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Divalproex Sodium Decreases Headaches by Half: Presented at AAFP

By Mike Fillon

NEW ORLEANS, LA -- October 15, 2003 -- The best prevention for migraine headache is divalproex sodium, it was noted here October 5^th during a seminar at the American Academy of Family Physicians 55^th Annual Scientific Assembly.

Randall L. Oliver, MD, president, Indiana Pain Academy, Evansville, United States, discussed the current thoughts about the treatment of migraines in his seminar.

"[Divalproex sodium] works in 50% of patients to decrease headaches by half in both frequency and intensity," Dr. Oliver said. "We now know the pathway of migraine involves more than one artery. The trigeminal or neurovascular model is widely accepted."

The neurovascular process is initiated by serotonin, a pain modulator, Dr. Oliver said. A drop in serotonin causes hypersensitivity or allodynia affecting the entire body. "It is well known that migraineurs tend to experience hypersensitivity to stimuli, such as lights, smells and weather, which can initiate the migraine process," he noted.

Migraine involves specific serotonin receptors, mostly the 5HT1B and 5HT1D receptors, according to Dr. Oliver. The 5HT1B receptors are located on the extracerebral arteries, while the 5HT1D receptors are located on the trigeminal nerve endings.

Activation of the 5HT1B receptors causes vasoconstriction of the extracerebral arteries, while activation of the 5HT1D receptors causes activation of the of the intracranial trigeminal nerve and blocks the subsequent release of neurokinins.

"We therefore think that the migraine process starts with a cerebral decrease in serotonin," said Dr. Oliver. "This releases the 5HT1B vasoconstriction, therefore causing vasodilation of the extracerebral artery, usually the middle meningeal artery. As a result of the vasodilation, the artery leaks neurokinins."

He said these neurokinins activate the intracranial trigeminal nerve, causing further leakage nucleus of neurokinins from this site. The result is a sterile inflammatory process that reflexes back to the trigeminal nucleus caudalis in the brain stem. From the trigeminal nucleus caudalis, the process reaches the cortex of the brain. The cortex then "tells" the migraineurs that pain is felt along the extracranial trigeminal nerve.

Dr. Oliver said preventative treatment of migraine should be based on total disability time, the total number of headaches, headache frequency, side effect of the medications and cost of the medication. He said there are two frequently used approaches to preventative treatment. One is behavioral management.

There are a number of known triggers leading to migraine attacks such as lack of sleep, too much sleep alcohol, stress or certain foods. The second approach is preventative medication. Dr. Oliver said there are only two medications approved by the U.S. Food and Drug Administration for migraine prevention. The first is propanolol, a beta blocker. The second is divalproex sodium, an anti-epileptic drug. "The best prevention we have is divalproex sodium," he noted.

Dr. Oliver said the process of selecting preventative medication is basically trial and error. "The best approach is to start at a low dose and increase it slowly," said Dr. Oliver. "If there is no response to the medication, discontinue it and try another."


[Study title: "Treatment of Migraines and Pain". Abstract 584]

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