Migraine is a commonly present, disabling, oftentimes life-long neurologic problem.  You are born with it and it is in your family.  For women Migraine is their most common medical problem affecting 25% of all women, and 6% of men.  12% of the world population has Migraine.

The next problem is what to do about it--ignore it and just treat when it comes up with over-the counter-drugs, or take a better thought out, more aggressive course and see a doctor and get on prescription drugs?  Which method works better?

Read my Migraine Mini book here.

This is an article by Britt Talley Daniel MD, member of the American Academy of Neurology, migraine textbook author, podcaster, YouTube video producer, and blogger.  

As a general rule prescription drugs work better than over the counters (OTC). Migraine is a complicated process that releases 3 neuroinflammatory chemicals. Triptans, and Gepants block the release of these chemicals and effectively treat Migraine attacks.

Over the counter drugs are only mild anti-inflammatory and pain killer drugs that are effective for only a small number of persons with mild Migraine attacks.

Related questions

How do OTCs work?

Over the counter drugs have no specific remedial action in the complicated Migraine process and only work on the pain part of a Migraine.  Yet, they are relatively cheap since Advil (ibuprofen) 200 mg #6 tabs is $6 dollars at Walmart.

Over the counter drugs modulate pain, but do not produce a headache free experience.  Over the counter drugs do not help with nausea, and if too many of them are taken over a short period of time, they increase the acid in the stomach, producing symptoms of gastritis with pain and nausea.

How do triptans work?

One of the seven triptans, taken at onset of a Migraine, interacts in the Migraine Timing Cycle to stop the release of Neurokinan A, Substance P, and Calcitonin Gene-related Protein (CGRP).  Triptans act as agonists for serotonin 5-HT1B and 5-HT1D receptors at blood vessels and nerve endings in the brain. 

Triptans enter into the pathophysiology of the Migraine process by blocking the release of the 3 neurochemicals that cause a Migraine headache.  Triptans give a headache free experience for 70-80 % of patients by 2 hours. Over the counter drugs can not do this.

Triptans treat all of the symptoms of a Migraine—the severe throbbing pain, nausea, and sensitivity to light and sound.  Plus, they are all generic now, have few side effects, and are reasonably priced.

Nine tablets of 100 mg sumatriptan costs $15 dollars, but you have to see a doctor to have one of them prescribed for you.  They are not available over the counter.  Triptans do not treat Tension Type Headache.

Read my article, “How to Treat Migraine Headaches,” on my website, www.doctormigraine.com. Please click here to read.

The new acute Migraine treatment drugs, Nurtec OTC, Ubrevly, and Reyvow also work, but not as well as the triptans.

What is the Migraine Timing Cycle?

It is generally thought that local vasodilatation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous pain pathways is a key mechanism underlying the generation of headache pain associated with migraine.

This activation of the 'trigeminovascular system' is thought to cause the release of vasoactive sensory neuropeptides, especially CGRP, that increase the pain response. The activated trigeminal nerves convey nociceptive (pain) information to central neurons in the brain stem trigeminal sensory nuclei that in turn relay the pain signals to higher centers where headache pain is perceived.

It has been hypothesized that these central neurons may become sensitized as a migraine attack progresses. The 'triptan' anti-migraine agents (e.g., sumatriptan, rizatriptan, zolmitriptan naratriptan) are serotonergic agonists that have been shown to act selectively by causing vasoconstriction through 5-HT1B receptors that are expressed in human intracranial arteries and by inhibiting nociceptive transmission through an action at 5-HT1D receptors on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brain stem sensory nuclei. These three complementary sites of action underlie the clinical effectiveness of the 5-HT1B/1D agonists against migraine headache pain and its associated symptoms.

The Migraine Timing Cycle

1 Trigeminal activation and cerebral arterial vasodilation.

2 20-40 minutes later the neurochemicals CGRP, Neurokinin A, and Substance P are released by the migraine process from ganglia to inflame the trigeminal nerve, the arteries, and later the thalamus.

3 At 2 hours the arteries vasodilate and are inflamed.  Blood pulsing through dilated, inflamed arteries causes pulsatile, pounding headache.

4 Past 3 hours the thalamus, also known as the pain center of the brain is turned on by the migraine process.

For most persons with Migraine taking a triptan at onset can give a headache free experience at 2 hours.  No other acute therapy drug can do this.  Triptans for the past 30 years have been and still are the best drugs for acute therapy for Migraine. 

Read my full article on “The Migraine Timing Cycle,” on my website, www.doctormigraine.com. Please click here to read.

What about the new acute therapy drugs that came out in 2020?

