When to Treat Migraine Headache?

 

When to Treat Migraine Headache?

Migraine headache occurs in 12% of the American population.  Twenty-five % of women and six % of men have migraine headache.  Migraine headache is the 5th most common cause of disability and the 10th most common cause of a visit to the emergency room.  The three most painful conditions are migraine, a kidney stone, and childbirth. 

When to Treat Migraine Headache?  Migraine headaches should be treated at the onset of headache pain with a triptan.  Migraine headaches have four phases:  prodrome, aura, the attack, and postdrome.  Migraine patients should either treat at prodrome, the onset of aura, or the onset of an attack. 

The prodrome may come 24 hours before the attack occurs and may consist of fatigue, drowsiness, food cravings, depression, irritability, trouble concentrating, phonophobia, and increased urination or diarrhea.  If these symptoms can be recognized by the patient as common and reliable occurring symptoms before the attack occurs, then the patient should treat before headache occurs at prodrome with a triptan.

If a migraine with aura patient has a visual aura before the headache starts, then the patient should treat at the beginning of the aura with a triptan.  Migraine visual auras usually last 20-30 minutes, but can be as long as an hour before headache follows.  Treating at prodrome or aura means that treatment is early, and the drug use is more likely to succeed.  The problem is some patients have their aura at the same time their headache starts, and these persons should treat at the onset of their aura, which comes at the same time as the start of their headache.  Some patients have their aura near the end of the attack of headache, but they should have treated at the beginning of the headache. 

Only migraine headache patients have the altered brain neurophysiology that leads to the headache, so that 94% of men and 75% of women who don’t have migraine, don’t have these physiologic changes, only migraine patients do this.  The migraine process releases three different neuropeptides and these chemicals cause arterial dilatation and inflammation of the trigeminal nerve, the arteries and the thalamus.  Triptans if taken early will stop this stage of the migraine process.  Over-the-counter drugs don’t do this.  That is why triptans, which came out in 1991 as injectable Imitrex subcutaneous 6 mg, have been so successful and important for treating migraine all over the world.  It can be said that 80% of persons who treat their migraine at the onset of headache as outlined above, may be headache free in 2 hours.  

Comments regarding the available triptans

Triptans

General triptan rules:  don’t use with a personal or strong family history of coronary artery disease.  Don’t use with uncontrolled hypertension.  Limit the dose in children, the elderly (defined here as over 65 years old.), and patients with basilar artery or complicated migraine (aura symptoms over 60 minutes.)  Don’t mix the triptans or take with ergotamine within 24 hours.

Common triptan side effects--chest tightness or pressure, near fainting, neck/back pain which may be burning, warm or hot, dizziness, or drowsiness.

Imitrex (sumatriptan) most effective when given via a gun type injector.  The medicine comes in a vial with a needle and is loaded into the injector like a bullet.  The medicine is then injected subcutaneously by pushing a trigger.  This is a very slick, high tech system.  The dose is 1 injection (6,4,3 mg) at the onset of a migraine, with one repeat dose within 1 hour (max 12 mg/24hrs).  An oral pill exists also: 25 mg (for kids) or 50, 100 mg (for adults).  The usual dose for an adult is 50-100 mg at the onset of headache (max 200mg/day).  An Imitrex nasal spray is also available as 1-20 mg squirt per nostril per migraine.  For Imitrex the highest drug levels are obtained with the shot, medium drug levels with the pills, and low drug levels with the nasal spray.  Some patients find the Imitrex nasal spray tastes bad when it goes down the back of the throat.  Rebound potential. Limit to 2 treatment days/week or 10 pills/month.

Zomig (zolmitriptan) should decrease the dose by 50% if taken with Tagamet (Cimetidine).  Comes as a 2.5 mg or 5 mg tab to be taken one as needed for migraine, trying the 2.5 mg dose size first and moving up to 5 mg (max 10mg/day).  Also comes as a dissolvable tablet 2.5/5 ZMT and as a nasal spray 5 mg. Rebound potential.  Limit to 2 treatment days/week or 10 pills-sprays/month.

