Management of Headaches Need Not Be a Pain in the Neck

Primary headache afflicts virtually all adults from time to time. Approximately 90% of adults experience occasional tension headache each year, but only about 3% of individuals seeking medical help for headaches are diagnosed with pure tension-type headache. Approximately one-third of adults experience sinus headache, particularly in association with seasonal allergy and acute rhinitis or sinusitis of other origins. Five percent of adults have chronic daily headache, and there is an annual prevalence of 0.1% of cluster headache, which may present as excruciating pain leading to the sobriquet “suicide headache.” Although approximately 12% of indi-viduals over the age of 12 years (approximately 28 million) suffer migraine headache, they comprise the vast majority of patients seeking medical assistance for headaches.

The differential diagnosis of headache is complicated because the conventional notion that each type is uniquely symptomatic is now largely rejected in favor of an understanding that there is a challengingly high degree of symptom overlap. Attempts to diagnose the roots of headache on the basis of symptoms may, in fact, be a leading factor in the high incidence of misdiagnosis.

The diagnosis and treatment of headache were the subjects of an adjunct symposium conducted during the Annual Meeting of the American Academy of Physician Assistants in New Orleans in May, 2003.

This program was supported byan unrestricted educational grant from GlaxoSmithKline.

A Practical Approach to the Patient with Headache

The vast majority of patients seen in family practice complaining of episodic disabling primary headache are migraine sufferers. This condition occurs in a female-to-male ratio of 3:1 and typically has its initial onset after puberty, suggesting a causal role for hormonal fluctuation. It peaks between the ages of 25 and 55 years.

Susan Hutchinson, MD, of the clinical faculty of Family Medicine at the University of California at Irvine, discussed migraine headache. Although secondary headache is quite rare, she urged the audience to rule out secondary headache attributable to such things as trauma, meningitis, aneurysm, or brain tumor before treating headache as a primary disorder. Once it is established that the patient has primary headache, the treatment goal is to render the patient headache-free within 2 hours without residual sedation.

Despite the high prevalence of migraine headache, almost half of individuals seeking clinical assistance remain undiagnosed. It has been demonstrated, for example, that 32% of patients with newly diagnosed migraine had previously been diagnosed as having tension headache and 42% as having sinus headache (Lipton RB et al. Headache 2001;4:638). These results appear in Figure 1. To illustrate the cause of such frequent misdiagnosis, Dr. Hutchinson described three patients with different presentations. The first patient, a woman in her late 30s, presented with a 15-year history of occasional 48-hour unilateral throbbing headache with photophobia, phonophobia, nausea, and vomiting accentuated by head movement and relieved only by rest. The second patient, another woman of about the same age, was holding the bridge of her nose and complaining of repeated 24- to 48-hour headaches each month that began in her sinuses and moved behind her eyes, often switching sides. She described her pain as moderate though worsened by movement, and reported that it was accompanied by a runny nose. Her headaches were partially relieved by nonprescription sinus medications. The third patient is the mother of four young children whose weekly stress headaches typically occur at dinnertime and are preceded and accompanied by throbbing aches in her neck and shoulders. The headache is bilateral and of moderate severity. Episodes last for 5 to 6 hours, and are partially relieved by nonprescription medications.

The symptom-based diagnostic guidelines of the International Headache Society (IHS) define migraine as an episodic headache lasting from 4 to 72 hours involving any two criteria from one category (unilateral, throbbing, worsened by movement, moderate or severe) plus one from a second category (nausea and vomiting or photophobia and phonophobia). However, in a retrospective chart analysis of 378 patients and 144 interviews, Kaniecki and colleagues found that 75% of migraineurs experienced neck pain, either unilateral (57%) or bilateral (43%), even though neck pain is conventionally associated with tension headache. In this study, 82% of patients were originally diagnosed as having tension headache as demonstrated in Figure 2 (Kaniecki RG et al. Poster. 10th IHC, 2001). These findings illustrate that overlapping symptomatology may contribute to the misdiagnosis of migraine as tension head- ache. The patient in Dr. Hutchinson’s third case presentation met the IHS criteria for migraine headache, but neck pain might have led to a misdiagnosis of tension headache. Moreover, neck pain accompanied by headache is also relieved with triptan, a migraine-specific therapy.