The triptans are all generic now and are cheap when compared with the new 2020 acute therapy drugs which are all name brand only and expensive.  These drugs are— Nurtec (Rimegepant), Ubrelvy (Ubrogepant), and Reyvow (Lasmiditan).

These new drugs are all delivered orally.  Nurtec and Ubrelvy block the CGRP receptor, while Reyvow works on 5HT 1E receptors which inhibit trigeminal nerve pain pathways.  Reyvow also inhibits release of neurotransmitters and neuropeptides. 

These drugs do not work as well as the triptans for Migraine treatment.  They could be tried for the 20-30% of persons who do not respond well to triptans and for Migraine patients who have cardiovascular restrictions for use of triptans, like a post-myocardial infarction patient or someone with out-of-control hypertension.

However, the advice for using Reyvow restricts the Migraineur who takes Reyvow from driving or operating machinery for 8 hours after, which is a significant restriction.  How could a Migraine patient working in an office treat their Migraine at work and ever be able to drive home by dinner?

What drugs are meant by over-the-counter drugs?

This list of drugs is usually divided into caffeine/aspirin drugs, NSAIDs, and Tylenol.

The names of the caffeine/aspirin drugs are:

Excedrin

BC Powder

Vivactin.

Caffeine/aspirin drugs are mainly used to treat Migraine headaches, caffeine for cerebral vasoconstriction and increased absorption of aspirin, and aspirin for pain.

The names of NSAIDs are:

Advil (ibuprofen) 200 mg

Aleve (naproxen) 200 mg

Orudis (ketoprofen) 50 mg 

Relafen (nambutetone 500 and 750 mg

Celebrex (celecoxib) 50, 100, 200, 400 mg

Clinoril (sulindac) 150, 200 mg

Motrin/Ibuprofen 400, 800 mg

Naprosyn, Anaprox (naproxen) 250, 375, 500 mg

Indocin (indomethacin) 25 and 50 mg

Orudis (ketoprofen) 75 mg           

Feldene 10/20 mg

Nonsteroidal anti-inflammatory drugs decrease pain and lower fever, and, in higher doses, decrease inflammation.

The names of Tylenol are:

Acetaminophen

Paracetamol

Tylenol is a medication used to treat pain and fever.

Could over-the-counter drugs aggravate the nausea that comes with Migraine?

All the over-the-counter drugs listed above increase the amount of acid in the stomach which can cause gastritis and aggravate a stomach ulcer or gastric reflux.

Triptans treat the nausea that comes with Migraine in 80% of persons.  

Do all acute therapy drugs for Migraine cause Medication Overuse Headache (MOH)?

Unfortunately, most of the usual acute therapy drugs for Migraine, except DHE, dihydroergotamine, can cause MOH if too many of them are used.

The International Classification of Headache Disorders v. 3 (ICHD) which is the “Bible” for classification of headache states that Medication Overuse Headache may develop from:

A. Non-opioid simple analgesics >15days/month (like Tylenol, caffeine, or Advil).

B. One triptan> 10 applications (pill, sc shot, nasal spray) per month.

C. Opioids or Analgesics combined with barbiturates >10days/month.  Barbiturates (like Fiorinal, Fioricet, Phrenilin, Esgic, or generic butalbital).

There is no place for the use of opioid narcotics or butalbital for Migraine and these drugs are notorious for causing MOH.

Caffeine is said by the American Headache Society to be the number one drug that causes MOH.

Are there limits to the amount of drugs to treat headache?  The deal here is to limit all headache drugs, over the counters, and triptans to no more than 2 days a week.  This usually means taking only 1 acute therapy drug at a time.

Persons who drink several cups of coffee a day and who have Migraine are warned.

Read my article, “How Does Caffeine Affect Migraine?” on my website, www.doctormigraine.com. Please click here to read.

Migraine causes the 3 neurochemicals to come out and it takes 3 days for these neurochemicals to be metabolized, to get from the brain, circulate through to the liver to be metabolized, and then leave via the toilet.

A transformation occurs if one continues treating with painkillers or headache medications more than 2 days a week; then every time a person takes one cup of coffee or one Tylenol, that individual gets 3 more days of neurochemical release and the headache just keeps on coming.

This process in the brain is like putting lighter fluid on a charcoal fire, the fire, or headache, keeps burning until one stops using the lighter fluid.  The reaction is exactly like this.

What can you take for Migraine headache relief if you have MOH?

There are other drugs to use for this, but patients need to work with a headache doctor for this type of treatment.

Dopamine antagonists

The dopamine antagonist group consists of drugs are usually indicated for psychiatric disorders such as schizophrenia or bipolar disease.  They may be used "off-label" for treatment of Medication Overuse Headache.  "Off label" means the drugs work for another indication than the usual illness the medication treats—a drug for bipolar disorder works for MOH.

