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Medication

Medication Summary

Pharmacologic agents used for the treatment of migraine can be classified as abortive (ie, for alleviating the acute phase) or prophylactic (ie, preventive). Abortive medications include the following:

Serotonin 5-HT1F agonists (ditans)
Selective serotonin receptor (5-HT1B/1D) agonists (triptans)
Calcitonin gene-related peptide (CGRP) receptor antagonists (ie, rimegepant, ubrogepant)
Ergot alkaloids
Analgesics
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Combination products
Antiemetics

Prophylactic medications include the following:

Antiepileptic drugs
Beta blockers
Tricyclic antidepressants
Calcium channel blockers
Selective serotonin reuptake inhibitors (SSRIs)
NSAIDs
Serotonin antagonists
Botulinum toxin
CGRP inhibitors

Class Summary

Serotonin 5-HT1F receptor agonists (ie, ditans) do not elicit a vasoconstrictive effect, whereas triptans cause vasoconstriction via agonistic action at 5-HT1B/1D receptors. Because of this ditans may be used for acute migraine attacks in patients with cardiovascular risks.

Lasmiditan (Reyvow)

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Serotonin 5-HT1F receptor agonist indicated to treat acute migraine with or without aura.

Class Summary

Triptans are used as abortive medications for moderately severe to severe migraine headaches. These drugs are selective serotonin agonists, specifically acting at 5-hydroxytryptamine 1B/1D (5-HT_1B/1D) receptors on intracranial blood vessels and sensory nerve endings.

The most common side effects of triptans are as follows: Asthenia, nausea/vomiting, dizziness, somnolence, chest, throat, or jaw tightness/discomfort, worsening of head pain (often transient)

Drug interactions occur with potent CYP450 3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir), which may increase toxicity, and with concurrent administration of ergot-containing drugs, which may increase vasospastic reactions. Zolmitriptan, eletriptan, and naratriptan are primarily metabolized by CYP450 3A4.

Sumatriptan (Imitrex, Sumavel DosePro, Alsuma, Onzetra, Sumavel, Zeculty, Zembrace)

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5-HT1B/1D receptor agonist. Sumatriptan has the most options for drug delivery. It is available in intranasal, subcutaneous, and oral formulations. The efficacy of sumatriptan is 82% at 20 minutes when administered by injection, 52-62% at 2 hours when administered intranasally, and 67-79% at 4 hours when administered orally.^{[132, 133, 134]}

Naratriptan (Amerge)

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A selective agonist for serotonin 5-HT1B/1D receptors, naratriptan has higher bioavailability and a longer half-life than sumatriptan, which may contribute to a lower rate of headache recurrences. Naratriptan has a slow onset of action and a duration of action of up to 24 hours, with low headache recurrence rate. It is useful for patients with slow onset, prolonged migraine, such as menstrual migraine.

Pain relief is experienced by 60-68% of patients within 4 hours of treatment and maintained for up to 24 hours in 49-67% of patients. Naratriptan is one of the few triptans that is not contraindicated for use in combination with monoamine oxidase inhibitors (MAOIs).

Zolmitriptan (Zomig, Zomig-ZMT)

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A selective agonist for serotonin 5-HT1B/1D receptors in cranial arteries, zolmitriptan suppresses the inflammation associated with migraine headaches. It has an efficacy of 62% at 2 hours and of 75-78% within 4 hours.

Rizatriptan (Maxalt, Maxalt-MLT)

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A selective agonist for serotonin 5-HT1B/1D receptors in cranial arteries, rizatriptan suppresses the inflammation associated with migraine headaches. It has a reported early onset of action (30 min) and an efficacy of 71% at 2 hours. It has the fastest onset of action of the triptans.

Almotriptan (Axert)

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A selective 5-HT1B/1D receptor agonist, almotriptan results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. It induces cranial vessel constriction, inhibits neuropeptide release, and reduces pain transmission in trigeminal pathways.

Frovatriptan (Frova)

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Frovatriptan is a selective 5-HT1B/1D receptor agonist with a long half-life (26-30 h) and a low headache recurrence rate within 24 hours of taking the drug. It constricts cranial vessels, inhibits neuropeptide release, and reduces pain transmission in trigeminal pathways. Frovatriptan is one of the few triptans that is not contraindicated for use in combination with MAOIs.

