Seymour Diamond, M.D., Executive Chairman,
National Headache Foundation

Propranolol (Inderal®); Timolol (Blocadren®); and, Divalproex Sodium (Depakote®). Headache specialists have been using many agents that have not as yet received approval for this indication, including the Calcium Channel Blockers and the AntiDepressants.

Sumatriptan (Imitrex®) Nasal Spray (Glaxo Wellcome)
For many years we have known that Serotonin was involved in the development of Migraine.

In 1985, the Serotonin receptors of the Brain and its surrounding tissues were identified. With this discovery, a brand new window of migraine research was opened, and with this breakthrough came approval from the Food and Drug Administration (FDA).

The first of these Serotonin (5-HT) Agonists, Sumatriptan (Imitrex®), was approved in 1993. It was previously available in preparations for oral and injectable administration. The FDA has recently granted approval for a nasal spray form of Sumatriptan.

With the 20mg dose, I have found that many patients obtain relief within 15 minutes after administration. Because nausea and vomiting are characteristic of many Migraine attacks, the nasal spray provides a treatment option in which the drug is directly absorbed through the mucous membrane of the nose - thus bypassing the Stomach.

The most common side effect, sour taste, usually lasts for about 15 minutes following use of the nasal spray. In my experience, most people tolerate the nasal spray because of the rapid relief of the headache. The nasal spray form of Sumatriptan may be preferred over the injectable preparation by those people who fear or object to self-injection.

The nasal spray also may be preferred over the oral tablets of sumatriptan by people who experience associated nausea and vomiting with their Migraine attacks.

Dihydroergotamine Mesylate (Migranal®) Nasal Spray (Novartis)
Dihydroergotamine Mesylate (DHE) has been used for decades in Migraine abortive therapy. In 1997, the FDA approved a new, nasal spray preparation - Migranal®, for the abortive treatment of Migraine headaches with or without Aura.

In clinical trials, DHE nasal spray has proven effective in providing relief of Migraine pain in up to 70% of patients, within 4 hours after a single 2mg dose. This single dose of DHE nasal spray was also shown to be effective in most patients for 24 hours after administration.

The nasal spray preparation bypasses the GastroIntestinal Tract - therefore it does not aggravate the associated symptoms of Nausea and Vomiting. In one clinical trial, DHE nasal spray demonstrated headache relief within 30 minutes after administration.

This preparation is generally well-tolerated with most side effects being mild and transient. DHE nasal spray is non-narcotic, not-habituating and non-sedating.

Zolmitriptan Tablets (Zomig®) (Zeneca)
The FDA recently granted approval for the oral preparation of Zolmitriptan (Zomig®), in 2.5mg and 5.0mg doses.

Zolmitriptan is a 5-HT1 Agonist similar to Sumatriptan. Studies have demonstrated rapid oral absorption of this agent, which may be beneficial for some people. It comes in 2.5mg and 5.0mg doses, the latter is the preferred dose at our clinic.

In clinical trials, over 4,759 patients have used a total of 34,296 doses of Zolmitriptan with extensive safety and tolerability. The results from long-term safety trials showed that Zolmitriptan effectively relieved pain within two hours in 81% of 2,058 patients who treated 24,161 moderate or severe Migraine attacks.

The incidence of adverse events is similar to those described for other Triptans, including Sumatriptan or Naratriptan and is not affected by gender, weight, age, selected Migraine prophylactic agents, or the presence of Aura.

For the 2.5mg dose, the most frequently reported adverse events include Nausea, Dizziness, Prickling or Tingling of the Skin, Tightness of Neck/Throat/Jaw pain/tightness/pressure, Drowsiness & Warm or Cold Sensations.

Naratriptan (Amerge®) (Glaxo Wellcome Inc.)
Naratriptan (Amerge®) received FDA approval in February 1998 for 1.0mg and 2.5mg oral tablets. This agent has demonstrated efficacy as early as one hour after administration. Naratriptan is long-acting, has a low rate of recurrence and few side effects.

The half-life of Naratriptan is 6 hours, which means that after 6 hours, this drug begins to lose its highest concentration in the circulation. Its half-life is longer than that of other Triptans, and may be a factor in lower recurrence rates.

Combined safety and tolerability of Naratriptan measures from all controlled studies, including Electrocardiograms (EKGs), laboratory tests, vital signs, and patient-reported symptoms, were similar among 1mg, 2.5mg and placebo doses, and showed no increase among patients taking a second dose of Naratriptan.

Acetaminophen, Aspirin and Caffeine (Excedrin Migraine®) (Bristol-Myers Products)

The FDA, in January 1998, granted approval for the first time to an over-the-counter analgesic for the relief of mild to moderate Migraine headache pain. Because of labeling differences, the FDA required packaging separate from that of Extra Strength Exedrin.

This drug is a combination of Acetaminophen, Aspirin, and Caffeine (AAC) (Excedrin Migraine®). The decision of the FDA was based on compelling clinical data from three double-blind, randomized, placebo-controlled trials of 1,250 Migraine sufferers.

These studies found that AAC was significantly effective in relieving the acute pain of Migraine attacks. The patients involved in these studies suffered headaches that typically lasted 24 hours if left untreated. AAC demonstrated rapid relief in some patients as early as 30 minutes after treatment.

Within 2 hours, almost two-thirds (59%) of patients with moderate to severe pain reported mild or no pain after treatment with AAC. At 6 hours after treatment, the results were even more dramatic, with 79% of AAC-treated patients reporting little or no pain.