Additional evidence of symptom overlap among headache syndromes comes from a study of autonomic symptoms in migraine. Conventionally, autonomic symptoms, particularly ocular and nasal symptoms, are associated with so-called “sinus headache,” a minor symptom of sinus disease that is not a formal diagnosis. In a study involving interviews with 148 migraine patients, however, Barbanti and colleagues determined that 45% of patients had at least one autonomic symptom during migraine episodes, of whom 45% reported both nasal and ocular symptoms, 21% reported only nasal symptoms, and 34% reported only ocular symptoms (Barbanti P et al. Cephalalgia 2001;21:295). In a small pilot study (N=30) involving patients who described themselves as having sinus headache, 96% of patients who actually met the IHS criteria for migraine headache complained of sinus headache (Cady RK et al. Poster. 10th ISH, 2001). In a larger study of sinus headache sufferers (N=3,038), 2,424 patients (80%) met the diagnostic criteria for migraine with or without aura, and another 8% met criteria for migrainous (migraine-like) headache. These three studies underscore the potential for the misdiagnosis of migraine headache as sinus headache as a result of overlapping symptoms, as might have occurred in Dr. Hutchinson’s second case presentation. Furthermore, when patients in the Cady study were treated with triptan, there was a two-fold increase in their satisfaction with treatment over prior interventions with antibiotics and anti- histamines. Because triptan is a migraine-specific therapy, the increase in satisfaction adds weight to a diagnosis of migraine headache despite the primary complaint of sinus involvement.

The current understanding of the pathophysiology of migraine headache explains the degree of symptom overlap with headache of other origins. Migraine appears to involve activation of the trigeminal nucleus caudalis, located at the point at which the trigeminal nerve enters the brain stem, potentially resulting in pain all along the trigeminal path including the frontal sinus area, the vicinity of the eyes, the cheeks, and the jaw. At a proximate location in the brain stem, sensory innervation for the cervical nerves is activated, potentially inducing pain at the back of the head and in the neck and shoulders during migraine episodes. Involvement of the superior salivatory nucleus may lead to nasal, sinus, and ocular symptoms conventionally associated with sinus headache. At the same time, neuro-inflammatory peptides may induce vasodilation, the origin of throbbing pain.

The therapeutic strategy in migraine headache is ideally to prevent, but secondarily to turn off, trigeminal activation and vasodilation by activating the inhibitory 5-HT1b and 5-HT1d receptors. This is done most effectively with triptan-based agents. These may be administered subcutaneously to patients who have nausea and vomiting or whose headaches are escalating rapidly. Triptans are not known to induce spontaneous miscarriages or to increase the incidence of birth defects in the cases reported thus far to the Pregnancy Data Based Registries for the triptans. All the triptans are Category C agents, requiring that the benefits of use in pregnant women be weighed against the potential dangers. The American Academy of Pediatrics has recently concluded that sumatriptan is safe for breast-feeding women. Until now, the common practice has been to discard breast milk for 6 to 8 hours after taking the triptan.

Butalbital is thought by some to be effective in the migraine setting, but there are no randomized and placebo-controlled trials demonstrating efficacy. Moreover, it does not meet the criterion for complete relief within 2 hours without residual sedation. It can also lead to addiction and excessive use, which have been associated with transformation of episodic migraine to chronic daily rebound migraine. Ergot alkaloids may be effective in some patients. The value of nonsteroidal anti-inflammatory drugs (NSAIDs) is limited to less severe headaches. However, for menstrual migraine its early use followed by a triptan appears to be helpful, with or without oral or transdermal estrogen supplementation. This strategy can be used either prophylactically or therapeutically. Opioids should be reserved for salvage therapy. Metoclopramide can be useful for treating emesis. Triptans can also relieve migraine-associated gastrointestinal symptoms.

Chronic daily headache afflicts approximately 4.1% of the United States population in a female-to-male ratio of 1.8:1. Approximately two-thirds of cases are classified as chronic tension-type headache and most of the remainder as transformed (chronic) migraine head-ache. Chronic daily headache occurs most frequently in the lower socioeconomic stratum (Scher AI et al. Headache 1998;38:497). An epidemiologic study conducted in Spain found a prevalence of 4.7%, but with an eight-fold greater prevalence among women than among men. Chronic tension-type headache and transformed migraine were approximately equal. Importantly, however, the study also revealed that 17% of patients with chronic tension-type headache and 32% of patients with transformed migraine (see below) abused analgesic medication (Castillo J et al. Headache 1999;39:190).

The effective management of chronic migraine consists of (i) diagnosing accurately, (ii) recognizing comorbidities, (iii) educating the patient about the disorder and its treatment, including her/his responsibilities, (iv) addressing medication overuse, and (v) developing a management program.

