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-inflammatory effect, and have fewer side effects.  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.  It can be dosed every four hours.

NSAIDS are a common cause of medication overuse headache.

This is an article by Britt Talley Daniel MD, member of the American Academy of Neurology, the American Headache Society, migraine textbook author, and blogger.

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 headache producing group but are not classified as NSAIDS. 

 Related questions.

1.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)

2.What are the medical side effects of using NSAIDS?

A common side effects of NSAIDS are GERD (gastroesophageal reflux disorder) which has symptoms of heartburn, nausea, vomiting, diarrhea, or headache.  MOH and GERD are co-morbid which means that these two medical problems come together more commonly than chance. Use of NSAIDs for headache can also cause or aggravate heartburn or GERD which will usually improve after they see their headache doctor and improve by quitting taking all their NSAIDS.

 

Gastric reflux—heartburn

Gastric reflux—heartburn

Other specific side effects of NSAIDS are:

nausea

vomiting

diarrhea

constipation

decreased appetite

rash

dizziness

headache, and medication overuse headache

drowsiness

kidney failure (primarily with chronic use),

liver failure

ulcers

prolonged bleeding after injury or surgery.

3.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.

 4.NSAID 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 just had mild migraines before which hasn’t been for them a big problem.

Migraine hides in the public experience, undiagnosed, with headaches that are not that bad and treated usually with over the counter drugs like Advil or Aleve.The patient may have migraine aliases like--sinus headache, hungry headache, nocturnal headache, let-down headache, week- end, Saturday or Sunday morning headache, or menstrual headache.

Too many pills for migraineurs = Medication Overuse Headache.

Too many pills for migraineurs = Medication Overuse Headache.

 5.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—headaches which are 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.

6.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.

The psychiatric symptoms usually improve when the patient detoxes off their painkillers and the headaches back off.

7.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 problems in their family.  Stress is always the number one migraine aggravating factor.

Life in the fast lane.

Life in the fast lane.

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.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 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, zolmitriptan, and almotriptan.

Eighty percent of patients who take a triptan at the onset for a migraine are headache free in 2 hours.  Triptans provide medication that is effective for acute therapy of migraine; the patient doesn’t have to take multiple doses of NSAIDs for days to get relief.  Patients taking triptans don’t need to take so many over the counter drugs for their migraine.

9.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.

10.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.

11. What 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.

12.Available Triptans

Pharmacokinetics  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

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

13. 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

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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 come n 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 of 30 minutes it takes for most of the generic triptans

20. Check this out.  Read my webpage article 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.

21. 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 for new patients

22. 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.  They don’t have the genetic make up of migraine and escape the problem of medication overuse  headache.

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 their 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 single migraine lasts. 

23. Headache transformation.  It is poorly understood scientifically exactly what happens when a drug, like Advil, is over consumed by a migraine patient and suddenly, usually after several days, Advil doesn’t help treat the migraine, but what happens is with the continued presentation of Advil, the brain releases the inflammatory neurochemicals continuously and the headache which started Monday, starts lingering by Wednesday, and then after that every time the patient takes their Advil the brain releases another load of neurochemicals and the headache lasts till Thursday, and the patient takes Advil again, and the headache lasts till Friday, and so on.  This is called transformation from episodic to chronic migraine headache.

24. A fire in the brain.  I tell patients using Advil as an example to tell a story, but it could be any painkiller such as caffeine, Tylenol, Aleve, NSAID, opioid narcotic, triptan, or butalbital, that overtreating with Advil is 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 a while 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—which releases inflamatory neurochemicals that inflames their brain.  Migraine and medication overuse headache are neurochemical problems that don’t show up on tests.

25. Known factors associated with medication overuse headache.

A. Caucasian background is a known statistical feature which is poorly understood.  Whether education, profession, economic status, or other factors were responsible is not certain.

