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Acute Migraine Headache Treatments

iHeadache Electronic Headache Diary

A large number of patients with migraine do not see a physician. Some do not realize they have migraine and are not taking therapy that is as effective as the therapy that is specifically approved for migraine. Others are taking over the counter pain medications and are doing fine. Many are taking over the counter medications or sinus medications for their migraines and are not doing well. Prior to the 1990’s, the prescription medications available for migraines were either not very effective, butalbital containing medications or narcotics. The butalbital containing medications and narcotics are potentially addictive and are much more likely to cause rebound headache than the newer prescription medications. The 1990’s brought a revolution of treatment for migraine headaches with the release of a new class of medication, the triptans. The triptans are available in multiple forms including tablets, nasal spray, and subcutaneous injection and all are extremely safe. They are clearly more effective than the medications that were previously available for migraines. With theses medications, we began to look not just headache symptom relief or headache pain relief, but rather total treatment of migraine symptoms including nausea, light and noise sensitivity, as well as sinus symptoms and neck pain. Patients with ischemic heart disease or ischemic brain disease should not use triptans. Physicians who are headache specialists do not agree with the FDA warnings concerning serotonin syndrome. If you are interested in this topic, than please read this

How Can I Help My Doctor Help Me

Having accurate counts of all of your acute headache medications is essential to good headache care. Dr. Loftus designed iHeadache (an iPhone and iPod Touch app) to do this. This program also tracks disability and symptoms to aide in proper diagnosis of your headaches.

What is a triptan?

Imitrex® (sumatriptan) was the first triptan brought to market. Imitrex is available as an injection, nasal spray, and tablet. The injection is associated with the highest incidence of side effects, which can be annoying but are quite transient. Another problem with the injection is its relatively high price however; sumatriptan injection is now available in generic form. The tablet is the most convenient, easiest, and commonly used form of Imitrex however the injection is clearly the fastest migraine reliever on the market. An alternative to both the injection and tablet is the Imitrex nasal spray, which sometimes works faster than the tablet. The sumatriptan tablet is also generically available. The combination of Imitrex with an NSAID is called Treximet® and is now available. It is clear the combination of Imitrex with naprosyn works better than either by itself. Another form of sumatriptan that is available is called Onzetra®. It is a nasal powder that is blown into the nose. This results in a deliver device that is faster than the nasal spray with few side effects compared to the sumatriptan shots.

The only other triptan offered in multiple forms is Zomig® (zolmitriptan) which comes in a tablet, dissolving tablet and nasal spray. The tablet and dissolving tablet are of equal efficacy with nearly identical times of onset for headache relief. By comparison, the Zomig nasal spray has an onset that is significantly faster than either Zomig tablet but not as fast as the Imitrex injection. The nasal spray may be effective in patients who do not respond to the tablets. Studies of the nasal spray included patients who were potentially already using Zomig® tablets and this may have biased the results. Without head-to-head data using patients who have never used triptans it is impossible to say with certainty which drug works faster.

The other triptans on the market; Amerge®, Axert®, Frova®, Maxalt® and Relpax® are only available in tablet form. Maxalt®, like Zomig® comes in a dissolvable. It is important to note that the dissolvable form is not absorbed more quickly into the bloodstream than the oral tablet.

The oral tablets are divided into two groups, the fast acting and slower acting. The faster acting group includes Axert®, Imitrex®, Maxalt®, Relpax® and Zomig®. The slower acting group includes Amerge® and Frova®.

The following table shows a comparison of the various triptans, the formulation that is available and their consumer characteristics.

Name Formulation Desirable Characteristics Other Characteristics
Imitrex® Injection Fast acting; highest response rate, most side effects Most expensive; most painful.
Imitrex®
Zomig®
Nasal spray Good for oral vomiting; works a little faster than tablets. Twice the price of the tablet.
Onzetra® Nasal powder Good for oral vomiting; faster than sumatriptan nasal spray; less side effects than sumatriptan shots.
Axert®
Imitrex®
Maxalt®
Relpax®
Zomig®
Tablet Good response to headache for lower cost. All fast acting tablets are similar in groups of patients but individual patient response may vary from drug to drug. All triptans listed are now generically available. Other options work faster but will cost more.
Amerge®
Frova®
Tablet Last longer than faster acting tablets. Generically available. Does not work as fast.

