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Medications for Migraine
What are Migraine medications?
Medications used for migraine headaches fall into two classes:
The treatment of migraine involves three important strategies: behavioral and educational intervention, symptomatic (acute) therapies, and preventive considerations. All three approaches need to be employed for successful management of migraine. Preventive Therapy
Prophylactic medications are not taken once a headache has begun. The goal of preventive (prophylactic) therapy is to improve quality of life by reducing migraine frequency, severity, and duration, and by increasing the responsiveness of acute migraines to treatment. However, prophylactic medications cannot be expected to eliminate migraine headaches completely. The success rate of most prophylactic medications is approximately 50%. Success in preventing migraine headaches is defined as more than a 50% reduction in the frequency of headaches. Therapy should be initiated with medications that have the highest levels of effectiveness and the lowest potential for adverse reactions. These should be started at low dosages and titrated slowly in order to minimize side effects. A full therapeutic trial may take two to six months. Some individuals may not notice a reduction in the frequency, severity, or duration of their headaches for 2-3 months after starting treatment. After successful therapy has been maintained for 6 to 12 months, discontinuation of preventive therapy can be considered. There are several classes of prophylactic medications:
Therapy to prevent migraine is indicated if:
Beta blockers
Beta-blockers are a class of drugs that block the effects of beta-adrenergic substances such as adrenaline (epinephrine). Beta-blockers relieve stress on the heart by slowing the rate at which the heart beats. They have been used for many years to prevent migraine headaches. However, tolerability is an issue with these medications, especially in the elderly population. It is not known how beta-blockers prevent migraine headaches. The beta-blockers used in preventing migraine headaches include:
Propranolol and timolol have been FDA-approved for the prevention of migraine. Evidence consistently supports the use of propranolol in migraine prophylaxis. Propranolol has been compared with placebo in about 60 trials Timolol has been compared with placebo in three trials; its effect size is comparable to propranolol. The 2002 American Academy of Family Physicians and American College of Physicians-American Society of Internal Medicine guidelines for migraine prophylaxis identifies both propranolol and timolol as first-line agents. There is limited evidence to support the use of atenolol, the long-acting preparation of metoprolol, or nadolol for migraine prevention. However, several other beta blockers, including acebutolol (Sectral) and pindolol (Visken), appear to be ineffective for this use. Beta-blockers are approved by the FDA for migraine prophylaxis but may not be the ideal choice for patients who are elderly or have depression, thyroid problems, or diabetes. Antidepressants
The data that support the use of SSRIs for migraine prevention are weak. Nevertheless, SSRIs are still commonly used for the anticipated goal of preventing migraine headache, perhaps with the intent to treat concomitant depression. Much stronger evidence supports the use of tricyclic antidepressants (TCAs) such as amitriptyline and nortriptyline for migraine prevention. Because the treatment of migraine with TCAs requires a much lower dose than treatment of depression, patients taking TCAs for migraine experience fewer adverse effects. Tricyclic antidepressants prevent migraine headaches by altering the neurotransmitters, norepinephrine and serotonin, that the nerves of the brain use to communicate with one another. The tricyclic antidepressants used in preventing migraine headaches include:
Amitriptyline is a first-line agent for migraine prophylaxis and is the only antidepressant with consistent evidence supporting its effectiveness for this use. One study involving 162 persons with migraines compared amitriptyline therapy (50 to 100 mg daily) with placebo over four weeks. Results showed an odds ratio (OR) of 2.4 (95% CI, 1.1 to 5.4) for the number of patients reporting a 50 percent improvement in migraine index, and a moderate effect size of 0.62 (95% CI, 0.15 to 1.10) on a migraine index that included frequency and duration. Results of a study comparing amitriptyline with propranolol suggest that propranolol is more effective in patients with a single migraine type, whereas amitriptyline is more beneficial for patients with mixed migraine and tension features. Amitriptyline also is useful in patients with comorbid insomnia or, when used at higher dosages, depression. Anticonvulsants (antiseizure medications)
Anticonvulsants also have been used to prevent migraine headaches, however, it is not known how they work to prevent migraines. Anticonvulsants that are used for migraine prophylaxis include:
