NEUROPSYCHIATRIC ASPECTS OF HEADACHE

-Headache is one of the most common human afflictions. Ten percent of all people report
that headache leads to impairment in their daily life. It has dramatic impact on
occupational and social disability and the use of health services.
-Because headache is commonly associated with psychiatric syndromes, psychiatrists are
often consulted for the evaluation and treatment of people suffering from headache.

DEFINITIONS
-The most frequent primary headache syndromes are migraine, tension-type headache,
and cluster headache. The other headache subtypes described in the IHS system are
secondary to a variety of acute and chronic conditions.

Migraine: Migraine is a complex debilitating condition characterized by either the

presence or absence of aura symptoms. Migraine presentation is multifaceted and
symptoms emanate from multiple systems, including vascular, neurological,
gastrointestinal, endocrine, and visual manifestations. These symptoms may be
accompanied by a variety of changes in behavior and cognition, including mood
alterations and confusion.
- The core features of most definitions of migraine include recurrent headache,
accompanied by gastrointestinal symptoms such as nausea or vomiting, and hyperesthesia
manifested by photophobia or phonophobia. The headache generally has a pulsatile or
throbbing quality exacerbated by routine physical activity involving movement of the
head, and is often unilateral. The IHS criteria operationalize these features of headache to
establish common thresholds and distinctions between migraine and other types of
headache.
-migraine is subtyped according to the presence or absence of aura symptoms (reversible
neurological dysfunction).

Tension-Type Headache: Tension headache is characterized by episodes of bilateral pain

lasting several days at a time. It is distinguished from migraine headache by its generally
longer duration, the lack of pulsating quality of the pain, the lack of worsening with
physical activity, and the absence of gastrointestinal concomitants. However, migraine
and tension-type headache may often coexist, either simultaneously or alternating over
time. Tension-type headache is no longer believed to result from muscle tension;

Cluster Headache: Cluster headache is a distinct syndrome characterized by frequent

attacks (often several per day) over a 1- to 2-month period, separated by headache-free
intervals for as long as 1 or 2 years. Although it is commonly grouped with migraine,
current evidence including epidemiological data, treatment response, and clinical features
suggests that cluster headache may comprise a distinct syndrome. Cluster headache is
generally retro-orbital in location and is accompanied by autonomic changes such as
lacrimation, rhinorrhea, erythema of the eye, and agitation. appearing almost manic in
their agitation. The pain can be so intense that the sufferer may appear to be psychotic
because of the screaming and thrashing that may be associated with the pain.
Posttraumatic Headache: Posttraumatic headache is variable in symptom presentation,
severity, and duration. The key symptoms include a headache following head trauma and
accompanied by a loss of consciousness, posttraumatic amnesia, and abnormal laboratory
tests. The major hypotheses of the pathogenesis of posttraumatic headache include
cerebral edema, cortical spreading depression, innate vulnerability to cerebral vasospasm,
and transient elevation of intracranial pressure.

Epidemiology and Course

-Epidemiological studies have shown that approximately 60 percent of the general
population report a history of severe headaches. Milder headaches are reported by about
80 percent of the general population.
-Migraine without aura and tension-type headache are the most common headache
syndromes in the general population. The lifetime prevalence of migraine derived from
systematic population surveys is about 12 percent.
-Migraine is more common among women and persons between the ages of 20 and 45
years, with the incidence decreasing after the fourth decade of life. Migraine may often
begin in childhood when boys and girls are equally likely to suffer from migraine
headache. Migraine in childhood is more likely to be associated with gastrointestinal
complaints, particularly episodic bouts of stomach pain, vomiting, or diarrhea, and the
duration is shorter than that commonly observed in adults. Children with migraine are
often misdiagnosed as suffering from “psychosomatic headaches” or school refusal. In
women, migraine is strongly associated with reproductive system function, with
increased incidence during puberty and the first trimester of pregnancy; migraine is also
associated with exogenous hormone use.
-A family history of migraine is one of the most potent and consistent risk factors for
migraine.
-Migraine is strongly associated with a variety of medical disorders, particularly asthma,
allergies, and cardiovascular disease. Comorbid psychiatric conditions include mood
disorders (particularly the bipolar subtype), phobias, and panic disorders. The course of
migraine is variable. In general, the frequency and duration of migraine decrease at
midlife in both men and women, and the symptomatic manifestations may change
substantially over time.

-The prevalence of tension-type headache has been estimated to range from

approximately 30 to 80 percent depending on the definitions used.
-Tension-type headaches are also more common in women and young adults, but there is
a less steep decrement in prevalence with age.

