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Table of contents
1. Tension-type headache................................................................................................................................ 1

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Document 1 of 1

Tension-type headache
Author: Speciali, JosGeraldo; Eckeli, Alan Luiz; Dach, Fabola
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Abstract: Tension-type headache (TTH) is the most prevalent of all headaches and also represents one of the
most expensive clinical conditions for the health system. Despite the high impact of this disorder and the
existence of well-established diagnostic criteria, knowledge about TTH is still quite limited. In most cases in
which crises are quite sporadic, the patients call this normal headache. However, there is a group of patients
with the chronic subtype of this headache whose quality of life is greatly compromised. According to the second
edition of the International Classification of Headache Disorders, TTH is a bilateral headache of the tight band of
pressure type of mild-to-moderate intensity that does not worsen with routine physical activities and whose
associated symptoms are less intense than those observed in migraine. Its physiopathology still awaits better
elucidation but the existence of central and peripheral mechanisms is already recognized. From a therapeutic
viewpoint, simple analgesics are used for the acute treatment of the condition, and tricyclic antidepressants are
the most effective class of drugs for its prevention. Follow-up of these patients over the years has demonstrated
that the course of TTH is quite favorable in most cases.
Full text: Tension-type headache (TTH) is the most common of all primary headaches and, despite its great
economic and social impact, it is still little studied. TTH used to be denoted psychogenic headache and
idiopathic headache, but more recent studies are beginning to delineate its physiopathology. With the use of the
diagnostic criteria proposed by the International Headache Society (IHS) it became possible to better
characterize this primary headache, permitting important advances [1]. The objective of this review is to discuss
the most important topics related to TTH.
Epidemiology
The lifetime prevalence of TTH can be as high as 89% and varies considerably throughout the world [2]. A
recent study has demonstrated differences in TTH prevalence among the various continents [3], with the
highest values being observed in Europe (86.5%) [2], and the lowest in Asia (12.9%) [2], and the lowest in Asia
(12.9%) [4] and the Americas (26.9%) [5].
When the condition is subdivided according to the frequency of headache, it can be seen that the prevalence
differs between TTH subtypes. The prevalence is 51% [2] for infrequent episodic TTH (ETTH), falling to 24.3%
for frequent ETTH [5], and being a little higher than 2% when the form of highest impact, chronic TTH (CTTH),
is considered [6].
Analysis of TTH prevalence as a function of age reveals that the peak of prevalence occurs between 20 and 39
years of age, followed by a reduction with increasing age [6,7].
Analysis of the curve of frequent ETTH incidence reveals a fall in incidence with increasing age [8]. Thus, cases
of headache of tension characteristics that start in patients older than 50 years have more chance of being
secondary.
The association of TTH with socioeconomic level is a matter of controversy, with some studies reporting
association between TTH and lower schooling and income [6,9], whereas others have not reproduced these
results in other populations [2,10]. It is not possible to state with the necessary certainty whether individuals of
low socioeconomic levels are subjected to more numerous external stressors that might cause TTH, or if TTH
reduces the ability to work, preventing these subjects from improving their socioeconomic level.
The male-to-female ratio is 4:5, with this difference starting in adolescence [11,12]. In childhood the prevalence
is similar in both sexes [13].
Impact
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Due to its high prevalence, TTH accounts for a large part of the socioeconomic impact of headaches. Although
60% of the patients with TTH report some disability related to headache, few studies have evaluated TTH
individually. A Danish study reports that 43% of migraineurs and 12% of TTH patients (representing 2 and 9% of
the population, respectively) took absence from work, the average number of days absent from work was 270
per 1000 migraineurs and 820 per 1000 TTH sufferers [14]. In a study conducted in Canada, 8.3% of the
patients with ETTH reported missed days of work due to headache. When missed days of work are added to
the reduced ability to work of persons who do not stay home during headache crises, the total is 4.2 days/year
lost due to TTH [15]. In a population survey, it was found that half of TTH sufferers discontinued normal
activities during their attacks and most required bed rest, preventing them from going to work or working
efficiently [16].
The quality of life related to health among patients with ETTH evaluated by the Medical Outcomes Study Short
Form (SF-36) is lower than that of a control population [17] and is similar to that of patients with migraine [18].
Patients with TTH attend fewer medical visits and have a smaller reduction of productivity while studying [19]
than migraineurs [20]. In addition, the direct and indirect costs of TTH are lower than those of migraine [21].
However, due to the high prevalence of TTH, the direct costs related to this type of headache are definitely not
negligible.
Clinical signs &symptoms
Tension-type headache is characterized by a tight band of pressure (nonpulsatile) type of headache, usually
bilateral, of mild-to-moderate intensity that does not worsen with routine physical activity. Its duration can vary
from 30 min to 7 days. Regarding the symptoms that accompany TTH, photophobia and phonophobia are not
present together, with only one of them usually occurring. Nausea and vomiting are not among the symptoms
associated with this type of headache, except for its chronic subtype, in which nausea of mild intensity can be
present [1]. Furthermore, stress and mental tension are the precipitating factors more commonly reported by
patients with TTH [22].
Tension-type headache is divided into three subtypes according to the frequency of headache: infrequent
ETTH, frequent ETTH, and CTTH. Infrequent ETTH corresponds to less than 1 day of pain per month (<12 days
of pain per year). The frequent subtype corresponds to cases in which the patient has 1-14 days of pain per
month for at least 3 months, while CTTH corresponds to cases in which the patient has headache for 15 days or
more per month for more than 3 months [1].
In general, patients with TTH are known to have a lower pain threshold than control individuals [23,24], and this
hypersensitivity is more frequently observed in patients with CTTH [25-27]. Thus, in addition to being subdivided
into different types according to the frequency of pain, TTH is also subdivided according to the presence or
absence of pain upon palpation of the pericranial region, so each TTH subtype (infrequent, frequent and
chronic) is also subdivided into two other subforms: associated with pericranial tenderness and not associated
with pericranial tenderness. On this basis, the second edition of the International Classification of Headache
Disorders (ICHD II) lists the following TTH subforms [1]: infrequent ETTH associated with pericranial tenderness
and infrequent ETTH not associated with pericranial tenderness, frequent ETTH associated with pericranial
tenderness and frequent ETTH not associated with pericranial tenderness, CTTH associated with pericranial
tenderness, and CTTH not associated with pericranial tenderness.
According to ICHD II, no instruments or complementary tests are necessary for the evaluation of the sensitivity
of the pericranial musculature [1]. Manual palpation by applying firm pressure with the second and third fingers
with rotary movements on the frontal, temporal, masseter, pterygoid, sternocleidomastoid, splenius and
