Migraine medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Andrea Tamayo Soto [2]

Overview

Conventional treatment focuses on three areas: trigger avoidance, symptomatic control, and preventive drugs. Migraine sufferers usually develop their own coping mechanisms for the pain of a migraine attack. Medical therapy can be divided into two treatment regimens: non-specific treatment such as non-steroidal anti-inflammatory drug and analgesics and specific treatment such as triptans and ergot derivatives. Patients who experience migraines often find that the recommended treatments are not 100% effective at preventing migraines, and sometimes may not be effective at all.

Non Pharmacological Therapy

• Migraine sufferers usually develop their own coping mechanisms for the pain of a migraine attack. A cold or hot shower directed at the head, a hot or cold wet washcloth, a warm bath, or resting in a dark and silent room may be as helpful as medication for many patients, but both should be used when needed.

• Some headache sufferers are surprised to learn that a simple cup of coffee is used daily around the world to control minor vascular headaches that are not quite migraines. Minor vascular headaches are frequently associated with the hormonal fluctuations of menstrual periods, irregular eating, and unusually hard work. For migraineurs, a well-timed cup of coffee can prevent outright migraine under the same conditions.

• A simple treatment, which has been effective for some, is a counteracting "ice cream headache", briefly provoked by placing spoonfuls of ice cream on the soft palate at the back of the mouth. This directs cooling to the hypothalamus, which is suspected to be involved with the migraine feedback cycle, and for some it can stop even a severe headache very quickly.

• For sufferers of weather-related migraines there is a simple treatment known as the Valsalva maneuver, which pilots and frequent fliers employ to relieve discomfort from pressure change. By holding your nose and gently pushing the air in your mouth back towards your ears and "popping" them you are opening your eustachian tubes. These normally open and close with regular chewing and talking but in some people may stay closed due to allergies or genetics. Regular opening and closing of the eustachian tubes allows a person to continually equalize to any change in the ambient barometric pressure. When this does not occur regularly the difference in pressure between the head and the environment can cause vascular swelling/constricting and trigger a migraine. Migraines can be stopped by doing the Valsalva maneuver three or four times. During changeable weather patterns doing the maneuver fifteen times per day can eliminate the headaches.

• For patients who have been diagnosed with recurring migraines, doctors recommend taking migraine abortive medicines to treat the attack as soon as possible. Migraine without aura presenting without prodrome or nausea can present with sudden onset. Many patients avoid taking their medications when an attack is beginning, hoping that "it will go away". However, in many cases once an attack is underway, it can become intensely painful, last for a long time, and become somewhat resistant to medical treatment. In contrast, treating the attack at the onset can often abort it before it becomes serious, and can reduce the near-term frequency of subsequent attacks.

Medical Therapy

Medical therapy can be divided into two treatment regimens:

• Non-specific treatment: Non-steroidal anti-inflammatory drug and analgesics
• Specific treatment: Triptans and ergot derivatives

Contraindicated medications

Migraine if patient is over age 35 is considered an absolute contraindication to the use of the following medications:

• Drospirenone and Ethinyl estradiol

Non Specific Treatment

Patients often start off with non specific analgesics such as paracetamol (known as acetaminophen in the USA), aspirin, ibuprofen, or other simple analgesics that are useful for tension headaches. Some patients find relief from taking over-the-counter sedative antihistamines or anti-nausea agents. Over the counter drugs may provide some relief, although they are typically not effective for most sufferers. It is one of doctors' practical diagnoses of migraine head pain when patients say typical OTC drugs "won't touch it".

Simple analgesics combined with caffeine may help. During a migraine attack, emptying of the stomach is slowed, resulting in nausea and a delay in absorbing medication. Caffeine has been shown to partially reverse this effect, and probably accounts for its benefit. Excedrin is an example of an aspirin with caffeine product. Caffeine is recognized by the U.S. FDA as an OTC treatment for migraine. Patients themselves often start off with paracetamol (known as acetaminophen in the USA), aspirin, ibuprofen, or other simple analgesics that are useful for tension headaches.

