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MIGRAINE HEADACHES: PHARMACOLOGIC AND NONPHARMACOLOGIC OPTIONS

Migraine headaches affect 2 million Americans annually and account for over $30 billion in lost productivity. In recent years, increasing awareness and research in the area of migraine has led to more frequent diagnoses of this condition. Recent research clearly shows that migraine is a chronic neurologic disorder with a strong genetic tendency. No cure is available for migraine, but this chronic condition can be very successfully managed with pharmacologic and nonpharmacologic treatment modalities. Migraine can be triggered by various stimuli, both environmental (eg, certain foods, light, odors) and internal (eg, stress, anxiety). Therefore, a holistic or multidisciplinary approach that treats the whole person, not just the headache, is more likely to be successful in the long term.

PHARMACOLOGIC TREATMENT

Pharmacologic treatment for migraine headache is broadly divided into short-term and prophylactic treatment.

Short-term migraine treatment

For the best chance of relieving migraine headache, medications should be taken within 15-30 minutes of the onset of headache and when the headache is mild.

Patients who have mild symptoms and disability can be treated adequately with acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), propoxyphene, or a combination of these. Patients with moderate disability may need migraine-specific oral medications, which fall into 2 categories: serotonin receptor (5-HT1) agonists (ie, triptans) and ergot alkaloids. Seven different medications in the triptans category are currently available on the US market. These include sumatriptan (Imitrex tablets, injection, or nasal spray), rizatriptan (Maxalt, Maxalt-MLT), zolmitriptan (Zomig tablets or nasal spray, Zomig-ZMT), naratriptan (Amerge), almotriptan (Axert), eletriptan (Relpax), and frovatriptan (Frova). Additionally, some triptans (ie, eletriptan, rizatriptan, zolmitriptan) are more selective for the specific serotonin receptor 5-HT1D. This increased affinity for 5-HT1D may result in decreased toxicity (eg, cardiovascular symptoms). The ergot alkaloids include ergotamine (eg, Er! gomar) and dihydroergotamine (eg, Migranal nasal spray, DHE 45 injection).

Various medication administration routes are available to tailor treatment to a patient’s migraine symptoms and severity. Drugs that treat migraines are available as subcutaneous, intravenous, sublingual, nasal, rectal, or oral preparations (conventional tablets or capsules or oral disintegrating tablets). Preparations that can bypass oral absorption are likely to be more effective for patients who experience nausea and vomiting. Additionally, oral disintegrating tablets or intranasal sprays are convenient to take and do not require water to swallow the dose.

Dihydroergotamine has poor bioavailability following oral administration. The bioavailability of intranasal administration is greater than that of oral administration but less than that of subcutaneous or intramuscular administration. The extent of sublingual ergotamine bioavailability is undefined and quite erratic.

Most triptans also have low oral bioavailability. (The exceptions include almotriptan [70-80% bioavailability] and naratriptan [60-70% bioavailability].) For example, sumatriptan demonstrates about 15% bioavailability when administered orally. When administered intranasally, bioavailability increases to about 25%. Subcutaneous administration has 97% bioavailability. The onset of action among various sumatriptan administration routes varies based on their bioavailability, as follows: 1-2 hours for oral administration, 1 hour for intranasal administration, and 10-60 minutes for subcutaneous administration. When administered orally, the other triptans have onsets of action that are similar to that of sumatriptan, with the exception of rizatriptan, which shows a faster onset of action (30 min), and frovatriptan, which has a slower onset of action (about 2 h).

Precise dose and the need to retreat within 24 hours because of rebound migraine should also be considered when a triptan is selected. About 40% of all migraine headaches do not respond to a given triptan or to any other substance. Patients experiencing this type of headache may need to be briefly hospitalized. These patients may be dehydrated, either in addition to their headache or as a consequence of it. Attention should be given to achieving adequate hydration status. Patients with severe nausea and vomiting at the onset of a migraine may respond best to intravenous prochlorperazine. If other treatments are ineffective, intravenous corticosteroids can also be used.

