eMedicine Specialties > Neurology > Headache and Pain
Migraine Variants: Treatment & Medication
Updated: Jan 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The first step in treatment is to establish the diagnosis. Once the syndromes are recognized, MVs respond to typical migraine preventive medications.
Treatment is divided into eliminating particular triggers, acute management of the specific attack, and long-term preventive approach. Patients should follow risk factor modifications including smoking cessation, and they should avoid the use of hormonal replacement therapy and birth control pills, all of which could potentially increase the risk of hypercoagulability migraineurs
- In hemiplegic migraine, acute treatment options include antiemetics, nonsteroidal anti-inflammatory drugs, and nonnarcotic pain relievers. Triptans and ergotamine preparations are contraindicated because of their potential vasoconstrictive effects.73 Prophylactic treatment is generally warranted because of the severity of the attacks. No data are available to support the use of any particular antimigraine agent. Beta-blockers, low-dose tricyclics, anticonvulsants, and calcium channel blockers can be administered. Acetazolamide has been frequently prescribed to patients with hemiplegic migraine, but its benefit in decreasing the frequency or severity of the attacks is questionable.74 No data support the use of antiplatelet therapy to decrease the risk of stroke.
- In ophthalmoplegic migraine, prednisone has been used with mixed results. The data on the benefit of prophylactic therapy with beta-blockers, such as propranolol, are anecdotal.
- In retinal migraine, vasoconstrictive agents such as triptans and ergots should be avoided. The use of prophylactic therapy is also anecdotal; when considered, calcium channel blockers are preferred.49,55
- In migraine-triggered seizures, antiepileptic agents are drugs of choice because of their dual benefit in migraine prevention and seizure control
- In childhood periodic vomiting syndrome, early use of intravenous fluids containing adequate glucose (to prevent a catabolic state) and analgesics may abort the attack. Some patients respond to the triptans or ergotamine classes of medication. Antiemetic drugs are usually not effective, but ondansetron may be more efficacious given its central mechanism of action. Preventive medications such as cyproheptadine and tricyclic antidepressants are preferred in children.
- Abdominal migraine symptoms are usually relieved with sleep. Antiemetics may help aborting an acute attack. For chronic prevention, low doses of tricyclic antidepressants and flunarizine, a calcium channel blocker, are effective.75 Other migraine prevention medications are occasionally of some benefit.
- Triptans, ergots, and dihydroergotamine are contraindicated in patients with migrainous infarction. These patients may respond to nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, and non-narcotic pain relievers. Prophylactic therapy is recommended, with tricyclics, beta-blockers, calcium channel blockers, or antiepileptic drugs. Long-term antiplatelet therapy is indicated in patients with migrainous infarction.
- Patients with vertiginous migraine rarely respond to migraine prophylactic therapy. Anecdotal data are available on the benefit of verapamil, a calcium channel blocker, and amitriptyline, a tricyclic antidepressant, because of their anticholinergic properties, which may help control the vertigo.
Consultations
Consultation with a neuro-ophthalmologist is warranted in patients who present with persistent visual aura, retinal migraine, or recurrent ophthalmoplegia. Children with cyclic vomiting syndrome rarely require an evaluation by a gastroenterologist to exclude other gastrointestinal disorders. An evaluation by an audiologist may be necessary to exclude other vestibulopathies in patients with vertiginous migraine.
Diet
Certain food products and food additives may trigger migraine attacks in some patients. Such triggers include monosodium glutamate, nitrates-containing processed meat, aged or smoked cheese, onion, pickled products, avocados, dairy products, nuts, chocolate, caffeine, and alcoholic beverages, in particular red wine. Identifying and avoiding individual food triggers is key in preventing migraine attacks.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Carbonic anhydrase inhibitors (diuretic)
Carbonic anhydrase (CA) is an enzyme found in many tissues. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid dehydrated. These changes may result in a decrease in cerebrospinal fluid by the choroid plexus.