Two anticonvulsants have been FDA-approved for the preventive treatment of migraine: topiramate and divalproex. Other anticonvulsants are used on an off-label basis. Divalproex (Depakote) and sodium valproate are well supported by evidence for use in migraine prevention. For a migraine frequency reduction of 50% or more, authors of a Cochrane review of anticonvulsants for migraine prophylaxis calculated a number needed to treat (NNT) of 3.1 (95% CI, 1.9 to 8.9) for sodium valproate and 4.8 (95% CI, 3.5 to 7.4) for divalproex. However, these medications have comparatively high adverse event rates. Because of their teratogenicity, valproic acid (Depakene) and derivatives should not be used in patients who are pregnant. They also should not be used in patients with a history of pancreatitis or hepatic disorder, such as cirrhosis or chronic hepatitis. Two clinical trials have found gabapentin to be effective at dosages of 1,200 to 2,400 mg per day. At a dosage of 2,400 mg per day, the NNT to reduce headache frequency by 50% or more was 3.3 (95% CI, 2.1 to 8.4). These studies have methodologic limitations, however, and further evaluation is warranted. The most common adverse events associated with gabapentin are dizziness and somnolence. Several open-label and controlled studies indicate that topiramate is effective in migraine prophylaxis, and it is considered a first-line agent for this use. In two concurrent randomized, double-blind, placebo-controlled trials, 937 participants were randomized to receive topiramate 50, 100, or 200 mg per day or placebo for 26 weeks. In both trials, more patients had at least a 50% reduction in monthly migraine frequency with topiramate 50 to 200 mg per day (36 to 52%, respectively) than with placebo (23%). The NNT for a dosage of 100 mg topiramate per day has been calculated as 3.5 (95% CI, 2.8 to 4.9). In both trials, participants reported improvement in migraine frequency within the first month of therapy. Adverse events included paresthesia, fatigue, nausea, and anorexia. More adverse effects occurred with the 200 mg per day dosage than with 100 mg per day. Comparative studies with other prophylactic agents have not been conducted. Angiotensin blockade agents (ACE inhibitors)
Lisinopril (Zestril) has demonstrated some effectiveness in the prevention of migraine. In a randomized, double-blind, crossover trial with 55 patients, lisinopril 20 mg per day for 12 weeks reduced the mean number of days with headache and the mean number of days with migraine compared with placebo (20.7 versus 24.7 days, respectively, with headache; 14.6 versus 18.7 days, respectively, with migraine). 30% of patients receiving lisinopril experienced a 50% or greater reduction in the number of days with migraine. Lisinopril was well tolerated, although it was associated with a higher incidence of cough than placebo. Candesartan (Atacand) was evaluated in a prospective, randomized, double-blind, crossover study with 60 patients. As with lisinopril, candesartan 16 mg per day was found to reduce the mean number of days with headache and with migraine compared with placebo. Candesartan also appeared to significantly decrease headache severity, level of disability, and days of sick leave due to headache. Adverse effects with candesartan were similar to those with placebo. Calcium channel blockers
Calcium channel blockers (CCBs) are a class of drugs that block the entry of calcium into the muscle cells of the heart and the arteries. By blocking the entry of calcium, these medications reduce contraction of the heart muscle, decrease heart rate, and lower blood pressure. CCBs also appear to block a serotonin, and have been used occasionally to prevent migraine headaches. The CCBs used in preventing migraine headaches include:
Evidence does not support the use of diltiazem in migraine prevention, and the evidence for several other calcium channel blockers, such as nifedipine (Procardia), is poor and suggests only modest effect. There is weak evidence to support verapamil as a first-line agent. Of three small trials comparing verapamil 240 or 320 mg per day with placebo, two reported positive findings, with a moderate calculated summary effect. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
These are used as prophylactic agents, but they are associated with a higher risk of adverse effects, particularly gastropathy or nephropathy, than when used as abortive medications. In controlled clinical trials, naproxen sodium (Anaprox) demonstrated better efficacy than placebo and efficacy similar to propranolol. Tolfenamic acid has also been tried for migraine prophylaxis, but the clinical efficacy is not as good as that of beta-blockers, valproate, or methysergide. Evidence supports the use of naproxen sodium and naproxen (Naprosyn) for migraine prevention. Menstrual migraines may be prevented with a course of an NSAID beginning several days before menstruation and continuing during the first few days of the period. Acute abortive treatment (treatment of a
migraine attack)
Acute treatment is used to prevent progression and reverse migraines once they have started. The best time to start acute treatment is at the onset of headache pain. The goal of acute treatment is to get individuals to achieve closer to normal functioning.