Eletriptan (Relpax)

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A selective serotonin agonist, eletriptan specifically acts at 5-HT1B/1D/1F receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute migraine.

Eletriptan is primarily metabolized by CYP3A4 and should not be used within at least 72 hours of potent CYP3A4 inhibitors. Eletriptan is one of the few triptans that is not contraindicated for use in combination with MAOIs.

Sumatriptan and naproxen (Treximet)

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This is a combination product containing sumatriptan, a selective 5-HT1B/1D receptor agonist, and naproxen sodium, an arylacetic acid NSAID, in a fixed combination of sumatriptan 85 mg and naproxen sodium 500 mg. It is 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. It decreases the activity of cyclo-oxygenase (COX), thereby interrupting prostaglandin synthesis.

Sumatriptan intranasal (Imitrex Intranasal, Onzetra Xsail)

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Selective 5-HT1B/1D receptor agonist in cranial arteries. Elicits vasoconstrictive and anti-inflammatory effects, It is associated with antidromic neuronal transmission and relief of migraine headache. It is indicated for treatment of acute attack of migraine headache with or without aura. Available as a liquid nasal spray or a dry powder administered using the Xsail breath-powered delivery device.

Sumatriptan transdermal (Zecuity)

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Selective 5-HT1B/1D receptor agonist. Indicated for treatment of acute migraine attack with or without aura. Delivered as a transdermal patch along with iontophoresis.

Class Summary

Ergot derivatives are nonselective 5-HT1 agonists that have a wider spectrum of receptor affinities outside of the 5-HT1 system, including dopamine receptors. They can be used for the abortive treatment of moderately severe to severe migraine headache.

Ergotamine tartrate (Ergomar)

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Ergotamine counteracts episodic dilation of extracranial arteries and arterioles. It has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic, and alpha-adrenergic receptors. Ergotamine causes constriction of peripheral and cranial blood vessels. The drug is available in a sublingual dosage form.

Dihydroergotamine (DHE-45, Migranal)

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Dihydroergotamine (DHE-45, Migranal)

Dihydroergotamine is an alpha-adrenergic blocking agent with a direct stimulating effect on smooth muscle of peripheral and cranial blood vessels. It depresses central vasomotor centers. Its mechanism of action is similar to that of ergotamine; it is a nonselective 5HT1 agonist with a wide spectrum of receptor affinities outside of the 5HT1 system; it also binds to dopamine. Thus, dihydroergotamine has an alpha-adrenergic antagonist and serotonin antagonist effect.

Dihydroergotamine is indicated to abort or prevent vascular headache when rapid control is needed or when other routes of administration are not feasible. It tends to cause less arterial vasoconstriction than ergotamine tartrate. It is usually administered in conjunction with antiemetics such as metoclopramide, which is a 5HT3-receptor antagonist and a dopamine antagonist, to treat migraine-associated nausea.

Dihydroergotamine is available in intravenous, intramuscular, subcutaneous, and intranasal preparations. The intravenous route is used when more rapid results are desired. A dose of 1 mg intravenously every 8 hours with or without metoclopramide is safe and effective for treatment of status migrainosus.

Class Summary

These agents are used for initial abortive therapy for patients with infrequent migraines. They can be used in combination with NSAIDs to alleviate headaches. Many oral analgesics, including acetaminophen, are not recommended for patients who require frequent medication, because they have been associated with rebound headaches.

Acetaminophen (Tylenol, FeverAll, Mapap, Acephen, Aspirin Free Anacin Extra Strength, Cetafen Extra, Little Fevers, Non-Aspirin-Pain Reliever, Nortemp Children's, Ofirmev, Pain & Fever Children's, Pain Eze, Pharbetol Extra Strength, Q-pap, Silapap, Triaminic Children's Fever Reducer Pain Reliever, Valorin)

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A potent analgesic and antipyretic activity with weak anti-inflammatory activity, acetaminophen is used to treat mild to moderate pain from migraine.

