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7 Articles in Volume 1, Issue #1
Breaking Down the Barriers of Pain: Part 1
Bringing Pain to the Forefront of Treatment
Microcurrent Electrical Therapy Mechanisms and Results
Relieving Pain with Pharmaceuticals
The Pain Relationship
The Perfect Treatment and Evaluation Tool
TMJ Repositioning

Relieving Pain with Pharmaceuticals

New pharmaceuticals are available to treat patients with migraines and other pain syndromes.

For years, the treatment of migraine headaches has presented clinicians with a difficult conundrum. An estimated 25 to 30 million Americans are afflicted with these painful, vascular, often unilateral headaches, and almost half that number go undiagnosed. In addition, many migraine sufferers feel that others don’t understand the severity of pain they experience with their headaches.

Seymour Diamond, chairman of the National Headache Foundation, notes that while there currently is no effective cure for migraine, getting an accurate diagnosis goes a long way toward effectively treating the symptoms, which includes vomiting, photophobia and sensitivity to sound and smell. Other less common symptoms include lightheadedness, scalp tenderness and diarrhea. Clinicians should encourage their patients to track the incidence of symptoms and patterns surrounding their migraines and any triggers they’ve noted. This aids the health care professional in selecting an appropriate treatment method.

In the past decade, the prevalence of migraine has increased almost 60 percent due to more accurate diagnostic methods, which—according to the National Headache Foundation—is the key to successful treatment and an increase in the number of people reporting their symptoms. Yet many migraine sufferers still go undiagnosed.

During the National Headache Foundation’s National Headache Awareness Week, the association presented its IMPACT acronym to identify approaches for the management of migraines:

  •  Identify symptoms.
  • Maintain a migraine diary.
  • Partner with a health care professional.
  • Avoid triggers, like certain foods and beverages.
  • Call the National Headache Foundation for more information and support.
  • Treat migraines effectively.

The preventive medications—best for frequent migraine sufferers—include beta-blockers, calcium channel blockers and antidepressants. Methysergide is an older medication and not recommended as a first-line treatment. Divalproex sodium, which goes by the trade name Depakote in the U.S. or Epival in Canada, was originally used for the treatment of epilepsy, a disease related to migraine. In smaller doses, divalproex sodium has proven to be effective as a prophylaxis for migraines, but not for treatment in the acute phase. It’s often used only after other preventive agents have been tried without success.

Trigger management simply means identifying and eliminating–when possible–any triggers that bring on a migraine episode. Lifestyle factors and caffeine, contrary to what many believe, are not considered to be true triggers of migraine.

The third category—attack-aborting drugs—should be taken as early as possible at the onset of migraine and include cerebral vasoconstrictive and non-vasoconstrictive abortive agents.

The last category comprises agents used for general pain management, including narcotic and non-narcotic analgesics, NSAIDs (non-steroidal anti-inflammatory drugs) and simple analgesics often available over the counter.

Researchers continue the quest for compounds that will provide migraine sufferers with more effective relief and fewer side effects. The following describes some recently approved medications, products awaiting approval and compounds still in various research phases.

Recently Approved Drugs

Amerge (naratriptan), provided in 1 mg and 2.5 mg tablets from Glaxo Wellcome, received FDA approval in February of 1998. Indicated for the acute treatment of migraine, Amerge is not to be used prophylactically, but rather at the onset of headache. Patients should start with the smallest possible dose but may repeat it after four hours if their symptoms are not resolved.

Similar to Glaxo Wellcome’s other migraine medication, Imitrex (sumatriptan), Amerge is a selective serotonin receptor agonist. However, preliminary results indicate that Amerge may have a longer duration of action than Imitrex; in fact, it appears to be the longest-acting triptan currently available. A higher bioavailability and longer half-life result in a lower rate of headache recurrence and make it well suited for patients who generally need additional medication after using other serotonin agonists.

In randomized clinical trials with naratriptan, more than 60 percent of patients reported relief from their migraine within four hours of dosing, and in a large percentage of these patients, relief lasted up to 24 hours.

Amerge is contraindicated for patients with uncontrolled hypertension or ischemic heart disease. It also should not be taken within 24 hours of other 5-HT1 agonists or ergot-type medications, nor should it be administered with an MAO inhibitor or within two weeks of discontinuing one.

Another recent addition to Glaxo Wellcome’s product line is Imitrex Nasal Spray. FDA approval in late 1997 brought this third form of sumatripta—already available in subcutaneous injection and tablet—to the market. For patients who can’t tolerate injections, the spray offers rapid relief from migraine.

Studies indicate that a small number of those treated experienced diminished pain within 15 minutes, while the majority of subjects noted relief within two hours after administration. As with Amerge, Imitrex is indicated only for acute treatment of migraine.

A recent study using nasal sumatriptan at doses of 5 mg or 20 mg in even younger children between the ages of five and 12 also showed promising results. Five of the nine subjects treated had 100 percent response in five different trials, while two subjects responded 50 percent of the time.