trapezius muscles can satisfactorily evaluate local sensitivity. In addition to looking for the presence of pain
during the examination of the head, neck and shoulder muscles, the physician should also observe whether or
not this pain refers to another region. The tender points are the points of the skeletal musculature that ache only
locally upon palpation and the myofascial trigger points (TrPs) are the points of the musculature which, when
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compressed, in addition to causing local pain, also generate pain referred to a site distant from the accessed
one [28].
These subdivisions of TTH according to the frequency of headache and the presence of pericranial tenderness
are quite important and also practical. From a research viewpoint, they contribute to a better elucidation of the
physiopathological mechanisms involved in this type of pain, and from a clinical viewpoint they help patient
differentiation regarding the impact of headache on their lives and contribute to the choice of the more adequate
therapeutic strategy for each case.
The last, but no less important criterion for the diagnosis of TTH is the one that establishes that neither the
onset nor the course of headache is due to any other clinical condition. Thus, during anamnesis and physical
examination, the physician should be on the lookout for certain signs and symptoms that may suggest a
secondary etiology for this type of headache. The term 'red flags'is commonly employed by neurologists to refer
to the signs and symptoms that alert to possible secondary etiologies of headaches [29-32]. The red flags in
headaches are:
*Onset of headache after 50 years of age: the patient should be investigated even when the characteristics of
headache are of the tension type since after this age there is a low probability of the beginning of a primary
headache [8], and a high probability of a secondary headache to disorders such as neoplasias [33,34].
*Report of worst headache ever experienced: the physician should suspect that this is not TTH. The intensity of
pain in TTH is mild to moderate, meaning that pain can interfere with the daily activity of the patient, but does
not disable the [1].
*Patients who seek a doctor after experiencing a headache of sudden onset: it is imperative to exclude
subarachnoid hemorrhage, cerebral venous sinus thrombosis, cervical artery dissection or intracranial infection,
among other diseases [35-37].
*Changes in the characteristics of headache; such as intensity, location, frequency and response to the
treatments applied. The change in the pattern of headache is a red flag alerting to the possible presence of
intracranial neoplastic processes [38] or abusive use of analgesics among other causes of secondary
headaches [1,39,40].
*Headaches occurring during physical effort; such as sexual activity, coughing or sneezing, which normally
causes a transitory increase in intracranial pressure, may be primary or secondary, and should therefore be
investigated [1].
*Headache associated with focal neurological changes; such as, papilledema, stiff neck, paralysis,
asymmetrical pupillary response or hemianopsia [41].
*A new onset headache may also be investigated in patients with acute or chronic systemic diseases or with
immunodeficiency. The need for investigation and the tests to be requested will depend on the disease that is
being suspected. For example, a headache attributed to a simple flu does not require any investigation.
However, if a patient with active systemic lupus erythematosus starts to complain of a new headache, this may
reflect distinct conditions such as intracranial infection (if the patient is under immunosuppressive treatment) or
vasculitis of the central nervous system (CNS). HIV-infected patients with headache should be investigated.
*Headaches that wake a patient during sleep may reflect intracranial hypertension and should be investigated.
Intracranial tumors, venous sinus thrombosis [42], encephalitis, meningitis and idiopathic intracranial
hypertension [43,44] may provoke headache, especially during sleep.
Regarding this last item, it should be pointed out that some primary headaches usually wake a patient up during
the night, but do not require investigation, as is the case for cluster headache (CH) and hypnic headache (HH).
These are rare primary headaches, but with well-defined diagnostic criteria [1]. CH is an intense, short-lasting
(15-180 min), unilateral headache associated with autonomic signs and symptoms (e.g., tearing, conjunctival
hyperemia, rhinorrhea and palpebral ptosis) occurring at a frequency of one crisis every 2 days to eight crises
per day [1,45]. A HH is characterized by pressing headache of mild-to-moderate intensity, as in TTH, but occurs
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only during sleep and wakes the patient, in contrast to TTH, which preferentially occurs during wakefulness.
Bilaterality and the absence of autonomic signs and symptoms differentiate HH from CH [1,46].
Since headaches secondary to the most diverse causes may present tension characteristics, it is mandatory not
to attribute headache to another disorder, this being the determining factor for the diagnosis of all primary forms
of headache [1,32,38,47,48]. In practical terms, this means that patients who present with red flags should be
properly investigated even when the characteristics of their headache are compatible with any of the primary
headaches listed by the ICHD II [1].
Box 1 lists the diagnostic criteria for TTH (episodic and chronic) and migraine without aura, and Box 2 presents
a list of red flags.
Co-occurrence of migraine &tension-type headache
In order to investigate whether migraine and TTH are a continuum of the same condition or are different
diseases, Ulrich et al. compared the frequency of TTH in individuals with and without migraine [49]. On the
basis of their results, the authors concluded that TTH and migraine are separate disorders and not part of a
continuum of headache disorders. They suggested that migraine may aggravate and precipitate TTH, possibly
due to a convergence of various noxious peripheral inputs into the trigeminal nucleus. A more recent population
study also demonstrated that the risk and frequency of TTH was significantly higher in subjects with migraine
than in subjects who had never had migraine [50]. But future large longitudinal follow-up studies are required to
firm conclusions on the inter-relations of these headaches [50,51].
Comorbidities
Comorbidity is defined as the nonfortuitous association of two clinical conditions (i.e., the occurrence of these
conditions at a frequency higher than expected by chance). Studies of comorbid conditions in TTH are still
scarce. However, some investigations have associated psychiatric conditions such as depression and anxiety
[52] with TTH, especially with its chronic subtype [53,54]. A multicenter study was carried out in Italy to evaluate
the presence of psychosocial stressors and psychiatric disorders in individuals with TTH. The psychosocial
stressful events were determined with an ad hoc questionnaire and the psychiatric disorders (depressive,
anxiety and somatoform disorders) were diagnosed using the Diagnostic and Statistic Manual of Mental
Disorders-III Revised. Of the 217 individuals with TTH recruited (108 with ETTH and 109 with CTTH), 84.8%
presented at least one stressful psychosocial event or a psychiatric disorder. The prevalence of depression was
36.4% and the prevalence of anxiety was 52.5%. In 21.7% of the subjects in this series, headache was
diagnosed as a somatoform disorder. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the
most frequent psychiatric conditions among the anxiety disorders and mood disorders, respectively. When the
subjects were considered separately according to frequency of pain, the prevalence of psychiatric conditions
was found to be lower among individuals with ETTH (70%) than among individuals with CTTH (84%) [55], with
these values being quite high compared with those detected in the general population [56]. In addition, Janke et

