Triptans in 2021 are still the best acute therapy drugs for migraine in spite of the arrival in 2020/2021 of 4 new drugs for acute migraine therapy.  Triptans treat migraine acutely better than the new drugs, act fast, and are cheaper since they are all generic. Medical insurance provides good coverages for all the triptans.

The new drugs Reyvow, Nurtec, Ubrelvy, and Quitalpa are currently name brand acute therapy drugs which are more expensive now than all the triptans.

Interested in learning more about Triptan use for Migraine? Then read my article, “How to Treat Migraine Headache” on my website, www.doctormigraine.com.

Triptans have side effects that limit patient tolerance. However. there are strategies that help using them which will be discussed in this article. Most persons with Migraine tolerate triptans well, but others may have side effects. It would be helpful to have a thorough discussion of Triptan side effects.

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

Triptan Side Effects:  Common side effects are: dizziness, injection site reaction, sedation, vertigo, nausea and vomiting, flushing sensation, tingling sensation, and an unpleasant taste.

Other possible side effects include: asthenia, a burning sensation, chest pain or discomfort, neck pain, neck stiffness, numbness, throat irritation, feeling of heaviness, flushing, sensation of pressure, and sensation of tightness.

Less common side effects are: Abdominal or stomach pain, anxiety, blurred vision, changes in patterns and rhythms of speech, chills, confusion, and muscle cramps and stiffness.

Migraine is an inherited, familial neurological problem present in 25% of women and 6% of men. Migraine is moderate or severe headache which is often one-sided, throbbing, disabling, and associated with sensitivity to light and sound and nausea and vomiting.

For women migraine is their most common medical condition and more prevalent than hypertension, diabetes, heart disease, or arthritis.

Migraine should be treated quickly, at the very beginning of the headache, or the beginning of the aura.

Migraine attacks may last from 4-72 hours and the prevalence of Migraine is presented in the graph below

Read my Mini Book on Migraine Here

Related questions.

Do triptan side effects prevent use of these drugs?

Triptans for acute treatment of Migraine are the gold standard treatment for Migraine all over the world. Triptans have changed the practice of Neurology now giving millions of patients effective, rapid treatment of their migraine attacks. Triptan side effects are real but not common enough or severe enough to prevent their remarkable widespread and universally accepted global use.

The side effect profile differs for the triptans.

Almotriptan 12.5mg, Naratriptan 2.5mg, and sumatriptan 50mg have the lowest risk of developing side effects. Neurologists should choose one of these 3 drugs first when prescribing a triptan. A common problem here, in my experience, is that the referring general practice or internal medicine doctor has already written one of the other triptans for the patient before I see them and the patient has paid their copay and often started that drug before I meet them.

Triptan side effect profiles relate to whether they produce active metabolites or have high lipophilicity. Eletriptan and Rizatriptan produce active metabolites. Almotriptan has the lowest lipophilicity, a fact likely reducing its side effect profile.

Many persons are, understandably reluctant to change to a different triptan because of the pricing and effort of going to the pharmacist. Probably the headache doctor faced with this dilemma should only change the triptan if the patients relates to suffering considerable side effect and lack of headache response to the previously prescribed triptan.

Different insurance tiers exist.

Another problem with this scenario is that major medical insurance companies have different “tiers” of drug coverage and they list their arbitrarily chosen #1 triptan as being cheaper than other triptans.

What if a patient can’t tolerate one of the triptans?

Triptan side effects are dose related. Hearing side effects in the office on return visit the doctor can reduce the dose and still provide effective Migraine therapy.

For instance, when sumatriptan first came out in 1991 as Imitrex it was dosed as a 6 mg subcutaneous injection, which still is the most effective dose of all the 7 different triptans. The first oral dose was a 25 mg tablet, which was used for a few years, and the the 50 mg dose, and finally the most commonly used dose of 100 mg came out.

If a specific patient has significant side effects on using the 100 mg dose, the doctor may write for the 50 mg sized tablet, which will hopefully work for Migraine treatment and eliminate or diminish side effects.

The important thing to remember is that a triptan taken at onset can give a headache free experience in 2 hours for 80% of migraineurs. Triptans block the release of the inflammatory neurochemicals Neurokinin A, Substance P, and CGRP which effectively cause migraine symptoms.

Over the counter drugs like NSAIDS, caffeine, or Tylenol don’t block the release of the neurochemicals and are only mildly effective. Opioid narcotics and butalbital drugs have no place in the treatment of Migraine.

Why is Sumatriptan used so often?