Class Summary

Patients who not respond to routine abortive treatment may require additional analgesics. Practice guidelines recommend nonopioid medications as first-line therapy. Opioid analgesics should be used sparingly, but they remain an option.^[4]Opioids should not be used long-term, because they are habit-forming. Also, they can contribute to rebound headaches. A review of opioid equivalents and conversions may be found in the following reference article: http://emedicine.medscape.com/article/2138678-overview

Oxycodone (OxyContin, Roxicodone, Oxecta, Oxaydo, Xtampza ER)

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Oxycodone is an opioid analgesic with multiple actions similar to those of morphine. However, it may produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine. It can be used as adjunctive therapy when patients do not respond to abortive treatment for migraines. It is habit-forming and should not be used long-term.

Morphine (Arymo ER, Astramorph, Depodur, MS Contin, Duramorph, Avinza, Infumorph, Kadian, MorphaBond)

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Morphine is the drug of choice for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered intravenously may be dosed in a number of ways and is commonly titrated until the desired effect is obtained. However, the use of morphine for aborting migraine should be very limited; it can be tried as adjunctive therapy when patients do not respond to first-line abortive treatment for migraines. It is habit-forming and should not be used long-term. Arymo ER is a morphine sulfate abuse-deterrent formulation.

Meperidine (Demerol)

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Meperidine is an analgesic with multiple actions similar to those of morphine. However, it may produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine.

Hydromorphone (Dilaudid, Dilaudid-HP, Exalgo)

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Hydromorphone is a potent semisynthetic opiate agonist similar in structure to morphine. It is approximately 7-8 times as potent as morphine on a milligram-to-milligram basis, with a shorter or similar duration of action. It can be used as adjunctive therapy when patients do not respond to abortive treatment for migraines. It is habit-forming and should not be used long-term.

Class Summary

NSAIDs inhibit COX, an early component of the arachidonic acid cascade, resulting in reduced synthesis of prostaglandins, thromboxanes, and prostacyclin. They elicit anti-inflammatory, analgesic, and antipyretic effects. NSAIDs are generally used as abortive therapy in mild to moderately severe migraine headaches. However, these agents, especially ketorolac, may also be effective for severe headaches.

NSAIDs are also used as prophylactic agents, but they are associated with a higher risk of adverse effects, particularly gastropathy or nephropathy, than when they are used as abortive medications.

Ketorolac intranasal (Sprix)

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Ketorolac is indicated for short-term (up to 5 days) management of moderate to moderately severe acute pain requiring analgesia at the opioid level. The bioavailability of a 31.5-mg intranasal dose (2 sprays) is approximately 60% of the 30-mg intramuscular dose. Intranasal spray delivers 15.75 mg per 100-µL spray; each 1.7-g bottle contains 8 sprays. Onset of analgesia is within 20 minutes, and time to peak is 0.5-0.75 hours.

Ibuprofen (Motrin, Advil, Neoprofen, Caldolor, Addaprin, EnovaRx-Ibuprofen, Goodsense Ibuprofen Children's, I-Prin, IBU-200, Ibuprofen Comfort Pac, NeoProfen, Provil))

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Ibuprofen is used for the treatment of mild to moderate pain if no contraindications are present. It inhibits inflammatory reactions and pain, probably by decreasing the activity of the enzyme COX, resulting in prostaglandin synthesis.

Naproxen (Naprosyn, Naprelan, Anaprox, Aleve, Midol Extended Relief, All Day Relief, Anaprox, EC-Naprosyn, EnovaRX-Naproxen, Equipto-Naproxen, Flanax Pain Relief, GoodSense Naproxen Sodium, Mediproxen, Naprelan, Naproderm,)

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Naproxen is used for relief of mild to moderate pain, as an abortive agent, and for prophylaxis. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclo-oxygenase, resulting in prostaglandin synthesis.

Ketoprofen (Active-Ketoprofen, Ketophene Rapidpaq)

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Ketoprofen reversibly inhibits COX-1 and COX-2 enzymes. It is indicated for mild to moderate pain. Administer small dosages initially to patients with small body size, elderly patients, and patients with renal or liver disease. Doses above 75 mg do not have increased therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

Aspirin (Acetylsalicylic acid, ASA, Bayer Advanced Aspirin)

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Aspirin is a mild analgesic that can be used to treat infrequent migraine episodes.

