Do NSAIDS Cause Medication Overuse Headache?

Do NSAIDS Cause Medication Overuse Headache?

NSAIDS is a mnemonic.  The letters make up the name; like SOB means shortness of breath to a doctor and the phrase really has no other meaning.  (Joke)  NSAIDS means “Non-steroidal anti-inflammatory drugs.”  These are class 2 over the counter or sometimes doctor prescription only pain killers and anti-inflammatory drugs.

Steroid hormones are made in the adrenal gland, which looks like Napoleon’s hat sitting on top of the kidneys in the back of the abdomen on both sides of the body.  Ad means “next to” and renal means “kidney.”  Cortisone, an artificial steroid hormone, was isolated by two Mayo Clinic doctors who won the Nobel Prize in Physiology and Medicine in 1950.

Common names for cortisone as it is now used in medicine are:  prednisone, hydrocortisone, medrol, solumedrol, or Decadron.  Cortisone drugs have significant side effects and their use is restricted to treatment for serious medical problems like rheumatoid arthritis.

NSAIDS are not cortisone drugs, have reduced anti-inflamatory effect, and have fewer side effects than cortisone.  When these drugs came out and were name brand, they all were prescription only.  But later they were released without need for a prescription (over the counter) at a lower dose.

An example of this would be Motrin, which came out as name brand and a doctor’s prescription as 400 mg, 600 mg, and 800 mg size.  Motrin is ibuprofen which is Advil and Advil came out over the counter at a dose size of 200 mg.

Medical side effects of NSAIDS are GERD (gastro esophageal reflux disorder) with symptoms of heartburn, nausea, vomiting, diarrhea, or headache.

Gastric reflux—heartburn

Gastric reflux—heartburn

NSAIDS are a common cause of medication overuse headache.

Do NSAIDS Cause Medication Overuse Headache?  Yes, NSAIDS are a very common cause of Medication Overuse Headache (MOH), especially in patients with migraine.  The International Classification of Headache Disorders III says that taking common NSAIDS, one pill 15 days a month may cause MOH.  Tylenol, aspirin, and caffeine are also in this group but are not classified as NSAIDS.  MOH and GERD are co-morbid which means that the two medical problems come together more commonly than chance.

Too many pills for migraineurs = Medication Overuse Headache.

Too many pills for migraineurs = Medication Overuse Headache.

 

Related questions.

What are the common NSAIDS used now in the United States?  The list would be:

aspirin

celecoxib (Celebrex)

diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)

ibuprofen (Motrin, Advil)

indomethacin (Indocin)

naproxen (Aleve, Anaprox, Naprelan, Naprosyn)

ketorolac (Toradol)

oxaprozin (Daypro)

piroxicam (Feldene)

What are the most common side effects of using NSAIDS?

nausea

vomiting

diarrhea

constipation

decreased appetite

rash

dizziness

headache

drowsiness

kidney failure (primarily with chronic use),

liver failure

ulcers

prolonged bleeding after injury or surgery.

What is the relationship between NSAIDS and medication overuse headache?  The problem here is that many persons may get daily, chronic headache, or an aggravation of headache by overtreating (1 pill>15/days/month) with these drugs.  Medication overuse headache happens with aspirin, Excedrin, and Tylenol (acetaminophen) also, but these drugs aren’t NSAIDS.

1.Overuse.  Use of NSAIDS more than 15 days a month can aggravate headache or cause daily headache.  This problem is worse for patients who overuse pain killers and have inherited the migraine gene and have had mild migraines before which hasn’t been for them a big problem, or they have migraine aliases like sinus headache, hungry headache, or menstrual headache.

2.TTH and migraine patients also.  Some patients with Tension Type Headache can also get medication overuse headache with overtreating.  Commonly the patient has lived with their episodic, mild migraine headaches for years but then they get into trouble when they start treating frequently with NSAIDS, taking multiple doses every day, and then they end up in the ER or headache doctor’s office with severe headaches with migraine features—one sided, throbbing, severe, behind one eye or on one side of the back of the head, with nausea/vomiting, and sensitivity to light and sound.

3.Serotonin levels drop.  Medication overuse headache causes serotonin, a calming brain neurotransmitter, to decrease and this results in psychiatric symptoms of insomnia, anxiety, panic attacks, decreased concentration, and irritability.  SRIs, serotonin receptive inhibitors, are approved by the FDA for treating depression, anxiety, and panic disorder, and many of these patients present in the neurologist’s office with daily headaches and taking an SRI like Lexapro, Prozac, or Paxil which isn’t working well because MOH is dropping their serotonin.