Maxalt®
Zomig®

Dissolvable Tablet Does not require water to swallow. Does not work faster than regular tablet.

Patients not currently satisfied with their current migraine treatment have preferred the triptans. They have also been shown to be cost effective. A typical response for the fast acting tablets will be substantial pain relief in less than 2 hours. The sumatriptan injection and nasal powder can begin working in less than 15 minutes. Occasionally, the triptans are used in migraine prevention where the trigger is clearly identified and predictable such as with menstrual cycles for example. Triptans are much likely to work when the headaches are daily and work much less effectively when the headaches are nearly daily.

Which triptan should I use?

The answer is relatively simple. Patients should use the triptan that works best for them. In Dr. Loftus’ practice, if a fast acting triptan is being prescribed, he gives the patient a couple of sample tablets of each of the triptan medications to try on different headaches.

Despite what others will claim, Dr. Loftus does not believe that any of the fast acting oral triptans can claim superiority to any other oral triptan medication. The studies demonstrating Relpax® to have superiority to other oral triptans have several design flaws. The most significant, in his opinion, is the inclusion of patients who previously used competitor's medication in the study. He has reviewed the Relpax® versus Encapsulated Sumatriptan studies in detail. Both current Imitrex® users who would probably actually favor Imitrex®, and prior users who would favor Relpax® are included. In addition, the Sumatriptan used has never been shown to be bioequivalent to brand name Imitrex® in migraine patients. The company and author have data that could address some of these concerns but will not share it.

Cambia

Cambia® is the only NSAID that is FDA approved to treat migraine. Its cost is in the same ballpark as the non-generic triptans. It has none of the typical triptan side effects so it is also an excellent therapy for those patients who cannot tolerate triptans for safety reasons. Cambia should be avoided in those patients that cannot tolerate or are told to avoid NSAIDs. Although no acute treatment is FDA approved for chronic migraine, NSAIDs like Cambia have been shown to continue to have efficacy in these types of patients where triptans tend to lose their efficacy.

For patients who do not respond to triptans or cambia, there is a group of medications based upon dihydroergoatmine (DHE). These medications, like the triptans, should not be used by someone with ischemic heart disease. The nasal form of DHE is called Migranal®. The response of the migraine to Migranal® is similar to the fast acting oral agents. Similar to the triptan drugs, Migranal® treats the entire migraine and its accompanying symptoms. It also seems to work well for patients who have failed multiple prior triptans. The only significant side effect is some nasal stuffiness. Injectable DHE is less expensive than nasal DHE but requires the patient to self-inject the medication. Unfortunately, Migranal® and injectable DHE are some of the older drugs that have risen in cost fairly dramatically. They are both single source generics.

Are triptans safe?

The triptans should not be used in patients with ischemic heart disease. All of the oral triptans cause approximately 5% of contraction of the coronary artery vessels. This is obviously not significant to patients unless a large percentage of the vessel is blocked by an obstruction in the artery known as a plaque. If any testing should be performed, each physician individualizes it for his or her patient. It should be noted the primary cause of heart attack in the age group of migraine patients is from plaque rupture, a sudden opening of the plaque and clot formation, and not from a slow narrowing of the artery.

Sphenopalatine Ganglion Block (SPG block)

SPG block is now possible using a device that is placed by a physician througth the nose. One of these devices is Allevio™. With this device, lidocaine, a local anethetic is used to produce the block. It also blocks the 2nd branch of the trigeminal nerve. This treatment not only treats an acute headache but appears to help prevent future headaches. There is limited controlled data at this time. Some insurances will pay for this therapy at this time. This therapy can safely be done during pregnancy. Bellaire Neurology currently offers this therapy to patients. Except in pregnancy, it is typically used as an adjunct to other therapies. You can learn more about SPG block here.

