HEADACHE

HEADACHE

  1. 1
    Evaluation and Diagnosis

    An accurate diagnosis is essential for effective management of patients with the more commonly encountered headaches. Because no biologic markers or diagnostic tests exist to determine headache type, the history is the single most important element in the evaluation of the headache patient. Various headache types sometimes have similar initial presentations, or patients may suffer with more than one type of headache (e.g., migraine and tension-type headache), which can be confusing at first, but the careful history usually differentiates the headache type. In general, little in the way of diagnostic testing is needed unless a physical cause is suspected. Some physicians prefer to perform simple laboratory tests to establish a baseline for medication toleration and monitoring as necessary (Table 1).

    Table 1

    Current Diagnosis

    • The headache complaint on occasion can be a sign of a more serious medical condition, such as a tumor, infection, or aneurysm. For this reason, the clinician always must be cautious and diligent in establishing an accurate and timely diagnosis. Certain so-called red flags in the history require immediate attention. These include any complex of symptoms or history that does not fit a typical headache type; report of a significant neurologic deficit; significant or prolonged neurologic deficit with aura; late-onset migraine (in a patient older than 30 years); sudden onset of a new head pain without history of similar headaches; changes in headache character; headache associated with elevated temperature; or completely unresponsive attacks in the absence of analgesic or caffeine overuse. When any of these symptoms are present or physical examination reveals significant findings, further diagnostic evaluation with imaging studies and consultation is imperative.
      The appropriate headache patient evaluation includes a thorough history; physical examination with special attention to the head and the neurologic, cardiovascular, and musculoskeletal systems; and diagnostic tests when appropriate. The history should include headache onset, location, pain character (e.g., pressure, throb), frequency, duration, associated symptoms, aura or prodrome, triggers, previous treatment, and family history. Certain clues in the history may lean toward the diagnosis of migraine, such as motion sickness; absence of headache during pregnancy; and headache relationship to menses, sun glare, oversleep, fatigue, fasting, foods, or alcohol.
      Various diagnostic screening questionnaires and tools have been developed over the years to assist busy clinicians in establishing the diagnosis of migraine. Most are long and cumbersome and do not easily become a part of routine patient evaluation. A simple three- question screener for migraine is helpful for generalist clinicians.
      A “yes” answer to all three questions indicates a strong possibility of the migraine diagnosis:
    1. Do you experience headaches severe enough to see a physician?
    2. Are your headaches accompanied by other symptoms?
    3. Are your headaches intermittent (i.e., nondaily)?
      Note: This screener should not be substituted for a complete history; it should be used only for screening purposes.
  2. 2
    Tension-Type Headache

    Tension-type headache (TTHA) is the most common of headaches and first was believed to be caused by sustained muscle contraction of the neck, jaw, scalp, or facial muscles. However, consideration is being given to the possibility that sustained muscle contraction can, in fact, be an epiphenomenon to possible central disturbances rather than a primary process. Evidence suggests that altered levels of serotonin, substance P, and neuropeptide Y in the serum or platelets of patients with TTHA are responsible.

    • TTHA is characterized by intermittent or persisting bilateral pain, usually described as a squeezing pressure or a band-like sensation around the head. Most patients experience their symptoms in the frontal, temporal, or occipital areas of the head. Location frequently varies with the attack, and tightness of the neck and shoulders is common. Intensity varies greatly. The attacks can last from hours to days, and in some extreme cases they may last for months. Aura, nausea, photophobia and phonophobia, and incapacitation are not typically associated with

    Many TTHA sufferers easily recognize the origin of their attacks. TTHA typically results from emotional upset, periods of stress, and major life changes. Anxiousness, poor adaptation skills, and anxiety and depression often are present. Physical causes, such as degenerative joint disease, trauma to the head or neck, awkward neck position, poor posture, temporomandibular joint dysfunction, bruxism, or heavy chewing also can precipitate attacks. Persons older than 50 years are prone to excessive muscle contraction because of arthritis of the neck and jaw, poor posture, or stress. TTHA that is consistently precipitated by tension or pathology of the neck frequently is referred to as a cervicogenic headache. In contrast to migraine headache, TTHA is more likely to begin in later life.

