Tension-Type Headaches and Coexisting Migraine

Tension-Type Headaches

The terms “muscle contraction” and “tension” headaches have been used interchangeably for several years. The Classification Committee of the International Headache Society (IHS) has established the term “tension-type” headache (TTH) as the most appropriate label for these headaches.

Tension-type headaches are a manifestation of the body’s reaction to:

• Stress
• Anxiety
• Depression
• Emotional conflicts
• Fatigue
• Repressed hostility.

In one proposed schema, the pathophysiological mechanisms of TTH can be divided into genetic factors, peripheral mechanisms and central mechanisms (Figure 5-1). Genetic factors play a role in TTH, with heritability estimated ranging from ~20% to ~50%. Very little is understood about the contribution of individual genes to TTH risk. Two loci that are linked to increased TTH risk include the 5-HTT-gene-linked polymorphic region (5-HTTLPR) and the COMT gene (coding for catechol-O-methyltransferase), specifically the V158M substitution. The APOE-ε4 gene variant is associated with reduced TTH risk. Peripheral mechanisms can be subdivided into myofascial and vascular mechanisms. Pericranial muscles may be affected by localized inflammation and/or ischemia in patients with TTH, causing tenderness and/or hardness; although this has been proposed to lead to nociceptor sensitization, the directionality of the causative relationship with TTH is not yet established. Vascular mechanisms – higher blood flow in cerebral arteries, abnormal blood flow in the carotids and abnormal extracranial vascular response – may also contribute to TTH development, although their role is comparatively less important than in migraine. Finally, central mechanisms, including sensitization of second-order neurons in spinal cord, second- and third-order supraspinal neurons and alterations in nociceptive activity of the thalamus, the limbic system, motor cortex and somatosensory cortex, play a role in the “chronification” of TTH (i.e., the transformation of episodic TTH into chronic TTH – see below).

The ICHD-3 subdivides TTH into three main classes: infrequent episodic TTH, frequent episodic TTH and chronic TTH. As implied by the nomenclature, the main feature distinguishing these subtypes is the duration and frequency of headache attacks. Infrequent episodic TTH lasts 30 minutes to several days, and occurs on average <12 days per year. Frequent episodic TTH has the same duration but greater frequency (1-14 days per month on average for more than 3 months). Chronic TTH may last from hours to days, and occurs on more than 180 days per year (or more than 15 days per month for more than 3 months). The full ICHD-3 diagnostic criteria for the three TTH subtypes are shown in Table 5-1.

Tension-type headaches are very common (with a prevalence of 30-78% in the general population), occur slightly more frequently in women (female:male ratio 1.2:1), and can occur at any age. Typically, the headaches start between the ages of 20 and 40 years. A family history of similar headaches may be noted. The pain associated with TTH is usually:

• A pressure or tightening sensation
• Of mild to moderate severity
• Bilateral in location
• Not exacerbated by physical activity
• Without prominent associated symptoms.

Patients usually describe TTH pain as steady and nonpulsating, but it may also be depicted as:

• Bitemporal or bioccipital tightness
• Bandlike sensations around the head
• Viselike ache
• A weight
• Pressure sensations
• Drawing
• Soreness.

The forehead, temples, and the back of the head or neck are the most commonly affected sites in TTH. Other locations may be affected and usually bilaterally, in contrast to the typically unilateral migraine. On palpation, sharply localized nodules may be noted. The pain may radiate to other areas, such as the neck or shoulders. Shivering or exposure to the cold may exacerbate the pain.

Patients with episodic, particularly infrequent episodic, TTH rarely consult a physician for their attacks and often treat themselves successfully with over-the-counter (OTC) analgesics. When these are not effective, combination analgesics such as aspirin plus butalbital and caffeine (Fiorinal), acetaminophen with butalbital (Phrenilin), or acetaminophen plus butalbital and caffeine (Fioricet, Esgic) may be prescribed. If more pain-relieving potency is required, a compound agent with aspirin or acetaminophen plus butalbital, caffeine and codeine may be considered (Fiorinal/Fioricet with Codeine). Esgic, Fioricet and Fioricet with Codeine are aspirin-free and avoid any aspirin-related GI problems. When used properly, these products are highly effective with little chance of abuse or habituation.

Chronic TTH are continuous or unremitting. These patients will present with prolonged histories of headaches. These headaches are often – thought not always – a manifestation of an underlying psychologic disorder, including anxiety or depression. The examining physician should review any family, work, school, or marital conflicts. If the patient is not forthcoming with this information, the review may need to take place over several visits. The psychological inventory should include questions about the following:

• Life stresses
• Occupation
• Habits
• Personality traits
• Marital relations
• Social relationships
• Sexual problems
• Methods of coping with stress.