Maxalt (rizatriptan) comes as an MLT (melt in your mouth) 10 mg wafer and 5/10 mg tablets. Both are absorbed in the stomach and the MLT, which some patients consider more convenient, is absorbed slower than regular Maxalt. Should reduce the dose by 50% if taken with Inderal (propanalol).  Max 30 mg/day.  Rebound potential. Limit to 2 treatment days/week or 10 pills/month.

Axert (almotriptan) Comes as a 6.25 and 12.5 mg tablet. In controlled clinical trials, single doses of 6.25 mg and 12.5 mg of Axert tablets were effective for the acute treatment of migraines in adults, with the 12.5-mg dose tending to be more effective.  If the headache returns, the dose may be repeated after 2 hours, but no more than two doses should be given within a 24-hour period.  Maxalt has the fewest side effects of all the triptans.  Rebound potential. Limit to 2 treatment days/week or 10 pills/month.

Relpax (eletriptan) comes as 20 and 40 mg tablet.  The 40 mg tablet seems to work the best.  If there are no good results the 40 mg tablet may be repeated at 2 hours.  Contraindicated with Antifungals, Macrolide Antibiotics, and Protease Inhibitors.  The longest acting of the acute therapy triptan list, works orally in 30 minutes. Rebound potential. Limit to 2 treatment days/week or 10 pills/month.

Amerge (naratriptan)—2.5 mg tablet which is the initial dose.  May repeat in 2 hours.  Amerge is a specialty niche migraine medication for those whose migraine generator in the brain produces a long, slow onset profile.  This drug stays around long enough to outlast this type of migraine.  The duration of activity is long—6 hours as opposed to 2-3 hours for most of the other triptans, except Frova.  Rebound potential. Limit to 2 treatment days/week or 10 pills/month.

Frova (frovatriptan) --- Like Amerge it is a niche, specialty triptan for migraineurs with long duration headache generators.  It has a very long duration (26-hour half-life) and lasts four times longer than any other triptan.  It is the drug of choice for menstrual migraine.  Taking birth control pills or Inderal may increase blood levels of Frova.  Treat with an initial 2.5 mg dose, may repeat in 2 hours.  Rebound potential. Limit to 2 treatment days/week or 10 pills/month. 

 Pharmokinetics           Onset        Peak     Half-Life   Usual Dose    Max Daily Dose

Imitrex (sumatriptan)

   Oral tablet PO          15 min        2 hrs       2 hrs           50-100 mg     200 mg

    Nasal Spray             20 min                       2 hrs          20 mg             40 mg                     

    Shot-subcutaneous  10 min      15 min      2 hrs      one shot-6mg  two shots-12mg

Zomig (zolmitriptan)

Oral tab ZMT               30 min     3.5 hrs      3 hrs          2.5-5 mg        10 mg

Nasal Spray                  10 min     3.5 hrs      3 hrs          5 mg               10 mg

 

Pharmokinetics           Onset        Peak     Half-Life   Usual Dose    Max Daily Dose

Maxalt (rizatriptan)    30 min 1.5-2.5 hrs    2 hrs          10-20 mg          30 mg

Axert (almotriptan)     30 min      1-3 hrs    3-4 hrs.      6.25/12.5 mg     25 mg

Relpax (eletriptan)       30 min      1.5 hrs    4-5 hrs       40 mg                80 mg

Amerge (naratriptan)   1-2 hrs      2-3 hrs    6 hrs          2.5 mg               5 mg 

Frova (frovatriptan)     1-2 hrs      2-4 hrs    26 hrs       2.5 mg               7.5 mg  
  

migraine timing cycle 300 dpi 1200.jpg

The migraine timing cycle.

There are 4 steps in the migraine process which I like to call the migraine timing cycle.  The first step is trigeminal inflammation by the brainstem.  Then the second step at 20-40 minutes the ganglion of the nerve and artery in the brain start to release the Neuropeptides:  Neurokinin A, Substance P, and CGRP.  Then at about 2 hours the release of these chemicals causes the 3rd step--meningeal artery vasodilatation, and the 4th step at 3-4 hours inflammation of the thalamus, a deep nucleus in the center of the brain which is called the “pain center” of the brain.  The 4th step is also called “Central Sensitization” because steps 1,2, and 3 occur in the skull but are outside the brain (trigeminal nerve, nerve and arterial ganglions, cerebral arteries.)  Step 4 inflames the thalamus, a deep nucleus inside the brain.

