique;
ST = suboccipital technique; AT+ST = Combined Technique. Only statistically significant interactive
effects are shown.

1
 ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE
EP
C
AC
 ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE
EP
C
AC
 ACCEPTED MANUSCRIPT

PT
RI
U SC
AN
M
D
TE
EP
C
AC
 ACCEPTED MANUSCRIPT
We think that implications to practice are very important: this study proposes that focusing treatment on
the suboccipital region can neutralize pain, and reduce both Tension-type headache (TTH)-related
physiological and psychological symptoms, reducing in negative emotional states associated with TTH.

PT
RI
U SC
AN
M
D
TE
C EP
AC