Uncategorized

Headache, Migraine

Introduction

Background

Migraine headache is a complex, recurrent headache disorder and is one of the most common complaints in medicine today. The term migraine is derived from the Greek word hemikrania. Later, this term was corrupted into low Latin as hemigranea, which eventually was accepted by the French translation as migraine. A typical episode is characterized by unilateral head pain that may be preceded by various prodromal symptoms. Other focal neurologic symptoms, collectively known as an aura, may also precede or coincide with the onset of a headache.

Introduction

Background

Migraine headache is a complex, recurrent headache disorder and is one of the most common complaints in medicine today. The term migraine is derived from the Greek word hemikrania. Later, this term was corrupted into low Latin as hemigranea, which eventually was accepted by the French translation as migraine. A typical episode is characterized by unilateral head pain that may be preceded by various prodromal symptoms. Other focal neurologic symptoms, collectively known as an aura, may also precede or coincide with the onset of a headache.

Although many more headache types are listed in the International Classification of Headache Disorders (ICHD) by the International Headache Society (IHS), the following are the most often encountered in practice, with migraine being the most challenging:

  • Migraine without aura
  • Probable migraine without aura
  • Migraine with aura
  • Probable migraine with aura
  • Chronic migraine
  • Chronic migraine associated with analgesic overuse
  • Tension-type headache
  • Cluster headache
  • Chronic daily headache

Pathophysiology

Historically, migraine has been associated with fluctuations in cerebral perfusion. Investigations show areas of hypoperfusion preceding the onset of a headache, followed by a period of reactive hyperperfusion and eventual normalization of flow, which is not explained by simple cerebral or meningeal vasodilation.[1,2 ]

Predisposing adverse vascular risk factors

  • Increased levels of C-reactive protein
  • Interleukins
  • TNF-alpha and adhesion molecules, which are markers of systemic inflammation
  • Oxidative stress and thrombosis
  • Increased body weight, high blood pressure, hypercholesterolemia
  • Impaired insulin sensitivity
  • High homocysteine levels, stroke, and coronary heart disease[3 ]

Cortical spreading depression

Cortical spreading depression (CSD) is a transient area of depressed neuronal activity, mediated by waves of cellular depolarization, causing the primary cortical phenomenon or aura phase, which, in turn, activates trigeminal fibers causing the headache phase. The initial cortical hyperperfusion in CSD is partly mediated by the release of trigeminal and parasympathetic neurotransmitters from perivascular nerve fibers, whereas delayed meningeal blood flow increase is mediated by a trigeminal-parasympathetic brainstem connection. According to Moulton et al, altered descending modulation in the brainstem has been postulated to contribute to the headache phase of migraine; this leads to loss of inhibition or enhanced facilitation, resulting in trigeminovascular neuron hyperexcitability.[4 ]

In addition, through a variety of molecular mechanisms, cortical spreading depression upregulates genes: such as COX-2, TNF-alpha and IL-1beta, galanin, and metalloproteinases. The activation of metalloproteinases leads to leakage of the blood-brain barrier, allowing potassium, nitric oxide, adenosine, and other products released by cortical spreading depression to reach and sensitize the dural perivascular trigeminal afferent endings.[5 ]Migraine without aura (MWA) patients seem to have an increased ratio of MMP-9/TIMP-1 in contrast to a lower MMP-9/TIMP-1 ratio in migraine with aura (MA) patients,[6 ]whereas MMP-9 when measured alone is the same for MA and MWA[7 ].

In an experimental study, acute hypoxia was induced by a single episode of CSD with dramatic failure of brain ion homeostasis and prolonging impairment of neurovascular and neurometabolic coupling.[8 ]

Endothelial dysfunction

Vascular smooth muscle cell dysfunction has impaired cyclic guanosine monophosphate and hemodynamic response to nitric oxide.[9 ]Nitric oxide (NO) released by microglia is a potentially cytotoxic proinflammatory mediator, initiating and maintaining brain inflammation through activation of the trigeminal neuron system, which continues to be increased even in the headache-free period in migraineurs.[10 ]

In premenopausal women with migraine, particularly in those with migraine aura (MA), increased endothelial activation, which is a component of endothelial dysfunction, is evident.[11 ]

Endothelial function is only one aspect of vascular reactivity, which, in turn, may be affected by many different factors: The most important measurable factors of vascular reactivity in conduit artery function are flow-mediated dilation (FMD), pulse wave velocity (PWV), and 4 measures of resistance or microvascular function (ie, forearm reactive hyperemia, reactive hyperemia index by finger plethysmography (RHI), skin reactive hyperemia, and fingertip temperature rebound); these may all have an association with the prognostic role in the assessment of cardiovascular risk in postmenopausal women.[12 ]

Neurogenic response in the neurovascular complex

Part of the neurogenic response in the neurovascular complex phenomenon is related to changes in neuropeptide levels of serotonin and dopamine. Certain symptomatic and prophylactic agents are effective in part through binding at specific serotonin (5-hydroxytryptamine [5-HT]) binding sites. Signs and symptoms (eg, anorexia, nausea, vomiting, pallor, yawning) respond to dopaminergic antagonists. The concept of an altered migrainous threshold in individual patients has been advocated. Imbalances in inhibitory and excitatory neuronal pathways may sensitize the trigeminovascular system and provoke a migraine event.

