You are in: eMedicine Specialties > Neurology > Headache and Pain Migraine VariantsArticle Last Updated: Sep 12, 2006AUTHOR AND EDITOR INFORMATIONAuthor: Rima M Dafer, MD, MPH, Associate Professor, Department of Neurology, Loyola University Chicago, Stritch School of Medicine Rima M Dafer is a member of the following medical societies: American Academy of Neurology, American Headache Society, and American Heart Association Editors: Joseph R Carcione, Jr, DO, MBA, Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Robert A Egan, MD, Director of Neuro-Ophthalmology, St Helena Hospital; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: migraine equivalents, migraine aura without headache, familial hemiplegic migraine, sporadic hemiplegic migraine, alternating hemiplegic migraine, basilar type migraine, childhood periodic syndromes, cyclic vomiting, abdominal migraine, benign paroxysmal vertigo of childhood, retinal migraine, ocular migraine, vertiginous migraine, vestibular migraine, migrainous infarction, migraine triggered seizure INTRODUCTIONBackgroundMigraine is a paroxysmal headache disorder affecting more than 13% of the general population in the United States. Migraine is a syndrome and not a disease; it is characterized by paroxysmal headache associated with others signs and symptoms. About 80% of migraineurs have migraine without aura, while migraine with typical aura accounts for 15-20% of cases. Isolated migraine aura without headache (acephalic migraine) may be encountered in 5% of patients. Migraine variant (MV) or migraine equivalent is the term applied to migraine, which exhibits itself in a form other than head pain. MV is characterized by paroxysmal episodes of prolonged visual auras; atypical sensory, motor, or visual aura; confusion; dysarthria; focal neurologic deficits; or gastrointestinal manifestations or other constitutional symptoms with or without a headache. The diagnosis of MV is determined by history of paroxysmal signs and symptoms with or without cephalgia, a prior history of migraine with aura, in the absence of other medical disorders that may contribute to the symptoms. Many of these patients usually have a family history of migraine. MVs are less recognized and poorly understood. They are less common than typical migraine without and with aura, and they usually affect children and young adults. MVs should be differentiated from trigeminal cephalic neuralgias and other primary headaches such as stabbing and thunderclap headaches, cough headaches, or hypnic headaches. MVs should also be differentiated from exertional headaches, a group of headache syndromes associated with physical activity such as running, coughing, sneezing, or sexual intercourse. Many MVs have been defined by the International Classification of Headache Disorders (ICHD-II) 2004 classification. These include hemiplegic migraines, basilar migraine, childhood periodic syndromes, retinal migraine, complicated migraines, and ophthalmoplegic migraine. Vertiginous migraine, acute confusional migraine of childhood, and nocturnal migraine, although well recognized entities, remain unclassified by the IHCD-II. PathophysiologyAlthough activation and sensitization of the trigeminovascular in migraine is believed to generate and maintain migraine pain, cortical spreading depression (CSD) is recognized as the phenomenon underlying migraine aura. CSD is believed to begin in the occipital region and to gradually spread rostrally. This phenomenon is accompanied by a transient oligemia, followed by hyperemia in other parts of the cortex. Various molecular and cellular mechanisms may lead to the increased susceptibility of CSD in migraineurs, which could potentially play an important role in the pathophysiology of MVs. Researchers have suggested that a vasogenic leakage from leptomeningeal vessels, with activation of the trigeminovascular system, probably contribute to the prolonged aura in patients with hemiplegic migraine. Migraine with prolonged auraThe typical duration of a migraine aura, predominantly visual, is up to 30 minutes. In rare cases, the aura could be prolonged, lasting up to 60 minutes, raising concerns of possible stroke. Migraine aura without headache or acephalic migraineAround 3-5% of migraineurs experience an aura without headache. This presentation is more common in older patients who have had a history of migraine with aura during early age. Symptoms may include scintillating scotomata, formed stereotyped visual hallucinations in a single visual field or bilaterally, micropsia, and tunnel vision. Other auras