al. reported that the presence of depression increases the vulnerability of patients with TTH to the triggering of
headache crises during experimental stressful tasks and is more associated with the presence of pericranial
tenderness [57]. Regarding psychiatric disorders, further studies are needed to clarify the implication of these
conditions in patients with TTH. Lack of recognition of comorbid conditions may contribute to treatment failure
and a consequent worsening of quality of life [58].
Pathophysiology
Despite the high occurrence of TTH in the population and its impact on quality of life, mainly the frequent ETTH
and CTTH types, fewer investigator groups are studying TTH than migraine, but its treatment is effective, even
when applied mostly on a clinical basis rather than in a double-blind placebo-controlled research.
The old concept that this disorder is caused by involuntary muscle contraction causing ischemia is not accepted
today. Some observations have proved that:
*Certain diseases involving hypertonia are not accompanied by pain, such as pyramidalism, extrapyramidalism,
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dystonia and others.

*There is no significant difference in the amplitude of electromyographic recordings from forehead and neck
muscles in patients with TTH, migraine and normal controls [59,60].
*The inhalation of nitrites (vasodilators) increases the intensity of pain or does not modify it in TTH [59].
*Intravenous injection of histamine in migraineurs and people with TTH can produce headache that looks like
migraine in the former and like TTH in the latter [61].
Today, the pathophysiology of TTH is considered to be multifactorial, with the involvement of the central and
peripheral nervous systems and of environmental factors. Some factors could be more important than others in
each subtype of TTH (infrequent episodic, frequent episodic and chronic).

Peripheral mechanisms
It has been demonstrated that the most prominent clinical finding in both adults and children suffering from TTH
is an increased tenderness to palpation of pericranial tissues and neck muscles and their tendon insertions. It
has also been determined that in CTTH, the pain threshold to pressure is reduced compared with control [23].
The muscle painful points detected in TTH are classified as tender points or TrPs. Tender points are muscle
points that produce spontaneous or provoked local pain, while TrPs are painful muscle points that, when
compressed or stretched, provoke pain both locally and at a distance from the stimulated site (i.e., referred
pain). TrPs can be divided into active and latent points. Active TrPs are responsible for spontaneous pain
whereas latent TrPs do not cause a clinical complaint of pain, but are diagnosed when manual palpation
demonstrates a hypersensitive muscle area from which pain is referred elsewhere in response to pressure.
Latent TrPs may be involved in TTH without sensitivity in pericranial regions [28].
Referred pain in the frontal region from TrPs in an extratrigeminal region, such as a cervical one, is explained by
the convergence of peripheral afferents (cervical and trigeminal) on the caudal nucleus of the trigeminus. Thus,
pain of cervical origin is perceived in a region of trigeminal innervation [62].
Simons et al. described various TrPs located in the cephalic segment which, when stimulated, produced
referred pain in the head [63]. The referred pain thus provoked was closely similar to TTH and could spread to
both sides of the head, being perceived as bilateral headache [63-65]. In addition, it has been demonstrated
that the produced pain is proportional to the intensity and frequency of TTH [23,24].
Fernandez-de-las-Pens et al. described TrPs in patients with CTTH that, when pressed, reproduced the
headache of CTTH [66,67].
Today it is generally accepted that there is sufficient scientific evidence to state that TrPs are involved in the
pathophysiology of TTH. Nociceptive stimuli from the TrPs which converge on the caudal nucleus of the
trigeminus may lead to central sensitization of the second sensory neurons and, secondarily, to suprasegmental
neuronal levels, thus inducing the typical pain of TTH. The more frequent the crises of TTH, the greater the
possibility of developing central sensitization. Sustained central sensitization appears to be the
pathophysiological basis of CTTH [68].
There is discussion about how the craniocervical TrPs are produced in TTH. The TrPs can be produced by a
slightly increased muscle activity during physical or mental stress, or by articular dysfunction of motor deficiency
that may result in microtrauma of muscle fibers and tendon insertions, and thereby in accumulation of
metabolites or excessive activity in a few motor units with consequent excitation of peripheral nociceptors. The
site with the highest nociceptor density in muscle is close to the myoneural plate, a region possibly involved in
the production of TrPs, which may be formed as a consequence of myoneural plate dysfunction [69]. The
mechanisms involved in the production of the TrPs may be related to the presence of substances particularly
effective in stimulating skeletal muscle nociceptors such as serotonin, histamine, bradykinin and potassium ions
[70]. The release of neuropeptides, such as substance P and calcitonin gene-related peptide, from muscle
afferents may also play a role in producing myofascial pain [71]. Other indirect evidence of the peripheral origin
of TrPs is the presence of these points in both ETTH and CTTH. Since in ETTH there is less central
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sensitization than in CTTH, if the cause of TrPs were central, a smaller number of TrPs would be expected to be
present in ETTH than in CTTH [66,67].
While a peripheral model is the most accepted one for the pathophysiology of ETTH, by contrast, a central
model is considered for CTTH. Repeated ETTH crises can lead to the transformation of ETTH to CTTH, with
little or no participation by the periphery. In this respect, in an elegant study, Ashina et al. showed that there are
no inflammatory mediators in the tender points of the trapezius muscle in patients with CTTH during rest and
static exercise [72]. The authors suggested that, once central and peripheral sensitization occurs, the muscle
factors become minimal or absent in the pathophysiology of TTH.