Celecoxib (Celebrex, Elyxyb)

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Available as capsule and oral solution (Elyxyb). The oral solution is approved by the FDA for acute treatment of migraine with or without aura in adults and reaches a peak plasma concentration at 1 h.

Class Summary

Acetaminophen is often used as abortive therapy for migraines. The combination of acetaminophen and codeine is indicated for the relief of mild to moderate pain.

Codeine/acetaminophen (Tylenol #3, Tylenol #4, Tylenol with Codeine)

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This drug combination is indicated for the treatment of mild to moderately severe headache. Note that some patients may respond to maximal acetaminophen alone, without codeine.

Class Summary

A combination drug containing isometheptene, dichloralphenazone, and acetaminophen is FDA approved for the relief of migraines and tension headaches.

Isometheptene, dichloralphenazone, and acetaminophen (Midrin, Epidrin)

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This combination drug has sympathomimetic properties. Isometheptene, in particular, dilates cranial and cerebral arterioles, causing a reduction in the stimuli that lead to vascular headaches. Dichloralphenazone has sedative and analgesic properties. Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system (CNS) and blocks pain impulses generated in the periphery.

Class Summary

Some agents are used in combination with aspirin and acetaminophen for pain relief and to induce sleep. Caffeine is also used to increase GI absorption. Analgesics like butalbital and narcotics are associated with rebound headaches. Increasing the use of combination preparations may fail to provide pain relief and may worsen headache symptoms.

Butalbital, aspirin, and caffeine (Fiorinal)

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This combination drug is effective for mild to moderately severe migraine headache. The barbiturate component has a generalized depressant effect on the CNS. Caffeine is used to increase GI absorption. However, butalbital and narcotics are associated with rebound headaches. Increasing the use of combination preparations may fail to provide pain relief and may worsen headache symptoms.

Butalbital, acetaminophen, and caffeine (Fioricet)

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Class Summary

Chlorpromazine can be used as monotherapy for acute migraine headaches.

Chlorpromazine (Thorazine)

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The mechanisms of chlorpromazine include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of the reticular activating system. The drug blocks alpha-adrenergic receptors and depresses the release of hypophyseal and hypothalamic hormones. As a rule, dopamine antagonists are avoided in patients with traumatic brain injury.

Class Summary

These drugs can be effective in prophylaxis of migraine headache.

Valproic acid (Depakote, Depacon, Depakene, Stavzor)

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Valproic acid reduces the frequency of migraines. This agent is believed to enhance gamma-aminobutyric acid (GABA) neurotransmission, which may suppress events related to migraine that occur in the cortex, perivascular sympathetics, or trigeminal nucleus caudalis. Divalproex has been shown to reduce migraine frequency by 50%.

Topiramate (Topamax, Qudexy XR, Topiragen, Trokendi XR)

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Topiramate is indicated for migraine headache prophylaxis in adults and adolescents aged 12 years or older. Its precise mechanism of action is unknown, but the following properties may contribute to its efficacy:

• Blockage of voltage-dependent sodium channels

• Augmentation of activity of the neurotransmitter GABA at some GABA-A receptor subtypes

• Antagonization of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate subtype of the glutamate receptor

• Inhibition of carbonic anhydrase, particularly isozymes II and IV

Class Summary

Agents in this class with potent serotonin antagonist activity have been reported to be effective in the treatment of migraine.

Promethazine (Phenergan, Phenadoz, Promethagan)

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Promethazine is a phenothiazine derivative that possesses antihistaminic, sedative, anti ̶ motion-sickness, antiemetic, and anticholinergic effects. It is commonly used in children older than 2 years.

Class Summary

Among antihypertensive medications, the evidence for migraine prevention is strongest with beta blockers. Beta blockers may prevent migraines by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues. Significant to their activity as migraine prophylactic agents is the lack of partial agonistic activity. Latency from initial treatment to therapeutic results may be as long as 2 months.

Beta blockers should not be used as first-line agents for migraine prophylaxis in smokers over age 60 years. Compared with other antihypertensive medications, beta blockers pose a higher risk of cardiovascular events.

Propranolol (Inderal, Inderal LA, Hemangeol, InnoPran XL)

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Propranolol is FDA approved for migraine prevention. The dose may be increased gradually to achieve optimum migraine prophylaxis. The long-acting form can be taken once daily.