• NSAIDs such as, naproxen, ibuprofen, ketoprofen and diclofenac, can be taken at the onset of the aura to avoid the subsequent headache, opposite to sumatriptans which should only be started when the headache starts.
  • Ketoprofen can be used for migraines with and without aura.
  • Ibuprofen can be used for mild and moderate migraines, with or without aura.
  • Naproxen can abort about one third of migraine attacks, which is 5% less that the benefit of sumatriptan.

• Acetylsalicylic scid (aspirin) can be taken as monotherapy. Metoclopramide could be co-administered in case of associated digestive symptoms (nausea and vomit).

• Acetaminophen (1000 mg) combined with metoclopramide is aas effective as oral sumatriptan 100 mg.

Shown below is a table summarizing the doses of non specific analgesics commonly used for the treatment of mild to moderate migraine.

Analgesic and NSAID	Doses	Max Doses per day Not more that 3 times per week
Aspirin	Tablet 1000mg 1000mg could be added	4000mg
Ibuprofen	Tablet 400mg 200 - 400mg could be added	1200mg
Acetaminophen	Tablet 500mg 500mg could be added	4000mg
Naproxen	Tablet 500 - 700mg 250 - 500mg could be added	1250mg
Ketorolac	IM 60mg IV 30mg	IM 120mg IV 120mg

Specific Treatment

Triptans

• Sumariptans and related triptans are selective serotonin receptor agonists, they act on the 5HT1 receptors, and so inhibit neurogenic inflammation and vasodilation.

• Triptans are excellent for severe migraines or those that do not respond to NSAIDs. or other over-the-counter drugs Triptans are a mid-line treatment suitable for many migraineurs with typical migraines. They may not work for atypical or unusually severe migraines, transformed migraines, or status (continuous) migraines.

• Triptans are proven to be efficient against photophobia and phonophobia.

• Before discontinuing them, triptans should be tested in at least three attacks, unless the patient shows intolerance. A patient that doesn´t respond to one type of triptan may respond to another.

Shown below is a table summarizing the doses of different types of triptans. Triptans are used among patients with moderate to severe headache, with nausea or vomiting, rapid progression to severe headache and mild to moderate headache that responds poorly to 1st-line treatment.

Triptan	Doses	Max Doses per day	Side Effects
Almotriptan	Tablet 12.5mg	25mg	Vasomotor hot flushes Dizziness Weakness Asthenia Somnolence Nausea Vomits
Eletriptan	Tablet 40mg	80mg
Fovatriptan	Tablet 2.5mg	5mg
Naratriptan	Tablet 2.5	5mg
Rizatriptan	Tablet 5 - 10mg Dry powder 10mg	20mg
Sumatriptan	Tablet 50mg SQ injection ampoule 6mg Nasal spray 10 - 20mg	300mg 12mg 40mg	Moderate or severe hypertension heat sensation suffocating feeling pressure sensation
Zolmitriptan	Tablet 2.5mg	10mg

Ergot Alkaloids

• Until the introduction of sumatriptan in 1991, ergot derivatives, were the primary oral drugs available to abort a migraine once it is established. Ergot drugs can be used either as a preventive or abortive therapy, though their relative expense and cumulative side effects suggest reserving them as an abortive rescue medicine.
• Ergotamine tartrate tablets (usually with caffeine), though highly effective, and long lasting (unlike triptans), have fallen out of favor due to the problem of ergotism. Oral ergotamine tablet absorption is reliable unless the patient is nauseated. Anti-nausea administration is available by ergotamine suppository. Pure ergotamine tartrate is highly effective for evening-night migraines, but is rarely or never available in the USA.
• Dihydroergotamine (DHE), which must be injected or inhaled, can be as effective as ergotamine tartrate, but is much more expensive.

Shown below is table summarizing the doses of the different types of ergot alkaloid derivatives.

