Comparison of a Drug and Placebo in the Prevention of Migraine Headaches

This is an interventional prevention trial for Headache, Migraine focused on measuring headache, migraine, depression, disability evaluation, weight gain Read More

Inclusion Criteria:

• Must be a veteran.
• The number of migraine days per 4-week period is to be 4-14 for a period of 3 months prior to screening for entry into the trial.
• Migraine must have been occurring for 6 months preceding entry into the trial and age of onset should be before age 60 years.
• Migraine must be at least moderate severity and interrupt daily activities in some respect at least 3 times per month.
• As long as the veteran can easily distinguish nonmigraine headaches from migraine, there is no limit on the number of non migraine headache days allowed. "Transformed migraine" headaches due to medication over usage will be excluded according to exclusion criteria #4.
• Migraine diagnosis:

Veterans with headache must have migraine categorized using the International Headache Society (I.H.S.) criteria as illustrated below for the two main types with and without aura.

Criteria for migraine without aura (I.H.S. 1.1)

• > 5 attacks
• headache lasting 4-72 hours when untreated or not successfully treated.

• headache with two of the following characteristics

  • unilateral,
  • pulsating,
  • moderate to severe intensity,
  • aggravation by exertion.

• one of the following occurs with headache

  • nausea and/or vomiting
  • photophobia and phonophobia

Criteria for migraine with aura (I.H.S. 1.2)

• at least 2 attacks

• at least three of the following characteristics:

  • One or more fully reversible aura symptoms indicating focal cerebral cortical - and/or brain stem dysfunction.

One or more aura symptoms of the following types:

• Homonymous visual disturbance
• Unilateral parenthesis and/or numbness
• Unilateral weakness

• Aphasia or unclassifiable speech difficulty

  • At least one aura symptom develops gradually over more than 4 minutes or, 2 or more symptoms occur in succession.
  • No aura symptom lasts more than 60 minutes. If more than one aura symptom is present, accepted duration is proportionally increased.
  • Headache follows aura with a free interval of less than 60 minutes. (It may also begin before or simultaneously with the aura). Headache, nausea and/or photophobia usually follow neurological aura symptoms directly or after a free interval of less than an hour. The headache usually lasts 4-72 hours, but may be completely absent (1.2.5, acephalgic migraine).

Exclusion Criteria:

• Veterans with migraine plus other systemic disorder will be excluded if migraine onset was temporally related to onset of the systemic disorder.
• Blood pressure elevations (must be < borderline values 135/85 for 4 weeks before enrollment into the study). Current treatment for hypertension with beta-blockers, calcium channel blockers, or ace inhibitors not allowed.
• Use of other prophylactic migraine drugs (requires a washout phase) and cannot have failed more than two other prophylactic drugs for migraine.
• Excessive use of acute pain medicines, including narcotics (>10 days month). Those using non-narcotics could be tapered off over 4-8 weeks.
• Receiving disability or seeking disability for headache or chronic pain.
• Significant neck pain or cervicogenic contributors to chronic headache.
• Significant depression, anxiety, post-traumatic stress disorder, or other disabling psychiatric condition.
• Known allergies or serious side effects with ESX or succinimides in the past.
• Known liver or significant renal disease.
• Women veterans of child-bearing age who do not have adequate birth control.
• Chronic bone marrow suppression.
• Using psychogenic or other sedating maintenance drugs.
• History of porphyria.
• History of cluster headache. 15.History of other CNS disease.
• Age younger than 18 years and greater than 65.
• Women veterans who are breastfeeding.
• Veterans with familial hemiplegic migraine (FHM).

Ongoing exclusions during the study:

• The addition of other migraine prophylactic headache medicines is not allowed. 2. New drugs cannot be added that aggravate headache (nitrates, dipyridamole, niacin).