EBHSG - SEPTEMBER 1997 MEETING
TOPIC: "NEW AND EXPERIMENTAL HEADACHE TREATMENTS"
Jerome Goldstein, M.D., was our guest speaker for the September 9th meeting of the East Bay Headache Support Group. The meeting was held in the Ball Auditorium at John Muir Medical Center with 41 people in attendance.
Dr. Goldstein, a neurologist, gave a slide presentation of the work being done at the San Francisco Headache Clinic, where he has been the director since 1978. The San Francisco Headache Clinic is the only clinic in the world that has evaluated every last drug that is used for the treatment of headaches, and was the first center in the United States to study sumatriptan (Imitrex). Dr. Goldstein told us this was the same presentation that he has given to headache foundations around the country and around the world.
Dr. Goldstein said that the brain is a quiet place--not much happens there except when a headache occurs. Headache is the most common presenting symptom.
History of the 5HT 1D Agonists
1972 - Migraine project was initiated by Humphrey and colleagues.
1984 - Synthesis by Glaxo-Wellcome.
1985 - The first trial--Imitrex (sumatriptan) was found to provide pain relief within
20 minutes and to end nausea.
1986 - Patent obtained.
1987 - First scientific report.
1989 - First clinical report published (by the San Francisco Headache Clinic).
1990 - New Drug Application (NDA) submitted its work to the FDA
(Federal Drug Administration).
1992 - FDA approval letter.
1993 - Imitrex injectable went on the market.
To be successful in evaluating new medications requires:
Quality of research
Reproducible results
Number of patients enrolled
24 to 36 patients are typically enrolled at each headache clinical research center.
Brain stem phenomena: migraine process--occurs in trigeminal vascular system deep in the brain stem. DHE (dihydroergotamine) has been around since 1944. Allegedly migraine comes from serotonin.
A perfect 5HT 1D Agonist (a medicine for relieving headaches which imitates the action of serotonin) would have the following characteristics:
1. Easily administered.
2. Total and long-lasting relief of all symptoms.
3. No noticeable side effects.
4. No recurrence of pain or other symptoms.
5. It is preferable that the medication prolong the time until the next migraine.
Six newest 5HT 1D Agonists that are being tested (with comments by Dr. Goldstein):
* Alniditan "Probably the best--No longer being tested (not economically feasible)--
Probably will surface later at different drug company."
* Avitriptan "Well received--Has potential of liver toxicity--No longer being studied--
Probably will surface later at different drug company."
* Naratriptan "Close to being released."
* Rizatriptan "Close to being released."
* Eletriptan "Sort of close to being released."
* Zolmitriptan "Allegedly has the best brain penetration--available now in England."
Each new medication has go through a subjective evaluation, called a Receptor Affinity Profile, which consists of the following:
1. Pharmacokinetics (ways of administering drug):
Oral availability.
How long it takes to get into system.
How long it lasts.
Brain penetration.
2. Therapeutic Benefits. Does the drug provide relief from the following?:
Visual hallucinations, dizziness (aura phase).
Head pain, either steady and on both sides, or lateralized or throbbing.
Associated symptoms: Nausea, vomiting, photophobia, phonophobia.
Receptor Affinity Profile (continued)
3. Headache Recurrence.
4. Side Effects.
5. Safety. Dr. Goldstein said, "We don’t ever want to kill the subject." He went on to say that the San Francisco Headache Clinic has never had a patient suffer a serious complication from the 5HT 1D Agonists studied there.
Dr. Goldstein talked about the medication Stadol NS (nasal spray). It is expensive; it prevents a trip to the emergency room, but the side effects are extremely unpleasant; it can be habituating.
And his comments about sumatriptan (Glaxo-Wellcome sells this drug under the brand name Imitrex) included:
* The first dose of sumatriptan (injectable) must be administered by a physician because the side effects can be very unsettling to the patient.
* Oral sumatriptan is not as good as the injectable form.
Dr. Goldstein said the route of administration is always an issue when discussing medications. Following are ways of administering headache medications:
* Oral: A tablet is the best, but absorption into the bloodstream is significantly impaired, which means it can take 20 to 40 minutes to get relief.
* Subcutaneous injection.
* Rectal: A suppository is one of the fastest routes of administration, which works well and has an efficacy equal to oral administration.
* Intranasal: A nasal spray is a very effective, speedy, and convenient method of administration, however it requires that the patient does not have significant sinus disease or a blocked nasal passage. Dr. Goldstein mentioned that sumatriptan is being released in a nasal spray in the next week.
After concluding his slide show, Dr. Goldstein talked about other drugs that have been developed over the years. In the 1940’s penicillin was considered a miracle drug. Since then researchers have developed even better antibiotics, but germs have also evolved to develop a resistance to some antibiotics.