Central mechanisms
In contrast to the theory involving TrPs in the genesis of the headache in question, there are theories that
propose a central genesis of TTH, especially CTTH. These theories are based on phenomena of sensitization of
second-order neurons located in the caudal nucleus of the trigeminus and/or of suprasegmental neurons, and
on the demonstration of failure of the supraspinal antinociceptive mechanisms that act at the level of the
trigeminal nucleus [73,74]. The decrease in the volume of the grey matter brain structure found in TTH, which is
also involved in the central processing of pain, could also support the central hypothesis [75]. This decrease is
positively correlated with the duration of headache, and can be interpreted as a consequence of central
sensitization generated by prolonged input from pericranial myofascial structures.
Neurophysiology studies have been conducted in order to prove the central hypothesis of TTH. Schoenen et al.
studied the exteroceptive suppression of jaw-closing muscle activity (temporalis muscle) after stimulation of
trigeminal nerve fibers and reported that this activity is reduced, especially the late temporalis exteroceptive
suppression period (ES2) [76]. The ES2 component is mediated by central polysynaptic pathways involving the
bulbar reticular formation, limbic structures, the orbitofrontal cortex, nucleus raphe magnus and periaqueductal
gray matter. According to the authors, the phenomenon recorded may be a consequence of suprasegmental
sensitization of the systems involved in TTH. These results, however, were not confirmed by another study [25].
The trigemino-cervical reflex is a method used to evaluate the trigeminal system in TTH. This reflex consists of
a bilateral positive/negative wave in the average of the uncertified surface electromyogram (EMG),
corresponding to a short period of inhibition of voluntary motor unit firing. This inhibition is better seen after
stimulation of the infraorbital nerve and when recording the EMG from tonically active sternocleidomastoid
muscles. Studies have suggested that the trigemino-cervical reflex is sensitive in disclosing trigeminal system
hypersensitivity and is significantly abnormal in CTTH when compared with ETTH [77]. According to the
authors, sensitization in CTTH may be predominantly located at the level of the trigeminal nucleus.
Sensitive thresholds have been recently studied in the cephalic and extracephalic regions of patients with ETTH
and CTTH, and the results have demonstrated that central sensitizations involve the projections of pain in a
more extensive manner in CTTH.
Pain thresholds are normal in patients with ETTH, while patients with CTTH have decreased pain thresholds to
pressure, electrical and thermal stimuli. These findings convincingly demonstrated increased suprathreshold
pain sensitivity both in skin and muscle, and in both cephalic and extracephalic regions in patients with CTTH
[26]. The conclusion was that changes in the modulation of the mechanisms involved in pain do not only affect
the cephalic region in CTTH, but also all regions of the body. This could be caused by prolonged nociceptive
input from tender pericranial myofascial tissues resulting in segmental central sensitization at the level of the
upper cervical spinal dorsal horn/trigeminal nucleus, with secondary sensitization of supraspinal neurons; for
example, in the thalamus or somatosensory cortex [78].
Thus, present knowledge strongly suggests that the CNS is sensitized both at the level of the spinal dorsal
horn/trigeminal nucleus and supraspinally in patients with CTTH, while central pain processing seems to be
normal in patients with ETTH.
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In conclusion, the concept accepted today is that peripheral mechanisms such as a local and reversible
sensitization of nociceptors in the pericranial muscles is very probable in ETTH, but sensitizations of the CNS
provoked by these same peripheral mechanisms are the more probable mechanism involved in CTTH.
Prolonged nociceptive stimuli from pericranial myofascial tissue may be of importance for the conversion of
ETTH to CTTH [79].
Psychopathology
Stress and mental tension are the precipitating factors most frequently reported by patients, but there is no
proof about this relationship in TTH. An extensive review of the literature about the relationship between TTH
and psychological mechanisms demonstrated that few methodologically correct studies have been conducted in
this field and that much remains to be done [80]. The main conclusions reached thus far about this topic are:
*The personality profiles of individuals with ETTH are normal.
*People with TTH experience a greater number of everyday stressful events (minor ups and downs or hassles)
than controls and judge them to have more impact.
*Verbal reports by patients with TTH differ from those by controls, with TTH patients being more sensitive and
having lower pain thresholds.
*TTH patients tend to interpret physical symptoms as threatening physical integrity.
*TTH patients pay more attention to stressful events, attributing more weight to them.
*TTH patients have greater difficulty in coping with the problems arising in their daily life.
The above conclusions are mainly reached about ETTH, whereas studies of subjects with the chronic subtype
often reveal a higher frequency of depression and anxiety. As in other chronic pain disorders, psychological
abnormalities in TTH may be viewed as secondary rather than primary, and anxiety and depression are
probably comorbid with CTTH [81].
Genetics
In 2006, Russell et al. published a study with the aim of assessing the importance of genetic factors in the
subtypes of TTH [82]. The study was conducted on 11,199 pairs of twins and demonstrated that the
concordance of TTH was statistically higher among monozygotic twins of the same sex than among dizygotic
twins of the same sex. The difference in the index of agreement between monozygotic and dizygotic twins
ranged from 8 to 15% and was detected in infrequent ETTH, frequent ETTH and CTTH among women, and in
frequent ETTH among men. When the agreement of TTH subtypes was compared between dizygotic twins of
the opposite sex and dizygotic twins of the same sex, it was found to be lower in the former group, probably
owing to the lower prevalence of TTH among men. Analysis of these data and of results obtained in other
studies suggested that genetic factors are involved, at least in part, in frequent ETTH and in CTTH, and that
infrequent ETTH is mainly caused by environmental factors [83,84]. In an investigation of the type of inheritance
of CTTH, Russell et al. observed that 56 of 122 probands selected had first-degree relatives who also had
CTTH [85]. Compared with the general population, the risk of CTTH was three-times higher among first-degree
relatives of individuals with CTTH. In addition, complex segregation analysis revealed that the model that best
explained the segregation of CTTH in the family nucleus was the multifactorial one. Since the multifactorial
model was even superior over the sporadic model of segregation, and since there was no increased risk of
CTTH among the spouses of the probands, this subtype of headache is believed to really have a genetic cause.
However, in view of the complex genetic influence on CTTH, the identification of the genes involved will
definitely be quite a difficult task [86].
In 2007, Russell et al. published another study whose objective was to investigate the importance of genetic
and environmental factors in TTH [87]. They used a quantitative genetic modeling of variance components
based on 7,360 twin pairs. The authors concluded that the heritability estimates of TTH were 48% in men and
44% in women. On this basis, genetic effects contribute to nearly half of the variance in the liability to TTH.
Treatments
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Nonpharmacological treatment
Nonpharmacological treatments can be of help as acute and preventative therapy for TTH. They should be
mainly considered in cases of patients for whom drugs known to be effective for the management of this type of
headache are contraindicated or cause adverse effects (intolerance). Priority should be given to the use of
these therapies for pregnant and nursing women.
Among psychological treatments are various relaxation techniques, cognitive-behavioral therapies, and
techniques for pain management. Relaxation techniques consist of training the patient to recognize the signs of
tension and to relax rapidly in order to prevent or abort TTH crises. Cognitive-behavioral therapy teaches the
patient to identify and modify thoughts and beliefs that generate stress and aggravate headache. There are
various techniques of pain management that are mainly based on teaching the patient to recognize and deal
with the emotional and physiological stress that accompanies the painful process. Studies on these techniques
are methodologically limited but seem to show that psychological treatments are more effective than placebo or
nontreatment techniques, especially for children and adolescents with chronic headache [88]. A detailed
description of the techniques of psychological treatment can be found in several studies [89-96].
Another nonpharmacological technique that has been studied in patients with TTH is acupuncture. In general,
studies on the use of acupuncture in TTH show that this intervention may be useful [97-99]. However, the
evidence in favor of this procedure is not fully convincing. Thus, further studies are needed for acupuncture to
be routinely indicated [100].
There are other nonpharmacological therapies, such as chiropractic spinal manipulation, connective
manipulation, physiotherapy, cranial electrotherapy, a combination of transcutaneous electrical nerve
stimulation (TENS) and electrical neurotransmitter modulation, a regimen of automassage, therapeutic touch,
TENS and stretching, which have also been tested in subjects with TTH. However, due to the poor
methodological quality and the clinical heterogeneity of these studies regarding the patients selected, according
to two systematic reviews published in 2004 [101,102], the available evidence is insufficient to support or to
refute the effectiveness of these therapies for TTH.
A later review concluded that physical therapy is more effective than massage or acupuncture for the treatment
of TTH and appears to be most beneficial for patients with a high frequency of headache episodes. However,
the authors still suggested further studies of improved quality to more firmly establish the place of physical
modalities in the treatment of primary headaches [103].
In 2006, additional studies on the physical therapies for TTH were published. One of them showed that
relaxation training induced the most pronounced effects directly after the treatment period compared with
acupuncture and physical training for patients with CTTH [104], and the other concluded that physiotherapy
including craniocervical training significantly reduced headache frequency, intensity and duration at 6-months
follow-up [105].