Patients with chronic anxiety usually:

• Report only one type of headache
• Describe headache as annoying and not associated with other symptoms, such as nausea and vomiting
• Complain of difficulty falling asleep, which is the feature that distinguishes anxiety from depression.

Because these patients usually worry excessively about their headaches, reassurance is a prominent aspect of their therapy.

In patients with chronic TTH associated with depression, a variety of symptoms may be present in addition to the headaches. Physical symptoms include:

• Sleep disturbance–early or frequent awakening
• Shortness of breath
• Constipation
• Weight loss
• Fatigue
• Decreased sexual drive
• Palpations
• Menstrual changes.

Patients with underlying depression may seem “blue” and in low spirits during the interview. Spontaneous crying may occur. Emotional complaints include:

• Feelings of guilt
• Hopelessness
• Unworthiness
• Basic fear of insanity
• Rumination over the past, present and future
• Fear of physical disease or death.

Patients may note that morning is the worst time of day and, similar to depression, a diurnal variation in pain may be identified. Psychic complaints include:

• Poor concentration
• Loss of interest
• Low or no ambition
• Indecisiveness
• Poor memory
• Suicidal ideation.

Patients may relate the onset of the headaches to a specific event, such as an accident. Patients may also relate the headaches to a bodily injury or alteration, although physical and radiologic examination will rule out these conditions. Patients may list other causes, including the death of a loved one, a minor illness, an injection, a surgical procedure, loss of a job, or divorce. The event may be perceived as much more serious and out of proportion to the actual occurrence or its impact.

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Treatment

Figure 5-2 provides a schematic drawing of the treatment of TTH, including both options for acute symptomatic relief applicable to all types of TTH and prophylactic options, both pharmacological and non-pharmacological, for patients with frequent episodic TTH and chronic TTH.

For infrequent episodic TTH, relief can usually be obtained with Over the counter (OTC) analgesics, such as:

• Aspirin
• Acetaminophen
• Ibuprofen
• Naproxen sodium
• Ketoprofen.

Caffeine has demonstrated efficacy as an analgesic adjuvant in the treatment of TTH. A combination agent containing ibuprofen and caffeine has demonstrated efficacy in the treatment of episodic TTH. A fixed combination ibuprofen/caffeine is not available in the United States. The amount of caffeine used in this combination is equivalent to two large cups of coffee.

For patients with frequent episodic and chronic TTH, pharmacologic therapy should be prescribed cautiously. Due to the long-term nature of these headaches, addicting anxiolytic agents (such as the benzodiazepines) should be avoided. A nonaddicting anxiolytic (e.g., buspirone) should be considered. Buspirone is a selective 5-HT_1A serotonin receptor-partial agonist with a low incidence of sedation.

Due to the continuous nature of chronic TTH, addicting analgesics should be avoided. The patient may use OTC analgesics, although caffeine-containing analgesics should also be avoided to prevent caffeine-withdrawal headaches. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used successfully in abortive therapy for these headaches.

Tricyclic antidepressants are the agents of choice in the prophylactic treatment of frequent episodic and chronic TTH associated with depression. These agents may be effective independent of their antidepressant actions since they have been recognized for their analgesic effects. Table 5-2 describes the various effects of the antidepressants. Selection of an antidepressant may be dependent on the presence of a sleep disturbance. Amitriptyline and doxepin are indicated for their sedative effects. Patients who do not require a sedative effect may respond well to protriptyline. A European Federation of Neurological Societies Task Force study found that the use of amitriptyline for prophylactic use in TTH is supported by high quality evidence. The most commonly used tricyclic antidepressants in prophylactic TTH therapy are:

• Amitriptyline (favored because of high quality evidence for efficacy in patients with TTH)
• Desipramine
• Doxepin
• Imipramine
• Nortriptyline
• Protriptyline.

Nontricyclic agents are the second generation of antidepressants. They are not associated with the anticholinergic effects present with the tricyclic agents. The antidepressants include:

• Mirtazapine (favored as a second-line option after amitriptyline on the basis of evidence from two randomized trials in patients with TTH)
• Venlafaxine (favored as a third-line option after amitriptyline and mirtazapine on the basis of evidence from one small randomized trial in patients with TTH)
• Bupropion
• Fluoxetine
• Fluvoxamine
• Maprotiline
• Paroxetine
• Sertraline
• Trazodone.

In those patients who are unresponsive to the tricyclic antidepressants, the monoamine oxidase inhibitors (MAOIs), such a phenelzine sulfate, isocarboxid and selegiline, may be considered. Patients treated with MAOIs must be carefully instructed to avoid tyramine-containing foods (Table 3-1). The patient should also be advised that certain concomitant drugs, including pressor agents and certain opiates, should be avoided.