The bottom line is customer satisfaction. The only difficulty is that there is only one game in town, like the U. S. Post Office. Glaxo-Wellcome is the only drug company developing the 5HT 1D Agonists.
What will the future hold? Dr. Goldstein mentioned research in genetics, 1D agonists, GABA drugs (depakote, neurontin), and nitric oxide.
Excedrin has long been advertised as a headache remedy for tension headaches. Surprise, now it is about to be the first over-the-counter medication recommended and approved by the FDA for the treatment of migraine headache. Excedrin may be just fine for occasional menstrual or vacation migraine, and Dr. Goldstein said it is best for mild to moderate migraine headaches, not the really severe attacks.
There are an estimated 20 to 40 million chronic headache sufferers in the United States, and people between the ages of 30 and 40 have the highest incidence of headache. 32% of all headache sufferers never consult a physician about their headaches. 17% access medical care for headache.
Rationale for OTC treatment:
Headache pain, including migraine headache pain, is:
Symptomatic
Self-recognizable
Acute and self-limiting
Episodic
Dr. Goldstein told us the San Francisco Headache Clinic has an Internet Website, which features a test headache sufferers can take. Their Internet address is: http://www.wwma.com/a1/sfhc/faq.html
Why is Excedrin ES good? Dr. Goldstein said it is a safe medication and it contains caffeine. He made the statement that, "Excedrin has sold as many pills as McDonald’s has sold burgers."
Why did Dr. Goldstein want to end his talk with Excedrin? "You’ll hear a lot about it in the future."
At the end of his presentation, Dr. Goldstein answered questions from the audience:
Q. Can Excedrin cause a rebound effect?
A. Taking 4 Excedrin tablets a week, or daily, would not be good.
Both Dr. Goldstein and Dr. Stein have seen patients taking a large amount of fiorinal with codeine tablets, or demerol; a large number of pills can escalate to mask other things, such as a divorce or depression.
(*Editor’s Note: I’m not certain if this was 20 to 40 tablets per day, week, or month.)
Q. How do you break the rebound effect?
A. One way is the hospital plan--4 days in the hospital, or as an outpatient.
"A part of headache work is an art, not all a science," per Dr. Goldstein.
A female patient of Dr. Goldstein’s was taking 200 Vicodin per month. He brought down the Vicodin use, but her Stadol use then increased. Dr. Goldstein then cut her off Stadol cold turkey and sat her down for a serious talk, and referred her to a psychiatrist.
Dr. Goldstein: "Everyone’s cup of life is full, and a headache patient’s cup of life has things that modify it, like pain."
500 to 1,000 mg of depakote is standard. Depakote is used to prevent headache from occurring, as a prophylactic. One member of the support group said that she’s taking 2,000 mg a day. Neurontin is similar to depakote, but Dr. Goldstein is not terribly impressed with Neurontin.
The GABA system interacts with the serotonin system. How does depakote work? It affects serotonin pathway indirectly.
Zoloft, Prozac and Paxil are not the right drugs for pain management. They are antidepressants. If you are significantly depressed, these may help, but to attack headaches directly with Zoloft is a mistake, according to Dr. Goldstein.
More questions and answers:
Q. As you get older, do headaches just go away?
A. Basically headaches in females start at menarche and go away with menopause, but not in all cases--everyone is different.
Q. What headache medication is best if headaches are daily after a hysterectomy?
A. Dr. Goldstein wouldn’t answer the question. He told her to see her doctor. There are lots of medications to try.
Q. Can inderal cause problems with concentration?
A. It’s possible, but don’t pin too much emphasis on it. Just because you have migraines doesn’t mean you have less intellectual capacity.
Dr. Goldstein mentioned UBO’s, which are specks of light in the brain.
Q. Imitrex--what is the limit? Should she be wary of taking Imitrex daily?
A. 2 to 3 Imitrex tablets per week may be OK for a short period of time, according to Dr. Goldstein.
Q. Is it common for a medication to work at first and then not later?
A. Yes. Migraine is a geometric progression, a curve. Many people can tell when an approaching migraine will be bad, so use the Imitrex then.
Q. Can Imitrex cause strokes?
A. Dr. Goldstein said not to worry about its safety. Most people who have bad reactions to Imitrex have pre-existing conditions, such as obesity, heart disease, etc.
Warning--Don’t combine Imitrex with ergots. Both have vasoconstrictor properties.
Sansert is great for cluster headaches.
Five new triptans will be released in the next year or two. Factors will be side effects and cost.
The notes provided above were taken by an EBHSG volunteer and have not been reviewed by the speaker for accuracy. If you have any questions regarding the notes, please contact the EBHSG.
The intention of the East Bay Headache Support Group is to provide information and resources. It does not provide medical advice, which should be obtained directly from a physician.