Acute pharmacological treatment

Simple analgesics are the drugs used most frequently for the acute treatment of TTH. Among the drugs
administered by the oral route are aspirin (500-1000 mg) [106-109], acetaminophen (1000 mg) [109-111],
dipyrone (500-1000 mg) [112], ibuprofen (400-800 mg) [113-115], ketoprofen (50 mg) [111,115], naproxen
sodium (375-825 mg) [110,115], diclofenac potassium (12.5-25 mg) [116,117], and formulations containing
simple analgesics in combination with caffeine [114,118,119].
The intravenous administration of dipyrone (1000 mg) [120,121] and chlorpromazine (0.1 mg/kg) [122], and the
intramuscular form of ketorolac (60 mg) [117] have also proved to be effective for the acute treatment of TTH.
The use of muscle relaxants is not indicated for the acute treatment of TTH because of the lack of studies and
of the risk of habituation.
Furthermore, physicians should alert the patients not to take simple analgesics on more than 14 days/month or
simple analgesics combined with caffeine on more than 9 days/month to avoid the development of analgesic
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rebound headaches and medication-overuse headache [1,40,123].

Preventive pharmacological treatment

Prophylactic treatment should be predominantly be considered for patients with CTTH and frequent ETTH who
are at risk for abusive use of analgesics, as well as for patients with pericranial tenderness and for patients who
are already abusing analgesic medications.
The main class of medications used for the prevention of TTH is that of tricyclic antidepressants. Among them,
amitriptyline (10-75 mg/day) is the prophylactic agent most extensively studied [124-127]. However, other
options such as nortriptyline (50 mg/day) [128], clomipramine (75-150 mg/day) [129], protriptyline (20 mg/day)
[128], protriptyline (20 mg/day) [130], and the tetracyclic antidepressants maprotiline (75 mg/day) [131] and
mianserin (30-60 mg/day) [129,132] can be used. Except for protriptyline that was tested as a single dose in the
morning, these drugs should be preferentially administered in a single dose at night in order to prevent sedation.
However, larger doses should be administered in two daily doses. The main side effects are sedation, weight
gain, dry mouth and constipation.
For doxepin, a tricyclic antidepressant used extensively today for the treatment of primary insomnia, depression
and other conditions [133], only two studies published in the 1970s mentioned its use in patients with TTH
[134,135]. Until new papers are published, it is not possible to draw conclusions about the role of this
medication in the prophylactic treatment of TTH.
Serotonin reuptake inhibitor antidepressants such as fluoxetine (20 mg/day) [127], paroxetine (20-40 mg/day)
[136,137] and fluvoxamine (50-100 mg/day) [132], and the serotonin-norepinephrine reuptake inhibitor
venlafaxine (37.5-300 mg/day) [138] also presented favorable results for the treatment of TTH. Although better
tolerated, they are less effective than tricyclic antidepressants [127,139]. They should be administered in the
morning in order to minimize the impact of some side effects such as anxiety, restlessness and insomnia.
Mirtazapine (30 mg/day), an antidepressive drug with noradrenergic and serotoninergic action, was also
superior to placebo for the treatment of CTTH in one study [140].
Other agents such as tizanidine (6-18 mg/day) [141], a muscle relaxant, and sulpiride (200-400 mg/day) [136], a
dopaminergic antagonist, have proved to be effective for the treatment of patients with CTTH. However, further
studies are needed before their routine use. Also, one study has suggested that the combination of tizanidine (4
mg/day) with amitriptyline (20 mg/day) is faster than amitriptyline alone in providing an improvement in the
CTTH pattern [142].
Several studies have been conducted over the last decade to assess the efficacy of botulinum toxin type A
(BTA) for the treatment of CTTH. The doses studied ranged from 20 to 500 units applied to various sites in the
pericranial region [143-150]. However, due to the marked methodological differences among the various
studies, the effect of BTA on CTTH continues to be contradictory, and the appropriate sites for its application
are still inconclusive. In addition, a systematic review of the literature demonstrated that currently available
results do not permit the indication of the use of BTA for the treatment of pain originating from the TrPs [151].
For bilateral infiltration of the major occipital nerves, two studies have demonstrated the ineffectiveness of this
procedure in the prophylactic treatment of individuals with TTH [152,153].
A recent study has shown the beneficial effects of local therapy of active TrPs on migraine symptoms in patients
in whom migraine sites coincide with the referred areas of the TrPs [154]. However, there are no studies
demonstrating the effect of TrP anesthetic infiltration in patients with TTH.
In general, some principles are followed for most of the prophylactic pharmacological treatments of TTH:
*The drugs must be started slowly, with a 7-day progression in the dose until the lowest effective dose is
reached. For example: to reach the lowest effective dose of nortriptyline (50 mg/day) you should first prescribe
12.5 mg/day for 7 days, raising the dose to 25 mg/day for a further 7 days, and finally, raising the dose to 50
mg/day. The objective of this conduct is to minimize the side effects and to reduce the chance of drug
intolerance.
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*After the lowest effective dose is reached, a period of 2-4 weeks should be allowed to elapse for the beginning
of the therapeutic effect.
*The therapeutic response should be evaluated after at least 8 weeks of daily use of fixed doses of the drug.
*When necessary, the dose should be increased later in a slow manner.
*Also, whenever possible, medications that simultaneously treat the headache and the comorbidities, when
present, should be prescribed. This means prescribing antidepressants when depression or dysthymia is
present in addition to TTH and indicating nonpharmacological therapies, such as relaxation and cognitivebehavioral therapy, when anxiety is present [155].
Some side effects and contraindications of the drugs most commonly used for the acute or preventive treatment
of TTH are listed in Table 1.
Prognosis
In 2005, Lyngberg et al. published a study whose objective was to determine the prognosis of migraine and TTH
in adults [156]. A cross-sectional study was first conducted on a population of 1000 inhabitants of Copenhagen.
