Another medication can now be added to the growing list of medications shown to be effective for prevention of headaches and Migraine attacks. Namenda (memantine HCL, Forest Pharmaceuticals) was approved for use in the United States in October, 2003, more than a decade after its use began in Europe under the brand names Ebixa and Axura. It's classified as an orally active NMDA receptor antagonist. Namenda (memantine hydrochloride) is approved for the treatment of "moderate to severe dementia of the Alzheimer's type."

Medications can also be utilized for off-label purposes when they're noticed to help other conditions. The vast majority of medications prescribed for headache and Migraine prevention are actually prescribed off-label.

John Claude Krusz, Ph.D., M.D., and Diane Cammarata, APRN, BC, conducted an open label trial of the use of Namenda in the treatment of chronic Migraine disease and tension-type headache (TTH) in Dr. Krusz's Dallas practice. The results have been quite promising.

Study Rationale/Objectives:
"We wanted to explore the efficacy of blockade of NMDA receptors in the treatment of Migraines and chronic tension-type headaches using a low-affinity antagonist, memantine. If one considers that there might be a commonality or overlap of signal barrage to the spinal cord or brainstem in chronic pain and chronic headache states, the glutamate system might be a point of amplification or reinforcement of the pain transmission cascade in these clinical conditions. In particular, memantine blocks excessive NMDA receptor activity without disrupting normal activity. Memantine does this through its action as an uncompetitive, low-affinity, open channel blocker; it enters the receptor-associated ion channel preferentially when it is excessively open, and, most importantly, its off-rate is relatively fast so that it does not substantially accumulate in the channel to interfere with normal synaptic transmission1-4. Numerous studies, both in animal models and in human clinical pain states, have demonstrated the ability of memantine to alter pain behaviors or parameters5-7; some studies failed to demonstrate clinical efficacy. No prior data exists in treating Migraine or TTH. The primary objective in this open-label study was to treat a cohort of refractory clinic patients from our clinic with memantine to see if the Migraine and headache patterns would change over time. The primary objective was to look for a reduction in the frequency of Migraines per month. The secondary objective consisted of reduction in tension-type headache frequency and severity."

Krusz and Cammarata studied the efficacy of memantine, a new moderate affinity NMDA receptor antagonist in the treatment of chronic Migraines and tension-type headaches (TTH). The primary endpoint of this open label study was reduction of frequency and severity of Migraines. Secondary endpoints included reduction of TTH and pain related to the head and neck in our study patients.

Twenty patients with chronic Migraines who had not responded to other prophylaxis measures were studied. They had an average of 9.2 Migraines per month. Fourteen of 20 (60%) had TTH as well (average of 12.5 days per month). Memantine was added at 5mg per day with weekly increases of 5 mg, up to a maximum of 20 mg per day, as tolerated. Patients kept headache diaries for Migraines and TTH as well as pain scores. Evaluations were made after one month of therapy on 20 mg (or maximally tolerated dose) of memantine.

The average length of treatment, including the initial titration of memantine dosage, was 4.6 months, with an average daily dosage of 19.25mg (range= 10-20mg/day). Migraine frequency fell to an average of 4.1 Migraines per month, or almost 56% less than at baseline, in 14 of 20 patients. Remaining Migraines were rated as less severe and easier to treat. Acute Migraine and rescue medication use dropped by two-thirds. TTH frequency fell by 62%, to 6 headaches per month. 6 patients saw no response of their Migraines to memantine. 4 patients reported dizziness and one nausea. 2 of these patients had betterment of their Migraines. Acute migraine and rescue medication use dropped by two-thirds.

Krusz and Cammarata conclude from this preliminary open-label study that memantine has the ability to offer successful prevention of chronic Migraines and TTH in situations where other regimens have not benefited the patient. It speaks to the potential role of NMDA glutamate receptors in the maintenance of Migraine and headache states. Memantine should be studied in Migraine therapy in a double-blind manner.

To view a copy of the poster presentation of this study presented to the 11th World Congress on Pain, please click HERE.

Resources:

Krusz, John Claude, Ph.D., M.D.; Cammarata, Diane, APRN, BC. "Memantine for Chronic Migraine Prophylaxis." Poster presentation to the annual conference of the American Headache Society, Philadelphia, June, 2005; and to the European Federation of Neurological Societies conference, Athens, Greece, September, 2005.