B. Female sex.  This is easier to understand because women have 3 times more migraine than men.  But why women have so much migraine is not fully understood.  The American Migraine Study of 100,000 persons found 25 % of women had migraine, maxing out at age 42 years old, while 6 % of men had migraine, peaking at 28 years of age.  Whether its estrogen hormones, some genetic issue, or stress level, women have more migraine than men and therefore overtreat and get more medication overuse headache.  Also, migraine and depression are 50% comorbid.  Comorbid means the 2 medical problems occur more commonly than by chance and women have more depression and psychiatric disease than men.  Migraine and GAD (general anxiety disorder) and Panic disorder are comorbid 40 % of the time.  Woman have an increased tendency to treat pain with medication.

C. Lower education.  These persons have lower income with more irregular employment and problems providing medical insurance.  It may have to do with increased stress and lower insurance coverage resulting in an increase in use of over the counter medication to treat migraine.  Research studies have found that more patients who take triptans for treatment of migraine have a reduced incidence of MOH, but a person usually has to have insurance to see the doctor and buy the triptan medication.  Lower education jobs may be physically more intense and often are outside working outside in cold or hot environments which may aggravate migraine occurrence.

D. Previous marriage.  This is another sociological issue.  Divorce is extremely stressful for persons who go through it and the stress may last for 2-3 years.  There are also child-care issues, place of living changes due to house sales after property settlement, job losses, and economic changes due to payment for alimony, lawyers, and court costs.

E. Overweight.  Overweight persons often don’t exercise well, and exercise is a powerful stress reducing activity that raises endorphins, internal analgesic chemicals that help pain and give a good night’s sleep. 

F. Obstructive Sleep Apnea (OSA).   OSA may have an increased risk of myocardial infarction (heart attack) or stroke.  OSA and medication overuse headache are comorbid.  Symptoms of OSA are:  hypersomnia, the tendency to fall asleep during the daytime, such as while driving, reading, watching movies or TV, snoring-noise produced by compromised air travel during sleep, and sleep apnea.  Apnea is observance by a bed partner that the patient stops breathing during the night.  OSA occurrence is closely tied to overweight and can be treated by weight loss.

G. Frequent caffeine use.  The American Headache Society has said that the number one drug that drives medication overuse headache is caffeine.  Caffeine is a drug

H. Stressful life event in the previous year.  This factor relates again to anxiety, insomnia, and depression stemming from some stressful event.

I. Head injury.  The International Classification of Headache Disorders III has an entry called “Headache attributed to trauma or injury to the head and/or neck.”  The main problem here is if the patient with the head injury has migraine and later overtreats with NSAIDS.

J. High baseline headache frequency. 

K. Overusing medication.  This has been explained but I want to make a plea for TV, newspaper and magazine ads for over the NSAIDS, like Advil, for example to state that overtreating with Advil can cause medication overuse headaches, because most patients and even many doctors don’t know this.

MOH occurs in families that have a history of substance abuse and MOH.  Behavioral therapy can change the addictive mindset from “have pain—take a tablet” to other less harmful ways of treating headache.

L Comorbid depression.  Migraine and depression are 50 % comorbid, which means they come together clinically more frequently than by chance.  Brain serotonin levels are decreased with depression and drugs called SSRIs, selective serotonin receptor inhibitors. are commonly used in the practice of medicine to treat depression.  Migraineurs also have decreased levels of serotonin and serotonin receptors are found on trigeminal nerve and cranial vessels.  Triptans are the most successful drugs for acute therapy of migraine and they act on the trigeminovascular system to work.  The Mayo Clinic states that women have twice the incidence of depression.  Depression links to insomnia and poor sleeping with migraine in general and in MOH very specifically.

M. Smoking.  Smoking is always listed as an associated factor with medication overuse headache, but the reason is not well understood.  It may relate to addictive patients as nicotine is an addictive drug and persons who smoke, oftentimes drink alcohol. 

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All the best.

Follow me at:  www.doctormigraine.com, Pinterest, Amazon books, and YouTube.

Britt Talley Daniel MD