Biofeedback has also demonstrated efficacy in the treatment of chronic TTH. Electromyographic (EMG) training has been effective in decreasing the severity of acute headaches as well as in diminishing the frequency of these attacks. (For more information on biofeedback and EMG training, refer to Migraine Headaches. Table 3-14 illustrates specific dialogue used in EMG training.) Additional non-pharmacologic options that that may be effective in patients with frequent episodic or chronic TTH include cognitive behavioral therapy, relaxation therapy and physical or occupational therapy. Psychological counseling may be indicated in those patients with severe depression. Lifestyle modification, including sleep hygiene, physical activity and stress management are beneficial for all patients.

Botulinum toxin (Botox) has been used for treatment of migraine and chronic daily headaches. However, long-term studies have not confirmed its efficacy.

For pediatric patients with TTH, acetaminophen and amitriptyline are evidence-supported pharmacological options for acute and prophylactic treatment, respectively; however, non-pharmacological interventions are preferred in this patient group. Non-pharmacological options are also preferred for the treatment of older adults with TTH, to limit the burden of polypharmacy. Acetaminophen is evidentially supported for acute pharmacological treatment, while amitriptyline is the preferred preventive option, with venlafaxine and mirtazapine available as fallback options.

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Coexisting Migraine and Tension-Type Headaches

Transformed Migraine, Chronic TTH, Mixed Headache

The phenomenon of central sensitization (increased central nervous system excitability) is an important component in the pathogenesis of migraine and chronic TTH. With central sensitization, changes in neural physiology lead to increased sensitivity to normal sensations that occur during migraine. These sensations occur when performing activities such as combing one’s hair, bending and wearing tight clothing. Over time, it is believed that cranial nociceptors are sensitized by multiple migraine attacks. Neuropeptides, such as substance P and CGRP, are released during the migrainous state and produce perivascular neurogenic inflammation. The inflammatory state likely sensitizes cranial nociceptors and subsequently lowers their threshold for activation and expands their receptive field. Second-order and third-order neurons are then activated. Exposure to repeated pain episodes ultimately results in increased hyperalgesia and cutaneous allodynia at both the painful and remote body regions.

Some patients will experience a combination of TTH and migraine; among patients with migraine, TTH is as common as in the general population. Previously known as the mixed-headache syndrome, this disorder is now identified as coexisting migraine and TTH. While not listed as a separate entity in the ICHD-3 classification, the criteria allow for coding of more than one headache disorder in a given patient. The following symptomatology is associated with these headaches:

• Daily, chronic TTH
• Hard or “sick” migraine-like headache
• Increased susceptibility of habituation to analgesics or ergots.

The majority of patients with both migraine and TTH note a history of periodic migraine headaches, dating from adolescence or their 20s with a daily, milder form of headache occurring at a later age. Other patients may depict a history of daily headaches that occasionally present as a hard or sick headache similar to migraine. They have difficulty distinguishing between the two types of headaches. Finally, some patients may describe a long history of migraine headaches that gradually become less vascular in nature and whose frequency increases to an almost daily pattern. During the taking of history, it is essential that the interviewer ask the patient, “How many types of headaches do you experience?”

The symptoms of each type of headache have been reviewed in their respective sections. Due to the lack of distinctive features, many patients with coexisting migraine and TTH have been misdiagnosed and treated inappropriately. They may present with long lists of treating physicians, unsuccessful treatments and repeated admission and visits to the emergency departments.

Because of the frequency of their headaches, many of these patients are habituated to analgesics, both OTC and prescribed. Such patients will be using large amounts of caffeine-containing analgesics and complain of caffeine-withdrawal headaches when the drugs are stopped. Some may be consuming excessive amounts of ergotamine preparations and experience ergot-rebound headaches when they attempt to discontinue the drugs. Other patients may have become dependent on benzodiazepines. Before initiating treatment, it is essential that the habituating agent be discontinued.

Treatment

Many patients diagnosed with coexisting migraine and TTH are suffering from an underlying depression. Tricyclic antidepressants have been recognized as the agents of choice for prophylactic treatment of this syndrome. Again, the antidepressants may be effective in these patients for both their antidepressant action as well as their analgesic effects.

Due to the complex nature of this syndrome, the use of combination therapy is often indicated. Although combined therapy with a tricyclic antidepressant and an MAOI was considered contraindicated, many patients with coexisting migraine and TTH have been successfully treated with this combination. Usually, these patients have been refractory to conventional forms of therapy, and the combined use of these agents is effective in treating both types of headaches. Ideally, this therapy should only be initiated in an inpatient setting in which the patient can be closely monitored for any symptoms of serious interactions between the drugs. The patient must be carefully instructed regarding the avoidance of tyramine-containing foods (Table 3-1) and drugs that interact with the MAOI. Combined therapy should only be undertaken by a physician experienced in this treatment.