Other related factors

In a study by Kruit et al, T2 values were compared and analyzed in 138 migraineurs and 75 control subjects. Migraineurs presented with increased local iron deposits in the putamen, globus pallidus, and red nucleus. This increase in iron deposits may be explained as a physiological response induced by repeated activation of nuclei involved in central pain processing, or to damage of these structures secondary to formation of free radicals in oxidative stress and possibly the cause of chronification of the disease.[13,14 ]

Genetic and acquired vascular mechanisms

Genetic and acquired vascular mechanisms are also related to migraine appearance. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD), and vascular endothelial dysfunction are among the possible explanations for the relationship between migraine and acquired vasculopathies such as ischemic stroke and coronary heart disease.

Migraine is a common symptom of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); retinal vasculopathy with cerebral leukodystrophy (RVCL); and hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy (HIHRATL). Although the mechanisms by which these genetic vasculopathies give rise to migraine is still unclear.[15 ]

Frequency

United States

Epidemiologic studies indicate that 23 million Americans, approximately 18% of females and 6% of males, will have one or more migraine headaches per year. Migraine accounts for 64% of all females and 43% of all males with severe headache.

Mortality/Morbidity

Migraine continues to be a major health problem.

  • In the American Migraine Study, more than 85% of women and 82% of men with severe migraine had some headache-related disability.
  • Estimated lost productivity is $1-13 billion a year.
  • Migraineur males required 3.8 bed rest days per year, whereas women required 5.6 bed rest days per year.

Race

  • One study showed that among women, 20.4% of Caucasians, 16.2% of African Americans, and only 9.2% of Asian Americans met IHS criteria for migraine.
  • Similarly in males, 8.6% of Caucasians, 7.2% of African Americans, and 4.8% of Asian Americans were considered to have migraine.

Sex

Migraine with aura: Incidence or age of onset appears to peak in patients aged 4-5 years (6.6 per 1000 person-years).[16 ]

  • The age-specific incidence of migraine without aura differs; the highest incidence occurs in persons aged 10-11 years (10.1 per 1,000 person-years).[16 ]In general, the incidence of migraine in males declines to a low rate by 28-29 years (1.0 per 1,000 person-years).
  • The incidence rate of migraine with aura peaks in females aged 12-13 years, 3-4 years before that of migraine without aura.
  • Among females, migraine prevalence increased sharply up to age 40 years and gradually declined. The male peak prevalence was slightly less and decreased over a broader age range.
  • Data further indicate that migraine is a chronic condition, although prolonged remissions are common. One study showed that 62% of young adults were migraine-free for more than 2 years, but only 40% continued to be migraine-free after 30 years. The severity and frequency of attacks tend to diminish with increasing age. After 15 years, approximately 30% of men and 40% of women no longer had migraine attacks.

Age

In patients younger than 10 years, prevalence appears to be higher in males than in females. After the onset of puberty, migraine is considerably more common in females than in males (3:1).

Clinical

History

The migraine headache is typically a unilateral and throbbing pain, but the features often vary. Migraineurs often experience a bilateral event. The pain can be felt anywhere around the head or neck.

  • Prodrome (60%)
    • Forewarning of a migraine may occur hours to days before a headache event.
    • Although the specific features of the prodrome vary, they tend to be consistent for a given individual and include the following:
      • Neurologic symptoms (eg, photophobia, phonophobia, osmophobia)
      • Lethargy
      • Mental and mood changes (eg, depression, anger, euphoria)
      • Polyuria
      • Meningismus
      • Anorexia
      • Constipation or diarrhea
  • Aura (10-20%)
    • In most cases, the headache follows the aura. However, the two events can occur at the same time, or the aura may develop after the headache is in progress.
    • Focal neurologic symptoms, listed below, evolve over a period of 5-15 minutes and last approximately 1 hour:
      • Visual (most common)
      • Negative scotomas or negative visual phenomena – Homonymous hemianopic or quadrantic field defects, central scotomas, tunnel vision, altitudinal visual defects, or even complete blindness
      • Positive visual phenomena or scintillating scotomas (most common migraine aura) – This consists of an absent arc or band of vision with a shimmering or glittering zigzag border and often is combined with photopsias or visual hallucinations that may take various shapes. A highly characteristic syndrome always occurs prior to the headache phase of an attack and is pathognomonic of a classic migraine. It is called a fortification spectrum because the serrated edges of the hallucinated “C” resemble a “fortified town with bastions around it.”
      • Photophobia
      • Photopsia (unformed flashes of light) or simple forms of visual hallucinations occur commonly with positive visual phenomena.
  • Motor
    • Hemiparesis
    • Aphasia
  • Headache
    • Unilateral (60-70%)
    • Typically gradual onset, lasting 4-72 hours
    • Usually described as a throbbing or pulsatile type of pain but can evolve into a chronic ache or bandlike pattern
  • Associated symptoms
    • Anorexia
    • Nausea
    • Vomiting
    • Blurred vision
    • Skin pallor
    • Photophobia
    • Phonophobia
    • Lightheadedness

Physical

Evidence of autonomic nervous system involvement can be helpful, although most patients with migraine may exhibit little or no findings. Serial neurologic examinations are recommended.