include paroxysmal vertigo, hemisensory dysesthesias, and rarely auditory hallucinations. Acephalic migraine should be differentiated from transient ischemic attack, occipital lobe seizures, or temporal lobe seizures. Hemiplegic migraineHemiplegic migraine is a very rare but well described form of MV. It was initially described in 1910 as a type of migraine consisting of recurrent headaches associated with temporary unilateral hemiparesis or hemiplegia, at times accompanied by ipsilateral numbness or tingling, with or without a speech disturbance. The focal neurologic deficit may precede or accompany the headache, which is usually less dramatic than motor deficit. Other migraine symptoms may variably be present. Patients may also experience disturbance of consciousness, and rarely coma. The neurologic deficit is transient and usually clears in minutes to hours, or resolves with the beginning of the headache phase. Two forms of hemiplegic migraine are known: familial and sporadic. Both familial hemiplegic migraine (FHM) and sporadic hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with aura, differentiated only by the unilateral motor symptoms. Familial hemiplegic migraine FHM is an autosomal dominant disorder. FHM is a channelopathy; most of the affected families bear mutations in the CACNA1A gene (a defect linked to abnormal voltage-dependent P/Q-type calcium channel alpha-1A) on 19p13. Mutations in ATP1A2 (R548H) on 1q23 (Mendelian Inheritance in Man #182340) and other genes have been identified. Alternating hemiplegic migraine (primarily in childhood) Alternating hemiplegia of childhood (AHC) is a chronic progressive disorder, associated with high prevalence of neurologic deficit. It is distinguished from familial hemiplegic migraine by its infantile onset and by its characteristic associated symptoms. The onset of the disorder is before age 18 months. It is characterized by vomiting, headache, alternating hemiplegia, loss of consciousness, paroxysmal ocular palsies, choreoathetosis, autonomic dysfunction, and mental retardation. Single-photon emission computed tomography (SPECT) studies have shown progressive decrease of cerebral perfusion in cases of alternating hemiplegic migraine. Sporadic hemiplegic migraine SHM is defined as migraine attacks associated with motor weakness in the absence of family history of similar attacks. Cases of SHM have also been linked to the CACNA1A gene. Diagnosis of FHM is usually confirmed with repeated stereotyped reversible episodes, particularly in the presence of positive family history of similar attacks. The absence of first- and or second-degree relatives with similar disorder raises suspicion of SHM. Differential diagnosis includes focal seizures with postictal paralysis, mitochondrial cytopathies, intracranial hemorrhage, mass, infection, or cerebral infarction. Basilar-type migraineBasilar migraine (BM), also known as Bickerstaff syndrome, consists of headache accompanied by dizziness, ataxia, tinnitus, decreased hearing, nausea and vomiting, dysarthria, diplopia, loss of balance, bilateral paresthesias or paresis, altered consciousness, syncope, and sometimes loss of consciousness. BM is observed most frequently in adolescent girls and young women. Localized vertebrobasilar vasoconstriction leading to transient posterior circulation ischemia may contribute to the symptomatology of the disorder. A novel mutation in the ATP1A2 gene, similar to FHM, has been reported in members of one family with BM. Differential diagnosis includes various causes of syncopal, inner ear disease, intoxication, and posterior fossa pathologies. Childhood periodic syndromes that are commonly precursors of migraineChildhood periodic syndromes are characterized by multiple cyclic attacks of pain or vomiting with our without migraine headaches. They are common in children and adolescents. Cyclic vomiting syndrome Cyclic vomiting of childhood is characterized by recurrent attacks of violent or prolonged vomiting without headache, which may last for hours. Attacks may be precipitated by infection, menstruation, or physical or emotional stress. During the attacks, patients characteristically show other symptoms of migraine such as nausea, lethargy, yawning, and drowsiness. Cyclic vomiting is thought to result from abnormal activity in the area postrema. Additionally, gastroparesis, which occurs during migraine, has been implicated as an etiologic factor for cyclic vomiting and abdominal migraine. Abdominal migraine Abdominal migraine most typically occurs in children, although it has been reported in