 Migraine is defined by the International Classification of Headache as lasting 4-72 hours and this is done not for some trivial, abstract, academic reason using 3 days or 72 hours as the time a migraine may last, but rather because that’s how long these inflammatory neuropeptides stay in the body.  They come into the brain, drain down the veins to the liver, and are discharged in the toilet after 3 days.  If one treats migraine with over-the-counter drugs like Advil or Tylenol, they don’t stop the release of the neuropeptides and the inflammation, yet triptans will do that and that’s why they are such important and effective drugs for treating migraine.

Patients with migraine should treat with triptans but never with opiate drugs or drugs with butalbital, like Fioricet.  Butalbital is a barbiturate drugs and is, in my opinion, the  worse drug in the world that causes medication overuse headache.  It has been banned in every country in the world except in Canada and the United States.  The use of these this drug in America is a political issue to be resolved about legislators and so far, neurologists and headache doctors have not been successful in eliminating the use of it.

Caffeine, Tylenol, Advil, Aleve, and triptans can cause medication overuse headache if taken too much.  The general rule of migraine patients to prevent medication overuse headache is to limit over-the-counter painkillers and triptans to no more than 2 days a month.  Medication overuse headache is the current term for persons who have chronic migraine from overuse of medication.  It used to be called rebound headache which is an old term.  Chronic migraine is defined by the International Classification of Headache as being 15 headaches or more per month, 8 of which have migraine features.  Episodic headache is defined as 14 or less headache days per month.

If the patient uses over-the-counter medications or a triptan, a transition occurs so that after several migraine headaches have occurred within a week or 2, every time the patient takes caffeine or Tylenol or a triptan, the inflammatory neurochemicals are released and they stay in the body for 3 more days and so the migraine process becomes continuous.  It is sort of like putting lighter fluid on a fire which makes the fire continue to burn.  If one considers that migraine can generate chemicals that last 3 days and multiple that by 2 days, the result may be 6 days of neurochemical release per week.  So, if the doctor allowed his patient to take Tylenol or a triptan 3 days a week that’s 9 days with chemical inflammation, more than the 7 days in a week, and explains the limitation of all painkillers and triptans to no more than 2 days a week.

 I have a more thorough discussion of the migraine timing cycle on my webpage at www.doctormigraine.com.  To get to it click:  blog, categories, then general migraine to find the above picture and discussion.  However, this timing cycle points to the reason why migraine should be treated early with a triptan.  The patient has only 20-40 minutes after the onset of pain before the neurochemicals are released and a triptan drug will block the release of these chemicals.  It’s just that simple.  Most patients don’t know to treat early and therefore the chemicals are released and inflame the trigeminal nerve, the arteries, and the thalamus.  The patient returns and states that the triptan doesn’t work.  It is reported that triptans well help migraine headache any time during a migraine, even if is treated late, but unless migraine is treated at onset, the patient will not be headache free within 2 hours.

 Headache free means that all migraine symptoms are gone:  headache, nausea, sound sensitivity, light sensitivity, olfactory sensitivity, mental cloudiness.  In my office I go over and over again this point with patients to treat early and then the next time they in they report that they did well with the triptan, and the migraine was gone early.  Many patients tell me that they get relief within 15 or 30 minutes, which is less than the reported time it takes the drug to work as published by the FDA. 

 Related Questions

 Why don’t patients treat their migraine early with a triptan?

1) Hoarding--patients only get a limited supply of drugs every month and they don’t want to run out.  “I’ve got to save them.”  “It’s the end of the month and I’ve only got one Maxalt left.”  Insurance companies limit sumatriptan 100 mg tablets to only 9 per month.  Some insurance companies will only give 2 triptans per week and if I write #10 per month the patient has to go back to the drug store every week to get their prescription filled.  One study found that 37% of patients with insurance plans that limited the number of triptans per month, didn’t treat with their triptan at the onset of a migraine and had more ER visits for headache per year than patients without insurance (79%) who were more likely to take their medicine at the onset of a headache.

2) Expense--with insurance there now is a co-pay of $10-40 per prescription which can add up if the patient is taking several drugs.  However, all of the triptans now are generic and cheaper than name brand.  Patients can sometimes find coupons online that are a better deal than using their drug insurance plan.

3) Nihilism--“Nothing works.”  Many migraine patients have ingrained previous experience that nothing will work.  These are the migraine patients who have been using over the counter meds, opioid narcotics, or butalbital for years and have developed medication over use headache and triptans don’t work in that situation.  Nothing works in this situation except DHE.  See my article on my webpage on Medication Overuse Headache at blog>categories>medication overuse headache.  Cursor down to the frowny face made of pills near the bottom and read the article. This group of patients with low expectations that anything will ever work includes migraine patients who have been prescribed triptans but were never instructed to treat at onset and when early and mild.  When these episodic migraine patients finally try their triptan early, the same drug that they have always waited to use, they are pleasantly surprised with how well the drug works.  They come back for their neurologic recheck visit with a smile on their faces.  They just never knew how to treat their migraine.

4) Fear of over treatment--“I don’t want to take too much medicine.”  Experienced migraine patients know that if they take “too much medicine” it may, like the snake on the ground that you try to bash on the head, rise up and bite you on the leg, resulting in more headaches.  In general, one is only supposed to treat headache 2 days a week.  This “two days a week treatment rule” is true for over caffeine, over the counter NSAIDs, opioids, and the triptans.  Each of the triptans has an individual total maximum recommended dose per 24 hours.  For instance, for oral Imitrex (sumatriptan), the patient may take up to 200 mg in 24 hours which is 2 of the 100 mg tablets, usually one at onset and another in 2 hours if needed.  However, the FDA approved dose in 24 hours for Maxalt (rizatriptan) is 30 mg, which is 3 of the 10 mg tablets as one 10 mg tablet at onset and then one every 2 hours up to 3 or 30mg.  Rizatriptan is the only one out of seven triptans that may be given as 3 doses in 24 hours.

Lawrence D. Newman, MD[i], director of The Headache Institute at St. Luke-Roosevelt Hospital Center in New York, NY, speaking in an interview with Primary Neuro News in 2007 was asked the following question:

“If you had a single piece of advice you could give to every healthcare professional treating patients with episodic migraines, to ensure that fewer of their patients with migraine would progress to chronic daily headache, what would it be?”

Newman’s response was:

“To limit the number of acute medications that they’re giving at one time, not to be liberal with refills, so that you keep a close watch on how many medications patients are using and initiate preventive treatment in appropriate patients.  If you do that, you can proactively, in many patients, prevent medication overuse headache and the progression of the disorder.”

5) Concern for side effects--the triptan treats the migraine but the patient dreads the side effects--the chest tightness or pressure, near fainting, neck/back pain which may be burning, warm or hot, dizziness, or drowsiness.  This is where the treating doctor should explain that triptan side effects are not serious.  Many patients hearing this will gladly tolerate a mild side effect for a miraculous drug that treats a bloody migraine!  These patients should be instructed that triptan side effects are “dose related” and merely decreasing the dose, like going from 100mg sumatriptan to 50 mg may avoid the side effect.  If that doesn’t work, then that patient is due for a trial of a different triptan.  There are 5 acute onset drugs which work in 30 minutes—oral sumatriptan, rizatriptan, zomatriptan, eletriptan, and almotriptan.  Sumatriptan and zolmitriptan nasal sprays work quickly for migraine, onset in 10 minutes, but they give a low dose of medication.  Subcutaneous sumatriptan 6 mg works in 10 minutes and gives a dose of medicine in the brain of 100 mg, while oral sumatriptan works in 30 minutes, gives a brain level of 30 mg, and nasal spray sumatriptan works in 10 minutes but a dose of medicine in the brain of only 10 mg.  This data is from an article by the American Academy of Neurology.  As a headache neurologist and writer, I and everyone else in the field have always wanted to know which is “the best triptan?”  That clearly is injectable sc 6 mg sumatriptan, just like the drug company, Glaxo brought it out back in 91 as the first triptan.

