With a lifetime prevalence over 90 percent, it is no wonder that headache is among the most common problems seen by primary care providers. The differential diagnosis of the symptom is one of the longest in medicine, but in our setting the overwhelming majority of headaches are common primary headache disorders such as migraine or tension-type headaches. This chapter reviews the approach to headache in the outpatient primary care setting and the therapy of tension and migraine headache.

TABLE 1: The differential diagnosis of headache

When it comes to nonspecific symptoms like headache, a careful systematic medical history will always be the single most important step in helping to focus the evaluation. Some physicians request a headache diary to help clearly define the features of the condition. The history of headache should include the following:

• Time course: age at onset, frequency, intensity, duration, time of day when symptoms begin, history of trauma and relationship to headache;
• Quality: type of pain
• Location: bilateral/unilateral, radiation;
• Associated features: nausea, vomiting, neck/muscle pain, flushing, tearing, rhinnorhea, rash;
• Presence of aura or prodrome;
• Precipitating/relieving factors: effect of activity, food, drinks, menses, weather, work or sleep;
• Systemic signs: weight gain or loss, visual problems, fever, night sweats, neck, nasal congestion, new medications;
• Response to medical or non-pharmacologic therapy: current medications, dose frequency;
• Family history of headaches.

Of note, the usefulness of some of the classic symptoms used to risk-stratify patients has been called into question. Although we are often taught that early wakening, nausea/vomiting, and exacerbation of headaches with sneezing, coughing or exertion should raise our suspicion of intracranial pathology, most of these "red flags" were developed prior to the availability of neuroimaging, at a time when intracranial lesions were diagnosed solely on clinical grounds and are neither sensitive nor specific markers.

The physical examination should focus on excluding a systemic, infectious, or traumatic event. Examination of the head and neck should check for signs that suggest intra-ocular, sinus, or oral/jaw pathologies. Ophthalmologic and fundoscopic examinations are a must, as they will help to rule out increased intracranial and/or intra-ocular pressures. Palpation of the jaw, neck, and shoulder areas may help to establish a musculoskeletal etiology. Although neither a sensitive nor specific finding, the temporal artery may be tender and palpable in one-third of patients with temporal arteritis.

Intracranial lesions that have not already presented with more obvious findings, such as seizures or neurological deficits, are usually clinically silent. In one series, less than 50 percent of patients with brain tumors experienced headaches. Sometimes even a large lesion will present very subtle initial neurological signs. More often then not, patients with intracranial lesions present with signs that are difficult to elicit on a standard physical exam such as personality change, inability to perform complex cognitive tasks, or mild memory deficit. Nevertheless, a careful, functional neurological exam should always be performed. This includes an examination of the cranial nerves, evaluation of gait and ability to tandem and heel/toe walk, assessment of the Romberg’s and pronator drifts, motor/sensory function, reflexes, cerebellar function, symmetry and mental status.

Lab tests are rarely helpful in the assessment of headache. If systemic conditions remain in the differential diagnosis after a careful history and physical examination, some laboratory testing may be indicated. For example, an ESR and/or CRP should be checked in an elderly patient presenting with headaches suspicious for temporal arteritis, although the positive predictive value of these tests is limited.

The prevalence of clinically significant intracranial structural abnormalities is very low in headache patients with normal physical and neurological examination seen in primary care settings such as our own. Several retrospective studies of headache patients already selected by their physicians to receive neuroimaging, have estimated that number to be less than one percent. For patients with typical migraine symptoms, the number is even lower. Unfortunately, all of the studies have been plagued by both case selection bias and referral filter bias and some authors argue that the prevalence of intracranial lesions among patients with headaches may be no different from that of the general population. In 1999, the U.S. Chronic Headache Guidelines Consortium performed a review of the literature² and concluded that imaging tests are usually not warranted for patients with typical migraine symptoms and normal neurological examination, and that neuroimaging should be considered in patients with both non-acute headache and an unexplained abnormal finding on neurological exam. There was insufficient data to recommend imaging in the presence or absence of neurological symptoms, or imaging in tension-type headache

Given the lack of definitive data, we recommend following the principles of Kumar et al. and obtaining neuroimaging studies in the following situations:

• Recent significant change in the pattern, frequency, response, or severity of headaches
• Progressive worsening of headache despite appropriate therapy
• Headache onset after age 40 years
• Focal neurologic signs or symptoms, or presence of papilledema or orbital bruit
• Onset of headache with exertion, cough, or sexual activity
• Patients with history of cancer, trauma, infection, or immunocompromised state

When clinical suspicion of intracranial pathology is low, the CT scan is a good screening tool. In this setting, the negative predictive value of a negative test will be excellent. A non-contrast CT scan is also the test of choice to exclude acute intracranial hemorrhage or bony lesions. MRI has been shown to be superior to CT scan, however, for most mass lesions, subtle abnormalities such as edema, lesions in the posterior fossa, and vascular lesions. If clinical suspicion is high, MRI is the test of choice.