adults. Patients usually complain of paroxysmal midabdominal pain lasting form 1-72 hours, associated with nausea and vomiting, flushing, or pallor. Like cyclic vomiting, attacks may be associated with other migraine prodromes such as fatigue and drowsiness. Aura and headaches are frequently absent or minimal. Patients may develop migraine late in their life, and family history of migraine is common. Gastroenterologic evaluation and workup is unremarkable. Benign paroxysmal vertigo of childhood Benign paroxysmal vertigo of childhood (BPVC) is another MV characterized by brief episodes of vertigo and disequilibrium lasting for hours, without headache, aura, hearing loss, or tinnitus. It affects children aged 1-4 years. Children usually complain of a spinning sensation during the attack. Typical migraine is common later in life, and a family history of migraine is helpful in confirming the diagnosis. Retinal migraineRetinal migraine (ophthalmic, ocular) is not an uncommon cause of transient monocular blindness in young adults. It is manifested by recurrent attacks of unilateral visual disturbance or blindness lasting from minutes to 1 hour, associated with minimal or no headache. This phenomenon is frightening to patients, who usually seek medical help to exclude amaurosis fugax due to ischemia of the retinal arteries. Patients describe a gradual visual disturbance in a mosaic pattern of scotomata that gradually enlarge, producing total unilateral visual loss. Postural changes, exercise, and oral contraceptive agents may precipitate attacks. The condition is thought to result from transient vasospasm of the choroidal or retinal arteries. A personal or family history of migraine confirms the diagnosis. The condition needs to be differentiated from ocular or vascular causes of transient monocular blindness, mainly carotid artery disease. Complicated migraineComplications of migraine include chronic migraine, status migrainosus, persistent aura without infarction, migrainous infarction, and migraine-triggered seizure. Complicated migraines are rare, accounting for less than 1% of total patients with migraine. Chronic migraine and status migrainosus are not considered MVs and therefore are not included in this article. Persistent auraA typical migraine aura usually lasts 20-60 minutes. When the aura of migraine is prolonged, lasting for hours or days, complicated migraine including ischemic strokes need to be excluded. Prolonged aura lasting beyond 60 minutes, in the absent of radiographic evidence of cerebral infarction, is referred to as migraine with persistent aura. Migraine infarctionsThe relationship between migraine, mostly migraine with aura, and ischemic stroke has been well recognized. Migraine, generally a benign condition, has been recognized as an independent risk factor for ischemic stroke. Additionally, migraine, predominantly migraine with aura, is associated with the presence of silent infarctions or white matter changes on brain MRI. When a cerebral infarction occurs during a typical migraine aura attack, the term migrainous infarction is used. The mechanism of migrainous infarction is complex. Whether the relationship between migraine and stroke is the consequence of other underlying etiologies or the presence of similar ischemic risk factors, or whether migraine is associated with conditions that could potentially cause stroke, is yet to be determined. Migraine-triggered seizures (migralepsy)Migraine and epilepsy are highly comorbid conditions probably sharing the same pathophysiology, but the nature of their association is unclear. Migralepsy is the term used when a seizure occurs during or within 1 hour of a typical migraine aura attack. Reversible brain MRI abnormalities have been reported in a patient with migraine-triggered seizure, possibly due to supratentorial focal cerebral edema. Electroencephalogram (EEG) findings are usually normal interictal, although various abnormalities, mainly diffuse slowing, have been reported in migraineurs. Ophthalmoplegic migraineThis is a very rare condition in children, characterized by a migrainelike attack, followed within days by periorbital pain and diplopia secondary to cranial neuropathies. The oculomotor nerve is most commonly involved, with pupillary abnormality and ptosis, followed by the abducens, and rarely the trochlear nerve. The attack usually lasts from days to months and resolves spontaneously. A number of adult cases have been reported. Although previously considered an MV, the condition has been classified as neuralgia by the IHCD-II. The condition