4.On the edge.  Many of these MOH patients have been on the edge of overuse headache for some time.  They may drink a lot of caffeine daily, like regular coffee (10oz-135 mg of caffeine) or Starbucks coffee which has 3X as much caffeine.  They may be under stress at work, in a relationship, or concerning their family and stress is always the number one migraine trigger.

Life in the fast lane.

Life in the fast lane.

5.Maybe the patient has never been given the best acute therapy drug for migraine-a triptan.  Maybe they’ve always treated their migraine headaches with an NSAID and no kind internist or general practice doctor has ever eferred them to a headache specialist.or prescribed the best drug for acute therapy at onset of migraine, which is a triptan.  There are now 7 triptans, 5 of them for regular migraines with medication effect onset in 30 minutes for oral drugs—sumatriptan, rizatriptan, eletriptan, zomatriptan, and almotriptan.

6.Triptans for menstrual migraine.  Two of the triptans are special niche headache drugs for menstrual migraine because they last so long—naratriptan 6 hours, and frovatriptan 26 hours.  But the problem with these long acting drugs is that their onset of action is 1-2 hours and the 5 acute drugs with onset of 30 minutes are a better choice for most non-menstruating migraine patients.

7.Educate to withdraw drugs.  The treatment for the common problem of medication overuse headache which is (80-90% of new patients in a headache doctor’s practice) is to educate and instruct the patient to withdraw from the offending medication.  Often times the doctor may start a preventive drug, use DHE shots or nasal spray, or timolol eye drops for acute therapy of headache and often a week of prednisone.

Stop overtreating. You get to take meds 2 days a week. Your teacher, Miss Scrimshaw.

Stop overtreating. You get to take meds 2 days a week. Your teacher, Miss Scrimshaw.

8.GERD.  Use of NSAIDs for headache can also cause or aggravate heartburn or GERD (gastroesophageal reflux disorder) which will usually improve after they see their headache doctor and improve by quiting taking their caffeine and NSAIDs,

9What are the triptans?  The first triptan to come out was injectable Imitrex (sumatriptan) 6 mg subcutaneously which is still the best, the strongest, and the fastest dose for treating migraine, but the next dose released was the 25 mg oral tablet which had an indication at first for treating adults, but now would be considered to be a pediatric dose.

The other point to be considered here is that the headache literature says that changing to another triptan is successful 60% of the time.  So, if a patient develops a side effect with sumatriptan, another triptan, like rizatriptan may work well with no side effects.

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 with legislators and so far, neurologists and headache doctors have not been successful getting legislators to eliminate 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.

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

The first, the fastest, the strongest, the BEST triptan—Injectable Sumatriptan 6 mg SC. Yeah it’s a tiny shot, but it really works.

The first, the fastest, the strongest, the BEST triptan—Injectable Sumatriptan 6 mg SC. Yeah it’s a tiny shot, but it really works.

 

10.Available Triptans

Pharmokinetics  Onset Usual Dose  Max

Imitrex                                   

(Sumatriptan)                                   

Oral tablet PO 15 min 50-100 mg       200 mg

Nasal Spray     20 min 20 mg  5-20 mg

Subcutaneous  10 min 4, 6, 3 mg        12 mg

Sumavel          10 min 6 mg    12 mg

Alsuma            10 min 6 mg    12 mg

Treximet          15 min 1 tablet 2 tablets

Zomig                        

(Zolmitriptan)                                   

Oral tab ZMT  30 min 2.5, 5 mg         10 mg

Nasal Spray     10 min 2.5, 5 mg         10 mg

Maxalt                                   

(Rizatriptan)  30 min 10, 20 mg        30 mg

Axert                         

(Almotriptan) 30 min 6.25, 12.5mg   25 mg

Relpax                                   

(Eletriptan)    30 min 40 mg  80 mg

Amerge                                  

(Naratriptan) 1-2 hrs 2.5       5 mg

Frova                         

(Frovatriptan) 1-2 hrs 2.5 mg 7.5 mg

11.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 is 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..

The Migraine Timing Cycle

The Migraine Timing Cycle

12.Definition of Migraine.  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 neck in the jugular veins to the liver, and are discharged in the toilet after 3 days.

If one treats migraine with pain killing  over-the-counter drugs or NSAIDS 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.

13.No, No drugs for 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 butalbital in America is a political issue to be resolved with legislators and so far, neurologists and headache doctors have not been successful getting legislators to change the law to eliminate the use of it.

14.Limited drugs for migraine.  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.  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.

15.Migraine transformation from episodic to chronic.  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 absolute limitation of all painkillers and triptans to no more than 2 days a week.

Transformation of Dr. Jekyl to Mr. Hyde.