Possible findings may include the following:

  • Cranial/cervical muscle tenderness
  • Horner syndrome (a constricted pupil on the same side of the headache)
  • Conjunctival injection
  • Tachycardia/bradycardia
  • Hypertension/hypotension
  • Hemisensory or hemiparetic deficits (complicated migraine)
  • Adie-type (dilated) pupil

Causes

No specific etiology is known. Various precipitants of migraine events have been identified, as follows:

  • Family history
  • Stress
  • Excessive or insufficient sleep
  • Medications (eg, vasodilators, oral contraceptives)
  • Smoking
  • Foods and food additives, such as alcohol, caffeine, chocolates, artificial sweeteners (eg, aspartame, saccharin), monosodium glutamate (MSG), citrus fruits, and meats with nitrites
  • Foods containing tyramines, such as aged cheese, yogurt, sour cream, chicken livers, sausages, bananas, avocados, canned figs, raisins, peanuts, soy sauce, pickled fish, fresh-baked breads, pork, vinegars, and beans
  • Exposure to bright or fluorescent lighting
  • Strong odors (eg, perfumes, colognes, petroleum distillates)
  • Hormonal changes, such as menstruation (common), pregnancy, and ovulation
  • Head trauma
  • Weather changes
  • Metabolic or infectious diseases
  • Physical exertion or fatigue
  • Motion sickness
  • Cold-stimulus (eg, ice cream headaches)

Risk factors

Previous studies have shown that people who suffer from migraine headaches are more likely to also have cardiovascular disease, such as a stroke and heart attacks.[17 ]The physiopathology of the mechanism is still unknown. Reliable evidence comes from the Women’s Health Study, which found that migraine with aura raised the risk of myocardial infarction by 91% (95% confidence interval [CI], 17-210%) and ischemic stroke by 108% (95% CI, 30-231%). Migraine without aura raised both risks by approximately 25%.[18 ]

Migraines during pregnancy are also linked to stroke and vascular diseases.[19 ]

Migraine with aura for women in midlife has a statistical significant association with late-life vascular disease (infarcts) in the cerebellum and only in women. No association is seen with aura free migraine.[20 ]

Differential Diagnoses

Giant Cell Arteritis
Idiopathic Intracranial Hypertension
Trigeminal Neuralgia

Other Problems to Be Considered

Carotid artery dissection
Meningitis
Subarachnoid hemorrhage
Sinusitis
Temporomandibular joint dysfunction
Brain pathology (eg, tumor, cardiovascular accident, arteriovenous [AV] malformation, aneurysm)
Seizures
Other headaches (eg, tension, cluster)
Drug-seeking behavior

Workup

Laboratory Studies

Rule out other etiologies using appropriate laboratory and/or radiographic tests.

Consider visual field testing in patients with persistent visual phenomena.

Migraine is a diagnosis of exclusion. Have a heightened sense of concern in patients with solely unilateral headaches that remain on the same side.

Imaging Studies

  • CT scan for bleeding, acute stroke, or previous head trauma
  • MRI/MRA (magnetic resonance angiogram) for mass or vascular anomaly (aneurysm or AV malformation)
  • CT angiogram for intracranial vascular lesions

Procedures

Lumbar puncture rules out infection, inflammation, elevated intracranial pressure, or possible subarachnoid hemorrhage.

Treatment

Medical Care

After making the appropriate diagnosis, counsel the patient in nonpharmacologic treatments, such as regular rest and exercise. Patients also should avoid potential triggering factors.

Patients may need to discontinue any medications that exacerbate the headache. If oral contraceptives or hormonal replacement therapy is suspected to be a potential trigger mechanism, reduce dosages, if possible. If headaches persist, consider discontinuing hormone therapy.

Novel treatments

The novel benzopyran compound tonabersat binds selectively to a unique site in the brain. In preclinical studies, tonabersat markedly reduced CSD and CSD-associated events by inhibiting gap-junction communication between neurons and satellite glial cells in the trigeminal ganglion. CSD depends on neuronal-glial cell communication to mediate by intercellular transfer of messengers through connexin-containing gap junctions as well as messengers released into the extracellular space by nonjunctional connexin-containing hemichannels. These processes are believed to be important in peripheral sensitization within the trigeminal ganglion and to lead to central sensitization.[21 ]

Many subjects (30-40%) do not respond to the 5-HT1B/1D agonists (the triptans) commonly used in the treatment of migraine attacks. Calcitonin gene-related protein (CGRP) receptor antagonism is a new approach to the treatment of migraine attacks. A Phase III clinical trial compared telcagepant, an orally active CGRP receptor antagonist, to zolmitriptan in subjects during an attack of migraine. Results showed telcagepant is better tolerated than zolmitriptan.[22 ]

Phase I, single dose, transdermal delivery of sumatriptan using the SmartRelief reducing the risk of triptan-like sensations associated with high peak plasma concentrations. Zelrix I (transdermal patch with 3 g of gel solution delivering 6 mg of sumatriptan transdermally), or Zelrix II (transdermal patch containing 2.6 g of gel solution delivering 6 mg of sumatriptan).[23 ]

Future drugs

The pipeline of future compounds for the treatment of acute migraine headaches will include TPRV1 antagonists, prostaglandin E receptor 4 (EP(4)) receptor antagonists, serotonin 5HT1(F) receptor agonists and nitric oxide synthase inhibitors. The immediate future of a preventative treatment for migraine headaches will be addressed by botulinum toxin type-A, glutamate NMDA receptor antagonists, gap-junction blocker tonabersat, and an angiotensin type 1 blocker candesartan.[24 ]

Surgical Care

Intramuscular injections of botulinum toxin (BOTOX®) around the scalp have proven to be an effective therapy for some patients.