  3. 3
    Migraine Headache

    Migraine headache is a familial disease characterized by unilateral or bilateral paroxysmal headache lasting hours to days. Adult women experience attacks more than men by a ratio of 3:1. Children and the elderly experience migraine equally. Attacks occur from as infrequently as one or two per year to several times weekly.

    Associated symptoms usually occur and frequently include throbbing, nausea, vomiting, photophobia, phonophobia, fluid retention, and mood changes.

    The two basic types of migraine headache are migraine with aura (previously called classic migraine) and migraine without aura (previously called common migraine). Migraine with aura is preceded by an aura, a transient neurologic symptom that usually is visual, such as scotoma, teichopsia, tunnel vision, or visual field deficit, lasting 5 to 30 minutes. However, aura can manifest as any neurologic deficit. Migraine without aura is more commonly experienced and comes on gradually or is present on awakening from sleep. In some patients, these headaches are associated with a nonspecific prolonged prodrome, such as mood changes, food cravings, or fluid retention hours before the pain.

    The underlying cause of migraine headache is not clearly established, and various theories are proposed. Migraine appears to be of genetic origin and to be an inflammatory disease that causes disturbances in serotonin use and activity. Strong evidence indicates that the migrainous attack originates in the central nervous system by stimulation of the locus ceruleus and dorsal raphe nuclei. Resultant changes alter cerebral and extracranial blood flow; activate the trigeminovascular system; and cause vascular dilation, neurogenic inflammation, and pain. Various precipitants are known, and many sufferers report that migraine attacks frequently are associated with menstruation or are triggered by foods containing vasoactive amines, strong odors, too much or too little sleep, sun glare, stress, altitude, weather changes, exertion, or fasting (Boxes 1 and 2).

    Box 1
    Common Migraine Dietary Triggers
    • Dairy: ripened cheese (cheddar, brie, camembert), sour cream >½ cup

    • Meats: processed lunch meats, hot dogs, sausage, bologna, salami, chicken liver

    •   Fish: pickled or dried herring

    •   Grains: sourdough bread

    •   Fruits: bananas, raisins, figs, avocado, citrus >½ cup

    •   Vegetables: broad and fava beans, onions, snow peas, garlic

    • Other: chocolate, nuts, peanut butter, pickled foods, most Chinese food

    •   Beverages: most wines and alcohol, caffeine > 200 mg

    •   Additives: MSG, soy sauce, meat tenderizers, aspartame, sulfites

     

    Box 2
    Migraine Triggers
    •   Altitude

    •   Alcohol

    •   Caffeine withdrawal

    •   Fluorescent or flickering lights

    •   Sun glare

    •   Weather changes

    •   Stress, stress letdown

    •   Foods

    •   Skipping meals

    •   Smoky environment

    •   Noisy environment

    •   Strong odors

    Some physicians classify migraine according to its precipitant or description (e.g., menstrual migraine, exertional migraine, coital migraine, cervicogenic migraine, cyclic migraine, “painless” or acephalic migraine). When a sufferer experiences headache for 50% of the month, it is referred to as chronic migraine. Regardless, the fundamentals of evaluation and treatment are similar.

  4. 4
    Cluster Headache

    The cause of cluster headache is unknown, and little credible research is available. Various possibilities or theories are suggested and include, but are not limited to, disturbances in histamine production or use; hypothalamic biorhythm dysfunction; or serotonin and neurotransmitter mechanisms similar to those of migraine. Some authorities consider cluster headache one of the most severe pain conditions known to humankind.

    • Cluster headache predominantly affects men, with a male-to- female ratio of 6:1. It occurs in well under 0.5% of the Onset later in life (after age 30 years) is common, and patients sometimes report head injury or a traumatic event occurring months before onset. Attacks occur on a daily or near-daily basis for weeks or months at a time and mysteriously disappear for months to years regardless of treatment, only to recur and cycle again. Although nonspecialist physicians only occasionally encounter the patient with cluster headaches, it is important to consider cluster headaches in the differential diagnosis.