Timolol (Apo-Timol, Nu-Timolol, Teva-Timolol)

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Timolol is FDA approved for migraine prophylaxis, although there is less scientific evidence of efficacy for timolol than for propranolol.

Class Summary

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and is a key neuropeptide that is central to migraine pathophysiology.

Erenumab (Aimovig)

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Human monoclonal antibody. Binds to the calcitonin gene-related peptide (CGRP) receptor, which is thought to be causally involved in migraine pathophysiology. It is indicated for preventive treatment of migraines in adults.

Fremanezumab (Ajovy, fremanezumab-vfrm)

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Human monoclonal antibody against human calcitonin gene-related peptide (CGRP), which may be causally involved in the pathophysiology of migraines. Fremanezumab in indicated for migraine prophylaxis.

Galcanezumab (Emgality, galcanezumab-gnlm)

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Monoclonal antibody that targets CGRP. Inhibition of CGRP interrupts migraine pathway. It is indicated for preventive treatment of migraine.

Eptinezumab (Vyepti)

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First IV GCRP monoclonal antibody approved for prevention of migraine. It is administered every 3 months.

Class Summary

These agents bind to the CGRP receptor.

Ubrogepant (Ubrelvy)

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First oral CGRP antagonist approved for treatment of acute migraine. Other CGRP antagonists are indicated for migraine prophylaxis.

Rimegepant (Nurtec ODT)

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First oral disintegrating tablet approved for acute treatment and prevention of migraine.

Atogepant (Qulipta)

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Indicated for preventive treatment of episodic migraine in adults. It is available as an oral tablet.

Zavegepant intranasal (Zavzpret)

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Indicated in adults to treat acute migraine (with or without aura).

Class Summary

Amitriptyline, nortriptyline, doxepin, and protriptyline have been used for migraine prophylaxis, but only amitriptyline has proven efficacy. It appears to exert its antimigraine effect independent of its effect on depression.

Amitriptyline (Elavil)

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Amitriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits the activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Nortriptyline (Pamelor)

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Nortriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits the activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Doxepin (Silenor)

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Doxepin has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. It also inhibits histamine and acetylcholine activity.

Protriptyline (Vivactil)

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Protriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. It inhibits the activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Class Summary

Calcium channel blockers are commonly used as prophylactic medication for migraine, although studies of their effectiveness have shown mixed results. Flunarizine has the best-documented efficacy but is not available in the United States. The efficacy of verapamil is supported by studies.

This class of drugs is particularly useful in patients with comorbid hypertension and in those with contraindications to beta blockers, such as asthma and Raynaud disease. Calcium channel blockers may have particular advantage in patients with prolonged aura, basilar-type migraine, or hemiplegic migraine.

Calcium channel blockers are considered second-line agents for patients with chronic migraines. Tolerance can develop with these drugs but can be overcome by increasing the dose or switching to another calcium channel blocker.

Verapamil (Calan, Isoptin SR, Verelan)

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Verapamil inhibits calcium ions from entering slow channels or voltage-sensitive areas of vascular smooth muscle during depolarization. Verapamil has an off-label indication for migraines. The drug is frequently the first choice for prophylactic therapy because of ease of use and a favorable side-effect profile. Patients may report an initial increase in headaches, with improvement after weeks of treatment.

Class Summary

SSRIs have limited efficacy for migraine prophylaxis in adults. Due to a lack of clinical studies, they are not recommended for this purpose in children.

Paroxetine (Paxil, Paxil CR, Pexeva, Brisdelle)

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Paroxetine is an atypical, nontricyclic antidepressant with potent, specific inhibition of 5-HT uptake inhibition and fewer anticholinergic and cardiovascular adverse effects than tricyclic antidepressants have.

Fluoxetine (Prozac, Prozac Weekly, Sarafem)

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Fluoxetine is a second-line agent for patients with chronic migraines. It is an atypical, nontricyclic antidepressant with potent, specific inhibition of 5-HT uptake and with fewer anticholinergic and cardiovascular side effects than tricyclic antidepressants have.