is thought to be due to recurrent demyelinating cranial neuropathies. Differential diagnosis includes conditions involving the parasellar, orbital, and posterior fossa leading to headache and ophthalmoplegia. Acute confusional migraine (primarily in childhood)Acute confusional migraine is a rare MV, almost exclusively seen in young children, manifested by episodes of confusion, disorientation, and vomiting, with or without headaches. The attacks are usually relieved by sleep. The condition should be differentiated from seizures, and various causes of confusion, including toxic, metabolic, mitochondrial, or infectious encephalopathies. Vertiginous migraineGrowing evidence suggests that recurrent episodes of vertigo are related to migraine. Vertigo, a common complaint among migraineurs, has been reported in one third of cases. Recurrent episodes of vertigo lasting between 5 minutes and 1 hour, with or without nausea, vomiting, photophobia, or headache, in the setting of a previous personal history or a positive family history of migraine supports the diagnosis of vestibular or vertiginous migraine. The pathophysiology of migraine-related vertigo is not fully understood. Differential diagnosis includes vertebrobasilar insufficiency and paroxysmal vestibular syndromes. Nocturnal migraineAlthough not a true MV, nocturnal migraine is unique because of its occurrence during the middle of the night or early morning hours. Its nocturnal occurrence is thought to be related to circadian activation of certain neurotransmitters during sleep, which are known to trigger a migraine attack. FrequencyUnited StatesMigraine affects nearly 13% of the adult US population, with a postpubertal female-to-male ratio of 4:1. The frequency of the less common MVs varies with type and age. The prevalence of hemiplegic migraine is 0.03%; both familial and sporadic forms are equally frequent. The prevalence of the distinct alternating hemiplegic migraine of infancy is unknown. Similarly, the frequency of ophthalmoplegic, retinal, and confusional migraine is unknown. SexSex prevalence may be observed in some types of MVs. Basilar migraine and migraine aura without headaches are more common in women than in men. Similarly, hemiplegic migraine is more common in women, with a sex ratio (male-to-female) of 1:3.
AgeSpecific MVs are observed at a higher incidence in different age groups. Ophthalmoplegic migraine, childhood periodic vomiting, and abdominal migraine are almost exclusively of childhood onset, affecting children younger than 10 years. In contrary, basilar and retinal migraines are more frequent in adolescents and young adults, while migraine aura without headache is mainly encountered in adults with long-standing history of migraine aura in early life. Hemiplegic migraine in its familial and sporadic forms has been reported in all age groups, while alternating hemiplegia of childhood is exclusive to children younger than 18 months. CLINICALHistoryA detailed headache history is necessary to establish the diagnosis of MVs. As many as 20% of patients with MV may experience prodromal symptoms without subsequent headaches. Such paroxysmal symptoms, with the recurrent attacks of transient neurologic symptoms, whether a headache is absent or present, with a positive family history of migraine, and with a normal neurologic examination interictally are confirmatory.
PhysicalThe neurologic examination in between attack is nonfocal. Ictally, hemiparesis, ophthalmoplegia, or altered consciousness may be observed. Abnormalities of oculomotor nerve with pupillary involvement are seen in ophthalmoplegic migraine, followed by the abducens, and less commonly trochlear nerve palsy. Children with abdominal migraine or cyclic vomiting may show subtle clumsiness, attention deficit, or development delay. In migrainous infarction, some form of neurologic deficit with abnormal neuroimaging is present. Rarely, when patients with retinal migraine are evaluated and examined during an attack of visual loss, optic pallor or narrowing of the retinal vessels can be seen. DIFFERENTIALSAbsence Seizures Anterior Circulation Stroke Arteriovenous Malformations Basilar Artery Thrombosis Benign Childhood Epilepsy Benign Neonatal Convulsions Benign Positional Vertigo Brainstem Gliomas Cardioembolic Stroke Cerebral Aneurysms Cerebral Venous Thrombosis Complex Partial Seizures Craniopharyngioma Dissection Syndromes Dizziness, Vertigo, and Imbalance Epilepsia Partialis Continua Frontal Lobe Epilepsy Headache: Pediatric Perspective Hydrocephalus Labyrinthitis And Related Conditions Metabolic Disease & Stroke: Fabry Disease Metabolic Disease & Stroke: Homocystinuria/Homocysteinemia Metabolic Disease & Stroke: Hyperglycemia/Hypoglycemia Metabolic Disease & Stroke: MELAS Metabolic Disease & Stroke: Methylmalonic Acidemia Metabolic Disease & Stroke: Propionic Acidemia Moyamoya Disease Partial Epilepsies Pseudotumor Cerebri Simple Partial Seizures Sudden Visual Loss Syncope and Related Paroxysmal Spells Temporal Lobe Epilepsy Temporal/Giant Cell Arteritis Viral Encephalitis