-posttraumatic headache is quite rare in the general population (i.e., about 1 percent
lifetime prevalence), it is not uncommon among those with a history of a concussion or
head injury.
-Children and young adults appear to be particularly susceptible to developing headache
after head trauma.
- Persistence of headache has been related to female sex; age over 45; the presence of
dizziness; lack of skull fracture; intracranial hematoma; disorders of smell, hearing, or
vision; depression; and impaired concentration.
-Cluster headache has a very low population prevalence (less than 1 percent of the
general population) and occurs nearly exclusively in males. The age at onset of cluster
headache is somewhat later than that of migraine and tension-type headache; the first
attack of cluster usually begins in the late 20s or 30s and may recur intermittently
throughout life; risk factors include smoking and heavy alcohol use.

ETIOLOGY
-Migraine is believed to result from a combination of external trigger factors such as
hunger, sensory input, and hormonal fluctuations that activate serotonin and
norepinephrine-containing neurons in the brainstem. This activation alters the physiology
of neurons, glia, and blood vessels, which provokes pain and generates
neuroinflammatory mediators in the brainstem, thalamus, cerebral cortex, and supporting
tissues. The activation of sensory vascular terminals within the blood vessel walls
releases substance P and other neuropeptides that trigger a sterile inflammatory process,
causing prolonged pain. Although disturbances in serotonin regulation are associated
with migraine, numerous other brain chemicals, particularly the neuropeptides and nitric
oxide, are also involved in a complex way.

-Current theory of the cause of cluster headache holds that hypothalamic and central pain
control regions trigger a cascade of events in the brainstem comprising afferent pain and
efferent parasympathetic pathways.

DIFFERENTIAL DIAGNOSIS AND CLINICAL EVALUATION

-A very skillful workup is essential because headache is a nonspecific complaint with an
enormous number of causes that range from the trivial to the acutely life-threatening. A
thorough examination should include a description of the type and location of pain,
timing, precipitants, prodromal events, and associated symptoms. The following factors
must be determined in order to define whether or not the headache is migrainous: (1)
onset; (2) frequency; (3) location; (4) duration; (5) quality; (6) severity; (7) precipitants;
(8) precursors; (9) triggers; (10) phenomena that worsen or relieve the pain; (11) warning
signs; (12) prodromal events; (13) specific symptoms including visual changes,
gastrointestinal symptoms, or neurological symptoms; (14) sensitivity to light, noise,
sound, or touch; (15) mood changes; and (16) cognitive changes. In addition, it is
important to obtain a detailed family history, description of course, and history of
previous evaluation and treatment.
-In addition to a history and physical examination, laboratory studies are crucial when
metabolic, structural, vascular, or other sources of headache are suspected.
-The diagnosis of headache requires the exclusion of other conditions, including
structural lesion, vascular malformation, viral or bacterial meningitis encephalitis,
intracranial abscess or hemorrhage, cerebral contusion, metabolic disorders (urea cycle
disorders, aminoacidopathies, mitochondrial disorders), pseudotumor cerebri, vasculitis,
brain tumors, sinusitis, and ocular disorders, any of which may be concurrent rather than
causal.
-An image of the brain is mandatory for the evaluation of patients with severe or
persistent headache, the first or worst headache, or when a subdural hematoma is
suspected. Magnetic resonance imaging (MRI) is indicated when hydrocephalus, brain
tumor, sinusitis, vasculitis, or posterior fossa lesions are suspected, or when exposure to
electromagnetic radiation is contraindicated. X-rays of the jaw and cervical spine are
useful to rule out malocclusions and the degenerative changes of arthritis.