Tension-type headache is the most common primary headache, with a one-year prevalence of 38 percent in the general population. It is also the least distinct, as diagnostic classification is based largely on the absence of particular features. Prevalence peaks at 30 to 39 years in both men and women, and the syndrome has significant functional impact at work, home, and school. Episodic tension-type headaches are more common among highly educated patients; chronic tension-type headaches are more common among less-educated patients. As a general rule, psychological factors play more of a role in tension-type headaches than in migraine or cluster headache, and stress adversely affects prognosis. Unlike migraines, the disorder is only slightly more common in women. Menstruation is a precipitant factor in tension-type headache more often than migraine, although the latter is influenced to a greater degree by menarche, pregnancy, menopause, and oral contraceptives.

The diagnosis of tension-type headache is a clinical one (see Table 2). Headaches classically feel like bilateral pressure or tightness, often described as "band-like." They are generally devoid of typical migraine features, although some patients with chronic headaches may have both migraine and tension-type headaches. Patients will usually report a history of similar headaches in the past. Remember that primary headaches are only diagnosed after secondary headaches have been excluded.

TABLE 2: Tension-type Headache (International Headache Society Diagnostic Criteria)

As with most chronic illnesses, patient education plays an important role in the management of headache. Interventions include helping patients to identify headache triggers, manage stress, and ovoid over-reliance on pharmacologic therapy. Diagnosis and treatment of comorbid psychiatric disorders can also have a beneficial effect on headaches, and routine screening for depression and anxiety is often recommended.

Episodic tension-type headache is best treated with analgesics such as aspirin, acetominophen, and other NSAIDS. Abortive therapy is most successful, and patients should be instructed to take medications at the onset of symptoms. Chronic recurrent tension-type headaches are more difficult to manage, and patients with this syndrome have are much more likely to overuse and abuse medication. The most successful approach is to focus on prophylaxis rather than on abortive therapy. Patients who require near-daily analgesics should undergo a trial of tricyclic antidepressants. Patients who have overlapping features of migraine and tension type headache may also benefit from migraine-specific prophylactic agents. Non-pharmacologic therapies such as biofeedback, physical therapy, relaxation therapy, stress management training, and psychotherapy have also been shown to be helpful.

Migraine is a chronic, episodic neurovascular disorder characterized by recurrent headaches that are often severe. The one year prevalence of migraine headache among adults is 11 percent. Migraines are three to four times more common in women than in men, and recent population studies suggest that nearly one in five women and one in 20 men have disabling migraine. Migraines tend to run in families. Although the attacks may start at any age, the peak incidence occurs in adolescence. The median frequency of attacks is 1.5 per month, and the median duration of an attack is 24 hours. At least 10 percent of patients have weekly attacks, 20 percent have attacks lasting 2-3 days.^16,

TABLE 3: Migraine Headache (International Headache Society Diagnostic Criteria)¹²

Diagnosis:

Features that distinguish migraine headache from other common primary headaches include nausea, vomiting, photophobia, phonophobia, and debilitation. Headaches are unilateral in 70 percent of cases and often begin in the early morning. Although aura is part of the classic description of migraine, less than one-third of patients will experience migraine with aura.¹⁶ When they are present, auras are usually visual and tend to precede the headaches. Prodromes, such as a change in mood, appetite, or fluid retention, may occur hours to days before the headache. Autonomic features like those seen in cluster headache are rarely present. Many things may trigger migraine headaches: changes in meals, sleep patterns, work schedules or weather, hunger, exertion, fatigue, stress, menstruation, oral contraception, medications, perfumes, noxious fumes, and certain foods (such as those that contain nitrite, glutamate, aspartate or tyramine). A headache diary may help your patients identify their triggers.

While non-pharmacologic therapy, such as avoiding triggers and managing stress, may be helpful, most patients with migraine will require medication. Pharmacologic treatment includes abortive and prophylactic interventions.