Other agents may be employed in combination or cotherapy. The use of the tricyclic antidepressants in combination with propranolol or the calcium channel blockers has been effective in some patients with this syndrome. Again, initiation of this combined therapy is best undertaken in a controlled, inpatient setting. A specialized hospital unit will have established criteria for admission. Table 5-3 lists the criteria established by the Diamond Headache Inpatient Unit at St. Joseph Hospital, Chicago, Illinois.

The NSAIDs have also been effective in the prophylaxis of coexisting migraine and TTH, similar to their action in both migraine and TTH alone. These agents have also demonstrated efficacy in the abortive treatment of the acute headaches and do not have the potential for habituation.

Fibromyalgia often accompanies migraine and chronic migraine. Pregabalin (Lyrica) may be used to treat symptoms of fibromyalgia.

Any drugs that may lead to dependency problems should be strictly avoided in these patients. Withdrawal from the habituating agents should be handled in an inpatient setting. Careful monitoring for withdrawal symptoms can be accomplished, as well as supportive therapy for the patient, during initiation of prophylactic treatment.

Finally, an essential aspect of treating the patient with coexisting migraine and TTH is continuity of care. These patients have run the gamut of physicians and therapies, and consistency in treatment is very important. Patients will also benefit from knowing that treatment is available and that they are not alone in combating this syndrome.

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Medication Overuse Headache

Medication overuse headache (MOH) is a condition in which patients with a pre-existing headache disorder (migraine or TTH in 90% of cases) develop a new headache or a substantial worsening of the existing headache as a consequence of acute headache medication overuse. First described in 1951, MOH has historically also been called drug-induced headache, medication misuse headache, medication adaptation headache and rebound headache. The ICHD-3 lists the following diagnostic criteria for MOH:

• Headache occurring on ≥15 days/month in a patient with a pre-existing headache disorder
• Regular overuse for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache
• Not better accounted for by another ICHD-3 diagnosis.

Medication overuse headache is further subdivided into one or more subtypes, depending on the medication (class) which is overused, including:

• Ergotamine (≥10 days/month for >3 months)
• Triptans (≥10 days/month for >3 months)
• Paracetamol (acetaminophen) (≥15 days/month for >3 months)
• NSAID (≥15 days/month for >3 months)
• Acetylsalicylic acid (≥15 days/month for >3 months)
• Other non-opioid analgesic (≥15 days/month for >3 months)
• Opioids (≥10 days/month for >3 months)
• Combination analgesics (≥10 days/month for >3 months)
• Other medication taken for headache treatment (≥10 days/month for >3 months).

It is important to note that MOH does not occur in patients without a pre-existing headache disorder, even those who overuse analgesic medications for treatment of non-headache pain.

The pathophysiology of MOH, like that of many other headache types, including primary headaches, is inadequately understood. Multiple influences – genetic, environmental and biopsychosocial – are likely to contribute to the development of MOH, but the currently favored hypothesis is that MOH modulates the aberrant pathophysiology of the underlying headache disorder. Medication overuse can impair descending pain modulation, leading to increased cortical excitability. Peripheral nociceptors may also be sensitized, resulting in hyperalgesia and allodynia. Molecularly, triptan and opioid overuse may lead to increased CGRP expression in the trigeminal ganglion, promoting the activation of the trigeminovascular system and the development of migraine-like attacks.

The burden of MOH is high; its prevalence has been estimated at 1-2% among the adult population, amounting to a worldwide estimate of 50-100 million affected individuals. Fortunately, MOH is both preventable and treatable, resolving in most cases after discontinuation of the medication overuse. This is why advice and education (i.e., instruction on how to reduce the intake of MOH-associated medication) is the cornerstone of MOH treatment – see Figure 5-3. For MOH without complications, the approach depends on whether the patient is willing to immediately discontinue overusing the medication. It they are, discontinuation under the guidance of a healthcare provider (HCP) is prioritized, with concomitant preventive treatment for migraine or other pre-existing headache. If they are not, preventive treatment for the pre-existing headache is favored, with HCP-guided discontinuation attempted only if there is no satisfactory response to the preventive therapy. Treatment of patients with complex MOH – ie, those with MOH associated with opioids, barbiturate-containing sedatives, addiction, or psychiatric comorbidities reducing the likelihood of treatment success – require multimodal (pharmacological and non-pharmacological) pain therapy in conjunction with HCP-guided discontinuation of the MOH-associated drug, and, if needed, a referral to a psychiatrist or addition specialist (Figure 5-3).

Finally, it should be noted that erroneous self-treatment is not always the cause of MOH; excessive or inappropriate prescribing and incorrect medical management also contributes to the prevalence of MOH. Thus, continuing education of the HCPs in charge of patients with headache is just as important a factor in decreasing the burden of MOH.

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