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| Drug Name | Acetazolamide (Diamox) |
|---|---|
| Description | For familial hemiplegic migraine. This recommended medication not typically used in migraine, but in hemiplegic MV. Available in 125 mg and 250 mg tab. |
| Adult Dose | 8-30 mg/kg IV/IM divided qid; optimal adult dose 250-1000 mg/dose |
| Pediatric Dose | 5-25 mg/kg IV/IM divided qid |
| Contraindications | Documented hypersensitivity; hepatic disease; severe renal disease; adrenocortical insufficiency; severe pulmonary obstruction; coadministration with aspirin |
| Interactions | Can decrease therapeutic levels of lithium and alter excretion of drugs (eg, amphetamines, quinidine, phenobarbital, salicylates) by alkalinizing urine |
| 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 | Patients with impaired hepatic function may go into coma; may cause substantial increase in blood glucose in some diabetic patients |
These agents typically are used in migraine and MVs, especially when nausea and vomiting are prominent.
| Drug Name | Ondansetron (Zofran) |
|---|---|
| Description | Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. |
| Adult Dose | 8 mg PO bid |
| Pediatric Dose | 4-12 years: 4 mg PO tid >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Although potential for cytochrome P-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance, dosage adjustment not usually required |
| 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 | To be administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting |
| Drug Name | Promethazine (Phenergan) |
|---|---|
| Description | Used to control symptoms of nausea and vomiting. |
| Adult Dose | 12.5-25 mg PO/IV/IM/PR q6h |
| Pediatric Dose | <2 years: Contraindicated >2 years: 12.5-25 mg PO/PR q6h prn |
| Contraindications | Documented hypersensitivity; asthma; children younger than 2 y (incidences of death due to respiratory depression) |
| Interactions | May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension |
| 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 cardiovascular disease, impaired liver function, seizures, sleep apnea, asthma, bone marrow depression, compromised respiratory function, stenosing peptic ulcer, seizure disorders, pediatric patients > 2 y |
These agents inhibit calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle.
| Drug Name | Verapamil (Calan, Calan SR, Covera-HS, Verelan) |
|---|---|
| Description | Relaxes smooth muscles and increases oxygen delivery during vasospasms. Used for migraine prophylaxis. |
| Adult Dose | 80 mg PO 3-4 times/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; severe CHF; sick sinus syndrome or second- or third-degree AV block; hypotension (<90 mm Hg systolic) |
| Interactions | May increase carbamazepine, digoxin, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and a decrease in cardiac output; when administered concurrently with beta-blockers, may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels |
| 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 | Depresses impulse formation, AV block, negative inotropism, and vasodilation, which can result in hypotension, shock, pulmonary edema, and death; hepatocellular injury may occur; transient elevations of transaminases levels with or without concomitant elevations in alkaline phosphatase and bilirubin levels have occurred (elevations have been transient and may disappear with continued verapamil treatment); monitor liver function periodically |
| Drug Name | Flunarizine |
|---|---|
| Description | Not available in the US. |
| Adult Dose | 10 mg PO qhs |
| Pediatric Dose | Not established; suggested dosing includes <40 kg: 5 mg PO qd >40 kg: 10 mg PO qd |
| Contraindications | Documented hypersensitivity; depression; extrapyramidal symptoms |
| Interactions | Avoid with beta-blockers |
| 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 | May cause drowsiness |
These agents prevent histamine response in sensory nerve endings and blood vessels. They are more effective in preventing histamine response than in reversing it.