Accurate diagnosis includes ruling out secondary headache. Robert G. Kaniecki, MD, of the University of Pittsburgh, recommended that all patients with chronic daily headache be referred for magnetic resonance imaging (MRI) for this purpose. Headache related to psychiatric conditions such as chronic depression and borderline personality disorder must also be ruled out as must chronic cluster headache, chronic paroxysmal hemicrania, SUNCT syndrome (sudden unilateral neuralgiform headache with conjunctival injection and tearing), hypnic headache (nocturnal headache that is uniquely responsive to lithium), and new daily persistent headache. In the last of these, the patient typically denies a history of headaches, but in recent weeks or months has had them almost daily. In contrast, chronic migraine is preceded by a history of episodic migraine that transforms into a pattern of headache more than 15 days per month for more than 6 months, with symptoms persisting for more than 4 hours if untreated. As is the case with episodic migraine, chronic migraine may be mixed with symptoms of tension headache (Table 1). Consequently, for diagnostic purposes, a description of symptoms is less useful than an estimate of their frequency, location, and severity.

The transformation from episodic to chronic daily migraine may be triggered by emotional or physical trauma, hormonal changes, a major life change, or perhaps by a natural history of uncontrolled episodic migraine. It may be fueled by analgesic rebound resulting from overuse of analgesic medications. Excessive use of migraine-specific therapies, decongestants, muscle relaxants, and anxiolytics may also fuel the transformation, as may overuse of such substances as caffeine, nicotine, and artificial sweeteners. When diagnosing chronic daily headache, therefore, a history of headache medications may be a clue to migraine transformation. A history of analgesic rebound usually includes increasing doses with declining satisfaction, switching or recycling analgesics, early morning headache, and insistence that analgesics for both prophylaxis and acute treatment are ineffective. Some patients will exhibit drug-seeking behavior in order to move up to more potent agents or to have access to larger quantities. This behavior may be accompanied by exaggerated “the-dog-ate-my- homework” stories.

Comorbidities are an important aspect of chronic migraine headache management because as headache symptoms intensify, manifestations of illness may broaden. Many patients become increasingly sensitive to internal stimulants such as hormones, stress, and chronobiologic changes or to external stimulants such as substances and weather changes. Frequently encountered expressions of central nervous system hypersensitivity and referred pain include sinus, neck, and posterior head pain; psychiatric manifestations including depression, bipolar disorder, generalized anxiety disorder, panic disorder, and anxiety; sensory sensitivity with intolerance of noise, light, or odors; insomnia; irritable bowel syndrome; and fibromyalgia. “The nervous system of a chronic migraineur has a lower threshold of sensitivity,” Dr. Kaniecki said, “resulting in depression or anxiety in two-thirds of patients, insomnia in two-thirds, irritable bowel in 50%, and fibromyalgia-like symptoms in 40%.” In light of the prevalence of these comorbidities, they are both useful diagnostic clues and special problems of symptom management.

The education of a patient with chronic daily migraine includes assurance that it is a disorder of hypersensitivity in the brain, and that it is neither a psychiatric nor a psychosomatic condition. The patient needs to be assured that through a therapeutic partnership with the clinician, there is a high probability of successful control. For her/his part, the patient must make lifestyle changes consisting of eating, sleeping, and exercising regularly and hydrating with as much as 60 ounces of nonalcoholic fluids daily. Trigger avoidance and external stimulant reduction are essential. Biofeedback, relaxation therapy, and meditation may help control headaches. A paramount issue of patient responsibility is addressing the issue of medication overuse. The patient must be prepared to spend 2 weeks away from work or school in order to ride out the discontinuation of all medications, and to understand that although the situation may worsen during that period, there is an 80% chance of subsequent improvement. During the 2 weeks preceding discontinuation, some patients may require bridge therapies such as clonidine for narcotic withdrawal, clonazepam for butalbital-withdrawal anxiety, and corticosteroids, NSAIDs, or triptans for extreme discomfort.

For the pharmacologic management plan for chronic daily headache, the United States Consortium guidelines call for the prophylactic use of propranolol, timolol maleate, amitriptyline hydro-chloride, or divalproex sodium. Adjunc-tive agents for treating comorbidities include tricyclic antidepressants, bupropion, or selective serotonin reuptake inhibitors (SSRIs) for depression, anxiety, and fibromyalgia; other antidepressants or non-benzodiazepine antagonists of the benzodiazepine receptors for insomnia; and divalproex for bipolar disorder. When all else fails, the patient may need botulinum toxin injections or monoamine oxidase inhibitors. Chronic opioid therapy should be used in the rarest of cases.

The centerpiece of therapy for acute episodes is the triptan class, administered either orally or by injection (subcutaneous sumatripan succinate). Two-tier therapy with a triptan plus NSAIDs or amitriptyline may be more effective. These therapies should be restricted to three times per week for a month to avoid overuse and analgesic rebound. “The most effective medications on the market for chronic as well as acute migraine headache are the injectable triptans,” Dr. Kaniecki said, but he cautioned that not all triptans are alike. Dihydroergotamine (DHE) frequently serves as second-line therapy. There is no evidence to support the use of butalbital or isometheptene compounds in acute migraine.