Migraine patients who fail to respond to one triptan have been shown to respond favorably to other triptans. The best reason for this response is that the migraine headaches are different, the patients are different, and the triptans are different.  Try another triptan.

6) Waiting--“I just wanted to wait and see if it would go away.”  “I wasn’t sure it was a migraine.”  “Sometimes they just go away on their own.”  “I was waitin’ to see if it was gonna be one of those.”  AND IT USUALLY IS.  This is the old “I want to wait to see what happens with this headache game of Russian roulette” patients play which is unproductive and usually self-defeating.  They wait and they lose.  Migraine sufferers should consider that 57% to77%[ii] of patients who take a triptan early are headache free at 2 hours.

Dahlof and Mellberg from the Gothenburg Migraine Clinic in Sweden were quoted in Neurology Reviews in 2007 as finding a “substantial difference in total pain in early versus late treatment with triptans.”  They found the difference was greatest with oral triptan treatment, as compared with injections and nasal sprays and early treatment had a “substantial impact” on pain, aura, nausea, photophobia, and phonophobia.  Dahlof and Mellberg stated:

“Overall, the total pain during the 72-hour follow-up period was lower after early treatment.  Pain intensity scores at zero, one, and two hours after treatment were also dependent on time of treatment administration.”

7) Ignoring night time migraines--“I woke up at 4 in the morning with a headache.  What can you do?  I just rolled over and went back to sleep, but I had a terrible wake up headache in the morning.”  This is the nocturnal migraine coming at the end of a REM event.  Many patients with headaches like this wake up in the morning with the migraine still there 2 or 3 hours later.  They are already at stage 4 of the migraine process in central sensitization and the triptans don’t work as well then.  These “early morning migraines” last all day and sometimes the next.  These patients should be instructed to sleep with their triptan pill open and available on the table with a glass of water next to their bed so they can sit up briefly, take their medicine early, and then go back to sleep.  Also, injectable sumatriptan or intranasal sumatriptan or zolmitriptan may help nocturnal headaches because they work in about 10 minutes as opposed to 30 minutes for the other acute onset triptans.  This is how to treat nighttime headache at onset when early and mild.

8) Excuses, excuses--“I was at work and I left my medicine at home.”  “I was in the middle of an important meeting.”  “I was driving to work in traffic.  It rained and the freeway backed up.”  “I had a deadline to get a project finished that day and I couldn’t do anything else.  I couldn’t even eat lunch.”  “My dog ate my:  medication, term project, homework…”

These are patients who haven’t faced up to a reality of life--migraine is a chronic problem.  It’s genetic and part of the genome.  The possibility of getting a migraine is always there, particularly if there are aggravating factors--stress, menstruation, barometric pressure change, skipped meals.  The Boy Scout motto is “Be prepared,” and migraine patients need to be Eagle scouts.  The patient needs to have their medicine with them at all times.  An attack could come anytime.  Get a grip.  Treat with a triptan at onset when early and mild.

Mild migraine headaches may be treated with over counter drugs such as caffeine, Tylenol (acetaminophen), Advil (ibuprofen) and Aleve (naprosyn), but more severe migraine headaches should be treated with a triptan and triptans are the best drugs for acute therapy for migraine.

Triptans are:  Imitrex (sumatriptan), Maxalt (rizatriptan), Zomig (zomatriptan), Relpax (eletriptan), Amerge (naratriptan), and Frova (frovatriptan).  They may be administered as an oral tablet, nasal spray, or subcutaneous injection.  Research studies show that more patients should use a triptan for their headache than an over the counter drug.  So, the fact is that many migraine patients undertreat their migraines with over the counter drugs like caffeine or Advil when they should be using a triptan.

I am a neurologist, headache doctor, and have written 3 textbooks on migraine (go to www.doctormigraine.com, scroll to bottom of first page, click shop books which links to my Amazon books.  I have a website on migraine at www.doctormigraine.com, and a Pinterest account at Britt Talley Daniel MD.