    The typical patient with a cluster headache experiences relatively brief attacks (45–90 minutes) of horrible unilateral head pain associated with ipsilateral lacrimation, scleral injection, rhinorrhea, or eyelid droop. The hallmark of the syndrome is its associated symptoms and its severe and intense pain. During attacks, most cluster patients move about, trying unsuccessfully to get more comfortable, similar to renal colic; this is in contrast to migraine sufferers, who prefer to lie quietly in a dark quiet room. Few triggers are identified, and alcohol almost always precipitates an attack during a cluster “on” cycle. A rare form of cluster headache, chronic cluster, does not cycle and continues on a daily or near-daily basis without cessation.

  5. 5
    Chronic Daily Headache

    A small percentage of headache sufferers present with chronic daily headache. The majority of these daily headaches are of the tension or migraine type. However, patients may present with daily nonincapacitating generalized headache. These headaches frequently are associated with major life changes (negative or positive), financial or relationship difficulties, and depression or emotional problems.

    The assessment of the chronic daily headache patient is similar to other headache syndromes, but may require particular attention to mental health and medication rebounding issues.

  6. 6
    Posttraumatic Headache

    Posttraumatic headaches are headaches resulting from physical injury to the head. The trauma can be direct or the result of a contra-coux type injury encountered with whiplash or forced movement of the head or neck. The degree of injury and headache is not necessarily related to the degree of trauma. Seemingly minor injuries sometimes can result in significant and prolonged headache while apparent severe blows to the head sometimes do not result in significant headache.

    Complicating the posttraumatic headache can be an associated spasm of shoulder, neck, and scalp muscles or reactive anxiety and depression. Patients with preexisting headaches may experience an increase in severity or frequency of headaches. It is not unusual for there to be a delay in the onset of headache.

    It is imperative that the detailed evaluation of the posttraumatic headache patient include psychological and cognitive examination while keeping in mind that presumed trivial injuries can have significant sequela. The more frequent type of headache encountered is of the tension or chronic daily type. Migraine and cluster are reported.

  7. 7
    Treatment

    The doctor-patient relationship frequently is the key to successful treatment in the headache patient. Although to some this statement seems an obvious truism, its importance cannot be overemphasized.

    Patients who experience frequent, near-daily, or daily headaches invariably require a comprehensive treatment program that necessitates good communication. Anxious patients sometimes do not comprehend medical explanations or instructions; busy doctors sometimes do not have or take the time to ensure that the patient understands.

    The two elements of headache treatment are abortive treatment, directed at attacks once they have begun, and prophylactic treatment, directed at preventing or reducing the frequency of attacks. In general, the abortive approach is used for patients who suffer infrequent attacks and for those who experience breakthrough attacks while undergoing prophylactic therapy.

    Prophylactic therapy should be instituted when headaches are frequent, when headaches are unresponsive to abortive medication, or when there are contraindications to abortive medications.

    • Headache treatment can include nonpharmacologic measures, such as physical exercise, stretching, stress avoidance, relaxation exercises, biofeedback, manipulation, massage, or cold/warm packs. Pharmacologic therapies can include a vast array of medicaments from over-the-counter (OTC) drugs to prescription drugs such as triptans, other vasoconstrictors, β-blockers, calcium channel blockers, antiepileptic agents, antidepressants, nonsteroidal antiinflammatory drugs (NSAIDs), analgesics, muscle relaxants, anxiolytics, and Treatment, whether prophylactic or abortive, should follow a definite plan incorporating the clinician and patient into a team focused on reducing the headache frequency, severity, and disability.

    As mentioned earlier, impressions and physical findings should be explained to the patient in as much detail as necessary to ensure the patient’s complete understanding. The complexity of the headache condition needs to be explained, emphasizing its chronicity, rather than its curability, and that the goal of treatment is disease control.

    • The comprehensiveness of the treatment plan depends on the frequency of the patient’s attacks. The more frequent and severe the attacks, the more detailed plan may be necessary. Patients experiencing infrequent attacks (e.g., once or twice monthly) may require only an abortive medication and little else. Patients with more frequent attacks may benefit from dietary restrictions, psychosocial intervention, biofeedback relaxation training, manipulation, and physical modality intervention, in addition to medication (Table 2).

