Over the last several years, neuronal stabilizing agents (aka anticonvulsants, epilepsy medications) have been increasingly prescribed for Migraine prevention. Out of the four medications that are actually FDA approved for Migraine prevention, two of them -- Depakote and Topamax -- are neuronal stabilizing agents. It has been thought that these medications are effective for Migraine prevention because they calm overactive neurons in the brains of Migraineurs.

Trileptal (oxcarbazepine) is one medication in this family that has been prescribed off-label for Migraine prevention. A new study has now shown that Trileptal apparently does not work well as a Migraine preventive. The results of this research are published in the February 12, 2008, issue of Neurology®, the medical journal of the American Academy of Neurology.

The study

Study objective: "To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs. placebo as prophylactic therapy for patients with migraine headaches."

Study methods:

• Participants were recruited from 23 headache and Migraine treatment centers in the United States.
• The 170 study participants were randomly assigned to two groups of 85. One group received oxcarbazepine; the other received placebo.
• Study participants were patients experiencing three to nine Migraine attacks per month.
• This study was conducted over a period of nearly five months.

Study results:

• There was no difference between the oxcarbazepine and placebo groups in change in number of migraine attacks from baseline during the last 28 days of double-blind (Neither the researchers nor the participants knew who was receiving oxcarbazepine and who was receiving placebo.) phase.
• Adverse events (side effects) were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity.
• The most common side effects (15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%).
• No side effect occurred in more than 15% of the placebo-treated patients.

Study conclusions: "Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches."

“The results of this trial do not support preliminary data which had suggested oxcarbazepine was effective in preventing migraine... While several epilepsy drugs have been used for decades to prevent migraine, oxcarbazepine did not prevent migraine in this study despite it being shown to be safe and well-tolerated.”

~study author Stephen D. Silberstein, MD
Director, Jefferson Headache Center, Thomas Jefferson University, Philadelphia
Fellow of the American Academy of Neurology

According to Silberstein, the three neuronal stabilizing agents that most effectively prevent Migraine are topiramate (Topamax), divalproex (Depakote), and gabapentin (Neurontin). These three medications impact Migaine through several mechanisms, including the ability to regulate a neurotransmitter known as GABA. Oxcarbazepine, however, has no apparent activity on GABA. Silberstein says it’s possible that these drugs must be able to regulate this neurotransmitter in order to prevent Migraine.

In addition, Silberstein says several factors may have contributed to the lack of response in this study, including that the participants had difficult-to-treat Migraines.

The study was supported by Novartis Pharmaceuticals Corporation, the manufacturer of oxcarbazepine.

Summary and comments

Although good results have been seen with several neuronal stabilzing agents including Topamax, Depakote, Neurontin, Zonegran, and others, this study shows that Trileptal is not helpful for Migraine prevention. It's worth noting that this study was funded by the manufacturer of Trileptal, Novartis.

We more often see studies that show positive results. However, as Dr. Silberstein commented, "It is just as important to print negative as well as positive trials."

At this time, there is no medication on the market that was developed for Migraine prevention. What we have is "hand-me-down" medications originally developed for other conditions. One reason for this is lack of NIH funding for basic Migraine and headache research. Hopefully, this will change, and we will start to see more effective preventive treatments.

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Resources:

Silberstein, S., MD; Saper, J., MD; Berenson, F., MD; Somogyi, M., MD; McCague, K., MA; D'Souza, J., PhD. "Oxycarbazepine in migraine headache." Neurology 2008;70:548-555.

Personal Interview. Dr. Stephen D. Silberstein, Teri Robert. February 11, 2008.

Press Release. "Drug Doesn’t Help Prevent Migraine After All." American Academy of Neurology. St. Paul. February 11, 2008.

© Teri Robert, 2008.

Last updated February 11, 2008.