Ergo derivatives	Doses	Max Doses per day	Side Effects
Ergotamine Tartrate	2 mg/ day	6 mg/day 10mg/week	Ergotism Nausea Vomits
Dihydroergotamine	Endonasal solution 1 spray 0.5 mg in each nostril SQ/IM injectable solution 1mg	2mg (4 sprays)/day 4mg (8 sprays)/week 2 mg/day 8 mg/week	Ergotism Nasal obstruction and rhinorrhoea (with Endonasal solution) Precordalgia (with the injectable solution)

Other Agents

• If over-the-counter medications do not work, or if triptans are unaffordable, the next step for many doctors is to prescribe Fioricet or Fiorinal, which is a combination of butalbital (a barbiturate), acetaminophen (in Fioricet) or acetylsalicylic acid (more commonly known as aspirin and present in Fiorinal), and caffeine. While the risk of addiction is low, butalbital can be habit-forming if used daily, and it can also lead to rebound headaches. Barbiturate-containing medications are not available in many European countries.

• Narcotic pain killers (for example, codeine, morphine or other opiates) provide variable relief, but their side effects, the possibility of causing rebound headaches or analgesic overuse headache, and the risk of addiction contraindicates their general use.

• Amidrine (a cocktail of a analgesic, a sedative, and a vasoconstrictor) is sometimes prescribed for migraine headaches.

• Anti-emetics by suppository or injection may be needed in cases where vomiting dominates the symptoms.

• Intravenous chlorpromazine has proven very effective in treating status migrainosus & mdash;intractable and unremitting migraine.Status migraine is an extremely rare life-threatening condition. In otherwise uncomplicated, non-nauseated cases, it can be treated with 20 mg of prednisone tablets every eight hours until the migraine ends, followed by mandatory tapering off doses (the classic steroid taper).

• Prednisone is a cortisol-like semi-synthetic adrenal hormone, a non-anabolic steroid, which strongly stimulates biosynthesis of proteins from DNA. The replicated proteins include enzymes that cure the migraine through numerous metabolic boosts, including molecular construction of more natural serotonin to be stored in blood platelets. Prednisone risks include immune system suppression, adrenal axis suppression, non-addictive dependence, and long-term osteoporosis. Vitamin Antioxidants taken with calcium and magnesium may reduce the damage caused by the extra free radicals released, and the bone lost, during long term prednisone use.

Comparative Studies

Regarding comparative effectiveness of these drugs used to abort migraine attacks, a 2004 placebo-controlled trial reveals that high dose acetylsalicylic acid (1000 mg), sumatriptan 50 mg and ibuprofen 400 mg are equally effective at providing relief from pain, although sumatriptan was superior in terms of the more demanding outcome of rendering patients entirely free of pain. Acetylsalicylic acid is OTC aspirin, ibuprofen is OTC Advil, and since migraineurs know they don't provide much relief, the results of this study are unexpected. They may be partly related to the dosage of acetylsalicylic acid used, which was considerably higher than the one or two 300 mg tablets normally recommended for OTC use. High doses of aspirin and ibuprofen may cause ringing of the ears, which is a sign of drug toxicity to the inner ear. Another randomized controlled trial, funded by the manufacturer of the study drug, found that a combination of sumatriptan 85 mg and naproxen sodium 200 mg was better than either drug alone.

Therapeutic Approach

Shown below is an algorithm depicting the management of acute migraine.

Acute Migraine

❑ Administer NSAIDs ❑ Administer triptans as a rescue medication in case of no relief within 1-2 hour after taking the NSAID

❑ Reevaluate the patient after 3 attacks

Was the NSAID effective after 1- 2hours?

Effective (At least 2 out of 3 times)

Not Effective (At least 2 out of 3 times)

❑ Consider NSAIDs a 1st line medication

❑ Consider triptans a 1st line medication

❑ Reevaluate the patient after 3 attacks

Triptan is effective and tolerated (At least 2 out of 3 times)

Triptan is ineffective and/or poorly tolerated (At least 2 out of 3 times)

❑ Consider triptan a 1st line medication

❑ Change to a different triptan ❑ Reevaluate after 3 attacks

Triptan is effective and tolerated

Triptan is ineffective

❑ Consider triptans a 1st line medication

❑ Consider combined therapy of NSAID and triptan