Prophylactic migraine treatment

For some patients who have frequent migraines, a neurologist can prescribe daily preventive therapy for a certain duration, such as a few months, to break the headache cycle in addition to prescribing short-term abortive treatment, as described above. Most patients who receive prophylactic treatment require continuation of therapy for at least 3-6 months.

Three classes of medications are effective for migraine prevention.

1. Antiepileptic agents

• Topiramate (Topamax) is indicated for migraine prophylaxis and is tolerated well. The principal adverse effects include weight loss and dysesthesia.



• Valproic acid (Depakote) is approved by the US Food and Drug Administration (FDA) as a migraine prevention agent and is a useful first-line agent. The medication is also a good mood stabilizer and can benefit patients who have concomitant mood swings.



• Only limited data are available on the efficacy of other antiepileptics (eg, gabapentin, lamotrigine, oxcarbazepine) in treating migraine headache.

2. Antidepressants

• Tricyclic antidepressants or beta-blockers are good second-line treatment alternatives based on their adverse-effect profiles and efficacy data. Currently available data indicate that amitriptyline and nortriptyline are the most efficacious agents in this category.



• Selective serotonin reuptake inhibitors (SSRIs) are widely used, but only limited data are available regarding their efficacy for migraine prevention.

3. Antihypertensives

• 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.



• Calcium channel blockers are the third line of treatment for migraine prophylaxis.



• Angiotensin-converting enzyme (ACE) inhibitors such as lisinopril (Prinivil, Zestril) and angiotensin receptor blockers such as candesartan (Atacand) have recently been shown to be efficacious for migraine prevention.

NONPHARMACOLOGIC TREATMENT

Americans spend over $13.7 billion per year on complementary medicine, and more than 70% of patients do not tell their doctors about such treatment. Patients experiencing headaches are increasingly interested in complementary and alternative medicine (CAM). A recent survey showed that more than 85% of patients who have headaches use CAM therapies, and 60% felt it provided some relief from headache symptoms.

Some CAM techniques are backed by good scientific evidence and have been proven by studies to be efficacious in preventing migraine. Biofeedback and behavioral therapy should be part of the standard of care for a patient whose migraine headaches are difficult to treat. Recently, some good studies have demonstrated the efficacy of the herb butterbur (Petasites hybridus) in preventing migraines. Another herb, feverfew, is also widely used; some studies have shown that it is safe and may be efficacious for migraine prevention.

Various other CAM techniques may be perceived to benefit patients with headache, although these techniques are not rigorously supported by scientific data.

Techniques that are commonly practiced for headache symptom relief include the following:

• Body work (eg, chiropractic treatment, massage)
• Creative arts (eg, dance, music)
• Nutritional or herbal treatments (eg, vitamins, herbs)
• Eastern medicine practices (eg, yoga, acupressure, acupuncture, Ayurveda)

REFERENCES

Foley KA, Cady R, Martin V, et al. Treating early versus treating mild: timing of migraine prescription medications among patients with diagnosed migraine. Headache. 2005;45:538-45.

Linde K, Vickers A, Hondras M, et al. Systematic reviews of complementary therapies - an annotated bibliography. Part I: acupuncture. BMC Complement Altern Med. 2001;1:3.

Lipton RB, Gobel H, Einhaupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63(12):2240-4.

Rapoport AM, Tepper SJ, Bigal ME, Sheftell FD. The triptan formulations: how to match patients and products. CNS Drugs. 2003;17:431-47.

Sahai-Srivastava S, Cowan R, Ko DY. Pathophysiology and Treatment of Migraine and Related Headache. eMedicine Journal [serial online]. 2006. Available at: http://www.emedicine.com/neuro/topic517.htm. Accessed October 20, 2006.

Silberstein SD. Migraine. Lancet. 2004;363:381-91.

von Peter SV, Ting W, Scrivani S, et al. Survey on the use of complementary and alternative medicine among patients with headache syndromes. Cephalalgia. 2002;22:395-400.