    Table 2

    Current Therapy

    Abbreviations: NSAID = nonsteroidal anti-inflammatory drug; OTC = over-the-counter drug; TCA = tricyclic antidepressant.

    • FDA
  8. 8
    TTHA Treatment

    TTHA is often associated with emotional stress and muscle strain or tension of the shoulders and neck. Simple self-administered measures, such as stress avoidance, stretching, warm packs, or relaxation techniques, can be helpful in reducing or relieving attacks. More comprehensive professional intervention, such as manual manipulation, physical therapy, local injections, or biofeedback training, is a consideration for more frequent or severe cases. The ultimate goal is to restore normal function of involved muscles.

    • Prophylactically, the use of OTC or prescription medications can be considered in addition to nonmedicinal measures for reducing the frequency and duration of attacks. NSAIDs, muscle relaxants, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), at the lowest effective doses, are more commonly used. Other categories of antidepressants are reported to be effective in some sufferers.
    • Daily use of the longer-acting NSAIDs, such as naproxen1 (Naprosyn) or celecoxib1 (Celebrex), in the appropriately screened patient over a 2- to 3-week period, can be an effective preventative.

    TCAs, such as nortriptyline1 (Pamelor) or amitriptyline1 (Elavil), in low doses at night over 1 to 3 months, are frequently effective, especially in patients with anxiety or mild depression. The SSRI drugs, such as fluoxetine1 (Prozac) or sertraline1 (Zoloft), similarly can be useful.

    The muscle relaxant cyclobenzaprine1 (Flexeril), at low doses, with a similar mechanism to the TCAs, can be administered at night for limited periods. Other muscle relaxants occasionally can be helpful.

    Potential side effects can limit the use of NSAIDs (gastrointestinal irritation) and the TCAs (fatigue and weight gain).

    OnabotulinumtoxinA (Botox)1 reportedly is helpful in the treatment of the tension-type headache, but controlled studies are limited. In this treatment, a diluted solution of botulinum toxin is injected into various muscles of the face, scalp, neck, or shoulders. It is imperative that these injections be administered by physicians skilled in the procedure to avoid complication and adverse events.

    • Abortive or symptomatic treatment of TTHA can include simple OTC medications (e.g., aspirin or acetaminophen), NSAIDs (short acting), muscle relaxants, combination analgesics, and, in rare cases, opioid or opioid-like drugs. Limited studies have shown analgesic qualities of riboflavin (vitamin B2)2 200 mg is recommended for patients who cannot tolerate NSAID type medications. Caution should be exercised in prescribing potentially habituating drugs. Daily or near-daily use of analgesics and especially those containing caffeine, can lead to analgesic rebound headache or medication overuse headache, which can compound the patient’s headache problem.
  9. 9
    Migraine Treatment

    Migraineurs are unique individuals, and the effectiveness and tolerance of medications can vary from patient to patient. Medication changes, combinations of medications, and trial and error may be necessary in the early stages of treatment.

    • Nonmedicinal measures for migraine sufferers include biofeedback stress reduction, caffeine and dietary restrictions, regimentation of meals and sleep, rest, exercise, stretching, and avoidance of work or activity overload. Strict limitation of caffeine to less than 200 mg/day is important to prevent caffeine headache (rebound headache) in most patients. Elimination of vasoactive foods, such as chocolate, aged cheese, and processed meats, and avoidance of fasting for more than 4 hours can be helpful for patients with more frequent attacks (see Box 1). Regular exercise and stretching, planned relaxation, regular sleep schedules, and following a healthy lifestyle are frequently included in a comprehensive treatment regimen. In some patients, especially children and adolescents, biofeedback stress reduction or psychotherapeutic intervention may be necessary.
    • The more commonly used medications for prophylaxis are β- blockers, calcium channel blockers, antiepileptics (neurostabilizers), and the antidepressants. Treatment should be continued for a 6- to 8-week trial before discontinuation for ineffectiveness. The determination of which medication to use depends on comorbidities, interactions with concomitant medications, and tolerability.