Sertraline (Zoloft)

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Sertraline is an atypical, nontricyclic antidepressant with potent, specific inhibition of 5-HT uptake and fewer anticholinergic and cardiovascular adverse effects than tricyclic antidepressants have.

Class Summary

As dopamine antagonists, these agents are effective if nausea and vomiting are prominent features. They also may act as prokinetics to increase gastric motility and enhance absorption.

Antiemetic agents are used to treat migraine and the emesis associated with acute attacks. Drugs in this category are commonly combined with diphenhydramine to minimize the risk of akathisia. This combination of drugs has been found to be superior to subcutaneous sumatriptan when administered intravenously to emergency department patients.^[122]

Prochlorperazine (Compro, Compazine)

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An antidopaminergic drug that blocks postsynaptic mesolimbic dopamine receptors, prochlorperazine has an anticholinergic effect. It can also depress the reticular activating system, a possible mechanism for relieving nausea and vomiting.

Class Summary

Injections of botulinum toxin A may be beneficial in patients with intractable migraine headaches that fail to respond to at least 3 conventional preventive medications. This agent is not recommended for use in the preventive treatment of episodic migraines.

OnabotulinumtoxinA (Botox)

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One of several toxins produced by Clostridium botulinum, onabotulinumtoxinA blocks neuromuscular transmission. Injections of the drug, which are administered to the scalp and temple, may reduce the frequency and severity of migraine attacks after 2-3 months of injections. This agent is FDA approved for the prophylaxis of chronic migraine headaches.

Questions

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Media Gallery

Migraine headache. Example of a visual migraine aura as described by a person who experiences migraines. This patient reported that these visual auras preceded her headache by 20-30 minutes.
Migraine headache. Example of a central scotoma as described by a person who experiences migraines. Note the visual loss in the center of vision.
Migraine headache. Example of a central scotoma as described by a person who experiences migraine headaches. Again note the visual loss in the center of vision.
Migraine headache. Example of visual changes during migraine. Multiple spotty scotomata are described by a person who experiences migraines.
Migraine headache. Frank visual field loss can also occur associated with migraine. This example shows loss of the entire right visual field as described by a person who experiences migraines.
International Headache Society criteria for migraine without aura.
Overview of migraine treatment. Five steps.
International Headache Society (IHS) classification of secondary headaches.

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Table 1. Abortive Medication Stratification by Headache Severity

Moderate	Severe	Extremely Severe
NSAIDs	Naratriptan	DHE (IV)
Isometheptene	Rizatriptan	Opioids
Ergotamine	Sumatriptan (SC,NS)	Dopamine antagonists
Naratriptan	Zolmitriptan	Lasmiditan
Rizatriptan	Almotriptan
Sumatriptan	Frovatriptan
Zolmitriptan	Eletriptan
Almotriptan	DHE (NS/IM)
Frovatriptan	Ergotamine
Eletriptan	Dopamine antagonists
Zavegepant intranasal	Zavegepant intranasal
Dopamine antagonists	Lasmiditan
DHE=Dihydroergotamine; NSAIDs=nonsteroidal anti-inflammatory drugs

Table 2. Preventive Drugs for Migraine

First line	High efficacy	Beta blockers Tricyclic antidepressants Divalproex Topiramate
First line	Low efficacy	Verapamil
Second line	High efficacy	Methysergide Flunarizine MAOIs CGRP inhibitors Botulinum toxin
Second line	Unproven efficacy	Cyproheptadine Gabapentin
MAOIs = monoamine oxidase inhibitors

Table 3. Preventive Medication for Comorbid Conditions

Comorbid Condition	Medication
Hypertension	Beta blockers
Angina	Beta blockers
Stress	Beta blockers
Depression	Tricyclic antidepressants, SSRIs
Overweight	Topiramate, protriptyline
Underweight	Tricyclic antidepressants (nortriptyline, protriptyline)
Epilepsy	Valproic acid, topiramate
Mania	Valproic acid
SSRIs = selective serotonin reuptake inhibitors

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Author

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Abbott Laboratories, advisory group.

Acknowledgements

Michelle Blanda, MD Chair, Department of Emergency Medicine, Summa Health System Akron City/St. Thomas Hospital; Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine

Michelle Blanda, MD, is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine