For Willow: August 2006 prophylactic list (migraine info)

Willow:

This is a list that is regularly posted on
alt.support.headaches.migraine. You may want to pass the info on to
your migraine-afflicted WW member.

I was able to reduce my migraines from one or two a week to one or two a
month (fewer if I avoid my triggers religiously) by adding 750mg of
magnesium (only once a day) to my supplements.

Sandy L wrote:

Changes in II.E. only.

Migraine Prophylaxis



This list of potential measures to prevent, or more precisely to decrease
the frequency and possibly severity of migraine headaches was developed for
participants of an on-line forum, alt.support.headaches.migraine (ASHM). On
ASHM, we frequently hear from people who feel they have tried everything for
their migraines. Sometimes that isn't quite true. This list is intended as
a crosscheck of possibilities for discussion with your doctor.

A number of things may help prevent migraine. One of the most successful is
a device, not a pill (See NTI-tss, below). Some are prescription drugs, a
few are over-the-counter (OTC) medicines or nutrition supplements. None of
them completely end migraines; you hope for a significant reduction in the
frequency and/or severity. Migraine prevention is an approved indication
for only a few of them. This list includes as many beta adrenergic blockers
and calcium channel blockers as I could easily identify, even though some
members of each class may be relatively poor choices within their class.
The list includes possibilities with little or no further comment and no
evaluation. Continuing feedback from the readers would help.

For another source, try: http://www.headachedrugs.com. The site is set up
by Lawrence Robbins M.D. Dr. Robbins wrote "Management of Headache and
Headache Medications," 2nd Edition, Springer Verlag; ISBN: = 0-387-98944-7,
2000. He and Susan Lang are authors of "Headache Help," Houghton Mifflin
Co; ISBN: 0618044361. 2000. The site also contains abstracts of recent
articles about migraine and other topics. A discussion of drugs is at:
http://www.headachedrugs.com/archives/ha_2002.html.

Teri Robert maintains http://headaches.about.com/, including more detail at
http://headaches.about.com/bl-all-meds.htm.

In-depth discussions may also be found in the FAQ (frequently asked
questions) page for ASHM at http://www.meldrum.demon.co.uk/migraine/. I
think this has not been revised in several years.

Some USENET participants have recommended

http://healthlibrary.epnet.com/GetCo...8a0-166a-4083-
8595-fcf396db9201&chunkiid=33729.

Others caution that an earlier website at Upstate Medical University
reflects the opinions of a single practitioner, who may at times be overly
dogmatic or voice opinions not widely shared among specialists.

In using this list, it is often helpful to look for "twofers," interventions
that may help more than one condition, giving a "two-for-the-price-of-one"
kind of bargain. Several of the drugs are used for treatment of high blood
pressure; a person with both migraine and high blood pressure might want to
discuss using one of the ones that are effective against migraine to control
the blood pressure. Some antidepressants have been shown to work, and
others are thought to be helpful against migraine; a person with depression
and migraine might benefit from choosing one of the more effective drugs
against migraine, if it is safe for them and if it would effectively treat
the depression. Magnesium often helps prevent leg cramps. The NTI-tss
would be an excellent choice for someone known to grind or clench his or her
teeth at night. (It would work for that even if it did not help the
migraine, but is especially likely to prevent migraine in that group.)

I. Non-prescription prophylactics

A. Magnesium, up to 750 mg twice a day. Allow at least three weeks
to begin to see an effect. Smaller amounts of calcium supplements may be
needed to maintain a proper balance. (Mg has the advantage of being
exceptionally safe and often prevents leg cramps.)

B. Co enzyme Q10. Used in fairly high doses (100 mg per day has been
shown effective and some patients tolerate as much as 600 mg/day), CoQ10 is
said to provide very good relief-better than many of the older prescription
prophylactics with few side effects. Gastrointestinal upset may occur at
high doses and limit dose. Allow up to 12 weeks for effect. In Drs. Young
and Silberstein's "Coenzyme Q10 as a Migraine Preventive, a trial of
coenzyme Q10," 61.3% of the patients treated had a greater than 50%
reduction in number of days with Migraine. Fewer than 1% reported any side
effects. Read it at:
http://headaches.about.com/library/w...oenzymeq10.htm.

C. Vitamin B2 (riboflavin) 400 mg/day. Readers advise that B2 is not
a commonly available supplement; it ís most likely found at the largest
specialty health stores. Judy N has used a cocktail of magnesium at 400-750
mg/day, Co-Q10 at 150-300mg/day, and fish oil at 1-2 gm/day with good
effect.

D. Over-the-counter 5-hydroxy triptophane (5-HTP) (not taken within
12 hrs of triptan)

E. A combination of magnesium, riboflavin, and feverfew
(MigreLief®).

F. 50 mg or 75 mg/day of Petasites hybridus rhizome extract
(Butterbur) was shown in a controlled trial to provide 50% or more reduction
in the number of migraines to 68% of participants in the 75 mg dose group,
56% in the 50 mg dose group and 49% in the placebo group after four months.
Native butterbur contains some carcinogenic compounds, but a purified
version, Petodolax®, does not. Some links to studies a
http://www.appneurology.com/showArti...leId=159400247,
http://www.headachedrugs.com/archives2/butterbur.html,
http://www.neurology.org/cgi/content...act/63/12/2240,
http://www.webmd.com/content/article...000_1000_tn_04,
http://www.herbalgram.org/default.asp?c=petadolex,
http://www.healthy.net/scr/news.asp?Id=7537,
http://www.migraineaid.com/pr/2004-12_WW/,
http://www.swedish.org/110833.cfm.

G. Lecithin (for choline) (1,200 mg/day)

H. Phosphatidyl serine (30 mg/day)

I. DL-phenylalanine, (DLPA) is a racemic mixture of an essential
amino acid, thought to act by inhibiting enzymes that degrade endorphins,
natural neurotransmitters that block pain. It may thus be more useful
during an attack than between attacks, but if there is a build-up phase,
some would be needed in advance of the attack.

J. One ASHM contributor reports good effect with melatonin, 3 mg at
bedtime. http://my.webmd.com/content/article/94/102559.htm.

K. Another contributor reported good results with chromium
picolinate. That thread included a caution that some forms of chromium have
been associated with chromosome damage and cancer. Chromium +6 is
dangerous; chromium +3 is not likely to cause trouble.

L. L-Taurine at 1.5-2.5 grams morning and night helped another
migraineur. That contributor found references to use of taurine plus
magnesium, but not for taurine alone.

M. Dehydration is a common trigger for migraine. Spigt MG, Kuijper
EC, van Schayck CP, et al. reported in a paper titled "Increasing the Daily
Water Intake for the Prophylactic Treatment of Headache: A Pilot Trial," Eur
J. Neurol. 2005;12:715-718, that patients instructed to drink and extra 1.5
L (a little over 3 pints) of water per day resulted in small but noticeable
decreases in frequency and intensity of migraine. (This was brought to out
attention through the Robbins Headache Clinic site. It was posted in May
2006.)

II. Prescription prophylactics

A. Calcium channel blockers. These drugs are used primarily for control of
high blood pressure, but their use by people with normal blood pressure does
not usually cause lowering. Their effect on migraine is entirely unrelated
to any effect on blood pressure. None list migraine as an indication (at
least in U.S. references), but many have been used with good effect. Some
are better than others, flunarizine proved more effective than nimodipine in
one study, but I am not aware of any good information on what the rank order
among all of them should be. Presumably, they would need to cross from the
blood into the brain to work. According to a manufacturer's representative,
amlodipine does not cross the blood-brain barrier well and therefore might
not work well. Diltiazem has two tertiary amine groups and is probably
highly polarized, therefore less likely to cross the blood-brain barrier.
Isradipine has three tertiary nitrogen atoms, but the side effects include
at least a few central nervous system effects, so perhaps it manages to
cross anyway. Nifedipine and nimodipine have only one tertiary nitrogen but
have an NO2 group (which would be expected to increase polarity); they list
few CNS side effects, suggesting they may not cross the blood-brain barrier
well. Nisoldipine has a structure somewhat like nifedipine and nimodipine,
but a number of CNS effects are listed, suggesting that it might work well.
Hemiplegic migraine, a special subtype, has been definitely linked to
defects in calcium channels in cell membranes; this class of drug should
always be tried for hemiplegic migraine. (Hemiplegic migraine is often
misdiagnosed as a seizure disorder. One such patient I encountered had been
taking amlodipine for blood pressure, without any evident effect,
reinforcing the idea that it may not be a good choice for this purpose. For
a list of hemiplegic migraine symptoms, consult http://www.i-h-s.org, the
website of the International Headache Society. Go to Guidelines, then
Criteria, then look for the section on this disorder.)

1. amlodipine (Norvasc®)

2. bepridil (Vascor®)

3. diltiazem (Cardizem®, Tiazac®)

4. felodipine (Plendil®)

5. flunarizine (Sibelium®) (not available in the U.S.)

6. isradipine (DynaCirc®)

7. nifedipine (Adalat®, Procardia®)

8. nimodipine (Nimotop®)

9. nisoldipine (Sular®)

10. verapamil (Covera®, Isoptin®, Verelan®)

B. Tricyclic antidepressants. (Amitriptyline tends to be sedating,
nortriptyline is less so, and desipramine even less so. They are usually
given as a single dose at bedtime, so the sedating effect may not be a
problem or might for some even be an advantage.)

1. amitriptyline (Elavil®, Saroten®, Retard® (Finland))

2. desipramine (Norpramin®)

3. doxepin (Sinequan®)

4. imipramine (Tofranil®)

5. nortriptyline (Pamelor®, Aventyl®)

6. trimipramine (Surmontil®)

C. Beta-adrenergic blocking agents. These drugs are used primarily
for control of high blood pressure, but their use by people with normal
blood pressure does not usually cause lowering. Care should be used in
prescribing for people with coronary artery disease or asthma. Only timolol
and propranolol two are listed as migraine drugs. Other beta blockers may
also be effective, but efficacy has not been proven by controlled clinical
trials or the proof has not been submitted to FDA. Propranolol is the one
most often used in the U.S., but nadolol crosses the blood-brain barrier
better and might be a better choice.

1. acebutolol (Sectral®)

2. atenolol (Tenormin®)

3. betaxolol (Kerlone®)

4. bisoprolol (Emconcor®, Zebeta®)

5. carteolol (Cartrol®)

6. metaprolol (Toprol®, Lopressor®)

7. nadolol (Corgard®)

8. propranolol (Inderal®)

9. timolol (Blocadren®)

D. Ergot drugs. These can have dangerous side effects and are rarely used
for prophylaxis.

1. dihydroergotamine (Migranal®)

2. ergotamine (Ergomar®, Migril®, Wigraine®)

E. Combination of COX-2 inhibitor and leukotriene blocker. The first
report I saw of this used rofecoxib (Vioxx®), which has been withdrawn, and
Singulair®. Other combinations might also work. More recently, a 2004
report using 20 mg Singulair® per day found only 15.4% success in the
treated group vs. 10.3% in the placebo group[1]. That was not significant,
but they used Singulair® alone or rofecoxib alone, not together. They also
excluded patients who had failed to benefit from two or more prophylactic
agents, so the group studied is not representative of migraineurs as a
whole, but they did not state the numbers excluded, so we cannot estimate
the magnitude of the difference. By contrast, a 2000 study showed almost
all of a small number given an open label trial (i.e., they knew what they
were getting) had a benefit, 53% had at least 50% reduction and 41% had 60%
reduction[2]. The placebo-controlled study has more validity (subject to
the reservation that it may not have used a COX-2 inhibitor), because there
is often a high placebo response rate in migraine trials. I have prescribed
the combination but not been greatly impressed with the results. Choose one
from group 1 and one from group 2 (¿or 3?). [Caution: the drugs in group 1
are chemically related to sulfa antibiotics and might cause allergic
reactions in people allergic to sulfas.]

1. COX-2 inhibitor--celecoxib (Celebrex®) is the only member
of this class currently marketed in the U.S. Rofecoxib (Vioxx®) was
withdrawn because of increased risk of cardiovascular complications and
valdecoxib (Bextra®) because of serious skin reactions.

2. Leukotriene blockers

a. montelukast (Singulair®) - One-a-day dose.

b. zafirlukast (Accolate®) - Two tablets per day, but
about 60% of the cost for a month's supply.

3. Leukotriene synthesis inhibitor - zyleuton (Zyflo®)

F. Anti-seizure medications. A variety of different medicines
originally developed for seizures were found to have incidental benefit in
preventing migraines. Migraine is not a seizure disorder. Nevertheless,
some of these drugs work for some people.

1. carbamazepine (Tegretol®)

2. clonazepam (Klonopin®)

3. clorazepate (Tranxene®)

4. divalproex (Depakote®) [see warning for valproate sodium.]

5. gabapentin (Neurontin®) Was promoted as a migraine
prophylactic. More recent information suggests that it failed in clinical
trials in Europe and was promoted for this purpose without FDA approval.
Specifically, the company is said to have planned telling physicians it was
effective if (and presumably only if) new studies were favorable. If they
had new studies to that effect, they would be required to submit data to the
FDA and seek approval for its marketing in that manner. In that setting,
good negative studies would have as much weight as positive studies. Warner
Lambert pled guilty to illegal and fraudulent promotion and agreed to pay
more than $430 million in fines.

6. lamotrigine (Lamictal®)

7. levetiracetam (Keppra®)

8 oxcarbazepine (Trileptal®)

9. topiramate (Topamax®) (For a review, see
http://www.aafp.org/afp/20051015/steps.html.)

10. valproate sodium (Depacon®, Depakene®, Convulex® (UK),
Depakine®, Orfiril®, Valporal®, and Valprosid®) [Sodium valproate causes
birth defects when taken immediately before (spina bifida and anencephaly)
and during (valproate syndrome) pregnancy. It may therefore be unsuitable
for women of childbearing age, but that this does NOT apply to men as it
does not damage the DNA. It has also been associated with pancreatitis and
hepatic failure.]

11. zonisamide (Zonegran®) Reported by one person to have milder
side effects than Topomax, but not very effective for her and by another to
have had good effect on tension headache and unexpected benefit at migraine
prophylaxis.

G. Selective serotonin reuptake inhibitors (SSRIs). These are used
as antidepressants and have other effects on mood. I have not encountered
any reports of clinical trials that show them to be effective, but have
noticed that many participants on alt.support.headaches.migraine take one or
another as prophylactics and some report success.

1. citalopram (Celexa®)

2. escitalopram oxalate (Lexapro®)

3. fluoxetine (Prozac®)

4. paroxetine (Paxil®, Seroxat® (UK), Deroxat® (FR))

5. sertraline (Zoloft®)

6. venlafaxine (Effexor®) (Potent inhibitor of neuronal
serotonin and norepinephrine reuptake and weak inhibitor of dopamine
reuptake.)

7. duloxetine (Cymbalta®) is a selective serotonin and
norepinephrine reuptake inhibitor (SSNRI). I cannot recall having seen
reports of its use for migraine prevention, but its similarity with other
drugs in this group suggests that it might be used thus.

H. Antihistamine/antiserotonin drugs have actions blocking both
histamine and serotonin (5-hydroxy triptamine)

1. cyproheptadine (Periactin®)

2. pizotifen (UK), pizotyline (US) (Sanomigran®)

I. Angiotensin system drugs. Angiotensin II is a key determinant
of blood pressure. Drugs that block conversion of angiotensin I to
angiotensin II have been used for migraine prophylaxis and a study published
in 2003 showed that a drug blocking the effect of angiotensin II had a
significant prophylactic effect.

1. Angiotensin II receptor antagonists

a. candesartan (Atacand® - the subject of the study)

b. eprosartan (Teveten®)

c. irbesartan (Avapro®)

d. losartan (Cozaar®)

e. olmesartan (Benicar®)

f. telmisartan (Micardis®)

g. valsartan (Diovan®)

2. Angiotensin converting enzyme (ACE) inhibitors

a. benazepril (Lotensin®)

b. captopril (¿Capoten?®)

c. enalapril (Vasotec®)

d. fosinopril (Monopril®)

e. lisinopril (Prinivil®, Zestril®)

f. moexipril (Univasc®)

g. perindopril (Aceon®)

h. quinapril (Accupril®)

i. ramipril (Altace®)

j. trandolapril (Mavik®).

J. Other, miscellaneous

1. trazodone (Desyrel®, Molipaxin®, Trialodine®, Beneficat®,
Bimaran®, Deprax®, Desirel®, Manegan®, Pragmarel®, Sideril®, Taxagon®,
Trialodine®)

2. botulinum toxin (Botox®) paralyzes muscles and may
thereby block tension type headaches which appear to be triggers for
migraine in some people.

3. baclofen, a muscle relaxer, has been shown effective.

4. bupropion (Wellbutrin®) is a mood elevator
(anti-depressant) also used as Zyban® to aid smoking cessation.

5. pregabalin (Lyrica®) is a chemical relative of gabapentin
developed and used for neurogenic pain, such as that in shingles or
diabetes. At least one participant on ASHM has received a prescription for
prophylaxis, but we do not yet have results of controlled trials.

6. nemantine (Namenda®), a drug used for treatment of
dementia, has been shown effective in a small, open-label trial. (See:
http://headaches.about.com/b/a/217343.htm.)

7. A poster reported that she has been put on dronabinol
(Marinol®), a cannaboid found in marijuana, as a prophylactic agent, with
good results. Marinol® is primarily indicated for nausea and vomiting with
cancer chemotherapy or as an appetite stimulant for patients with AIDs. It
is a class II controlled substance; many physicians are likely to be
reluctant to prescribe it.

III. Devices.

A. NTI-tss. Dr. Jim Boyd, a long-term headache sufferer himself,
found that a large number of migraines are triggered by bruxism, or
clenching of teeth. He devised an appliance called a Nociceptive Trigeminal
Inhibitor-tension suppression system (NTI-tss) that is fitted over the upper
front two teeth at night and triggers a reflex that prevents forceful
clenching. A version is available for daytime use, but is rarely needed.
See: http://www.nti-tss.com/.

B. Bite guards are often fitted by dentists to deal with bruxism, but
by permitting clenching of the back teeth, they not only do not stop
bruxism, but may encourage more forceful clenching.

C. Transcranial electrical stimulation has helped some people. I
have no details on success/failure rates but have seen two patients in whom
relief lasted several months after a small number of treatments.

D. One participant reported benefit from a continuous positive airway
pressure (CPAP) device after a sleep study (aka polysomnogram) showed sleep
apnea.

IV. Other treatment modalities

A. Chiropractic care seems to help many stave off headaches.

B. Acupuncture - The Medical Letter in the spring of 2006 said:
"Headache -A randomized study in 401 patients with chronic headache (mainly
migraine) compared acupuncture to usual care; after one year, the
acupuncture group had used less medication, had fewer headaches and missed
fewer days of work.[3] Another randomized trial in patients with migraine
found acupuncture and sham acupuncture similar in efficacy, and both were
more effective than no treatment.[4] A large randomized controlled trial in
patients with migraine found that true acupuncture, sham acupuncture and
standard prophylactic drug therapy were all about equally effective in
preventing migraine attacks.[5]" A Cochrane Review of acupuncture in
idiopathic headache (which may not be relevant to migraine) concluded,
"Overall, the existing evidence supports the value of acupuncture for the
treatment of idiopathic headaches. However, the quality and amount of
evidence are not fully convincing. There is an urgent need for well-planned,
large-scale studies to assess the effectiveness and cost-effectiveness of
acupuncture under real-life conditions.[6]

C. Aroma therapy - One participant in ASHM reported that the smell of
green apples would abort migraines, and others have reported effectiveness
of yellow and black Tibetan incenses, burned together, as a migraine
abortive, but I have no information on prophylactic use. Another
participant referred us to
http://www.relieve-migraine-headache...-headache.html.

D. Relaxation training, meditation - See discussion in
http://www.meldrum.demon.co.uk/migraine/.

E. Massage therapy

F. One poster to ASHM said that Nyquil, taken after onset of an
aura, blocked the pain phase of her migraines and that others she had told
about it had similar luck.

G. In early 2005, attention was drawn to case series in which
patients who had both migraine and a patent foramen ovale (PFA)-a hole
between the right and left atria of the heart-often were relieved of their
migraines after repair of the PFA. People with PFA and people with migraine
are both at somewhat higher risk of stroke. An early series suggested that
about one-third of people with PFA had migraine (compared with about 12
percent of the general population) and that many of those had complete
remission after surgery, while a number of others had significant remission.
Closing a PFA is still risky enough that experts are not advocating it
solely to treat migraine, but for those who have evidence of microstrokes
(not necessarily clinically evident), it might be indicated. Microstrokes
are usually discovered as multiple small regions of dense white matter on
magnetic resonance imaging (MRI). The percentage of migraineurs who have
PFA is not known, but is probably small.

H. A continuing education course suggests smoking cessation and
regular exercise. It was not clear whether those recommendations applied to
headaches in general or migraine in particular. It is sound advice, in any
case.



Last edited August 4, 2006, at 9:51 a.m., EDT

Sanford S. Leffingwell





Other sources of information on migraine:

World Headache Alliance: http://www.w-h-a.org/wha2/index.asp

(Includes '?????????? ?? ??????? ???????? ???? [Izbavitsia Ot Bremeni
Golovnoi Boli],' 'Las Cefaleas,' and 'Aliviando El Agobio De Los Desordenes
De Las Cefaleas')

Another contributor posted the following links. I have not checked them
out. http://www.migraines.org/, http://www.achenet.org/.
http://www.headaches.org/, http://ahsnet.org/, http://www.neuroland.com/,
http://www.ninds.nih.gov/disorders/h...e/headache.htm,
http://www.nlm.nih.gov/medlineplus/migraine.html,
http://www.migraine-aura.org/EN/Soma..._Symptoms.html,
http://www.medem.com/medlb/article_d...ZZSQSNVKIC&sub
_cat=567,

A discussion of feverfew (Tanacetum parthenium) is at
http://www.umm.edu/altmed/ConsHerbs/Feverfewch.html.

Auras are said to be well-discussed at
http://www.migraine-aura.org/EN/index.html.





------------------------------------------------------------------

[1] Brandes JL, Visser WH, Farmer MV, Schuhl AL, Malbecq W, Vrijens F, Lines
CR, Reines SA; Protocol 125 study group. Montelukast for migraine
prophylaxis: a randomized, double-blind, placebo-controlled study. Headache.
2004 Jun;44(6):581-6.

[2] Sheftell F, Rapoport A, Weeks R, Walker B, Gammerman I, Baskin S.
Montelukast in the prophylaxis of migraine: a potential role for leukotriene
modifiers. Headache. 2000 Feb;40(2):158-63.



[3] AJ Vickers et al. Acupuncture of chronic headache disorders in primary
ca randomised controlled trial and economic analysis. Health Technol
Assess 2004; 8:1.

[4] K Linde et al. Acupuncture for patients with migraine: a randomized
controlled trial. JAMA 2005; 294:2118.

[5] HC Diener et al. Efficacy of acupuncture for the prophylaxis of
migraine: a multicentre randomised controlled clinical trial. Lancet Neurol
2006; 5:310.

[6] Melchart D, Linde K, Fischer P, Berman B, White A, Vickers A, Allais G.
Acupuncture for idiopathic headache. The Cochrane Database

of Systematic Reviews 2001, Issue 1. Art.No.: CD001218. DOI:
10.1002/14651858.CD001218. This version first published online: 22 January
2001 in Issue 1, 2001.

My migraine preventers are first and foremost, get my sleep. When my doc
put me on hormone therapy, she chose b.c. pills because my risk of breast
cancer was elevated due to radiation for Hodgkins. They gave me insomnia
every 28th night followed religiously by migraine. I quit using them. The
other things I do to prevent insomnia a exercise; limit alcohol; limit
caffeine; do a nightly ritual; go to bed at the same time even on weekends;
and I have learned how to put myself to sleep first by not stressing about
waking up and second by having little tricks like telling myself a story.

Second limit processed meat.

Third when an Alberta Clipper weather front comes through, do stress
management so I don't worry about having insomnia, which can promote it.
The combination of this weather and insomnia is 100% guaranteed to result in
migraine.

I take aspirin for the pain because ibuprofen and tylenol do weird things to
my head.

My migraines have decreased from 20 a year to possibly 2 incidents of
twinkly lights but no real migraines.


"The Queen of Cans and Jars" wrote in message
. ..
Willow:

This is a list that is regularly posted on
alt.support.headaches.migraine. You may want to pass the info on to
your migraine-afflicted WW member.

I was able to reduce my migraines from one or two a week to one or two a
month (fewer if I avoid my triggers religiously) by adding 750mg of
magnesium (only once a day) to my supplements.

Sandy L wrote:

Changes in II.E. only.

Migraine Prophylaxis



This list of potential measures to prevent, or more precisely to decrease
the frequency and possibly severity of migraine headaches was developed
for
participants of an on-line forum, alt.support.headaches.migraine (ASHM).
On
ASHM, we frequently hear from people who feel they have tried everything
for
their migraines. Sometimes that isn't quite true. This list is intended
as
a crosscheck of possibilities for discussion with your doctor.

A number of things may help prevent migraine. One of the most successful
is
a device, not a pill (See NTI-tss, below). Some are prescription drugs,
a
few are over-the-counter (OTC) medicines or nutrition supplements. None
of
them completely end migraines; you hope for a significant reduction in
the
frequency and/or severity. Migraine prevention is an approved indication
for only a few of them. This list includes as many beta adrenergic
blockers
and calcium channel blockers as I could easily identify, even though some
members of each class may be relatively poor choices within their class.
The list includes possibilities with little or no further comment and no
evaluation. Continuing feedback from the readers would help.

For another source, try: http://www.headachedrugs.com. The site is set
up
by Lawrence Robbins M.D. Dr. Robbins wrote "Management of Headache and
Headache Medications," 2nd Edition, Springer Verlag; ISBN: =
0-387-98944-7,
2000. He and Susan Lang are authors of "Headache Help," Houghton
Mifflin
Co; ISBN: 0618044361. 2000. The site also contains abstracts of recent
articles about migraine and other topics. A discussion of drugs is at:
http://www.headachedrugs.com/archives/ha_2002.html.

Teri Robert maintains http://headaches.about.com/, including more detail
at
http://headaches.about.com/bl-all-meds.htm.

In-depth discussions may also be found in the FAQ (frequently asked
questions) page for ASHM at http://www.meldrum.demon.co.uk/migraine/. I
think this has not been revised in several years.

Some USENET participants have recommended

http://healthlibrary.epnet.com/GetCo...8a0-166a-4083-
8595-fcf396db9201&chunkiid=33729.

Others caution that an earlier website at Upstate Medical University
reflects the opinions of a single practitioner, who may at times be
overly
dogmatic or voice opinions not widely shared among specialists.

In using this list, it is often helpful to look for "twofers,"
interventions
that may help more than one condition, giving a
"two-for-the-price-of-one"
kind of bargain. Several of the drugs are used for treatment of high
blood
pressure; a person with both migraine and high blood pressure might want
to
discuss using one of the ones that are effective against migraine to
control
the blood pressure. Some antidepressants have been shown to work, and
others are thought to be helpful against migraine; a person with
depression
and migraine might benefit from choosing one of the more effective drugs
against migraine, if it is safe for them and if it would effectively
treat
the depression. Magnesium often helps prevent leg cramps. The NTI-tss
would be an excellent choice for someone known to grind or clench his or
her
teeth at night. (It would work for that even if it did not help the
migraine, but is especially likely to prevent migraine in that group.)

I. Non-prescription prophylactics

A. Magnesium, up to 750 mg twice a day. Allow at least three
weeks
to begin to see an effect. Smaller amounts of calcium supplements may be
needed to maintain a proper balance. (Mg has the advantage of being
exceptionally safe and often prevents leg cramps.)

B. Co enzyme Q10. Used in fairly high doses (100 mg per day has
been
shown effective and some patients tolerate as much as 600 mg/day), CoQ10
is
said to provide very good relief-better than many of the older
prescription
prophylactics with few side effects. Gastrointestinal upset may occur at
high doses and limit dose. Allow up to 12 weeks for effect. In Drs.
Young
and Silberstein's "Coenzyme Q10 as a Migraine Preventive, a trial of
coenzyme Q10," 61.3% of the patients treated had a greater than 50%
reduction in number of days with Migraine. Fewer than 1% reported any
side
effects. Read it at:
http://headaches.about.com/library/w...oenzymeq10.htm.

C. Vitamin B2 (riboflavin) 400 mg/day. Readers advise that B2 is
not
a commonly available supplement; it ís most likely found at the largest
specialty health stores. Judy N has used a cocktail of magnesium at
400-750
mg/day, Co-Q10 at 150-300mg/day, and fish oil at 1-2 gm/day with good
effect.

D. Over-the-counter 5-hydroxy triptophane (5-HTP) (not taken
within
12 hrs of triptan)

E. A combination of magnesium, riboflavin, and feverfew
(MigreLief®).

F. 50 mg or 75 mg/day of Petasites hybridus rhizome extract
(Butterbur) was shown in a controlled trial to provide 50% or more
reduction
in the number of migraines to 68% of participants in the 75 mg dose
group,
56% in the 50 mg dose group and 49% in the placebo group after four
months.
Native butterbur contains some carcinogenic compounds, but a purified
version, Petodolax®, does not. Some links to studies a
http://www.appneurology.com/showArti...leId=159400247,
http://www.headachedrugs.com/archives2/butterbur.html,
http://www.neurology.org/cgi/content...act/63/12/2240,
http://www.webmd.com/content/article...000_1000_tn_04,
http://www.herbalgram.org/default.asp?c=petadolex,
http://www.healthy.net/scr/news.asp?Id=7537,
http://www.migraineaid.com/pr/2004-12_WW/,
http://www.swedish.org/110833.cfm.

G. Lecithin (for choline) (1,200 mg/day)

H. Phosphatidyl serine (30 mg/day)

I. DL-phenylalanine, (DLPA) is a racemic mixture of an essential
amino acid, thought to act by inhibiting enzymes that degrade endorphins,
natural neurotransmitters that block pain. It may thus be more useful
during an attack than between attacks, but if there is a build-up phase,
some would be needed in advance of the attack.

J. One ASHM contributor reports good effect with melatonin, 3 mg
at
bedtime. http://my.webmd.com/content/article/94/102559.htm.

K. Another contributor reported good results with chromium
picolinate. That thread included a caution that some forms of chromium
have
been associated with chromosome damage and cancer. Chromium +6 is
dangerous; chromium +3 is not likely to cause trouble.

L. L-Taurine at 1.5-2.5 grams morning and night helped another
migraineur. That contributor found references to use of taurine plus
magnesium, but not for taurine alone.

M. Dehydration is a common trigger for migraine. Spigt MG, Kuijper
EC, van Schayck CP, et al. reported in a paper titled "Increasing the
Daily
Water Intake for the Prophylactic Treatment of Headache: A Pilot Trial,"
Eur
J. Neurol. 2005;12:715-718, that patients instructed to drink and extra
1.5
L (a little over 3 pints) of water per day resulted in small but
noticeable
decreases in frequency and intensity of migraine. (This was brought to
out
attention through the Robbins Headache Clinic site. It was posted in May
2006.)

II. Prescription prophylactics

A. Calcium channel blockers. These drugs are used primarily for control
of
high blood pressure, but their use by people with normal blood pressure
does
not usually cause lowering. Their effect on migraine is entirely
unrelated
to any effect on blood pressure. None list migraine as an indication (at
least in U.S. references), but many have been used with good effect.
Some
are better than others, flunarizine proved more effective than nimodipine
in
one study, but I am not aware of any good information on what the rank
order
among all of them should be. Presumably, they would need to cross from
the
blood into the brain to work. According to a manufacturer's
representative,
amlodipine does not cross the blood-brain barrier well and therefore
might
not work well. Diltiazem has two tertiary amine groups and is probably
highly polarized, therefore less likely to cross the blood-brain barrier.
Isradipine has three tertiary nitrogen atoms, but the side effects
include
at least a few central nervous system effects, so perhaps it manages to
cross anyway. Nifedipine and nimodipine have only one tertiary nitrogen
but
have an NO2 group (which would be expected to increase polarity); they
list
few CNS side effects, suggesting they may not cross the blood-brain
barrier
well. Nisoldipine has a structure somewhat like nifedipine and
nimodipine,
but a number of CNS effects are listed, suggesting that it might work
well.
Hemiplegic migraine, a special subtype, has been definitely linked to
defects in calcium channels in cell membranes; this class of drug should
always be tried for hemiplegic migraine. (Hemiplegic migraine is often
misdiagnosed as a seizure disorder. One such patient I encountered had
been
taking amlodipine for blood pressure, without any evident effect,
reinforcing the idea that it may not be a good choice for this purpose.
For
a list of hemiplegic migraine symptoms, consult http://www.i-h-s.org, the
website of the International Headache Society. Go to Guidelines, then
Criteria, then look for the section on this disorder.)

1. amlodipine (Norvasc®)

2. bepridil (Vascor®)

3. diltiazem (Cardizem®, Tiazac®)

4. felodipine (Plendil®)

5. flunarizine (Sibelium®) (not available in the U.S.)

6. isradipine (DynaCirc®)

7. nifedipine (Adalat®, Procardia®)

8. nimodipine (Nimotop®)

9. nisoldipine (Sular®)

10. verapamil (Covera®, Isoptin®, Verelan®)

B. Tricyclic antidepressants. (Amitriptyline tends to be sedating,
nortriptyline is less so, and desipramine even less so. They are usually
given as a single dose at bedtime, so the sedating effect may not be a
problem or might for some even be an advantage.)

1. amitriptyline (Elavil®, Saroten®, Retard® (Finland))

2. desipramine (Norpramin®)

3. doxepin (Sinequan®)

4. imipramine (Tofranil®)

5. nortriptyline (Pamelor®, Aventyl®)

6. trimipramine (Surmontil®)

C. Beta-adrenergic blocking agents. These drugs are used
primarily
for control of high blood pressure, but their use by people with normal
blood pressure does not usually cause lowering. Care should be used in
prescribing for people with coronary artery disease or asthma. Only
timolol
and propranolol two are listed as migraine drugs. Other beta blockers
may
also be effective, but efficacy has not been proven by controlled
clinical
trials or the proof has not been submitted to FDA. Propranolol is the
one
most often used in the U.S., but nadolol crosses the blood-brain barrier
better and might be a better choice.

1. acebutolol (Sectral®)

2. atenolol (Tenormin®)

3. betaxolol (Kerlone®)

4. bisoprolol (Emconcor®, Zebeta®)

5. carteolol (Cartrol®)

6. metaprolol (Toprol®, Lopressor®)

7. nadolol (Corgard®)

8. propranolol (Inderal®)

9. timolol (Blocadren®)

D. Ergot drugs. These can have dangerous side effects and are rarely
used
for prophylaxis.

1. dihydroergotamine (Migranal®)

2. ergotamine (Ergomar®, Migril®, Wigraine®)

E. Combination of COX-2 inhibitor and leukotriene blocker. The first
report I saw of this used rofecoxib (Vioxx®), which has been withdrawn,
and
Singulair®. Other combinations might also work. More recently, a 2004
report using 20 mg Singulair® per day found only 15.4% success in the
treated group vs. 10.3% in the placebo group[1]. That was not
significant,
but they used Singulair® alone or rofecoxib alone, not together. They
also
excluded patients who had failed to benefit from two or more prophylactic
agents, so the group studied is not representative of migraineurs as a
whole, but they did not state the numbers excluded, so we cannot estimate
the magnitude of the difference. By contrast, a 2000 study showed almost
all of a small number given an open label trial (i.e., they knew what
they
were getting) had a benefit, 53% had at least 50% reduction and 41% had
60%
reduction[2]. The placebo-controlled study has more validity (subject to
the reservation that it may not have used a COX-2 inhibitor), because
there
is often a high placebo response rate in migraine trials. I have
prescribed
the combination but not been greatly impressed with the results. Choose
one
from group 1 and one from group 2 (¿or 3?). [Caution: the drugs in group
1
are chemically related to sulfa antibiotics and might cause allergic
reactions in people allergic to sulfas.]

1. COX-2 inhibitor--celecoxib (Celebrex®) is the only
member
of this class currently marketed in the U.S. Rofecoxib (Vioxx®) was
withdrawn because of increased risk of cardiovascular complications and
valdecoxib (Bextra®) because of serious skin reactions.

2. Leukotriene blockers

a. montelukast (Singulair®) - One-a-day dose.

b. zafirlukast (Accolate®) - Two tablets per day, but
about 60% of the cost for a month's supply.

3. Leukotriene synthesis inhibitor - zyleuton (Zyflo®)

F. Anti-seizure medications. A variety of different medicines
originally developed for seizures were found to have incidental benefit
in
preventing migraines. Migraine is not a seizure disorder. Nevertheless,
some of these drugs work for some people.

1. carbamazepine (Tegretol®)

2. clonazepam (Klonopin®)

3. clorazepate (Tranxene®)

4. divalproex (Depakote®) [see warning for valproate
sodium.]

5. gabapentin (Neurontin®) Was promoted as a migraine
prophylactic. More recent information suggests that it failed in
clinical
trials in Europe and was promoted for this purpose without FDA approval.
Specifically, the company is said to have planned telling physicians it
was
effective if (and presumably only if) new studies were favorable. If
they
had new studies to that effect, they would be required to submit data to
the
FDA and seek approval for its marketing in that manner. In that setting,
good negative studies would have as much weight as positive studies.
Warner
Lambert pled guilty to illegal and fraudulent promotion and agreed to pay
more than $430 million in fines.

6. lamotrigine (Lamictal®)

7. levetiracetam (Keppra®)

8 oxcarbazepine (Trileptal®)

9. topiramate (Topamax®) (For a review, see
http://www.aafp.org/afp/20051015/steps.html.)

10. valproate sodium (Depacon®, Depakene®, Convulex® (UK),
Depakine®, Orfiril®, Valporal®, and Valprosid®) [Sodium valproate causes
birth defects when taken immediately before (spina bifida and
anencephaly)
and during (valproate syndrome) pregnancy. It may therefore be
unsuitable
for women of childbearing age, but that this does NOT apply to men as it
does not damage the DNA. It has also been associated with pancreatitis
and
hepatic failure.]

11. zonisamide (Zonegran®) Reported by one person to have
milder
side effects than Topomax, but not very effective for her and by another
to
have had good effect on tension headache and unexpected benefit at
migraine
prophylaxis.

G. Selective serotonin reuptake inhibitors (SSRIs). These are
used
as antidepressants and have other effects on mood. I have not
encountered
any reports of clinical trials that show them to be effective, but have
noticed that many participants on alt.support.headaches.migraine take one
or
another as prophylactics and some report success.

1. citalopram (Celexa®)

2. escitalopram oxalate (Lexapro®)

3. fluoxetine (Prozac®)

4. paroxetine (Paxil®, Seroxat® (UK), Deroxat® (FR))

5. sertraline (Zoloft®)

6. venlafaxine (Effexor®) (Potent inhibitor of neuronal
serotonin and norepinephrine reuptake and weak inhibitor of dopamine
reuptake.)

7. duloxetine (Cymbalta®) is a selective serotonin and
norepinephrine reuptake inhibitor (SSNRI). I cannot recall having seen
reports of its use for migraine prevention, but its similarity with other
drugs in this group suggests that it might be used thus.

H. Antihistamine/antiserotonin drugs have actions blocking both
histamine and serotonin (5-hydroxy triptamine)

1. cyproheptadine (Periactin®)

2. pizotifen (UK), pizotyline (US) (Sanomigran®)

I. Angiotensin system drugs. Angiotensin II is a key
determinant
of blood pressure. Drugs that block conversion of angiotensin I to
angiotensin II have been used for migraine prophylaxis and a study
published
in 2003 showed that a drug blocking the effect of angiotensin II had a
significant prophylactic effect.

1. Angiotensin II receptor antagonists

a. candesartan (Atacand® - the subject of the
study)

b. eprosartan (Teveten®)

c. irbesartan (Avapro®)

d. losartan (Cozaar®)

e. olmesartan (Benicar®)

f. telmisartan (Micardis®)

g. valsartan (Diovan®)

2. Angiotensin converting enzyme (ACE) inhibitors

a. benazepril (Lotensin®)

b. captopril (¿Capoten?®)

c. enalapril (Vasotec®)

d. fosinopril (Monopril®)

e. lisinopril (Prinivil®, Zestril®)

f. moexipril (Univasc®)

g. perindopril (Aceon®)

h. quinapril (Accupril®)

i. ramipril (Altace®)

j. trandolapril (Mavik®).

J. Other, miscellaneous

1. trazodone (Desyrel®, Molipaxin®, Trialodine®,
Beneficat®,
Bimaran®, Deprax®, Desirel®, Manegan®, Pragmarel®, Sideril®, Taxagon®,
Trialodine®)

2. botulinum toxin (Botox®) paralyzes muscles and may
thereby block tension type headaches which appear to be triggers for
migraine in some people.

3. baclofen, a muscle relaxer, has been shown effective.

4. bupropion (Wellbutrin®) is a mood elevator
(anti-depressant) also used as Zyban® to aid smoking cessation.

5. pregabalin (Lyrica®) is a chemical relative of
gabapentin
developed and used for neurogenic pain, such as that in shingles or
diabetes. At least one participant on ASHM has received a prescription
for
prophylaxis, but we do not yet have results of controlled trials.

6. nemantine (Namenda®), a drug used for treatment of
dementia, has been shown effective in a small, open-label trial. (See:
http://headaches.about.com/b/a/217343.htm.)

7. A poster reported that she has been put on dronabinol
(Marinol®), a cannaboid found in marijuana, as a prophylactic agent, with
good results. Marinol® is primarily indicated for nausea and vomiting
with
cancer chemotherapy or as an appetite stimulant for patients with AIDs.
It
is a class II controlled substance; many physicians are likely to be
reluctant to prescribe it.

III. Devices.

A. NTI-tss. Dr. Jim Boyd, a long-term headache sufferer himself,
found that a large number of migraines are triggered by bruxism, or
clenching of teeth. He devised an appliance called a Nociceptive
Trigeminal
Inhibitor-tension suppression system (NTI-tss) that is fitted over the
upper
front two teeth at night and triggers a reflex that prevents forceful
clenching. A version is available for daytime use, but is rarely needed.
See: http://www.nti-tss.com/.

B. Bite guards are often fitted by dentists to deal with bruxism,
but
by permitting clenching of the back teeth, they not only do not stop
bruxism, but may encourage more forceful clenching.

C. Transcranial electrical stimulation has helped some people. I
have no details on success/failure rates but have seen two patients in
whom
relief lasted several months after a small number of treatments.

D. One participant reported benefit from a continuous positive
airway
pressure (CPAP) device after a sleep study (aka polysomnogram) showed
sleep
apnea.

IV. Other treatment modalities

A. Chiropractic care seems to help many stave off headaches.

B. Acupuncture - The Medical Letter in the spring of 2006 said:
"Headache -A randomized study in 401 patients with chronic headache
(mainly
migraine) compared acupuncture to usual care; after one year, the
acupuncture group had used less medication, had fewer headaches and
missed
fewer days of work.[3] Another randomized trial in patients with migraine
found acupuncture and sham acupuncture similar in efficacy, and both were
more effective than no treatment.[4] A large randomized controlled trial
in
patients with migraine found that true acupuncture, sham acupuncture and
standard prophylactic drug therapy were all about equally effective in
preventing migraine attacks.[5]" A Cochrane Review of acupuncture in
idiopathic headache (which may not be relevant to migraine) concluded,
"Overall, the existing evidence supports the value of acupuncture for the
treatment of idiopathic headaches. However, the quality and amount of
evidence are not fully convincing. There is an urgent need for
well-planned,
large-scale studies to assess the effectiveness and cost-effectiveness of
acupuncture under real-life conditions.[6]

C. Aroma therapy - One participant in ASHM reported that the smell
of
green apples would abort migraines, and others have reported
effectiveness
of yellow and black Tibetan incenses, burned together, as a migraine
abortive, but I have no information on prophylactic use. Another
participant referred us to
http://www.relieve-migraine-headache...-headache.html.

D. Relaxation training, meditation - See discussion in
http://www.meldrum.demon.co.uk/migraine/.

E. Massage therapy

F. One poster to ASHM said that Nyquil, taken after onset of an
aura, blocked the pain phase of her migraines and that others she had
told
about it had similar luck.

G. In early 2005, attention was drawn to case series in which
patients who had both migraine and a patent foramen ovale (PFA)-a hole
between the right and left atria of the heart-often were relieved of
their
migraines after repair of the PFA. People with PFA and people with
migraine
are both at somewhat higher risk of stroke. An early series suggested
that
about one-third of people with PFA had migraine (compared with about 12
percent of the general population) and that many of those had complete
remission after surgery, while a number of others had significant
remission.
Closing a PFA is still risky enough that experts are not advocating it
solely to treat migraine, but for those who have evidence of microstrokes
(not necessarily clinically evident), it might be indicated.
Microstrokes
are usually discovered as multiple small regions of dense white matter on
magnetic resonance imaging (MRI). The percentage of migraineurs who have
PFA is not known, but is probably small.

H. A continuing education course suggests smoking cessation and
regular exercise. It was not clear whether those recommendations applied
to
headaches in general or migraine in particular. It is sound advice, in
any
case.



Last edited August 4, 2006, at 9:51 a.m., EDT

Sanford S. Leffingwell





Other sources of information on migraine:

World Headache Alliance: http://www.w-h-a.org/wha2/index.asp

(Includes '?????????? ?? ??????? ???????? ???? [Izbavitsia Ot
Bremeni
Golovnoi Boli],' 'Las Cefaleas,' and 'Aliviando El Agobio De Los
Desordenes
De Las Cefaleas')

Another contributor posted the following links. I have not checked them
out. http://www.migraines.org/, http://www.achenet.org/.
http://www.headaches.org/, http://ahsnet.org/, http://www.neuroland.com/,
http://www.ninds.nih.gov/disorders/h...e/headache.htm,
http://www.nlm.nih.gov/medlineplus/migraine.html,
http://www.migraine-aura.org/EN/Soma..._Symptoms.html,
http://www.medem.com/medlb/article_d...ZZSQSNVKIC&sub
_cat=567,

A discussion of feverfew (Tanacetum parthenium) is at
http://www.umm.edu/altmed/ConsHerbs/Feverfewch.html.

Auras are said to be well-discussed at
http://www.migraine-aura.org/EN/index.html.





------------------------------------------------------------------

[1] Brandes JL, Visser WH, Farmer MV, Schuhl AL, Malbecq W, Vrijens F,
Lines
CR, Reines SA; Protocol 125 study group. Montelukast for migraine
prophylaxis: a randomized, double-blind, placebo-controlled study.
Headache.
2004 Jun;44(6):581-6.

[2] Sheftell F, Rapoport A, Weeks R, Walker B, Gammerman I, Baskin S.
Montelukast in the prophylaxis of migraine: a potential role for
leukotriene
modifiers. Headache. 2000 Feb;40(2):158-63.



[3] AJ Vickers et al. Acupuncture of chronic headache disorders in
primary
ca randomised controlled trial and economic analysis. Health Technol
Assess 2004; 8:1.

[4] K Linde et al. Acupuncture for patients with migraine: a randomized
controlled trial. JAMA 2005; 294:2118.

[5] HC Diener et al. Efficacy of acupuncture for the prophylaxis of
migraine: a multicentre randomised controlled clinical trial. Lancet
Neurol
2006; 5:310.

[6] Melchart D, Linde K, Fischer P, Berman B, White A, Vickers A, Allais
G.
Acupuncture for idiopathic headache. The Cochrane Database

of Systematic Reviews 2001, Issue 1. Art.No.: CD001218. DOI:
10.1002/14651858.CD001218. This version first published online: 22
January
2001 in Issue 1, 2001.