An "off label" example would be that chlorpromazine is indicated for bipolar disorder but also helps treat Migraine.  Chlorpromazine works for Migraine patients because dopamine is a major brain neurochemical released during the Migraine process and blocking dopamine helps headache.  This group of drugs may have a side effect of drowsiness.

Dopamine antagonists may be used.  Dopamine modulates processes involved in migraine such as nociception, autonomic response, and vasodilatation.  Dopamine antagonists also help with many of the symptoms of Migraine including nausea, vomiting, mood changes and fatigue.  Dopamine antagonists are appropriate for patients who do not respond to triptans.  They should be limited to using only 10 days per month.

Examples of Dopamine antagonists:

Prochlorperazine (Compazine) can be given 5/10 mg oral or rectal 25 mg repeat q 6-8 hours PRN for status Migrainosus.

Chlorpromazine (Thorazine) 25 mg orally every 6 hours to a total dose of 100 milligrams for cluster headache or refractory Migraine.

Droperidol (Inapsine) intramuscularly 2.7 mg, is highly effective for intractable Migraine, but it can prolong QT on an EKG test and should not be used with patients with heart disease.

Haldol (Haloperidol) 5 mg IV gives significant relief or 2 mg/5 mg oral haloperidol outpatient treatment to abort headache.

Prokinetic Agents

The prokinetic drugs listed below are usually indicated for treating nausea or vomiting but also help Migraine.

Oral metoclopramide (Reglan) can be used 10 mg three times a day (TID).

Promethazine (Phenergan) can be given 12.5, 25, 50 mg every 4-6 hours.

Atypical Antipsychotics

Olanzapine (Zyprexa) can be used orally as 2.5-5 also 7.5, 10, 15, 20 ODT mg nightly for 5 to 10 nights to break status Migrainosus.

Quetiapine (Seroquel) at 25 to 75 mg orally, reduces headache frequency and severity, can be used as rescue medicine.  Quetiapine may help with sleep and headache for treating medication overuse headache also.

The most beneficial oral medication is olanzapine followed by chlorpromazine.

NSAID

Ketrolac 60 mg IM every 6 hours.  An NSAID (nonsteroidal anti-inflammatory drug) which may be given intramuscularly as an injection 60 mg as single dose or 30 mg every 6hr, not to exceed 120 mg/day.

Betablocker eye drop.

Timolol (Timoptic) eye drops 0.5 % solution 1-2 drops in each eye every 2-4 hours.  Betablockers work orally for migraine prevention but do not work for acute therapy, yet some patients respond well to Timolol given as an eyedrop and there is no rebound problem.  See my article on Timolol eye drops under acute treatment of Migraine.

What is the difference between Chronic Migraine and Medication Overuse Headache?

These are both terms from the International Classification of Headache Disorders.  Chronic Migraine is a term that implies having headache over 15 days a month, 8 of which have Migraine features.  Episodic headache refers to have 8 or less headaches a month.

These Migraine features are that the headaches are severe, usually one-sided, throbbing, and associated with nausea, vomiting and sensitivity to light and sound.  A significant number of these patients have MOH which is now 80-90% of new patients seen in specialty headache clinics and affects 4 million people yearly.

MOH may come from over treating with simple pain killers like caffeine, Tylenol or Advil, opioid narcotics, pain killers with barbiturates, or triptans.  Patients typically rotate different drugs and take many drugs at the same time that may cause MOH.

After a while the preexisting headache problem, which is usually migraine, but may also be tension type headache, becomes transformed from an intermittent to a chronic headache problem.

It is like what happens to the patient who drinks a lot of coffee every day and then gets a headache when they do not.  When the brain becomes sensitized to these drugs repeat dosing causes neuro-inflammatory chemicals to be released in the brain which keeps the headache going.

There are two features to medication overuse headache:

1. Daily or very frequent headaches which may come with sensitivity to light and sound, nausea, and irritability.

2. This syndrome causes serotonin, a calming brain neurochemical, levels to drop so the patient may also develop anxiety, depression, poor concentration, panic attacks, and insomnia, which also are core symptoms of the disorder. 

First these folks need to learn that they are taking too many painkillers or headache medicines and that this causes or aggravates headaches.  If you do not believe me then Google “medication overuse headache from caffeine, or Tylenol, or Advil, or sumatriptan” and read what comes up.

When to see a Headache specialist?

When headache is more frequent and severe and medical treatments have not worked, or the diagnosis is uncertain, then it is time to see a headache specialist.  When headache is disturbing your life, your work, your general health, and your sleep, it is time to see a headache specialist.

Headache specialists have their own personal interest in headache, and they like to read about it in scientific journals and books.  They go to headache meetings.  Many of them have migraine themselves.  During training they may take a headache fellowship program.

Because most headache patients a doctor sees occur in persons who are generally healthy and have a normal neurologic exam and tests, headache doctors gain a lot of experience seeing the same kind of problem over and again.

Eighty to ninety percent of new patients to a headache clinic have medication overuse headache which is a syndrome due to overuse of pain killers and headache medication.

The doctor may hear that their patient used to have episodic headaches lasting hours to 2-3 days but during the past 6 months the headaches have occurred continuously and daily.

The headache pattern may have migraine features of being one-sided, severe, throbbing or stabbing pain, nausea or vomiting, and sensitivity to light or sound.

Then on interview the doctor may find the patient is drinking 4 cups of Starbucks coffee a day and taking tramadol several times a day.  Caffeine is the number one drug over the counter that causes medication overuse headache and Tramadol is an opiate narcotic that should never be used for headache because of addiction and headache provocation issues.

The doctor will do a careful neurologic exam on that patient and review or order tests such as blood work or CAT or MRI scan, but the rest of the interview will be educating that patient that he needs to stop caffeine and tramadol, either suddenly or slowly by tapering off.

Then the doctor will substitute treating the daily severe headache with 1 or 2 weeks of cortisone, which usually helps, start a preventive drug, like one of the new CGRP drugs, and offer an acute treatment drug like Timolol eye drops or DHE which do not cause the medication overuse problem but help treat the severe headaches.

At this point, to learn more about treating medication overuse headache, go to my website at www.doctormigraine.com/blog/medicationoveruseheadache and read my full article on medication overuse headache, it is the one with the frowny face.

There are concerning symptoms, “red flags,” that should provoke a patient to see a headache specialist in the clinic or go to the ER?  These symptoms may be:

Complicated headaches with unusual symptoms.

Feeling weak or numb on one side of the body; change in level of consciousness, trouble walking, change in memory, vision, or ability to speak.

Having a migraine longer than 72 hours (the International Classification of Headache Disorders 3 states that a migraine may last only 4-72 hours.

Persons with complicated medical or psychiatric problems such as patients with fibromyalgia, asthma, epilepsy, insomnia, anxiety, depression, or panic disorder.

Having headaches more than 2 days a week.

Headaches that make you miss social events, school, or work.

Headaches that affect relationships with family, friends, or coworkers.

Headaches occurring while pregnant or nursing.

Thunderclap Headache: very severe sudden onset headache that reaches its maximum immediately (within a couple of minutes).  Thunderclap headaches require emergent medical evaluation to rule out intracerebral aneurysm bleed.  These headaches are “the worst ever, explosive, like something ruptured in my head.”

Positional Headache: headache that substantially changes in intensity in association with changes in position, such as standing from lying or vice-versa.

Exertion related headaches: headache from straining at the toilet, sneezing, or coughing.

New onset headaches--especially if the patients are over 50 years of age, or if there are other medical conditions like cancer, or a blood clotting disorder.

A documented change in headache occurrence, such as an increase in frequency or change in headache characteristics.

Constant headache which is always on the same spot in the head.

Migraine with aura patients that have long or quick onset aura symptoms.  Migraine aura symptoms may be the visual aura which may be a bright light or zig-zag image, numbness in the one side of the body which start in the fingers, next move to the forearm, then arm, and then commonly to the same body side of the face or cheek.

Migraine with aura patients may also have trouble speaking, called dysphasia, where they cannot find the right word to say and cannot write or read well.

The progression of these aura symptoms should have a slow onset and resolve within 60 minutes.  But if they do not improve in an hour, emergency medical attention is then required with a visit to the ER and emergency scanning to rule out a stroke or a brain tumor.

Headache that never goes away.

Headache plus systemic symptoms such as fever, chills, weight loss, or night sweats.

New headache in a patient with cancer.

Headache that keeps getting worse over 24 hours.

Headache after head injury.

Headaches that come with visual blackouts, pain while chewing, body arthritis, or weight loss (temporal arteritis).

Read my article, “When To See A Headache Specialist?” on my website, www.doctormigraine.com. Please click here to read.

What about taking preventive medication?

When to Start Preventive Therapy for Migraine?

Preventive therapy may be called daily treatment or prophylactic treatment.  It means that the doctor intends his patient to take a daily drug to reduce the intensity and frequency of the patient’s Migraine headaches.