TREATMENT OF HEADACHE SYNDROMES

Migraine: The mainstay of migraine treatment is pharmacological intervention.
Treatment of migraine can be prophylactic, with medication taken daily; abortive, with
medication taken at the onset of an attack; or palliative, with medication taken after the
pain has begun.
-Prophylactic treatments for migraine are of varying effectiveness.
-There are also a variety of nonpharmacological approaches to reduce headache. These
include eliminating the triggers of attacks; maximizing the regularity of daily schedule,
particularly with respect to sleeping and eating habits; biofeedback; and relaxation
treatment.
-Symptom Relief- The nonsteroidal anti-inflammatory drugs (NSAIDs), including
ibuprofen (Motrin), naproxen (Naprosyn), and indomethacin and the analgesics aspirin
and acetaminophen (Tylenol) are commonly used as first-line treatment of mild to
moderate migraine. In 1998 the Food and Drug Administration (FDA) approved an
acetaminophen-aspirin-caffeine formulation (Exedrin) for the treatment of migraine.
Other classes of drugs that are commonly prescribed for more severe attacks include
ergot derivatives, serotonin agonists, and narcotics. Combination agents generally
comprised of barbiturates, analgesics, and caffeine are also highly effective in the
treatment of migraine episodes. In order to counterbalance the common adverse effect of
nausea, metoclopramide (Reglan) or prochlorperazine (Compazine) are recommended.
Sumatriptan (Imitrex), a selective serotonin (5-hydroxytrytamine [5-HT]) subtype 1D (5-
HT1D) agonist, was introduced for self-administered parenteral treatment of acute, severe
migraine. It is also available for oral administration and more recently as a nasal spray.
Although relief from headache is almost instantaneous, the major criticism of this drug is
the high frequency of rebound headache, which may be a function of the short half-life of
the drug. The efficacy of sumatriptan has spurred the development of other serotonin
agonists with attempts to reduce the adverse effects associated with sumatriptan. In
general, the use of narcotics for the treatment of migraine should be restricted to a severe
attack that is difficult to abort with other agents. Morphine usually is a better choice than
the synthetic narcotics opioids such as meperidine (Demerol) and hydromorphone
-Migraine Prophylaxis- There are six major classes of drugs that have been investigated
in the prophylaxis of migraine headaches. These include the b-adrenergic receptor
antagonists, antidepressants, calcium channel blockers, serotonin antagonists, NSAIDs,
and anticonvulsants. Use of the NSAIDs, particularly aspirin, on a daily basis may be
highly effective in migraine prophylaxis. Similarly, antihypertensive drugs of the
calcium-channel class or b-adrenergic receptor antagonists have also been widely
employed to prevent migraine. Recent studies suggest that the angiotensin-converting-
enzyme (ACE) inhibitors and enalapril (Vasotec) may also be effective in the prevention
of migraine. The b-adrenergic receptor antagonists are currently the most popular
treatment choice in migraine prophylaxis. Clinicians should be particularly cautious in
prescribing this class of drugs to individuals with a history of depression, since b-
adrenergic receptor antagonists are associated with the development of anhedonia,
irritability, and lassitude, which may occur after many months on any of these agents. the
antidepressant drugs, particularly the tricyclic drugs, have also been shown to be superior
to the conventional first-line agents of migraine treatment irrespective of comorbid
depression or anxiety. However, patients often report excessive sedation from tricyclic
agents, as well as dry mouth, constipation, and weight gain. Tricyclic drugs plus b-
adrenergic receptor antagonists and tricyclic drugs plus monoamine oxidase inhibitors
(MAOIs) have been used concomitantly in the preventive treatment of severe migraine.
The MAOIs have also been reported to be efficacious in the prevention of migraine
headache, particularly in patients who have been unresponsive to first-line prophylactic
treatment. Phenelzine (Nardil) has been considered to be one of the most efficacious
antimigraine agents. However, clinicians have generally been reluctant to prescribe
MAOIs because of the possibility of a hypertensive reaction to dietary tyramine and the
other adverse effects of these agents (i.e., orthostatic hypotension, weight gain, and
excessive stimulation). Addition of a b-adrenergic receptor antagonist such as atenolol
(Tenormin) may reduce the cardiovascular adverse effects of phenelzine. valproate may
be the treatment of choice in patients with migraine and bipolar I disorder or recurrent
depression. The strong association of migraine with both depression and anxiety should
be considered in the treatment of individuals with migraine. Systematic evaluation of the
lifetime history of depression and anxiety is necessary for determining the optimal
treatment strategy. If there is a subtype of migraine associated with anxiety and
depression, it is critical to treat the entire syndrome rather than to limit the treatment goal
to headache cessation. In general, comorbid depression and anxiety are more important in
the selection of migraine prophylaxis than in the treatment of an acute attack of migraine.

Tension-Type Headache: Treatment of tension-type headache may be either

pharmacological or nonpharmacological, depending on the frequency and severity of
headaches. Nonpharmacological approaches such as biofeedback, massage, relaxation,
cervical traction, chiropractic manipulation, hot packs, and cold packs have all been
reported to be effective. analgesics and the NSAIDs are the first-line treatment for
tension-type headache. Aspirin is the most commonly used agent, followed by ibuprofen
and naproxen. It is important to note that symptoms of tension-type headache may arise
iatrogenically from drugs such as ergotamine used to treat migraine, often as a result of
overuse of the drug. the most commonly used drug treatment for chronic tension-type
headache is the tricyclic drug amitriptyline (100 to 150 mg per day).

Cluster Headache: Prophylactic medicine is almost always indicated for treating cluster
headache because of the extreme severity of pain induced by an acute attack, which often
occurs at night. Inhaled oxygen, narcotics, and self-injected dihydroergotamine and
sumatriptan are the most commonly used agents for the treatment of acute attacks.
Medications that have been shown to be effective in preventing attacks of cluster
headache are lithium (Eskalith), the corticosteroids, methysergide (Sansert), the calcium
channel inhibitors and valproic acid (Depakote); combinations of these agents are often
necessary to achieve success.

Posttraumatic Headache: Posttraumatic headache is often treated on an emergency basis

but long-term posttraumatic headache is commonly encountered in psychiatry. Steroids
are often given immediately subsequent to the acute injury. NSAIDS are the most
commonly prescribed agents for headache that persists beyond the acute injury;
thereafter, the prophylactic treatment approaches to migraine can be implemented.