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Topiramate May Help Prevent Migraine Headaches, AAN Study
Efficacy results presented from a 26-week, Phase III multi-center, randomized, placebo-controlled study with TOPAMAX demonstrated the average number of migraines per month was at least cut in half for 49 percent of patients treated with 100 mg of TOPAMAX, 47 percent of patients taking the 200 mg dose, and 39 percent of patients taking the 50 mg dose. TOPAMAX was found safe and generally well tolerated with no unexpected adverse events attributed to treatment.
"Too many migraine sufferers who get frequent headaches rely exclusively on acute treatments. This study shows that using topiramate as preventive therapy may help reduce their attacks," said study investigator Jan Lewis Brandes, MD, Director of Nashville Neuroscience Center in Nashville, TN. "While acute treatment can alleviate the symptoms of a migraine attack once it has started, preventive treatment may be able to stop many attacks from even occurring."
In December 2002, Ortho-McNeil Pharmaceutical, Inc. filed a supplemental New Drug Application with the U.S. Food and Drug Administration seeking an indication for the use of TOPAMAX in the prevention of migraine in adults. Data from the presented study were among those included in the submission.
Current treatment guidelines developed by the US Headache Consortium recommend initiating preventive (prophylactic) treatment for migraine headaches when the patient's migraines significantly impact his or her life, when acute therapy is not working or when attacks occur so often, such as more than two times per week, that acute treatments would be overused. An estimated 25 percent of people with migraine headaches meet the frequency criteria for preventative therapy; however, only 5 percent of those who may benefit from preventive treatment are receiving it. Additional information about migraine prevention is available from the National Headache Foundation.
Nearly 32 million Americans suffer from migraine headaches, a condition that is three times more prevalent among women than men. Only approximately half of migraine patients receive diagnosis and, according to a published survey, only 29 percent of those receiving acute treatment report being very satisfied with their medication.
For migraine patients, headaches occur an average of seven days over a three-month period and up to 53 percent experience severe impairment of activity including the need for bed rest during attacks. Migraines can result in significant disability and impairment with nearly half of women and 38 percent of men losing a week or more of work per year due to their attacks.
The primary efficacy measure in this study was the change in mean monthly migraine frequency between baseline and the blinded phase. Secondary efficacy measures included an assessment of the responder rate (the percentage of patients who experienced at least a 50 percent reduction in monthly migraines) and the mean change in the number of monthly migraine days.
At doses of 100 and 200 mg, TOPAMAX demonstrated significant improvements in mean monthly migraine frequency. The mean number of migraines decreased significantly for patients receiving TOPAMAX at 100 mg (49 percent decrease) and for those taking 200 mg/day (48 percent decrease) versus patients taking placebo (19 percent decrease).
In the study, four hundred eighty-three patients were randomized to receive TOPAMAX or placebo at 50, 100 or 200 mg/day. There were no unexpected adverse events related to treatment with TOPAMAX. The most common adverse events were paresthesia (tingling), anorexia (loss of appetite), hypoesthesia (less than normal sensitivity to stimuli such as touch), fatigue and weight decrease. Patient body weight was assessed during the study with weight loss reported with TOPAMAX at 50 mg/day (2.2 percent decrease in body weight), 100 mg/day (3.3 percent decrease) and 200 mg/day (4.6 percent decrease) versus a 0.2 percent increase in patients in the placebo group.
Although the precise mechanism of action of TOPAMAX is unknown, the drug is believed to modulate the activity of various neurotransmitters, receptors, and channels whose dysfunction may be involved in numerous illnesses. TOPAMAX is currently being studied for a number of neurological and metabolic disease states.
Currently, TOPAMAX is indicated in the United States as adjunctive (add-on) therapy for adults and children aged 2-16 with partial-onset seizures, primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome. TOPAMAX is approved around the world as adjunctive treatment for a variety of seizure types, and more than 35 countries also have approved its use as stand-alone (monotherapy) treatment for epilepsy. In the United States, Ortho-McNeil has filed an application for monotherapy use in epilepsy with the Food and Drug Administration.
In clinical trials of adjunctive therapy for these indications, the most common side effects observed in children included excessive drowsiness, loss of appetite, fatigue, nervousness, difficulty with concentration/attention, weight loss, aggressive reaction and memory difficulties. In adults, the most common side effects were sleepiness, dizziness, poor coordination, speech difficulties, slowed thinking (psychomotor slowing), blurred or double vision, memory difficulties and changes in sensation. However, these effects were generally temporary.