Drug therapy Of Migraine

Pharmacotherapy Of Migraine

Medical treatment of migraine consists of two approaches, which are not mutually exclusive:

§    Acute (also known as symptomatic or abortive treatment)

§     Prophylactic therapy.

Acute Migraine Therapy

A wide range of medications with variable routes of administration may be used to abort migraine headaches, including aspirin (ASA), non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen (APAP), selective serotonin agonists, ergot derivatives, combination drugs 

(e.g., an

analgesic plus caffeine), and phenothiazines. 

Rarely, opioids or corticosteroids may be necessary. Useful, acute migraine treatment principles include:

• taking an abortive medication as early as possible after

the onset of headache increases the likelihood of terminating

it;

• rest, and especially sleep, in a dark, quiet environment

is helpful in decreasing the duration of the attack;

• regular use of abortive medications, especially the combination

drugs, can lead to chronic daily headache .

A “Step-Care” treatment approach is prudent. This entails utilizing ASA, APAP, or an NSAID for mild-moderate headaches; if this fails, an OTC combination preparation could be tried; if nausea and vomiting are prominent, and the patient can afford to go to sleep, an anti-emetic, such as promethazine (orally or rectally) or metoclopramide, may be used along with the analgesic.

 In more difficult situations, a prescription combination medication (such as isometheptene/ dichloralphenazone/ APAP), an ergotamine, or a triptan may be necessary. The patient’s comorbidities and other medications are important in the decision-making process as well.

Table 3 lists the most commonly used acute migraine medications and doses, along with their potential adverse effects and relative costs per dose.

Triptans

Triptans are effective in the acute treatment of migraine (with or without aura). Treatment should begin as soon as possible after onset of a migraine attack. Oral dosage forms of the triptans are the most convenient but may not be used in patients experiencing migraine-associated nausea and vomiting. Many individuals report significant headache relief from a 6-mg subcutaneous dose of sumatriptan. This dose may be repeated once within a 24-hour period if the first dose does not relieve the headache.

·   The recommended oral dose of sumatriptan is 25–100 mg, repeatable after 2 hours up to a total dose of 200 mg over a 24-hour period.

·   When administered by nasal spray, from 5–20 mg of sumatriptan is recommended. The dose can be repeated after 2 hours up to a maximum dose of 40 mg over a 24-hour period.

Zolmitriptan is given orally in a 1.25–2.5-mg dose, repeatable after 2 hours, up to a maximum dose of 10 mg over 24 hours, if the migraine attack persists.

 Naratriptan is given orally in a 1–2.5-mg dose, which should not be repeated until 4 hours after the previous dose; the maximum dose over a 24-hour period should not exceed 5 mg.

 Rizatriptan oral dose of is 5–10 mg, repeatable after 2 hours up to a maximum dose of 30 mg over a 24-hour period.

  The safety of treating more than 3–4 headaches over a 30-day period with triptans has not been established. Triptans should not be used concurrently with (or within 24 hours of) an ergot derivative ,nor should one triptan be used concurrently  within 24 hours of another.

Methysergide

Actions of ergot alkaloids at 5-HT1B/1D receptors likely mediate their acute antimigraine effects. The ergot derivative methysergide 5-HT receptor antagonist has been used for the prophylactic treatment of migraine headaches. 

The use of ergot alkaloids for migraine should be restricted to patients having frequent, moderate migraine or infrequent, severe migraine attacks. The patient should take ergot preparations as soon as possible after the onset of a headache.

 Mechanism of action: Methysergide inhibits the vasoconstrictor and pressor effects of 5-HT, as well as the actions of 5-HT on various types of extravascular smooth muscle. It can both block and mimic the central effects of 5-HT. Methysergide is not selective: it also interacts with 5-HT1 receptors, but its therapeutic effects appear primarily to reflect blockade of 5-HT2 receptors.

Available preparations include sublingual tablets of ergotamine tartrate and a nasal spray and solution for injection of dihydroergotamine mesylate.

·   The recommended dose for ergotamine tartrate is 2 mg sublingually, which can be repeated at 30-minute intervals if necessary up to a total dose of 6 mg in a 24-hour period or 10 mg/week.

·   Dihydroergotamine mesylate injections can be given intravenously, subcutaneously, or intramuscularly. The recommended dose is 1 mg, which can be repeated after 1 hour if necessary up to a total dose of 2 mg (intravenously) or 3 mg (subcutaneously or intramuscularly) in a 24-hour period or 6 mg in a week.

·   The dose of dihydroergotamine mesylate administered as a nasal spray is 0.5 mg (one spray) in each nostril, repeated after 15 minutes for a total dose of 2 mg (4 sprays). The safety of more than 3 mg over 24 hours or 4 mg over 7 days has not been established.

 Methysergide has been used for the prophylactic treatment of migraine. The protective effect takes 1–2 days to develop and disappears slowly when treatment is terminated, possibly due to the accumulation of an active metabolite of methysergide, methylergometrine, which is more potent than the parent drug.

Prophylactic Migraine Therapy

Initiating prophylactic therapy depends to a great extent on patient preference, but there are some useful, general guidelines. Prophylactic migraine medications are indicated if: attacks occur more than 2-3 times a month; attacks last more than 48 hours; migraines are so severe, that the patient is unable psychologically to cope with them; abortive therapy(ies) are inadequate or cause significant side effects; attacks are associated with prolonged aura.

        The goal of migraine prophylaxis is to decrease the frequency and severity of attacks. Patients should be told that prophylaxis is infrequently curative, so that they have real expectations. once successful prophylaxis is achieved, it need not be continued indefinitely, but gradually discontinued after 9-12 months.

       Prophylaxis initiated in a patient who is abusing analgesics will likely fail; with the patient off of the analgesics, that same agent may be an effective prophylactic; since the prophylactic medications are potentially teratogenic, women of childbearing potential should not be placed on one unless they are utilizing reliable birth control, preferably barrier contraception.

      Medications from several different drug classes may be useful prophylactic agents. While there is some variance in expert opinion about which medications are the most efficacious, which is complicated by the paucity of well designed trials implemented to answer this question, there is a relative consensus that first-line medications include certain beta-blockers, such as propranolol and nadolol; the tricyclic anti-depressants (TCAs) amitriptyline and nortriptyline; and the anti-convulsant divalproex sodium (VPA). As with acute migraine treatment, choosing the most appropriate agent for a given patient should entail consideration of coexisting illnesses and medications taken regularly, so that the prophylactic medication with the highest benefit/ risk ratio can be selected