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The term “chronic daily headache” (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose and treat. Medication overuse, or drug rebound headache, is the most treatable cause of refractory daily headache. A pathologic underlying cause should be considered in patients with recent-onset daily headache, a change from a previous headache pattern, or associated neurologic or systemic symptoms. Treatment of CDH focuses on reduction of headache triggers and use of preventive medication, most commonly anti-depressants, antiepileptic drugs, and beta blockers. Medication overuse must be treated with discontinuation of symptomatic medicines, a transitional therapy, and long-term prophylaxis. Anxiety and depression are common in patients with CDH and should be identified and treated. Although the condition is challenging, appropriate treatment of patients with CDH can bring about significant improvement in the patient’s quality-of-life.

Family physicians frequently care for patients who have migraine and other primary headache disorders. In recent years, the number of headache-related consultations has doubled, and the number continues to increase.1 Although most headaches are episodic, an estimated 4 to 5 percent of adults have chronic daily headaches (CDH).2,3 Patients with CDH have a poorer quality of life than patients with episodic migraine headaches.4 CDH is the cause for most referrals to specialist headache clinics.5

Key clinical recommendationsLabelReferences
Consider neuroimaging for patients with chronic headache and unexplained abnormal findings on the neurologic examination.B12
Neuroimaging is generally not indicated in patients with migraine and a normal neurologic examination.B12
Symptoms of particular concern in patients with nonacute headache include increasing headache frequency or progressive symptoms (including lack of coordination, subjective numbness or tingling), or headache awakening the patient from sleep (not explained by cluster headache or typical migraine).B12
Drug rebound headache should be considered in the patient who repeatedly presents to the office or emergency department requesting narcotics for relief.C27
Many tricyclic antidepressants and certain anticonvulsants are recommended as effective treatments for chronic daily headache, with amitriptyline (Elavil) having the best documented efficacy.A35

Patients with CDH most commonly have a history of episodic migraine that has evolved to a daily headache (chronic migraine). Regardless of the original headache syndrome, overuse of medication occurs in approximately one third of patients who develop daily headaches. Medication-induced headache, or drug rebound headache, has been described as an “unrecognized epidemic.”6 In tertiary headache treatment centers, 50 to 82 percent of patients who have CDH have medication overuse.7

Patients with daily headaches are categorized as having primary or secondary headaches. The primary headaches are further divided into those lasting less than or longer than four hours8,9 (Table 1).9

Primary headachesSecondary headaches
Headache duration > 4 hours (with or without medication overuse)
Chronic (transformed) migraine
Chronic tension-type headache
New daily persistent headache
Hemicrania continua
Headache duration < 4 hours
Strictly unilateral—prominent autonomic features
Cluster headache
Paroxysmal hemicrania*
Unilateral or bilateral—no autonomic features
Trigeminal neuralgia
Idiopathic stabbing headache
Cough headache
Benign exertional headache
Headache associated with sexual activity
Headache associated with vascular disorders
Arteriovenous malformation
Giant cell arteritis
Carotid dissection
Vasculitis
Headache associated with nonvascular intracranial disorders
Neoplasm
Idiopathic intracranial hypertension (pseudotumor cerebri)
Infection
Post-traumatic headache
Subdural hematoma
Myofascial pain
Cervical spine disorders
Temporomandibular joint dysfunction
Headache caused by sleep disorders
Obstructive sleep apnea

Patient Assessment

In a systematic approach to the patient with CDH, the physician evaluates the patient for potential ominous pathology, determines the primary headache type, and assesses underlying physical contributors to headache, triggering factors, comorbidities, and the patient’s medication history (Table 2).10 The elements of the clinical history, physical examination, and laboratory tests that are suggestive of specific diagnoses causing CDH are summarized in Table 3.

Are there worrisome features (SNOOP)?10
 Systemic symptoms or illness (especially fever, change in mentation, anticoagulation, current or recent pregnancy, or cancer)
 Neurologic symptoms or signs (papilledema, asymmetric cranial nerve or motor function, or abnormal cerebellar function)
 Onset is recent or sudden
 Onset after 40 years of age
 Previous headache history is different or progressive
What is the primary headache type? (Determine original headache pattern and any changes over time)
 Duration longer than four hours
 Migraine features: chronic (transformed) migraine
 Lacking migraine features: chronic tension-type headache
 Abrupt onset headache pattern: new daily persistent headache
 Strictly unilateral: hemicrania continua
 Duration shorter than four hours
 Strictly unilateral/autonomic features: indomethacin-responsive headaches
 Unilateral or bilateral/no associated autonomic features
Evidence of medication overuse (including nonprescription drugs and caffeine)
Evidence for underlying physical factors
 Myofascial factors
 Cervical
 Temporomandibular
 Fibromyalgia
 Other chronic pain
 Sinus symptoms
 Sleep disturbance
Evidence for psychiatric comorbidity
 Depressive disorders
 Anxiety disorders
 Chemical dependency
 Personality disorders
Patient evaluationSuggested diagnosis
Clinical history
 Recent onset; recent change; progressive symptoms of headachePossible secondary headache
 Fever; weight loss; history of cancerPossible systemic illness/secondary headache
 Daily headache with occasional migraine-like flaresChronic migraine
 Daily headache without migraine-like flaresChronic tension-type headache
 Headache started “out of the blue”; has occurred daily from onsetNew daily persistent headache
 Near-daily use of symptomatic medications; no worrisome featuresMedication-overuse headache
 Severe headache lasting < 4 hours; strictly unilateral; tearing and/or rhinitis; clock-like regularity; clustering of episodesCluster headache
 History of cervical trauma; headaches triggered by cervical movementCervicogenic headache
 Obese, fertile woman; transient visual symptoms; pulsatile tinnitusIdiopathic intracranial hypertension (pseudotumor cerebri)
 Anxiety or depressionIdentifies comorbidity but does not influence primary headache diagnosis
Physical examination
 PapilledemaIntracranial mass; idiopathic intracranial hypertension (pseudotumor cerebri)
 Any abnormality on neurologic examinationPossible secondary headache
 Restricted or painful cervical motion, or temporomandibular motionCervicogenic headache; temporomandibular dysfunction
Laboratory examination
 Anemia; elevated liver enzyme levels; hypothyroid or hyperthyroidEvaluate and treat underlying condition.

Potentially Significant Pathology

All patients with daily headache require a careful evaluation to exclude secondary causes. Although they may not specifically express it, most patients with CDH are concerned about serious pathology.11 Potential indicators of intracranial pathology in patients with sudden-onset acute headache are occipitonuchal location, age greater than 40 years, and an abnormal neurologic examination. Symptoms of particular concern in patients with nonacute headache include increasing headache frequency or progressive symptoms, neurologic signs or symptoms (including lack of coordination, subjective numbness and tingling), or headache awakening the patient from sleep (not explained by cluster headache or typical migraine).12

In the absence of neurologic findings, episodic migraine does not require imaging studies12,13; the evidence is less clear for chronic migraine and chronic non-migraine headaches. Based on the low rate of detection of significant pathology, a work group of the American Academy of Neurology (AAN) came to this conclusion: “At this time, there is insufficient evidence to define the role of CT [computed tomography] and MRI [magnetic resonance imaging] in the evaluation of patients with headaches that are not consistent with migraine.”13 A more recent guideline12 from the AAN recommends that neuroimaging be considered in patients with unexplained abnormal findings on the neurologic examination, but states that there is no clear evidence to recommend MRI or CT as the initial examination.

Table 210 lists significant features that raise the index of suspicion for a pathologic cause in patients with chronic or recurrent headaches. Patients who have had a stable headache pattern for at least six months rarely have significant intracranial pathology. In the absence of worrisome features, these patients do not require imaging.12 An imaging study for the sake of reassurance is occasionally warranted, but a thorough clinical evaluation usually obviates the need.

Isolated headache without neurologic symptoms is an unusual presentation of brain tumor that occurs in only 8 percent of cases.14 Although a classic profile of a brain tumor headache has been described (severe headache that is worse in the morning and associated with nausea or vomiting), the pattern is not commonly encountered.15

In adults, it is unusual for headache to be the presenting symptom of an underlying systemic disease in the absence of other symptoms. Clinical suspicion should guide testing for anemia, thyroid disease, liver disease, connective tissue disorders, and infectious diseases (i.e., human immunodeficiency virus antibody and Lyme serology) in patients who have risks or features raising the likelihood of these conditions. Diagnostic testing for a systemic cause may have a greater yield in patients with recent onset of daily headache syndromes. Patients often attribute headache to elevated blood pressure, but only sudden or extreme elevations of blood pressure cause headache.16

Identifying the Primary Headache

Episodic headaches are usually diagnosed on the basis of the signs and symptoms of the individual headache attack. In patients with CDH, diagnosis is best reached by examining the history of the original headache pattern and its evolution over time.

MIGRAINE

Most patients with CDH who present to physicians with headache have chronic (transformed) migraine.17 These patients have a history of episodic migraine that has evolved (transformed) over time into a pattern of almost daily headaches. These daily headaches may be mild, but migraine flares may continue to be superimposed on the daily headache symptoms. The most common causes of migraine transformation are frequent headaches at baseline and obesity.18 Other modifiable risk factors for transformation include medication overuse, snoring, and stressful life events. Risk factors that cannot be modified are female gender, low education/socioeconomic status, and head injury. Sudden transformation may be associated with trauma to the head or neck, medical illness, surgery, or psychologic trauma.7

Interestingly, chronic tension-type headaches and other daily headaches (such as post-traumatic headache) may evolve into a pattern of chronic migraine.19 Chronic migraine may represent a final pathway for several different primary headache types.

TENSION-TYPE HEADACHE

Patients with chronic tension-type headache have daily or near-daily headaches that typically are occipital or diffuse and pressure-like. It is unclear whether psychologic or muscle tension is actually present and, if present, whether these are primary events or epiphenomena. Psychologic and muscle tension also are present with migraine.20 The role of cervical pathology in chronic tension-type headache continues to be defined. Limited evidence from a single small case series shows that selective blocks of the C1-C2 lateral joint completely relieve headache in two thirds of a highly selected group of patients with occipital headaches.21

NEW DAILY PERSISTENT HEADACHE

This type of headache develops “out of the blue” and persists. Patients with new daily persistent headache have no history of headache; if headaches did pre-exist, there is a sudden change to daily headache. A precipitating event is noted in over one half of patients. The most common events are a febrile or viral illness, general surgery, or a stressful life event.22 These headaches are often refractory to therapy and may persist indefinitely. New daily persistent headache may occur with or without features of migraine.

HEMICRANIA CONTINUA

Although rare, hemicrania continua is an important disorder to consider because it responds consistently to therapy with indomethacin (Indocin). The headache is constant, with exacerbations of pain, strictly unilateral, and often associated with autonomic symptoms of tearing and rhinorrhea.

BRIEF AND UNILATERAL SYNDROMES

Cluster headache is commonly misdiagnosed as migraine, and migraine is occasionally mislabeled as cluster headache. Cluster headache is readily recognized as a daily or near-daily headache, strictly unilateral, of excruciating severity, and associated with tearing, rhinitis, or other facial autonomic symptoms on the side of the headache. The key feature distinguishing this condition from migraine is that cluster headache has a briefer duration, usually 30 minutes to three hours. Other diagnostic clues to cluster headache are clock-like regularity of headache recurrence and reliable triggering by alcohol consumption. Cluster headache is usually episodic, persisting for weeks to months at a time and remitting for months or years between episodes. Approximately 10 percent of cases, however, are reported to be chronic, with continuous daily episodes. Clinical features and therapies for cluster headache have recently been reviewed.23

Other brief headache syndromes are uncommon but merit recognition. Brief headache syndromes that are strictly unilateral usually are associated with autonomic features such as tearing and rhinitis. Other than cluster headache, these headaches are consistently responsive to indomethacin therapy, to the extent that a positive response to this agent is a diagnostic feature.

Drug Rebound and Medication Overuse

Patients who do not stop analgesic overuse fail to improve despite use of preventive therapy.24,25 Conversely, patients who stop taking analgesics on a daily basis have a marked reduction in frequency of headache. Drug rebound headache is a common treatable cause of transformed migraine, and some experts believe it is important in other daily headache syndromes, including post-concussive headache.26 Patients who have drug rebound headache are typically refractory to usual acute and prophylactic interventions. The patient who repeatedly presents to the emergency department requesting narcotics for headache relief most commonly has drug rebound headache.27

There is no established threshold for the quantity, frequency, or duration of medication use required for the development of drug rebound headache. Affected patients typically take headache-relieving medication daily or near daily, but the sustained use of these medications more than three days per week is probably sufficient to develop drug rebound headache. All symptomatic headache medications, including triptans,28 have the potential to cause drug rebound headache. The agents most commonly reported to cause drug rebound headache are narcotics, butalbital products, and combination products containing caffeine.25

Physicians should remain alert to signs of secondary headache in patients who are self-medicating frequently. Only after a careful evaluation for secondary headache should drug rebound headache be suspected in patients with medication overuse.

Headache History

An initial, open-ended question, such as “Tell me about your headaches,” will yield valuable information that may not be acquired by a relentless pursuit using closedended questions. Patients may report having several different types of headache and give each one a label, such as “migraine,” “tension headache,” or “sinus headache.” The patient should be allowed to describe each of these headache types, even though they may all represent different manifestations of the spectrum of a migraine headache.29

Particular attention should be given to the patient’s age at onset, the circumstances of headache onset, the time when headaches worsened or began occurring daily, and associated life events. Medical or surgical illnesses, trauma involving the head or neck, and life stressors commonly are identified with the onset of headaches or the transformation of headaches from episodic and/or manageable to CDH.

Physical Examination

The neurologic examination is crucial to exclude even subtle signs of cerebral dysfunction. The patient’s ability to communicate the history is a valuable measure of mental status. The funduscopic examination must be documented. Subtle signs of frontal lobe dysfunction may be demonstrated by testing stereognosis (such as the ability to identify an object placed in the patient’s palm). A thorough examination also will reassure the patient and may obviate the need for imaging studies when there are no historical features of concern.

A myofascial evaluation should include cervical range-of-motion, trigger points of the upper back, and temporomandibular motion and tenderness. However, positive physical findings are common and do not necessarily indicate the cause of the headache. Seventy-five percent of patients with migraine complain of associated neck pain; triptan therapy resolves both neck pain and headache.30

The question of sinus abnormalities as a cause of headache remains controversial.31,32 Nearly 90 percent of patients with frequent episodes of “sinus” headache fulfill criteria for migraine headache.33 CT imaging or nasal endoscopy may occasionally identify a treatable cause of headache in a patient with sinus symptoms.

Assessing Psychiatric Comorbidity

Anxiety and depression are highly prevalent in patients who have CDH7 and, when present, may negatively influence prognosis. All patients who have CDH should be screened for psychiatric comorbidity. Direct questioning (such as, “Are you depressed?”), indirect questioning, and screening instruments (such as the Beck Depression Inventory) may be used. The Primary Care Evaluation of Mental Disorders (PRIME-MD), a multidimensional psychiatric screening tool that also identifies other somatic complaints,34 may be particularly useful for screening patients with headache.

Treatment

The appropriate treatment of patients with CDH emphasizes the reduction of headache triggers and the use of preventive therapy (Tables 4 and5). The goals of migraine preventive therapy are to (1) reduce attack frequency, severity, and duration; (2) improve responsiveness to treatment of acute attacks; and (3) improve function and reduce disability.13 Many tricyclic anti-depressants and certain anticonvulsants appear to be effective treatments, with amitriptyline (Elavil) having the best documented efficacy.35,36 Beta blockers are commonly used if there is a migraine component. Patients with refractory headaches often require therapy with several agents such as a tricyclic antidepressant plus an anticonvulsant and a beta blocker. Selective serotonin reuptake inhibitors appear to be most useful in patients with psychiatric comorbidity.

1. Treat medication overuse, if present (see Table 6).
2. Select pharmacologic therapies (see Table 5).
3. Treat potential underlying pathology.
 Myofascial pain
 Physical therapy
 Temporomandibular treatment
 Psychiatric comorbidity (antidepressants, anxiolytics)
 Sinus evaluation and treatment
4. Limit symptomatic medication use to two days per week (after withdrawal [“detoxification”] is completed).
 Recommend use of nonsteroidal anti-inflammatory drugs.
 Recommend use of triptans for migraine flares.
 Avoid use of medications prone to drug rebound, especially combination analgesics, caffeine-containing compounds, butalbital products, and narcotics.
5. Consider behavior therapy
 Encourage lifestyle management
 Regular exercise
 Regular meals; no caffeine; migraine diet
 Sleep hygiene
 Stress reduction
 Biofeedback
 Cognitive-behavior therapy
6. Monitor progress (using headache calendar).
Drug classDosingContraindications/side effectsComments
TCAs
Amitriptyline (Elavil)10 mg at bedtime; increase weekly up to 50 to 75 mg at bedtimeSedation, dry mouth, constipation, weight gainObtain baseline ECG.
Maximum: 150 mg at bedtime
Nortriptyline (Pamelor)10 to 25 mg in morning or at bedtime; increase weekly up to 75 to 100 mgLess anticholinergic than amitriptylineObtain baseline ECG.
Maximum: 150 mg per day
Desipramine (Norpramin)10 to 25 mg in morning or at bedtime; increase weekly up to 75 to 100 mgNonsedating, no weight gainObtain baseline ECG.
Maximum: 150 mg per day
SSRIs
Fluoxetine (Prozac)10 to 20 mg in morning or at bedtimeDiminished libido, nausea, constipation, weight gainMost useful if depression is present
Paroxetine (Paxil)Same as aboveSame as aboveSame as above
Antiepileptic drugs
Valproic acid (Depakene)125 to 250 mg at bedtime; increase up to 250 to 500 mg twice dailyNausea, sedation, tremor, hair loss, weight gain; teratogenic; may cause polycystic ovariesObtain baseline liver function tests.
Maximum: 1,000 mg twice daily
Gabapentin (Neurontin)100 to 300 mg at bedtime; titrate slowly up to 300 mg three times daily, then more rapidly up to 800 mg three times dailySedation, nausea, weight gainMay help sleep and anxiety
Topiramate (Topamax)15 to 25 mg at bedtime; increase weekly up to 50 mg twice daily or 100 mg at bedtimeVery common: paresthesias and cognitive side effectsPromotes weight loss
Maximum: 100 mg twice dailyRare: acute glaucoma syndrome, anhydrosis; kidney stones in 1.5%
Beta blockers*
Propranolol (Inderal)20 to 40 mg twice daily; increase as toleratedFatigue, depression, sexual dysfunctionUseful only if migraine component
Antispasmodics
Tizanidine (Zanaflex)2 to 4 mg at bedtime, up to 4 mg three times daily if sedation level is tolerableSedationPromotes sleep; reported useful in fibromyalgia
Botulinum toxin25- to 100-unit injections every three monthsEyebrow ptosis; lacks internal side effectsExtremely costly; consider for use in patients with refractory headaches

If the patient is overusing medications, the overuse must be managed before prophylactic agents will be effective (Table 6). The treatment of drug rebound headache involves (1) withdrawal from all symptomatic agents, including caffeine; (2) a transition therapy to support the patient during detoxification; and (3) initiation or adjustment of headache prophylaxis. The literature is insufficient to recommend any one treatment over another.37 Patients often have exacerbation of headache in the first two weeks following withdrawal from analgesics and may require four to 12 weeks after withdrawal (occasionally, even longer) to show improvement.

1. Withdrawal of symptomatic medications, including caffeine.
 A. Gradually taper medications in patients where physiolgic withdrawal is a concern (i.e., narcotics, butalbital).
 B. Use abrupt withdrawal or taper medications in all other patients.
2. Preventive therapy
 Any preventive therapy, or combination, from Table 4
3. Transition therapy (one medication from group A may be combined with one from group B)
 A. Daily migraine-specific therapy
 Dihydroergotamine (DHE), intranasal, intramuscular, or intravenous
 Long-acting triptan: naratriptan (Amerge) or frovatriptan (Frova)
 B. Anti-inflammatory agents
 Short course of corticosteroids
 Long-acting nonsteroidal anti-inflammatory drugs
4. Rescue therapy, as needed
 A. Non-narcotic analgesics: parenteral ketorolac (Toradol)
 B. Antiemetics
 C. Sedating antihistamines: diphenhydramine (Benadryl) or hydroxyzine (Atarax)

Once the patient has completed an adequate period of medication withdrawal, the use of symptomatic medications again may be allowed, but on a limited basis—no more than two days per week. Nonsteroidal anti-inflammatory drugs and triptans are most commonly used in patients with occasional migraine flares. The use of medications that are highly prone to drug rebound, such as narcotics and combination products containing butalbital or caffeine, should be avoided. Dihydroergotamine (DHE)ay be used safely over an extended period.

The primary care physician can provide behavioral support by helping the patient identify lifestyle triggers and psychosocial stressors. Behaviors that help to prevent headache flares include establishing a habit of regular meal times, sleep and awake times, and exercise. It is useful to help the patient to identify any connection between psychosocial stressors and headache flares. Most headache patients can benefit from basic stress-reduction techniques such as yoga and meditation. There is compelling evidence for the efficacy of biofeedback, relaxation techniques, and cognitive-behavior therapy for headache prophylaxis.38 Referral to a medical psychologist or a pain psychologist should be considered for patients with significant psychosocial stressors or refractory headache.

Referral

Patients who do not respond to appropriate prophylaxis or who frequently use narcotics or butalbital products should be referred to a headache specialist. Patients with significant psychiatric comorbidity, associated chronic pain, and/or chemical dependency may require the services of a multidisciplinary pain clinic. Tertiary headache centers that provide inpatient care should be considered for patients who have not responded to aggressive outpatient therapy.

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