This is really a drug trial and the patient should be asked to log their headaches in a diary and use the drug for 6-8 weeks to judge results and improvement, or no response for their Migraine headaches before giving up. 

When to Start Preventive Therapy for Migraine.  Preventive therapy should be considered for patients who:

Experience 3-4 or more migraines per month

Have Chronic Migraine-defined as 15 headache days per month, 8 of which have Migraine features.

Present with medication overuse headache.

Who prefer this type of treatment?

Have significant pain that hampers their life.

Take a lot of over the counter, narcotic, opioid or barbiturate pain killers.

Do not get enough relief from the acute treatment medication they are currently taking.

Have side effects from drugs used for acute therapy.

Related questions:

1. Preventive treatment might not be an option for patients who:

Can control their headaches with anti-inflammatory drugs (NSAIDS) like naproxen or ibuprofen.

Have other health conditions that do not allow taking preventive drugs.

Might already be taking drugs that would not mix well with any proposed preventive medication they might take.

Prefer treatments that do not involve taking medications.

Can get relief from exercise relaxation therapy, stress-management, or biofeedback.

Prefer a medical device called Cefaly, which is an FDA approved treatment for migraine prevention.  It is worn on the head, delivers electrical impulses, and is used once a day for 20 minutes.

Are pregnant, as migraine usually improves in the 2nd or 3rd trimesters of pregnancy.  Most OB doctors allow their pregnant Migraineurs to use Tylenol and neurologists allow triptans and CGRP drugs when needed.

Read my article, “When to Start Preventive Therapy For Migraine?” on my website, www.doctormigraine.com. Please click here to read.

So, what is to be done?  Take an over-the-counter drug or a prescription?

I must admit to having been a Neurologist, headache specialist for over forty years, and I would answer—see a doctor and start prescription medication for Migraine!  If the Migraines occur more than 3-4 attacks per month, consider one of the CGRP preventive drugs.

Consider this, most persons with very mild Migraine, the take 2 Aspirin and take a short nap group, are not spending their time reading web articles about treatment of Migraine, because they do not need to.  Their Migraines are not very severe, and they are living with their “hungry,” “menstrual,” “sinus headaches” very well, thank you, and they do not need to see a doctor until or if they develop MOH sometime in their lives.

However, persons who are having Migraine attacks more than 3 or 4 days per month are skirting on the edge of Medication Overuse Headache and a sit-down visit with their regular doctor might discover this risk.

I usually ask the patient “what is the usual time between onset of your Migraine, and the peak?”  It is said that over-the-counter drugs work better for Migraineurs with long, like 60 minutes, onset to peak Migraine onset times.  If it is a short time, then short acting triptans like 6mg sc sumatriptan or 5 mg zolmitriptan nasal spray which both work in 10 minutes are preferred.  Playing the triptan game one wants to get the medicine in the patient’s brain before the neurochemicals are released.

Many persons have it in their heads that they do not want to take a daily preventive drug and I understand that with the older drugs for this such as amitriptyline, topiramate, Depakote, and propranolol which have track records of only preventing Migraine about 30% of the time.  They work, but not that well.  However, the new CGRP preventive drugs mentioned above are something else.

They are a subcutaneous injection, but it is given only once every month.  Remember type 2 diabetics get shots 4 times a day unless they are on an insulin pump.  It reminds me of the conversations I have had with younger adolescent or sometimes teenage Migraine patients who could not swallow a pill.

The situation with the new CGRP preventive drugs is that they have rare, mild side effects and they work so very well it is amazing.  Fifty percent of Migraine patients get 50% attack reduction, another 25% get 75% Migraine reduction, and another 25% get complete 100% Migraine reduction!

I have seen many patients in this “no Migraine attack” group and recall that these had been persons dealing with long-term Migraine for much of their earlier life.

The question of cost of CGRP drugs presents itself.  They are more expensive, and many insurances require the patient to fail previous treatment with one of the older preventive drugs. 

Although the pharmaceutical creators of the new GCRP drugs, such as Eli Lilly, Teva, Amgen, and other drug companies have aggressively marketed CGRP medications and even given the drugs away for free to get people to try them, sales growth has been slow. Only Aimovig and Emgality are used by at least 10 percent of Migraine patients.

This is a sad treatment experience from my point of view considering how prevalent and how disabling Migraine can be.  I have heard that if a person has no medical insurance but submits their financial data to one of the large pharmaceutical firms, they may be able to get the medicine.  This situation requires that the patient work with their doctor, which would likely be more successful if their doctor were a headache specialist, because the pharmaceutical drug maker usually mails the free prescription to the doctor’s office for the patient to pick up.

Check out my Big Book on Migraine here.

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All the best.

Britt Talley Daniel MD