| Drug Name | Cyproheptadine (Periactin) |
|---|---|
| Description | Occasionally useful for migraine prophylaxis. An antihistamine that has been used for migraine prevention in children more than in adults. Usually well tolerated. Mechanism of action not clarified and hypotheses include antihistaminic and anti-5-HT 2 effects. |
| Adult Dose | 4 mg PO bid/tid; not to exceed 20 mg/d |
| Pediatric Dose | <2 years: Not established 2-6 years: 2 mg PO bid/tid; maximum dose 12 mg/d 7-14 years: 4 mg PO bid/tid; maximum dose 16 mg/d >14 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; stenosing peptic ulcer; symptomatic prostatic hypertrophy; bladder neck obstruction; pyloroduodenal obstruction; lower respiratory tract symptoms |
| Interactions | Potentiates effects of CNS depressants; MAOIs may prolong and intensify anticholinergic and sedative effects of antihistamines |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Caution in patients with a predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties and may inhibit expectoration and sinus drainage |
These agents are used for migraine prophylaxis that is effective independent of antidepressant effect. Mechanism of action is unknown. These agents inhibit activity of such diverse agents as histamine, 5-HT, and acetylcholine.
| Drug Name | Amitriptyline (Elavil) |
|---|---|
| Description | Tricyclic antidepressant used traditionally for migraine prophylaxis. Antimigraine effect is independent from antidepressant effects. Mechanism of action is not clear, but possibly is due to enhanced central serotoninergic and noradrenergic. Cannot be formally recommended for individuals <12 y. Amitriptyline also has been used for long-term prophylactic treatment of chronic tension-type headache. Mechanism of action is possibly central serotonin enhancement but has never been proven. |
| Adult Dose | 10-175 mg PO qd; effective dosage varies; start at 25 mg qhs, increase by 10 mg qwk; highest dosages used for patients with comorbid depression |
| Pediatric Dose | <12 years: 1-10 mg PO hs >12 years: 10-25 mg PO; titrate up slowly |
| Contraindications | Documented hypersensitivity; use of MAOIs within 14 d of initiating therapy; history of seizures, cardiac arrhythmias, glaucoma, or urinary retention |
| Interactions | Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram |
| 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 cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; avoid using in elderly persons |
Anticonvulsants, particularly those that interact with the GABAergic system, seem to have a positive effect in reducing migraine attacks. Valproate and gabapentin are most commonly used in this manner.
| Drug Name | Topiramate (Topamax) |
|---|---|
| Description | Indicated for migraine headache prophylaxis. Precise mechanism unknown, but the following properties may contribute to its efficacy: (1) electrophysiological and biochemical evidence showing blockage of voltage-dependent sodium channels, (2) augments the activity of the neurotransmitter GABA at some GABA-A receptor subtypes, (3) antagonizes AMPA/kainate subtype of the glutamate receptor, and (4) inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV. |
| Adult Dose | 100 mg/d PO divided bid |
| Pediatric Dose | <2 years: Not established >2 years: 50 mg/d PO divided bid |
| Contraindications | Documented hypersensitivity |
| Interactions | Phenytoin, carbamazepine, and valproic acid can significantly decrease topiramate levels; 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; 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 |
| 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 have 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, nonanion gap metabolic acidosis or 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 |
| Drug Name | Valproic acid (Depakote, Depakene) |
|---|---|
| Description | Delayed-release or extended-release dosage forms are used for prophylaxis of migraine headaches. Although mechanism of action is not established, activity may be related to increased brain levels of GABA, or enhanced GABA action. |
| Adult Dose | Delayed-release: 250 mg PO bid initially; may titrate upward, not to exceed 1000 mg/d divided bid Extended-release: 500 mg PO qd initially; may increase dose, not to exceed 1000 mg/d |
| Pediatric Dose | <10 years: Not established >10 years: 250 mg PO bid; 1000 mg/d maximum |
| Contraindications | Documented hypersensitivity; hepatic disease/dysfunction; hyperammonemic encephalopathy and urea cycle disorders |
| 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 |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Thrombocytopenia and abnormal coagulation parameters have occurred; 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 |
Benign coital headache: If coital headaches have been a problem for a significant period of time, the patient or couple may need psychological counseling.
Article Last Updated: Sep 12, 2006