    β-Blockers such as propranolol and timolol (Blocadren) are nonselective and are approved by the FDA for migraine prevention. Other β-blockers, such as nadolol1 (Corgard), metoprolol1 (Lopressor), and atenolol1 (Tenormin), also can be effective. The mechanism of action in migraine is not wholly understood, but it is thought to involve anxiolytic effects and vascular changes and stabilization. The usual dosage is recommended (e.g., timolol 10–30 mg/day,

    propranolol 120–160 mg/day), and many consider the nighttime dose the more significant.

    Calcium channel antagonists are well tolerated in general and can be effective in many patients. They are believed to alter serotonin release and inhibit platelet serotonin uptake and release within the brain. Verapamil1 (Calan) is considered the more effective and is commonly recommended to patients. Dosage can vary from 120 to 480 mg/day. Nimodipine1 (Nimotop) is equally effective, but has been rarely used in the United States because of its high cost.

    • Antiepileptic medications such as phenytoin1 (Dilantin) and carbamazepine1 (Tegretol) have been prescribed for migraine prevention over the years, with mixed results. Their use is now limited with the advent of newer, more easily tolerated agents, such as divalproex sodium (Depakote ER) and topiramate (Topamax).
    • Divalproex sodium is effective in reducing migraine attacks and is particularly useful in patients with coexisting head injury, seizure disorders, and bipolar disorders. It is thought to improve inhibitory and excitatory amino acid imbalance in the brain. It is best to start with a lower dose and to gradually increase as needed and tolerated. The dosage of 500 to 1000 mg/day is more frequently prescribed. A commonly experienced side effect is sedation, which can sometimes be used to the patient’s advantage when anxiolytic effects are needed.
    • Topiramate is a preventive medication approved by the FDA for migraine prophylaxis. It has multiple mechanisms of action, but its exact mechanism in migraine headache is unknown.

    Its effectiveness is believed to involve sodium ion channel stabilization, calcium ion channels, GABA (γ-aminobutyric acid) receptors, and neuronal membrane stabilization. The average daily dose is variable and ranges from 30 to 100 mg/day. A most unusual side effect of weight loss or appetite suppression can be used to the patient’s advantage in preventing weight gain, which frequently accompanies migraine prophylactic medications.

    The TCAs can be useful for patients who experience frequent attacks and for those who experience anxiety and depression. The TCAs inhibit synaptic reuptake of serotonin, thereby reducing neuron firing and release of neurotransmitters. Starting with a low dose in the evening and titrating up to efficacy and tolerability is recommended. Significant anticholinergic and sedation effects sometimes limit their use. The SSRIs are reported helpful in some patients, but their use in migraine prevention is limited.

    Other medications have been utilized in migraine prophylaxis with varying success. These include NSAIDs, cyproheptadine (Periactin),1 clonidine (Catapres),1 phenothiazines, anxiolytics, ergotamine (Ergomar), magnesium,1 feverfew,2 and others.

    • In general, prophylactic medications should be taken for 6 to 8 weeks to determine efficacy. If effective, a course of 4 to 6 months is recommended before an attempt is made to discontinue medication.
    • Onabotulinum toxinA has been approved by the FDA for the treatment of chronic migraine. Multiple injections to the head and neck can be helpful for patients who experience symptoms for more than 14 days per month and it can be repeated after 3 months. Because this treatment is administered by physicians in headache specialty and pain practices, simultaneous comprehensive treatment measures and medication can contribute to positive patient results. Side effects are relatively low when injected by experienced physicians; alteration of facial expressions is the most common. Proper administration of the toxin is imperative.

    A large meta-analysis of 27 controlled clinical trials concluded that onabotulinumtoxinA injections showed a small to moderate benefit over placebo in patients experiencing chronic migraine and chronic daily headache. Patients with chronic tension type or episodic migraine showed no benefit.

    • A trigeminal nerve stimulator, Cefaly device, was approved by the FDA in 2014. The Cefaly head-band apparatus can be self administered 20 minutes daily to reduce migraine frequency. Experience with this TENS device is limited.
    • A variety of abortive treatment options are available for migraine sufferers. Although the triptans (Table 3) have generated much interest and are frequently prescribed, other medications continue to be used, including ergotamine and its derivatives, isometheptene, and NSAIDs. Many of the abortive medications carry significant prescribing limitations that must be taken into consideration. Vasoconstrictor medications are contraindicated in patients with cardiovascular or peripheral vascular disease. NSAIDs should not be used in those with gastrointestinal or bleeding disorders. As with all medications, the clinician must consider appropriate prescribing, contraindications, and side-effect information.