Acetazolamide (Diamox)
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
8-30 mg/kg IV/IM divided qid; optimal adult dose 250-1000 mg/dose
Pediatric
5-25 mg/kg IV/IM divided qid
Can decrease therapeutic levels of lithium and alter excretion of drugs (eg, amphetamines, quinidine, phenobarbital, salicylates) by alkalinizing urine
Documented hypersensitivity; hepatic disease; severe renal disease; adrenocortical insufficiency; severe pulmonary obstruction; coadministration with aspirin
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
Antiemetics
These agents typically are used in migraine and MVs, especially when nausea and vomiting are prominent.
Ondansetron (Zofran)
Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally.
Adult
8 mg PO bid
Pediatric
<4 years: Not established
4-12 years: 4 mg PO tid
>12 years: Administer as in adults
Although potential for cytochrome P-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance, dosage adjustment not usually required
Documented hypersensitivity
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
Promethazine (Phenergan)
Used to control symptoms of nausea and vomiting.
Adult
12.5-25 mg PO/IV/IM/PR q6h
Pediatric
<2 years: Contraindicated
>2 years: 12.5-25 mg PO/PR q6h prn
May have additive effects when used concurrently with other CNS depressants or anticonvulsants; coadministration with epinephrine may cause hypotension
Documented hypersensitivity; asthma; children younger than 2 y (incidences of death due to respiratory depression)
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
Calcium channel blockers
These agents inhibit calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle.
Verapamil (Calan, Calan SR, Covera-HS, Verelan)
Relaxes smooth muscles and increases oxygen delivery during vasospasms. Used for migraine prophylaxis.
Adult
80 mg PO 3-4 times/d
Pediatric
Not established
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
Documented hypersensitivity; severe CHF; sick sinus syndrome or second- or third-degree AV block; hypotension (<90 mm Hg systolic)
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
Flunarizine
Not available in the US.
Adult
10 mg PO qhs
Pediatric
Not established; suggested dosing includes
<40 kg: 5 mg PO qd
>40 kg: 10 mg PO qd
Avoid with beta-blockers
Documented hypersensitivity; depression; extrapyramidal symptoms
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
Antihistamines
These agents prevent histamine response in sensory nerve endings and blood vessels. They are more effective in preventing histamine response than in reversing it.
Cyproheptadine (Periactin)
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
4 mg PO bid/tid; not to exceed 20 mg/d
Pediatric
<2 years: Not established
2-6 years: 2 mg PO bid/tid; maximum dose 12 mg/d
6-14 years: 4 mg PO bid/tid; maximum dose 16 mg/d
>14 years: Administer as in adults
Potentiates effects of CNS depressants; MAOIs may prolong and intensify anticholinergic and sedative effects of antihistamines
Documented hypersensitivity; narrow-angle glaucoma; stenosing peptic ulcer; symptomatic prostatic hypertrophy; bladder neck obstruction; pyloroduodenal obstruction; lower respiratory tract symptoms
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
Tricyclic antidepressants
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.
Amitriptyline (Elavil)
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
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
<12 years: 1-10 mg PO hs
>12 years: 10-25 mg PO; titrate up slowly
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
Documented hypersensitivity; use of MAOIs within 14 d of initiating therapy; history of seizures, cardiac arrhythmias, glaucoma, or urinary retention
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
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.
Topiramate (Topamax)
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
100 mg/d PO divided bid
Pediatric
<2 years: Not established
>2 years: 50 mg/d PO divided bid
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
Documented hypersensitivity
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
Valproic acid (Depakote, Depakene)
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
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
<10 years: Not established
>10 years: 250 mg PO bid; 1000 mg/d maximum
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
Documented hypersensitivity; hepatic disease/dysfunction; hyperammonemic encephalopathy and urea cycle disorders
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
More on Migraine Variants |
| Overview: Migraine Variants |
| Differential Diagnoses & Workup: Migraine Variants |
 Treatment & Medication: Migraine Variants |
| Follow-up: Migraine Variants |
| References |
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Further Reading
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