This first stage of the study was conducted in 1989, and in 2001 a follow-up study of the 1989 cohort was
conducted on the 643 eligible cases. Of the 146 individuals with frequent ETTH and 15 with CTTH in 1989, 45%
presented infrequent ETTH or complete remission of headache in 2001. Of the individuals with CTTH in 1989,
47% no longer presented this diagnosis during follow-up. In general, a good prognosis was observed in 84% of
cases and a poor one (CTTH) in 16%. The factors predicting a poor prognosis were: coexistence of migraine,
being unmarried, presence of sleep disorders and sedentarism. The factors predicting a good prognosis were:
more advanced age and absence of a CTTH diagnosis in 1989. On this basis, it can be seen that in most cases
TTH has a favorable prognosis. The good course of this headache was also observed in children and
adolescents studied by Guidetti and Galli [157].
Expert commentary
The most frequent type of headache is TTH. Approximately 87% of the population has had or will have TTH at
some time in their life. However, in doctors'offices, TTH is seen less frequently than migraine. Patients usually
do not consider it a sufficient reason to look for a doctor or for another health professional. They are able to
relate the episodes of headache to certain events in life and are therefore not concerned with it.
Few papers about TTH are available in the specialized literature, especially regarding the infrequent subtype
(<12 days of pain per year). Frequent ETTH (which occurs >1 day and <15 days per month) has been more
extensively studied, and more patients seek professional help due to this type of headache.
It is quite probable that patients, nonspecialist doctors and the remaining health professionals consider this type
of headache to be the consequence of psychological problems, proposing a central physiopathology for this
disorder. However, current studies agree by determining a peripheral physiopathology related to the presence
of TrPs in the craniocervical musculature. TTH would be one of the symptoms provoked by these sensitized
muscular points.
Although many patients do not have much disability due to ETTH, it is necessary to inform all health
professionals about the possibility that ETTH will progress to CTTH and about the factors that facilitate this
progression. From this perspective, TTH strongly resembles migraine. Processes of sensitization at the level of
the nucleus of the trigeminus nerve and of other suprasegmental regions (the thalamus and regions that
process pain in all its dimensions) are involved in the progression of ETTH to CTTH. The main facilitators of
progression are: an increase in the number of TrPs, an increase in the frequency of crises, and the abusive use
of analgesic medications. The idea that ETTH can progress to CTTH should be disseminated to all health
professionals. Patients with CTTH have a worse quality of life, with an impact on various spheres such as job,
family and society. In addition, affected subjects have comorbid diseases such as depression, anxiety and
somatoform disorders.
In conclusion, all existing means of communication should be used to inform the general population and health
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professionals that TTH can be as disabling as migraine and should be treated before its progression to CTTH.
Five-year view
Today, the concept of TTH has changed in a profound manner from the definition given by the Bethesda
Committee in 1962 [158] when TTH was considered to be a tight band of pressure or constriction commonly
affecting the occipital region. The maintained contraction of cervical muscles was the cause of pain and a
response to stress. Muscle contraction was thought to lead to circulatory difficulty and muscle ischemia and
consequently to pain. However, this physiopathology for TTH is no longer accepted today.
An important step was taken in 1988, when the IHS introduced the Classification and Diagnostic Criteria of
Headaches, Cranial Neuralgias and Facial Pain using rigid diagnostic criteria that were slowly accepted in
several countries and by practically all researchers dealing with headache [159]. From that time on, it became
possible to compare investigations and results and to determine the prevalence and incidence of the various
types of headache, with the classification modifying clinical practice. In this classification, TTH was subdivided
into ETTH and CTTH (each with and without disorders of the pericranial musculature).
The 2004 classification introduced an important modification, with the inclusion of the infrequent and frequent
TTH subtypes [1]. The current assumption is that the former may have an exclusive peripheral physiopathology,
while the latter may be the consequence of central sensitizations at the trigeminal and suprasegmental levels.
These concepts have influenced the approach to and the management of the two subtypes. The recognition of
TrPs as a factor triggering TTH, modified and added options to the treatment of infrequent ETTH. The
recognition of the central sensitizations in frequent ETTH increased the options of drug treatment and indicated
the need to prevent progression to CTTH.
We may predict that in the near future infrequent ETTH will be recognized as a nosologic condition differing
from the remaining subtypes of TTH.
The evolution of information about the comorbidities that influence the severity of TTH will be fundamental for
the development of new broad-spectrum pharmacological therapies to be used to treat TTH and its
comorbidities simultaneously. With this, drug combinations and interactions directly associated with lower rates
of treatment compliance could be avoided.
It is expected that the interest in TTH will increase, as has been observed for migraine for many years. We need
more investigators involved in this topic, so that more physiopathological mechanisms may be determined and
new treatments proposed.
Congresses and scientific meetings about headache might devote more time to TTH. The researchers who
investigate this condition should be better appreciated and new researchers should be encouraged. Thus, the
larger the number of studies and results obtained, the greater the interest in this condition. With this, a cycle of
interests will be closed, resulting in better proposals for coping with TTH.
In conclusion, we can optimistically predict that the prevalence of CTTH will be reduced over the next few years
if government prevention programs are set up at various levels of healthcare for the population in order to
intervene with the factors responsible for the chronification of TTH.
Table 1.