Diet

Patients should avoid foods and food additives as well as foods containing tyramines that could trigger migraine. See Causes.

Activity

Patients should avoid physical exertion or fatigue. See Causes.

Medication

Pharmacologic therapy is directed primarily at alleviating the acute phase. Repeated episodes of migraine may require long-term prophylactic therapy.

5-HT1 receptor agonists

For acute treatment of migraine.

Sumatriptan (Imitrex); frovatriptan (Frova); eletriptan (Relpax); naratriptan (Amerge, Naramig)

Vascular 5-HT1 receptor subtypes (to which these agents bind selectively and through which they presumably exert antimigrainous effects) have been shown to be excellent first-line therapy for acute migraine events. Naratriptan has a duration of action of up to 24 hours with low headache recurrence rate. Useful for patients with slow onset, prolonged migraine (eg, menstrual migraine). Frovatriptan possesses long half-life (ie, 26-30 h), decreasing recurrence of migraine within 24 h after treatment. Eletriptan has half-life of 18 h.

Dosing

Adult

Sumatriptan: 6 mg SC injection; if no response, repeat after 1 h; not to exceed 2 doses in 24 h
25-100 mg PO single dose; repeat at intervals of at least 2 h; not to exceed 200 mg/d (100 mg/d if injection)
5-20 mg intranasally; reevaluate if no response; may repeat once after 2 h; not to exceed 40 mg/d
Frovatriptan: 2.5 mg PO once at onset of migraine attack
Eletriptan: 20-40 mg/dose PO at onset of migraine; if initial dose ineffective, may repeat dose once after 2 h; not to exceed 80 mg/d
Naratriptan: 1-2.5 mg PO initially PO q4h; not to exceed 5 mg/d

Pediatric

Not recommended

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP450-3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity

Contraindications

Documented ischemic cardiac, cerebrovascular, or peripheral vascular syndromes; vasospastic coronary artery disease; uncontrolled hypertension; basilar or hemiplegic migraine; within 24 h of ergot-type drugs (eg, methysergide, dihydroergotamine) or other 5-HT1 agonists; during or within 2 wk after discontinuing MAOIs

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Confirm diagnosis; avoid excessive use; exclude underlying cardiovascular disease, supervise first dose, and consider monitoring ECG in patients with a likelihood of unrecognized coronary artery disease (eg, postmenopausal women, those with hypercholesterolemia, men >40 y, patients with hypertension, those with a strong family history, and patients who are obese, diabetic, or smoke); hepatic or renal dysfunction

Zolmitriptan (Zomig, Zomig-ZMT); almotriptan (Axert); rizatriptan (Maxalt, Maxalt-MLT)

Selective agonists for serotonin 5-HT1 receptors in cranial arteries and suppress the inflammation associated with migraine headaches.

Dosing

Adult

Zolmitriptan: 2.5 mg PO initially; repeat dose after 2 h if headache returns; not to exceed 10 mg/24h
Almotriptan: 6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d
Rizatriptan: 5-10 mg intranasally initially; repeat after 2 h; not to exceed 30 mg/d; concomitant administration of 5 mg/dose PO propranolol; not to exceed 3 doses/d

Pediatric

Not recommended

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP450-3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity

Contraindications

Documented hypersensitivity; documented ischemic cardiac, cerebrovascular, or peripheral vascular syndromes; vasospastic coronary artery disease; uncontrolled hypertension; basilar or hemiplegic migraine; within 24 h of ergot-type drugs (eg, methysergide, dihydroergotamine) or other 5-HT1 agonists; during or within 2 wk after discontinuing MAOIs

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Confirm diagnosis; not recommended in Wolff-Parkinson-White syndrome or arrhythmias that are associated with other cardiac accessory conduction pathway disorders; exclude underlying cardiovascular disease, supervise first dose, and consider monitoring ECG in patients with likelihood of unrecognized coronary artery disease (eg, postmenopausal women, hypercholesterolemia, men >40 y, hypertension, those with strong family history, and patients who are obese, diabetic, or smoke); hepatic or renal dysfunction

Combination antimigraine drugs

The first combination product of a 5HT receptor agonist and an NSAID, Treximet, was approved by the US Food and Drug Administration in April 2008. Efficacy was demonstrated in 2 randomized, double-blind, multicenter, parallel-group trials comparing the combination product to placebo and each individual active component (ie, sumatriptan and naproxen sodium). The percentage of patients remaining pain free without use of other medications through 24 hours postdose was significantly greater (p<0.01) among patients receiving a single dose of Treximet (25% and 23%) compared with placebo (8% and 7%) or either sumatriptan (16% and 14%) or naproxen sodium (10%) alone.[25 ]