    Table 3

    Triptans

    Abbreviations: MLT = oral disintegrating; NS = nasalspray; TD =  transdermal.

    • The vasoconstrictor ergotamine is available in oral, rectal (with caffeine [Cafergot]), and sublingual forms (Ergomar). Ergotamine has a relatively long half-life and duration of action (up to 3 days) and should be used no more frequently than every 4 to 5 days to avoid ergotamine rebound headache. The ergot derivative dihydroergotamine (DHE-45, Migranal NS) is available for intramuscular, subcutaneous (SC), and intranasal use. Intravenous DHE-45 sometimes is used for intractable migraine (status migrainosus) in emergency departments and inpatient settings. The intranasal form (Migranal) is an effective treatment when administered correctly by the patient. Unfortunately, DHE-45 is not absorbed by the gastrointestinal tract, and unlike other abortive nasal sprays, any swallowed medication will be wasted. DHE-45 has a low headache recurrence rate of approximately 12%. All forms of ergotamine and DHE-45 are more effective when taken early in attacks.
      Isometheptene is used in combination with dichloralphenazone and acetaminophen (Midrin). It is slow acting and more effective when taken early in attacks and when used for attacks preceded or accompanied by stress and muscle tension of the neck. Although isometheptene is considered less potent than ergotamine and triptans, it is preferred by many patients whose headaches have features of both migraine and tension type.
      At the present time, seven serotonin agonists (triptans) are approved for abortive migraine treatment in the United States (see Table 3). As a category, the triptans are approximately 65% to 70% effective in published clinical trials. Their similarities are greater than their differences, but each triptan is not necessarily effective for all patients, and familiarity with their differences can be helpful to the treating physician. Half-life, onset and duration of action, adverse events, tolerability, recurrence of headache, and routes of administration may vary and allow the physician to match the medication to the individual patient. For example, a slower onset of action and longer-lasting triptan may be appropriate for slow-onset, longer-lasting migraine attacks.
    • As with other headache treatments, oral triptan tablets are more effective in the early phases of migraines. It is thought that peripheral sensitization—allodynia—is a sign of later phase migraine, and treating the attack before this phenomenon occurs is important. When treatment is delayed or the patient awakens with severe migraine, the injection, nasal spray, or rapidly acting triptans may be more beneficial. Although triptans as a group are very effective, recurrence of headache, after initial relief, requiring retreatment is common and can be as high as 40%. The recurrence rate tends to be less with triptans having a longer half-life.

    The ergotamines and triptans are contraindicated in patients with ischemic heart disease, uncontrolled hypertension, and cerebrovascular disease. Physicians initially were extremely cautious about recommending triptans to their patients when they were first introduced in the United States. However, significant human exposure to the triptans has shown that myocardial infarction or serious ischemia is rare. Chest pain following triptan use affects a small percentage of patients, and because its significance continues to be unclear, it is recommended that triptan use be held pending cardiac evaluation.

    • Sumatriptan (Imitrex), the first triptan approved in the United States, is available in nasal spray (5, 20 mg), SC (6, 4 mg), oral formulations (25, 50, 100 mg), and transdermal (Zecuity; 6.5 mg). Its half-life is approximately 1.5 hours, and its duration of action is less than 4 hours. The injectable form produces rapid relief in 70% to 80% of patients, and it appears to be the most effective of all the available triptan forms. Conversely, it appears to cause the most side effects, and, for this reason, it should be used only for the more severe attacks. The oral forms are more favorable with regard to adverse effects, and their effectiveness is similar to that of other triptans (approximately 65%). Because of sumatriptan’s short half-life and duration of action, recurrence of headache is common, necessitating repeat dosing.
    • Naratriptan (Amerge) was the first to be approved of the gradual onset, longer-acting triptans. It is available as oral 1 and 2.5 mg tablets and has a half-life of 6 hours. Naratriptan is well tolerated by patients and often is used by patients with slow-onset migraine. Some specialists prescribe daily naratriptan1 for limited periods for treatment of menstrual or intractable migraine attacks.
    • Zolmitriptan (Zomig) is available in 2.5 and 5 mg oral and oral disintegrating tablets (ZMT) and as 2.5 and 5 mg nasal sprays. The efficacy of oral zolmitriptan is approximately 65% and that of the nasal form is 70%. The half-life of oral zolmitriptan is 3 hours, and its duration of action is longer than the nasal form, which improves on the need to remedicate. The nasal spray has a biphasic absorption curve, which accounts for its favorable adverse effect profile over the 5 mg oral tablet.
    • Rizatriptan (Maxalt) is available as oral 5 and 10 mg tablets and as an oral disintegrating form (MLT). It’s half-life is 2 to 3 hours and it has a favorable one-dose 2-hour response rate. Patients who are undergoing concomitant treatment with propranolol should take the lesser 5 mg rizatriptan dose because of higher resultant rizatriptan plasma levels.
    •  Almotriptan (Axert) is available in 6.25 and 12.5 mg tablets. It has a half-life of 3.5 hours and, because of a broad Tmax (time of maximal concentration) range of 1.4 to 3.8 hours, a relatively rapid onset of action. Almotriptan has favorable adverse effect and headache recurrence profile. Chest pain symptoms after almotriptan use were similar to placebo in clinical trials.
    • Frovatriptan (Frova) is a long-acting triptan available in 2.5 mg oral tablets. It has the longest half-life of 25 hours and a favorable recurrence rate. Frovatriptan is frequently used for treatment of menstrual migraine and for attacks of longer duration. Some specialists prescribe daily frovatriptan1 for a limited period for menstrual and prolonged migraine attacks.
    • Eletriptan (Relpax) was the last triptan to be approved. It is available in 20 and 40 mg oral tablets and has a half-life of nearly 5 hours. Eletriptan has a relatively rapid onset but a longer duration of action and a favorable recurrence rate. In studies, some patients who were unresponsive to other triptans responded to eletriptan. Various attempts have been made to compare triptans. Head-to-head trials mostly have compared one triptan to sumatriptan. A meta- analysis of 53 clinical trials published in 2001 compared the efficacy, recurrence, duration of action, and tolerability of all available triptans. Almotriptan and eletriptan were rated favorably across the major parameters of onset of action, efficacy, adverse events, and recurrence. In spite of efforts to adjust for variations in protocols and placebo response, specialists reached no clear consensus as to the validity or value of the meta-analysis or the preferability of one triptan over another.
    •  NSAIDs frequently are recommended for treatment of acute migraine and can be effective when taken early. Their effects on the physiology of pain, inflammation, and platelets are thought to be the mechanisms responsible. Some physicians recommend taking a NSAID with the first dose of a triptan for added efficacy. Various agents are used, but none of the rapid-acting NSAIDs appears to have significant efficacy superiority. Naproxen sodium 500 mg in combination with sumatriptan 85 mg (Treximet), OTC ibuprofen (Motrin, Advil), and aspirin combination with caffeine and acetaminophen (Excedrin Migraine) are approved by the FDA for treatment of acute migraine.
    •  Symptomatic treatment of pain may be necessary in patients who do not respond to recommended abortive treatment. Any effective analgesic can be appropriate, provided it is used infrequently and not on a daily or near-daily basis. In general, the more effective analgesics have antiinflammatory and sedative properties.
  10. 10
    Cluster Headache Treatment

    Cluster headache is one of the more unusual pain conditions occasionally encountered by physicians. Pain onset is rapid, and the duration of the attack is brief. For this reason, prophylactic treatment usually is the most practical. Abortive prescriptions frequently are given, but, for the most part, the cluster attack is resolving by the time medication is absorbed.

    • Nonmedicinal prophylactic measures are extremely limited. The reduction of cigarette smoking and the addressing of individual stress and hostility during cluster periods should be part of any treatment program. There are no FDA-approved medications for the prophylactic treatment of cluster headache. Numerous medications can be helpful and include the calcium channel blockers verapamil (Calan, Isoptin, Verelan, Covera, Verap)1 and nimodipine,1 the neurostabilizers valproate (Depakote)1 and topiramate,1 various NSAIDs, ergotamine,1 lithium (Eskalith),1 cyproheptadine,1 combination H1 and H2 histamine antagonists, and, in extreme cases, short intervals of steroids. The addition of magnesium1 500 to 750 mg can be helpful in some sufferers. These medications are used in average therapeutic doses, and combinations of medications are commonly needed. The preventatives should be used during the cluster cycle and discontinued during off-cycle periods.
    • Abortive treatment is less preferred for cluster headache, as noted previously. However, inhalation oxygen via facial mask at 6 L/min terminates cluster attacks in 75% to 80% of sufferers within 12 minutes. Other possibilities include sumatriptan1  SC or nasal spray, zolmitriptan1 nasal spray, ergotamine1 sublingual, or DHE- 45 injection1 or nasal spray (Migranal).1 The occasional patient reports relief with the oral triptans or potent analgesics. When triptans, ergotamine, or analgesics are used, appropriate prescribing and frequency guidelines should be followed. In general, with the exception of oxygen, daily as-needed medications should be avoided.
  11. 11
    Chronic Daily and Posttraumatic Headache Treatment

    The care of patients with chronic daily and posttraumatic headaches is determined by the type or types of headache being experienced.

    Treatment of each type follows what has been described above. In the patient experiencing posttraumatic headache, frequent follow-up visit monitoring is most appropriate. Extra care should be taken when prescribing medications, especially those that could affect cognitive function and recovery. Often, posttraumatic headache patients benefit with concomitant psychologic and cognitive professional support.

  12. 12
    Conclusion

    Headache continues to present a challenging problem for clinicians as well as for suffering patients. In spite of recent treatment advances and more public awareness, millions continue to needlessly endure pain and debilitation. Desperate sufferers in a quest for relief sometimes resort to unorthodox therapies or anxiolytics, habituative analgesics, or excessive caffeine that ultimately worsen their headache problems.

    At first glance, the headache problem appears complex and difficult when, in actuality, most sufferers experience straightforward, easily diagnosed headaches. The interested generalist or specialist who takes the time to elicit a careful history can establish the headache diagnosis and direct a simple treatment plan that can make a tremendous difference in the headache sufferer’s life.

  13. 13
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    Ferrari M.D., Roon K.I., Lipton R.B., et al. Oral triptans (serotonin 5HT-IB/ID-agonists) in acute migraine treatment: A meta-analysis of 53 trials. Lancet. 2001;358:1668–1675.

    Gallagher R.M., Kunkel R. Migraine medication attributes important for patient compliance: Concerns about side effects may delay treatment. Headache. 2003;43:36–43.

    Goadsby P.J., Lipton R.B., Ferreri M.D. Migraine current understanding and treatment. N Engl J Med. 2002;346:257–270.

    Haberer L.J., Walls C.M., Lener S.E., et al. Distinct pharmacokinetic profile and safety of a fixed-dose tablet of sumatriptan and naproxen sodium for the acute treatment of migraine. Headache. 2010;50:357–373.

    Jackson J.L., Kuriyama A., Hayashino Y., et al. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: A meta-analysis. JAMA.

    2012;307(16):1736–1745.

    Silberstein S.D., Lipton E.B., Dalessio D.J. Wolff’s Headache and Other Head Pain. ed 7th New York: Oxford University Press; 2001.

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    Vernon H., McDermaid C., Hagino C. Systematic review of randomized clinical trials of complementary/alternative therapies in the treatment of tension-type and cervicogenic headache. Complement Ther Med. 1999;7:142–155.

    1  Not FDA approved for this  indication.

    2  Not available in the United  States.

KNOWLEDGE BASE
About Genomic Medicine UK

Genomic Medicine UK is the home of comprehensive genomic testing in London. Our consultant medical doctors work tirelessly to provide the highest standards of medical laboratory testing for personalised medical treatments, genomic risk assessments for common diseases and genomic risk assessment for cancers at an affordable cost for everybody. We use state-of-the-art modern technologies of next-generation sequencing and DNA chip microarray to provide all of our patients and partner doctors with a reliable, evidence-based, thorough and valuable medical service.

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