Drug

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Rout
e

Recommended dose

Some side effects

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Some
contraindications

ProQuest

Acute treatment

Aspiri
n;
Aceta
mino
phen;
Dipyr
one
(meta
mizol
); ;
Ibupr
ofen;
Ceto
proph
en;
Napr
oxen
sodiu
m;
Diclof
enac
potas
sic

O; O; O; IV; O; O; O;
O

Peptic ulcer, renal

failure, the first and
last 3 months of
pregnancy, blood
dyscrasias;
acetaminophen can
be used throughout
pregnancy

Prop
hylact
ic
treat
ment:
tricycl
ic
drugs

Amitriptyline;
Nortriptyline;
Clomipramine;
Protriptyline

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500-1000 mg; 7501000 mg; 500-1000

mg; 1000 mg; 400800 mg; 50 mg; 375825 mg; 12.5-50 mg

Gastric pain or
bleeding, hepatic or
renal dysfunction,
hypotension and
agranulocytosis

O; O; O; O

10-75 mg/N; 50
mg/N; 75-150 mg/N;
20 mg/M

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Dry mouth,
constipation,
sedation and weight
gain

Heart
cond
uctio
n
disor
ders,
narro
wangle
glauc
oma
and
prost
ate
hyper
troph
y

Prophylactic
treatment: SSRIs

Fluoxetine;
Paroxetine;
Venlafaxina

O; O; O

Box 1.
Diagnostic criteria of infrequent episodic, frequent episodic and chronic tension-type headache, and migraine
without aura.