Abortive migraine therapy:

For patients with mild to moderate migraine symptoms, simple analgesics such as actetominophen, aspirin, NSAIDS, and Exedrin™ are as effective as migraine-specific agents. Starting medication at the earliest hint of the onset of migraine is an important factor in achieving a therapeutic effect. The initial dose is felt to be the most important one, and high doses are most effective. Recommended initial doses of simple analgesics include naproxen 750 mg; aspirin 900 mg; ibuprofen 1200 mg; acetaminophen 1000 mg; or Excedrin (acetaminophen/aspirin/caffeine) two extra strength tablets. For patients with more debilitating headaches, however, these agents may be insufficient and migraine-specific medications such as "triptans" are required.

"Triptans" – sumatriptan, zolmitriptan, naratriptan, rizatriptan, and almotriptan – are selective serotonin 1b/1d agonists used for abortive therapy of migraines. The distinctive advantages of triptans include their selective pharmacology, established efficacy, and their availability as oral, intranasal, and intramuscular agents. The main disadvantages are their high cost, alarming side effects, and restricted use in patients with cardiovascular disease. The most frequent side effects are tingling, paresthesia, and a sensation of warmth in the head, neck, chest, and limbs; it is important to warn patients of these possibilities. Given the drugs’ ability to constrict even coronary arteries, patients may experience chest pain after use. In rare instances, myocardial infarction has been associated with these agents and they should generally not be used in patients with uncontrolled hypertension, ischemic heart disease, or cerebrovascular disease.

As a rule, opiates are not advised for the therapy of migraine given the risks associated with overuse. Combination analgesic therapies containing barbiturates or benzodiazepines, such as Fioricet™, Fiorinal™, and Esgic™ should not be used in patients with chronic headaches. These agents are potentially addictive, are difficult to discontinue, and have been consistently related to rebound headaches due to overuse.

In an attempt to balance efficacy, safety and cost, several treatment strategies have been suggested. In "step care within attack," the safest and cheapest analgesics are used at the onset of each headache. Migraine-specific medication is then tried if initial therapy fails. In "step care across attacks," patients are treated with simple analgesics during their first migraines. If treatment fails, then more expensive migraine-specific therapy is used at the onset of subsequent attacks. Finally, in "stratified care" a patient’s migraine-related disability is evaluated via a functional disability assessment tool. Patients with the least disability are assigned a simple analgesic, while more expensive migraine-specific medications are given to patients with moderate to severe disability.

A study by Lipton et al. compared these three strategies using aspirin and metaclopramide for patients with mild disability and zolmitriptan for patients with more severe symptoms. The authors found that patients treated with step care across attacks and with stratified care had significantly better outcomes, measured by headache response and disability scores, than patients treated with step care within attack. Patients who were placed on stratified care experienced the most adverse drug effects. These findings are consistent with recommendation from the U.S. Headache Consortium that promote the use of migraine-specific therapy, such as triptans, for patients with moderate to severe migraine once it is established that they do not respond to first line agents

TABLE 4: Treatment characteristics of 5-HT agonists ("triptans")

Patients who have frequent migraine headaches and experience substantial disability may be helped by preventive therapy. Patients who have migraines three to four times a month or more, those who experience less frequent, but severe, prolonged, and/or debilitating headaches, and those who overuse analgesics and are at risk for rebound headaches are all good candidates. On average, about two thirds of the patients given any of these prophylactic agents will have a 50 percent reduction in the frequency of headaches. Common drugs and dosages include propranolol 40-120mg twice a day, metoprolol 100-200mg daily, amitriptyline 10-75 mg at bedtime, and valproate 400-600 twice a day.¹⁵ Patients should understand that these drugs will have no acute effect, and that it may take months to notice an improvement.

Headaches should not be treated without an understanding of the important role that medications may play in exacerbating primary headache disorders. Overuse of analgesics has been shown to exacerbate and prolong pain. This condition is most frequently associated with the use of combination agents, but even simple agents like acetaminophen have been implicated. Although the etiology is unclear, alteration of pain threshold by medication overuse and withdrawal may play a role. At some headache centers, patients may even be admitted in house for "detoxification." Up to 75 percent of patients improve when drug overuse is discontinued and minor analgesics are used with preventive measures. The acute withdrawal of the drugs does worsen headache, but treatment of the primary headache will fail when drugs are not terminated.