Triptans (selective 5-HT1 agonists)
Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine. They are the most important migraine drugs currently available. They are vasoconstrictors and help maintain serotonin levels in the brain, and so specifically target one of the major components in the migraine process. Triptans are now recommended as first-line drugs for many adult patients with moderate to severe migraines when NSAIDs are not effective. Patient satisfaction is high with these drugs. Available triptans include:
Comparison studies with sumatriptan are suggesting that the newer agents have fewer side effects and are superior to sumatriptan for providing immediate, sustained, and consistent pain relief. Recurrence rates are also lower. Of these agents, almotriptan is emerging as being both effective and having fewer side effects, particularly chest pain, than other triptans. It may prove to be one of the most cost effective of these agents. Naratriptan also has few side effects and has been referred to as the "gentle" triptan. Ergotamines (ergotamine tartrate)
The ergotamine drugs were first used for acute migraine management in the 1950s. Drugs containing ergotamine (commonly called ergots) constrict smooth muscles, including those in blood vessels, and are useful for migraine. They were the first specific anti-migraine drugs available. Ergotamine is available in the following preparations:
Ergotamine drugs 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. Their role since the introduction of triptans is now less certain. Only the rectal forms of ergotamine are superior to rectal triptans. Simple analgesics
Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first such medication approved for the temporary relief of migraine and its associated symptoms. Studies have reported significant relief in nearly 70% of patients. It may also help menstrual migraines. Advil Migraine and Motrin Migraine Pain, both containing ibuprofen, are also approved to treat migraine headache. These medications are not usually effective for severe migraine. NSAIDs
NSAIDs are first-line drugs tried for mild to moderate migraines. They are not very effective when used alone against severe migraine headache. NSAIDs used for migraine headaches include:
Combination analgesics
Combination analgesics may be used when simple analgesics are not effective and the patient is not a candidate for treatment with 5-HT1 agonists or when the patient needs an alternative drug. Butalbital (Fiorinal), Isometheptene and dichloralphenazone (Midrin) are combination drugs effective for mild to moderately severe migraine headache. Lidocaine
Nasal drops containing lidocaine, a local anesthetic, can provide effective pain relief within 15 minutes for many migraine sufferers. One case report suggests that taking it during the aura phase may offer significant protection against developing the full-blown headache. The drug does not cause drowsiness or heart rhythm disturbances as some other migraine treatments do. And its fast effectiveness and safety make it a promising first drug during a migraine attack. It should not be used for any other form of headache. Opiates
If the pain is very severe and does not respond to other agents, physicians may try pain killers containing opiates (e.g., morphine, codeine, meperidine, or oxycodone). Butorphanol is an opiate in nasal spray form that may be useful as a rescue treatment when others fail. A number of such opiates use combinations of NSAIDs (ibuprofen or aspirin) or acetaminophen with an opioid. One study reported that about half of patients who start opioid therapy for migraine respond well and the benefits persist over time. Medications for nausea and vomiting
Antiemetics (dopamine antagonists) are effective if nausea and vomiting are prominent features and also may act as prokinetics to increase gastric motility and enhance absorption. Droperidol (Inapsine), chlorpromazine (Thorazine), metoclopramide (Reglan), domperidone (Motilium) are used alone or in combination with other analgesics as adjuncts, especially if migraine attack is associated with significant nausea and vomiting. Its role in migraine based on findings that increased dopamine concentration is associated with prominent migraine symptomatology. Some evidence indicates that antiemetics may also relieve the headache of migraine. References
Published: August 14, 2007 |
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