Infrequent episodic tension-type headache

A At least ten episodes occurring on less than 1 day/month on average (<12 days/year) and fulfilling criteria B-D
B Headache lasting from 30 min to 7 days
C Headache has at least two of the following characteristics:
C -Bilateral location
-Pressing/tightening (nonpulsating) quality
-Mild or moderate intensity
-Not aggravated by routine physical activity such as walking or climbing stairs
D Both of the following:
D -No nausea or vomiting (anorexia may occur)
-No more than one of photophobia or phonophobia
E Not attributed to another disorder

Frequent episodic tension-type headache

A At least ten episodes occurring on 1 or more days (but <15 days) per month for at least 3 months (12 and
<180 days per year) and fulfilling criteria B-D
B Headache lasting from 30 min to 7 days
C Headache has at least two of the following characteristics:
C -Bilateral location
-Pressing/tightening (nonpulsating) quality
-Mild or moderate intensity
-Not aggravated by routine physical activity such as walking or climbing stairs
D Both of the following:
D -No nausea or vomiting (anorexia may occur)
-No more than one of photophobia or phonophobia
E Not attributed to another disorder

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Chronic tension-type headache

A Headache occurring on 15 or more days per month on average for more than 3 months (180 days per year)
and fulfilling criteria B-D
B Headache lasts hours or may be continuous
C Headache has at least two of the following characteristics:
C -Bilateral location
-Pressing/tightening (nonpulsating) quality
-Mild or moderate intensity
-Not aggravated by routine physical activity such as walking or climbing stairs
D Both of the following:
D -No more than one of photophobia, phonophobia or mild nausea
-Neither moderate or severe nausea nor vomiting
E Not attributed to another disorder

Migraine without aura

A At least five attacks fulfilling criteria B-D
B Headache attacks lasting 4-72 h (untreated or unsuccessfully treated)
C Headache has at least two of the following characteristics:
C -Unilateral location
-Pulsating quality
-Moderate or severe pain intensity
-Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
D During headache at least one of the following:
D -Nausea and/or vomiting
-Photophobia and phonophobia
E Not attributed to another disorder
Box 2.
Red-flag list.
*Onset of a new different headache in patients over 50 years of age.
*Worst headache ever experienced.
*Headache that awakes the patient at night.
*Change in a well-established headache pattern.
*Headache related to exertional, sexual activity or coughing.
*Focal neurologic findings on physical examination (e.g., papilledema, stiff neck or paralysis).
*New onset headache in immunocompromized patients.
*Headache related to systemic illness.
Key issues
*Why should we be interested in tension type headache (TTH)? TTH is the most common of all headaches and
therefore physicians working in the most diverse areas may face this condition. In addition, TTH is responsible
for a large part of the socioeconomic impact of headaches. The expenses involved in medications, the use of
health services and the reduction in quality of life attributed to TTH are significant.
*TTH is related to some psychiatric conditions such as depression and anxiety. The lack of recognition of
comorbid diseases in TTH may be responsible for treatment failure and the chronification of headache.
*The diagnosis is clinical and is based on the characteristics of the headache: bilateral, of a tight band of
pressure type (nonpulsatile), of mild or moderate intensity, does not worsen with routine physical activity such
as walking or climbing steps, and in general is not associated with photophobia or phonophobia. Mild nausea is
assumed to occur only in the chronic subtype of TTH.
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*For a diagnosis of TTH, it is important that neither clinical history nor physical examination suggest organic
causes of the headache. When a headache with tension characteristics is associated with red flags, the
exclusion of secondary headaches by appropriate investigation is mandatory.
*From the pathophysiological viewpoint, infrequent ETTH is related to the presence of trigger points of cervical
and pericranial structures, while chronic TTH (CTTH) is related to central segmental (caudal nucleus of the
trigeminus) and suprasegmental sensitizations. Frequent episodic TTH (ETTH) appears to be an intermediate
form between these two extremes.
*Psychological factors do not seem to be important for infrequent ETTH. In CTTH, psychiatric comorbidities are
common, especially depression and anxiety disorders.
*Nonpharmacological therapies should be indicated for patients with contraindications or intolerance of the
drugs used for TTH treatment. They are more important for the treatment of children, adolescents, pregnant
women and nursing women.
*Simple analgesics can be prescribed for the acute treatment of TTH. Amitriptyline is the main drug for
preventive treatment. Selective serotonin reuptake inhibitors are less effective, but are better tolerated than
tricyclic agents.
Financial &competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received
or pending, or royalties .
No writing assistance was utilized in the production of this review manuscript .
Footnote
Reproduced with permission from [1].
Data from [29-32,41].
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AuthorAffiliation
JosGeraldo Speciali, [dagger] Author for correspondence, Department of Neurology, University Hospital,
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Faculty of Medicine of Ribeiro Preto, University of So Paulo, 3900 Bandeirantes Avenue, Ribeiro Preto, So
Paulo 14049 900, Brazil. speciali@netsite.com.br
Alan Luiz Eckeli, Department of Neurology, University Hospital, Faculty of Medicine of Ribeiro Preto, University
of So Paulo, 3900 Bandeirantes Avenue, Ribeiro Preto, So Paulo 14049 900, Brazil.
eckeli_alan@yahoo.com.br
Fabola Dach, Department of Neurology, University Hospital, Faculty of Medicine of Ribeiro Preto, University of
So Paulo, 3900 Bandeirantes Avenue, Ribeiro Preto, So Paulo 14049 900, Brazil. fabioladach@usp.br
MeSH: Humans, Tension-Type Headache -- classification, Treatment Outcome, Analgesics -- therapeutic use
(major), Antidepressive Agents -- therapeutic use (major), Clinical Trials as Topic -- trends (major), TensionType Headache -- diagnosis (major), Tension-Type Headache -- drug therapy (major)
Substance: Analgesics; Antidepressive Agents;
Publication title: Expert Review of Neurotherapeutics
Volume: 8
Issue: 5
Pages: 839-53
Publication year: 2008
Publication date: May 2008
Year: 2008
Publisher: Informa Healthcare, Expert Reviews Ltd.
Place of publication: London
Country of publication: United Kingdom
Publication subject: Pharmacy And Pharmacology, Medical Sciences--Psychiatry And Neurology
ISSN: 1473-7175
Source type: Scholarly Journals
Language of publication: English
Document type: Review, Journal Article
DOI: http://dx.doi.org/10.1586/14737175.8.5.839
Accession number: 18457540
ProQuest document ID: 889788599
Document URL: http://search.proquest.com/docview/889788599?accountid=49910
Copyright: 2008 Expert Reviews Ltd
Last updated: 2014-03-19
Database: ProQuest Medical Library

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