Sumatriptan and naproxen (Treximet)

Combination product containing sumatriptan, a selective 5-hydroxytryptamine (5-HT1) receptor agonist, and naproxen sodium, an arylacetic acid nonsteroidal anti-inflammatory drug (NSAID). Fixed combination contains sumatriptan 85 mg and naproxen sodium 500 mg. Indicated for acute migraine. Sumatriptan mediates vasoconstriction of the basilar artery and vasculature of dura mater, which correlates with migraine relief. Naproxen provides analgesic, anti-inflammatory, and antipyretic properties. Decreases activity of cyclooxygenase, thereby interrupting prostaglandin synthesis.

Dosing

Adult

1 tab PO at onset of migraine; do not exceed 2 tab/24 h; if second dose administered, do not administer until at least 2 h after first dose

Pediatric

Not established

Interactions

Do not split, crush, or chew tab
Sumatriptan: Do not administer within 24 h of ergotamine-containing or ergot-type drugs (eg, dihydroergotamine, methysergide); coadministration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) may increase risk for serotonin syndrome; coadministration with MAOIs or within 2 wk of discontinuing MAOIs may increase sumatriptan levels (see Contraindications)
Naproxen: Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; ischemic heart disease (eg, stable angina, vasospastic forms of angina, myocardial infarction, silent myocardial ischemia); uncontrolled hypertension; cerebrovascular or peripheral vascular disease; history of coronary artery bypass graft (CABG) surgery; peptic ulcer disease; recent GI bleeding or perforation; renal (CrCl <30 mL/min) or hepatic insufficiency; coadministration with MAOIs or within 2 wk of discontinuing MAOI; hemiplegic or basilar migraine; patients in whom aspirin or other NSAIDs induce asthma, rhinitis, nasal polyps, or urticaria

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Sumatriptan may increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke
Naproxen may increase risk of serious GI adverse events (eg, bleeding, ulceration, stomach or intestinal perforation); acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug; preexisting asthma

Nonsteroidal anti-inflammatory agents (NSAIDs)

May alleviate migraine pain by inhibiting prostaglandin synthesis, reducing serotonin release and blocking platelet aggregation. Although effects of NSAIDs in treatment of migraine pain tend to be patient specific, ibuprofen is usually DOC for initial therapy. Other options include naproxen, ketoprofen, and ketorolac.

Ibuprofen (Ibuprin, Motrin, Advil)

For acute treatment of mild-to-moderate migraine headaches.

Dosing

Adult

400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d

Pediatric

20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Precautions

Pregnancy

B – Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Category D in third trimester of pregnancy; caution in CHF, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Ketorolac (Toradol)

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors.

Dosing

Adult

30-60 mg IM initially, followed by 15-30 mg q6h prn; not to exceed 5 d of treatment

Pediatric

Not established

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; do not administer into CNS

Precautions

Pregnancy

B – Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts (rare) usually return to normal during ongoing therapy; discontinue therapy if persistent leukopenia, granulocytopenia, or thrombocytopenia occur

Aspirin (Bayer Aspirin, Ascriptin, Anacin)

Treats mild to moderate pain and headache. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Dosing

Adult

1.3 g/d PO divided bid/qid

Pediatric

Not established

Interactions

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

Contraindications

Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; due to association of aspirin with Reye syndrome, do not use in children ( <16 y) with flu

Precautions

Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants

Analgesics

Initial therapy for patients with infrequent migraines can be treated with simple analgesics.

Acetaminophen (Tylenol, Feverall, Aspirin-Free Anacin)

DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.

Dosing

Adult

325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d

Pediatric

Not established

Interactions

Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity

Contraindications

Documented hypersensitivity; known G-6-P deficiency

Precautions

Pregnancy

B – Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; APAP is contained in many OTC products and combined use with these products may result in cumulative APAP doses exceeding recommended maximum dose

Ergot preparations

For use in acute treatment of migraine.

Dihydroergotamine (DHE 45, Migranal)

Alpha-adrenergic blocking agent with direct stimulating effect on smooth muscle of peripheral and cranial blood vessels. Depresses central vasomotor centers. Indicated to abort or prevent vascular headache when rapid control needed or when other routes of administration not feasible.

Dosing

Adult

1 mL IV/IM at attack’s onset, then 1 mL after 1 h, if needed; not to exceed 2 mL IV or 3 mL IM per attack, 6 mL/wk
Premedicate with metoclopramide (10 mg IV/IM) or another antiemetic
Intranasal administration: Spray once in each nostril, then repeat 15 min later; not to exceed 6 sprays/24 h and 8 sprays/wk

Pediatric

Not recommended

Interactions

Increases effects of heparin and toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin

Contraindications

Documented hypersensitivity; coronary or peripheral vascular disease; hypertension; impaired hepatic or renal function; sepsis; breastfeeding

Precautions

Pregnancy

X – Contraindicated; benefit does not outweigh risk

Precautions

Caution in angina, hypertension, impaired renal or hepatic function, or peripheral vascular disease

Anticonvulsants

For use in acute and prophylactic treatment of migraine

Agents that interact with the GABA-ergic system, seem to have a positive effect in reducing migraine attacks. Valproate and topiramate are most commonly used.

Topiramate (Topamax)

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, potentiates inhibitory activity of neurotransmitter GABA. In addition, may block glutamate activity. Not necessary to monitor plasma concentrations to optimize therapy.

Dosing

Adult

50 mg/d PO; titrate by 50 mg/d at 1-wk intervals to target dose of 200 mg bid; not to exceed 1600 mg/d

Pediatric

<2 years: Not established
2-16 years: 1-3 mg/kg PO initially; not to exceed 25 mg/d, then titrate dose upward by 1-3 mg/kg/d divided bid (not to exceed dosage increases of 25 mg) q1-2wk until total daily dose is 5-9 mg/kg/d divided bid
>16 years: Administer as in adults

Interactions

Phenytoin, carbamazepine and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels, when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use topiramate with extreme caution when administering concurrently with CNS depressants since may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Risk of developing a kidney stone formation is increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients taking topiramate should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop, can lead to glaucoma; primary treatment is discontinuation of topiramate; if left untreated, serious sequelae, including permanent vision loss, may occur; oligohidrosis and hyperthermia has been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior and during activity and warm temperatures); may cause hyperchloremic, non-anion gap metabolic acidosis acute or chronic metabolic acidosis resulting in hyperventilation, and nonspecific symptoms, such as fatigue and anorexia, or more severe adverse effects including cardiac arrhythmias or stupor; chronic, untreated metabolic acidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate

Valproic acid (Depakote)

There is no evidence that valproic acid is useful in the acute treatment of migraine headaches. The mechanism of action is unknown.

Dosing

Adult

250 mg PO bid initially; not to exceed 1 g/d

Pediatric

<16 years: Not established
>16 years: Administer as in adults

Interactions

Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients

Contraindications

Documented hypersensitivity; hepatic disease/dysfunction

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Thrombocytopenia and abnormal coagulation parameters have occurred; the risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and 135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or a hemostasis/coagulation disorder occur; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness

Barbiturates

For acute treatment of mild-to-moderate migraine headaches.

Isometheptene, dichloralphenazone, acetaminophen (Midrin, Midchlor, Isocom)

Acetaminophen/aspirin combinations are indicated for initial migraine events. Isometheptene acts by constricting dilated cranial and cerebral arterioles, reducing stimuli that lead to vascular headaches. Acetaminophen raises threshold to painful stimuli, thus exerting an analgesic effect against all types of headaches.

Dosing

Adult

2 cap PO initially, followed by 1 cap PO q1h until desired response obtained; not to exceed 5 cap per 12 h

Pediatric

Not recommended

Interactions

Concurrent use of MAOIs with isometheptene may result in severe headache, hypertension, and hyperpyrexia, which in turn may result in hypertensive crisis

Contraindications

Documented hypersensitivity; glaucoma, hypertension, organic heart disease, severe renal disease, or hepatic disease; do not administer within 2 wk of taking MAOI

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypertension, peripheral vascular disease, and recent cardiovascular injuries

Butalbital, acetaminophen, caffeine (Fioricet); butalbital, aspirin; caffeine (Fiorinal)

Drug combination for tension headaches. Barbiturate component has generalized depressant effect in CNS.

Dosing

Adult

1-2 tab or cap PO q4h prn; not to exceed 6 doses/d

Pediatric

Not recommended

Interactions

Effects decreased by coadministration of phenothiazines, quinidine, tricyclic antidepressants, theophylline, haloperidol, chloramphenicol, ethosuximide, corticosteroids, warfarin, doxycycline, and beta-blockers; effects are increased with coadministration of CNS depressants, methylphenidate, valproic acid, propoxyphene, and benzodiazepines; aspirin may increase effect of anticoagulants

Contraindications

Documented hypersensitivity; porphyria; varicella or influenza in teenagers; bleeding or coagulation disorders; peptic ulcer; third trimester pregnancy

Precautions

Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with history of substance abuse; impaired hepatic or renal function; acute abdomen; depression; suicidal tendencies; asthma; bleeding disorders; gastritis; monitor blood pressure, BUN, and uric acid levels; elderly persons; those who are debilitated

Beta-adrenergic blockers

Are effective in prophylactic therapy, possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues.

Propranolol (Inderal)

Indicated for prophylaxis of migraine headache.

Dosing

Adult

80 mg/d PO divided tid/qid initially; may increase to 160-240 mg/d PO

Pediatric

Not recommended

Interactions

Potentiated by alcohol, CNS depressants, other antihypertensives, antithyroid drugs, haloperidol, chlorpromazine, and cimetidine; bradycardia with catecholamine-depleting drugs; antagonized by NSAIDs, barbiturates, rifampin, and phenytoin; may increase cardiac effects of calcium channel blockers, digitalis, and lidocaine; potentiates theophylline, antipyrine, and lidocaine; may block epinephrine; may interfere with glaucoma screening tests

Contraindications

Documented hypersensitivity; asthma; sinus bradycardia; second- or third-degree AV block; overt heart failure; cardiogenic shock

Precautions

Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

CHF, Wolff-Parkinson-White syndrome; renal or hepatic dysfunction; bronchospastic disease and COPD; diabetes; hyperthyroidism; surgery; SLE; avoid abrupt cessation; discontinue if results are poor after 4-6 wk of therapy

Antidepressants

Used for prophylaxis (mechanism of action is independent of antidepressant effect, but unknown). Inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain. Mechanism of action in migraine headaches unknown.

Dosing

Adult

10-300 mg PO qd in divided doses or hs; titrate dose to alleviate symptoms

Pediatric

Not recommended

Interactions

Hyperpyretic crisis, convulsions, death with MAOIs; potentiates alcohol; CNS stimulation with reserpine; antagonized by barbiturates, carbamazepine, and phenytoin; paralytic ileus, hyperpyrexia with anticholinergics; blocks guanethidine; potentiated by hepatic enzyme inhibitors; monitor serum levels with cimetidine

Contraindications

Documented hypersensitivity; during or within 14 d of MAOIs; acute post-MI

Precautions

Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; avoid using in elderly persons

Nortriptyline (Pamelor, Aventyl HCl)

Has demonstrated effectiveness in the treatment of chronic pain. Mechanism of action in the treatment of migraine headaches unknown. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane this drug increases the synaptic concentration of these neurotransmitters in the central nervous system.
Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.

Dosing

Adult

10-125 mg PO qd in divided doses or hs; titrate dose to alleviate symptoms

Pediatric

Not established

Interactions

Cimetidine may increase nortriptyline levels when used concurrently; nortriptyline may increase prothrombin time in patients stabilized with warfarin

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; do not administer to patients that have taken MAOIs in past 14 d

Precautions

Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; due to pronounced effects in cardiovascular system, best to avoid in elderly persons

Follow-up

Further Outpatient Care

Closely follow up with the primary care physician or a neurologist.

Inpatient & Outpatient Medications

Take medications as prescribed. See Medication.

Deterrence/Prevention

Patients should avoid migraine precipitants.

Patient Education

For excellent patient education resources, see eMedicine’s Headache Center. Also, visit eMedicine’s patient education articles Causes and Treatments of Migraine and Related Headaches; Alternative and Complementary Approaches to Migraine and Cluster Headaches; Migraine Headaches, Vision Effects; and Understanding Migraine and Cluster Headache Medications.

Miscellaneous

Medicolegal Pitfalls

Beware of potentially dangerous intracranial process (eg, subarachnoid hemorrhage, aneurysm, meningitis) that presents as an atypical migraine.

References

  1. Schoonman GG, van der Grond J, Kortmann C, van der Geest RJ, Terwindt GM, Ferrari MD. Migraine headache is not associated with cerebral or meningeal vasodilatation–a 3T magnetic resonance angiography study. Brain. Aug 2008;131:2192-200. [Medline].

  2. Shevel E. Comments on Schoonman et al.: Migraine headache is not associated with cerebral or meningeal vasodilatation: a 3 T magnetic resonance angiography study (Brain 2008; 131:2192-2200). J Headache Pain. Aug 2009;10(4):307-8. [Medline].

  3. Hamed SA. The vascular risk associations with migraine: relation to migraine susceptibility and progression. Atherosclerosis. Jul 2009;205(1):15-22. [Medline].

  4. Moulton EA, Burstein R, Tully S, Hargreaves R, Becerra L, Borsook D. Interictal dysfunction of a brainstem descending modulatory center in migraine patients. PLoS One. 2008;3(11):e3799. [Medline][Full Text].

  5. Richter F, Lehmenkühler A. [Cortical spreading depression (CSD): a neurophysiological correlate of migraine aura]. Schmerz. Oct 2008;22(5):544-6, 548-50. [Medline].

  6. Martins-Oliveira A, Speciali JG, Dach F, Marcaccini AM, Gonçalves FM, Gerlach RF, et al. Different circulating metalloproteinases profiles in women with migraine with and without aura. Clin Chim Acta. Oct 2009;408(1-2):60-4. [Medline].

  7. Imamura K, Takeshima T, Fusayasu E, Nakashima K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache. Jan 2008;48(1):135-9. [Medline].

  8. Piilgaard H, Lauritzen M. Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex. J Cereb Blood Flow Metab. Sep 2009;29(9):1517-27. [Medline].

  9. Napoli R, Guardasole V, Zarra E, Matarazzo M, D’Anna C, Saccà F, et al. Vascular smooth muscle cell dysfunction in patients with migraine. Neurology. Jun 16 2009;72(24):2111-4. [Medline].

  10. Gruber HJ, Bernecker C, Lechner A, Weiss S, Wallner-Blazek M, Meinitzer A, et al. Increased nitric oxide stress is associated with migraine. Cephalalgia. Aug 11 2009;[Medline].

  11. Tietjen GE, Herial NA, White L, Utley C, Kosmyna JM, Khuder SA. Migraine and biomarkers of endothelial activation in young women. Stroke. Sep 2009;40(9):2977-82. [Medline].

  12. Minson CT, Green DJ. Measures of vascular reactivity: prognostic crystal ball or Pandora’s box?. J Appl Physiol. Aug 2008;105(2):398-9. [Medline].

  13. Kruit MC, Launer LJ, Overbosch J, van Buchem MA, Ferrari MD. Iron accumulation in deep brain nuclei in migraine: a population-based magnetic resonance imaging study. Cephalalgia. Mar 2009;29(3):351-9. [Medline].

  14. Welch KM. Iron in the migraine brain; a resilient hypothesis. Cephalalgia. Mar 2009;29(3):283-5. [Medline].

  15. Stam AH, Haan J, van den Maagdenberg AM, Ferrari MD, Terwindt GM. Migraine and genetic and acquired vasculopathies. Cephalalgia. Sep 2009;29(9):1006-17. [Medline].

  16. Stewart WF, Linet MS, Celentano DD, et al. Age- and sex-specific incidence rates of migraine with and without visual aura. Am J Epidemiol. Nov 15 1991;134(10):1111-20. [Medline].

  17. Klein E, Spencer D. Migraine frequency and risk of cardiovascular disease in women. Neurology. Aug 25 2009;73(8):e42-3. [Medline].

  18. Woodward M. Migraine and the risk of coronary heart disease and ischemic stroke in women. Womens Health (Lond Engl). Jan 2009;5(1):69-77. [Medline].

  19. Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ. Mar 10 2009;338:b664. [Medline][Full Text].

  20. Scher AI, Gudmundsson LS, Sigurdsson S, Ghambaryan A, Aspelund T, Eiriksdottir G, et al. Migraine headache in middle age and late-life brain infarcts. JAMA. Jun 24 2009;301(24):2563-70. [Medline].

  21. Durham PL, Garrett FG. Neurological mechanisms of migraine: potential of the gap-junction modulator tonabersat in prevention of migraine. Cephalalgia. Nov 2009;29 Suppl 2:1-6. [Medline].

  22. Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet. Dec 20 2008;372(9656):2115-23. [Medline].

  23. Pierce M, Marbury T, O’Neill C, Siegel S, Du W, Sebree T. Zelrix: a novel transdermal formulation of sumatriptan. Headache. Jun 2009;49(6):817-25. [Medline].

  24. Farinelli I, De Filippis S, Coloprisco G, Missori S, Martelletti P. Future drugs for migraine. Intern Emerg Med. Oct 2009;4(5):367-73. [Medline].

  25. [Best Evidence] Brandes JL, Kudrow D, Stark SR, O’Carroll CP, Adelman JU, O’Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. Apr 4 2007;297(13):1443-54. [Medline].

  26. Capobianco DJ, Cheshire WP, Campbell JK. An overview of the diagnosis and pharmacologic treatment of migraine. Mayo Clin Proc. Nov 1996;71(11):1055-66. [Medline].

  27. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9-160. [Medline].

  28. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. Apr 26 1999;159(8):813-8. [Medline].

  29. Hupp SL, Kline LB, Corbett JJ. Visual disturbances of migraine. Surv Ophthalmol. Jan-Feb 1989;33(4):221-36. [Medline].

  30. Jackson CM. Effective headache management. Strategies to help patients gain control over pain. Postgrad Med. Nov 1998;104(5):133-6, 139-40, 143-7. [Medline].

  31. Saper JR. Diagnosis and symptomatic treatment of migraine. Headache. 1997;37 Suppl 1:S1-14. [Medline].

  32. Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA. Jan 1 1992;267(1):64-9. [Medline].

  33. Troost BT. Botulinum toxin type A (Botox) in the treatment of migraine and other headaches. Expert Rev Neurother. Jan 2004;4(1):27-31. [Medline].

Keywords

migraine headache, migraines, aura, ophthalmoplegic migraine, retinal migraine, migrainous disorder, 5-hydroxytryptamine, 5-HT, dihydroergotamine, DHE, selective serotonin reuptake inhibitor, SSRI, monoamine oxidase inhibitor, MAOI, headache disorder

Contributor Information and Disclosures

Author

Jacqueline Freudenthal, MD, Co-Investigator, Ophthalmic Consultants Centre, Toronto
Jacqueline Freudenthal, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, and Canadian Ophthalmological Society
Disclosure: Nothing to disclose.

Coauthor(s)

Ronald Braswell, MD, Associate Professor, Department of Ophthalmology, University of Alabama-Birmingham
Ronald Braswell, MD is a member of the following medical societies: American Academy of Ophthalmology and North American Neuro-Ophthalmology Society
Disclosure: Nothing to disclose.

Medical Editor

Edsel Ing, MD, FRCSC, Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Consulting Staff, Toronto East General Hospital, Canada
Edsel Ing, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Society of Ophthalmic Plastic and Reconstructive Surgery, Canadian Ophthalmological Society, North American Neuro-Ophthalmology Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Brian R Younge, MD, Professor of Ophthalmology, Mayo Clinic School of Medicine
Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John’s Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

Jacqueline Freudenthal, MD, Co-Investigator, Ophthalmic Consultants Centre, Toronto
Ronald Braswell, MD, Associate Professor, Department of Ophthalmology, University of Alabama-Birmingham

Updated: Sep 20, 2010

© 1994-2011 by Medscape.
 
 

 

Leave a Reply