Gammacore

Gammacore® is an electronic device that delivers current to the Vegas Nerve by holding the device up to one's neck. It is FDA approved to treat acute migraine headaches as well as acute cluster headaches.can treat acute migraines very effectively without the need of adding a chemical into the blood stream. In sham controlled trials, about 50% of patient received pain relief more than 50% of the time at 2 hours. About 1/3rd were pain free more than 50% of the time. This is clearly the strongest data we have for any of the patient administered migraine treatments that have no systemic side effects. Although relatively expensive at $500 per month, it has several advantages besides the absence of side effects. It can be used multiple times per day and it can be used every day if needed. For full disclosure, Dr. Loftus is a speaker and physician trainer for this treatment. We keep one in the office for patient training as well. You can learn more about gammacore here.

Spring TMS®

Spring TMS® is an electronic device that delivers a magnetic pulse to the occipital lobe. It has been shown effective for the acute treatment of migraine with aura in a double blind sham controlled trial. It is the only acute treatment approved for migraine that targets the actual aura. At a cost of $250 per month, it can be very useful in frequent migraine aura. You can learn more about Spring TMS here.

Cefaly

Cefaly® is an electronic device that delivers current to a branch of the Trigeminal Nerve called the supraorbital nerve. There are multiple devices available as there is both a potential acute treatment mode and a preventative mode.  The cost of the device is up to $500 but this is a one time fee. The monthly cost of disposable pads is about $25. Like Gammacore® it has no systemic side effects. For acute treatment, a small open label study showed a 50% benefit but the double blind study - which has been completed - has not had its results posted. It does have a 60 day return policy so this is a relatively cheap therapy to try. You can learn more about cefaly here.

Coming Soon - Nerivio Migra®

Nerivio Migra® is an electronic device that delivers current to a nerve in the arm. The device is applied to the arm and an app on your smart phone is used to connect to it via Blue Tooth to activate it. The company is promising a fairly low cost per treatment. Not as low as $1-$2 per treatment but on the cost scale of the more expensive generic triptans ($10-15) per headache. This price is well under the expected price of the newer oral agents. The company expects regulatory approval during 2019.

Coming Soon - Oral CGRP medications - Rimegepant, Ubrogepant, Atogepant

Rimegepant (Biohaven) is an oral CGRP receptor antagonist that is being initially targeted for acute migraine but could, at least in theory, be used for migraine prevention if taken frequently enough. CGRP is released by some neurons of the trigeminal nerve and land on other neurons on the trigeminal nerve and appear to help maintain a migraine. Triptans and the new monoclonal antibody medications target this pathway. Triptans help to decrease release of the CGRP from the neuron. Rimegepant is designed to block the CGRP receptor to help end a migraine. It does not cause vasoconstriction (like triptans and dhe)) but it does block some vasodilitation. Some far, there is no public data related to its ability to treat prior triptan failures. From a business standpoint, this is critical as this is its largest market. Hopefully, we will see it in 2019 or 2020

Ubrogepant (Allergan) is another CGRP receptor antagonist. It has been demonstrated to treat acute migraine in multiple trials according to Allergan press releases. Like Rimegepant, it will not cause vasoconstriction but will block vasodilitation. Its business model will depend upon its ability to treat prior triptan failures. Allergan is expected to file for approval to the FDA in 2019. While Ubrogepant could act as a migraine prevention agent if taken frequently enough, it is unlikely Allergan will attempt this. Instead, Allergan is also developing Atogepant to fulfill this role. It too is a CGRP receptor antagonist but all of its public testing has been geared to using it as a preventative. It will presumably compete against the injectable monoclonal antibody drugs against CGRP (MAAC - Ajovy, Emgality) or its receptor (MAACR - Aimovig)

Coming Soon - Lamiditan

Lamiditan is a drug that targets the 5HT1F receptor. Like the triptans, this drug targets a serotonin receptor. It does not, however, target the serotinin 5HT1B receptor and therefore does not cause vasoconstriction of blood levels. It also does not like vasodilitation. Like Remegepant, its business success will primarily depend upon its ability to treat triptans failures. It will compete against Rimegepant and others for those patients that cannot safely take triptans or DHE compounds. Lasmiditan has been submitted to the FDA in November 2018 so we should see it in 2019.