One of the newer serotonin agonists, Maxalt (rizatriptan)—approved in 1998 and marketed by Merck & Co.—appears to have an earlier onset of action than sumatriptan, along with a higher oral bioavailability. Onset of relief appears as early as 30 minutes after a 10 mg dose, and trials have shown that up to 71 percent experienced diminished symptoms within two hours. Another formulation, Maxalt-MLT Orally Disintegrating Tablets, dissolves on contact with the tongue and may prove a distinct advantage to patients experiencing nausea with migraine.

New information presented in 1999 at the Ninth International Headache Society in Barcelona, Spain showed that Maxalt, as well as other triptans, is also effective for treating migraines specifically associated with the menstrual cycle. While a 5 mg dose alleviated pain, the 10 mg dose brought complete pain relief to a higher percentage of subjects.

Zomig (zolmitriptan)—another 5-HT receptor agonist— was approved in late 1997 in the U.S. as well as the United Kingdom and Sweden for the treatment of acute migraine. In mid-1999, AstraZeneca’s fast-dissolving formulation, Zomig Rapimelt, was approved for use in Sweden.

Another nasal spray formulation for migraines, Migranal (dihydroergotamine mesylate) from Novartis pharmaceuticals secured FDA approval in December 1997 with an indication for acute treatment. As with the triptans, this ergot-type drug should not be taken within 24 hours of other ergot compounds or 5-HT1 agonists.

Ergot compounds are vasoconstrictors and counteract cranial vasculature dilation. Gastrointestinal side effects, as well as the likelihood of rebound headache, generally limit their use, although this nasal formulation may diminish the incidence of nausea.

Awaiting Approval

In early 1999, the FDA accepted a New Drug Application (NDA) for frovatriptan, which will be marketed under the trade name Miguard; Marketing Authorization was also applied for in Europe. Developed by the Vanguard Medica Group in London and marketed by Elan Corporation of Ireland, Miguard is seeking an indication for acute migraines.

One distinguishing feature of this new triptan is a lower incidence of headache return after dosing, with only 10 to 18 percent of clinical subjects reporting recurrence compared to a rate of approximately 40 percent with sumatriptan. Frovatriptan also appears to have the longest half-life of any other drug in this class, and in pre-clinical studies, no effect on cardiac function was demonstrated.

While the company received an approvable letter in May 2000, the FDA’s request for additional trials in mice is expected to delay frovatriptan’s launch in the US until at least early 2001; European approval is expected sometime this year.

Pfizer’s Relpax (eletriptan) received an approvable letter from the FDA in the fall of 1999 with an indication for treatment of acute migraine. A serotonin agonist, eletriptan has shown a significantly higher affinity for 5-HT receptors when compared to sumatriptan. Pain relief was noted as quickly as one hour after administration with 20 mg, 40 mg and 80 mg doses, although most patients preferred the 80 mg dose.

In a meta-analysis of three separate trials, 65 percent of patients taking 80 mg of eletriptan were able to resume some normal activities after two hours, compared to only 51 percent of those taking sumatriptan, with side-effect profiles similar to other triptans. Relpax is currently in Phase III trials in Europe.

Other drugs awaiting approval for indication of migraine include Abbott Laboratories’ Depakote ER (divalproex sodium). Depakote is a sustained-release formulation of valproate sodium, which was approved in 1996 for the treatment of migraine and complex partial seizures (CPS), a common form of epilepsy. In Europe, Novartis Pharmaceuticals’ Cataflam (diclofenac potassium), a non-steroidal anti-inflammatory that also goes by the name Voltaren and Sanofi-Synthelabo’s Migpriv (lysine acetylsalicylate and metoclopramide) are seeking indications for migraine. Nippon Glaxo’s drug SN-308 (sumatriptan), which was developed in three different formulations–tablet, injection and nasal spray, is currently being reviewed in Japan.

Almotriptan, a new serotonin antagonist currently under study, not only shows promise for treating acute migraine but also offers a much better safety profile than sumatriptan. Almirall Prodesfarma in Barcelona, Spain, developed the compound, which is currently in Phase III trials. In Phase II trials, Glaxo Wellcome is researching GV196771, a glycine antagonist, for migraine prophylaxis, while Eli Lilly is studying a compound identified as ly334370.

One distinguishing feature of this new triptan [Miguard] is a lower incidence of headache return after dosing...

Positive results for Topamax (topiramate) in the prophylactic treatment of migraine were presented at the American Headache Society’s Annual Meeting in June 2000. Ortho-McNeil’s Topamax is currently indicated for epileptic seizures, and many antiepileptic medications play an ever-increasing role in the treatment of migraine as well.

In late 1999, the FDA granted an expanded indication to Excedrin Migraine to include the full migraine syndrome. However, MAGNUM cautions that most over-the-counter medications don’t have the strength to handle migraine pain and notes that Excedrin Migraine uses the exact same formula as Extra Strength Excedrin, a combination of aspirin, acetaminophen, and caffeine.

Last updated on: December 27, 2011
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