Transformation of Dr. Jekyl to Mr. Hyde.

16.Migraine timing cycle.  I have a more thorough discussion of the migraine timing cycle on my webpage at www.doctormigraine.com/blog/categories/general migraine. 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.

17.Headache free?  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 usually 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

18. Check this out.  Read my webpage articles at www.doctormigraine.com/blog/categores/medication overuse headache.  Scroll down and read my article on medication overuse headache, the picture with a frowny face made up of pills.

19.Who Gets Medication Overuse Headache?  Persons with migraine who overtreat get Medication Overuse Headache.  The old term for Medication Overuse Headache is “Rebound Headache.”  The terms are synonymous, but Medication Overuse Headache is preferred.  According to the International Classification of Headache III, chronic migraine is 15 or more headache days a month, 8 of which have migraine features and episodic migraine is less than 14 headache days a month.

About 90% of persons with chronic migraine also have a diagnosis of medication overuse headache, a condition due to overtreatment with painkillers, caffeine, triptans, NSAIDS, opioid narcotics, or butalbital.  The cause of headache in the remaining 10% of persons with chronic migraine is uncertain.  Medication overuse headache occurs in 3-4 % of the world population, but chronic migraine occurs in 1-2 %.  Headache clinics have an 80-90% incidence of MOH in new patients

20.Persons with high baseline headache frequency get MOH.  The problem here is that only migraine patients release the inflammatory neurochemicals (neurokinin A, substance P, and CGRP) in the brain that are part of the migraine timing cycle.  So, 75 % of women and 94 % of men don’t release the neurochemicals and they don’t usually get daily headaches if they drink lots of coffee every day or use Advil, Tylenol, or Aleve frequently.

The majority of MOH patients have migraine, but there is also is a poorly understood inherited genetic quality, so that it is thought that not every migraine patient will get MOH, only certain ones.  The way doctors know them is that they eventually show up in the doctor’s office with severe, disabling headaches with migraine features, and with a history of frequently taking a lot of painkillers. 

Metabolism of the inflammatory chemicals occurs so that after the chemicals are released in the brain by the ganglia of the cerebral arteries and the trigeminal nerve.  The chemicals leave the brain through cerebral veins, are metabolized in the liver, and eventually end up in the toilet after 3 days.  The definition of episodic migraine as lasting 4-72 hours is not some abstract time period made up by a headache committee at a medical school.  72 hours is the real, continuously observed and charted period of time a migraine lasts. 

21.Headache transformation.  It is poorly understood scientifically exactly what happens when a drug, like caffeine, is consumed by a migraine patient and suddenly, usually after several days, caffeine doesn’t help treat the migraine by causing vasoconstriction of a dilated cerebral artery.  But what happens is with the continued presentation of caffeine, the brain releases the neurochemicals continuously and the headache which started Monday, starts lingering by Wednesday, and then after that every time the patient takes their caffeine (Excedrin, Starbucks grande vente) the brain releases another load of neurochemicals and the headache lasts till Thursday, and the caffeine comes again, and the headache lasts till Friday, and so on.  This called transformation from episodic to chronic migraine headache.

22.A fire in the brain.  I tell patients using Advilas an example to tell a story, but it could be any painkiller such as caffeine, Advil, Tylenol, Aleve, NSAID, opioid narcotic, triptan, or butalbital, that overtreating with Advilis like putting kerosene on a wood fire that just keeps burning as long as there is wood and kerosene.  I compare MOH to diaper rash.

I know it’s a dirty job.  I am the father of 5 kids.  The baby has loose stools with diarrhea from some virus they got at school.  Stool in the colon is where it is supposed to be, the bowel can handle it, but when it gets on the baby’s buttocks, then it causes inflammation and redness and pain.  The mother will clean up the baby and then put cortisone cream on the baby’s bottom to soothe the inflammation.

I know this is gross, but it makes the point and is similar to what goes on in the head of a migraine patient who overtreats and gets daily headaches.  The cortisone treatment here also is done by headache doctors when they give a week of prednisone orally (prednisone is cortisone) while they detox a patient off their painkillers.

Patients come in really puzzled—all their tests are normal, blood work, medical exam, CAT or MRI scan of the brain.  Okay, they don’t have a brain tumor or a ruptured aneurysm, what is causing their severe disability, headache, nausea and vomiting, light and sound sensitivity?  It takes awhile and a lot of doctor talking and explaining for them to learn that the cause is all the medications they are taking, which through the migraine process—inflames their brain.  Migraine and medication overuse headache are neurochemical problems that doesn’t show up on usual ests.

Good luck with this.

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Britt Talley Daniel MD