Sumatriptan has always been the most common go-to triptan because of the different dosing forms-nasal spray, 3 sizes of tablets, and 3 sizes of subcutaneous injection. It was the first to come out and its insurance coverage is more prevalent.

Using sumatriptan a Migraine patient can take an oral dose for a developing Migraine and then inject with 6 mg sc in 2 hours if the headache hasn’t responded to the pill.

Also the sumatriptan sc 6 mg dose works in 10 minutes and gives a dose in the brain of 100 mg while the 100 mg generic tablet works in 30 minutes and provides a brain dose of 30 mg.

Injectable 6 mg sumatriptan is the fastest and highest dose triptan Migraine dose available.

What about switching to another triptan?

The migraine literature and headache practice has shown that switching to second triptan because of limiting side effects of the first triptan used, will work 60 % of the time.

What is the reason for the triptan side effects?

Migraine causes cerebral arteries to vasodilate and one of the ways triptans work is by causing cerebral smooth muscle vasoconstriction. Sometimes the smooth muscle in the esophagus or trachea also contracts, giving the very common triptan side effect of chest or neck tightness. Explaining this process to patients helps them understand and often accept the observed symptoms as not being serious so they may continue with their triptan therapy.

Can anything be added to an acute therapy sumatriptan dose that will help?

Glaxo, the original maker of Imitrex, did the original pharmacological research that answered this question when they brought out Treximet, a combo drug of 85/500 mg of sumatriptan and naproxen sodium.

After this was used clinically, many Migraine articles showed that using 500 mg of naproxen sodium with any of the triptans would work better for Migraine treatment.

Four of the triptans have side effect problems when taken with other drugs. 

These problems are:

Relpax (eletriptan)—is contraindicated with antifungals, macrolide antibiotics, or protease inhibitors.

Maxalt (rizatriptan)—requires a 50% decreased dose when taken with Inderal (propranolol).

Frova (frovatriptan)----should have a decreased dose when used with Birth Control Pills and Inderal (propranolol).

Zomig (zolmitriptan)---should have a decreased dose with Tagamet (cimetidine).

If the doctor and the patient abide by these problems, the listed triptans should work well for acute migraine treatment.

General triptan rules

Don’t use triptans with a personal or strong family history of coronary artery disease, TIA, or stroke.

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 40 minutes.)

Don’t mix the triptans or take with ergotamine within 24 hours. This means one shouldn’t mix sumatriptan with eletriptan, or any other triptan, within 24 hours. Ergotamine drugs are Cafergot, Wigraine, DHE, or Migranal.

Available triptans

• Zomig (Zolmatriptan) 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). Dose at onset 2.5 or 5 mg, may repeat in 2 hours. Also comes as a dissolvable tablet 2.5, 5 ZMT and as a nasal spray 2.5, 5 mg. Rebound potential. Limit to 2 treatment days/week.

• Maxalt (Rizatriptan) comes as a 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 (Propranolol). Dose is 1 at onset, may repeat in 2 hours, or take another dose 2 hours later. Maxalt is the only triptan that can be dosed 3 tablets/day. Max 30 mg/day. Rebound potential. Limit to 2 treatment days/week.

• 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. Dose is 1 at onset, may repeat in 2 hours. Rebound potential. Limit to 2 treatment days/week.

• Relpax (Eletriptan) Comes as a 20 and 40 mg tablet. The 40 mg tablet seems to work the best. Dose is 1 at onset, may repeat at 2 hours. Contraindicated with Antifungals, Macrolide Antibiotics, and Protease Inhibitors. Rebound potential. Limit to 2 treatment days/week.

• Amerge (Naratriptan)—2.5 mg tablet which is the initial dose. May repeat in 2 hours. Onset is 1-2 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.

• Frova (frovatriptan) ---Onset 1-2 hours. Good 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. Thus, 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.

     Drug                Onset             Usual dose               Maximum 24 hours       Duration of Activity

     Imitrex

     Sumatriptan    

     Oral tablet      15-30 min        50-100 mg                200 mg                            2.5 hours 

     Treximet         15                     1 tablet                      2 tablets                          same

     Nasal Spray   10 min            5, 20 mg                   40 mg                              same

     Subcu 10 min              3, 4, 6 mg                  12 mg                              same

     Dose Pro         10 min             6 mg                          12 mg                              same  

     Zomig

     Zolmitriptan

     Oral tablet    30 min              2.5, 5 mg                  10 mg                                 3 hours

     Nasal Spray   10 min             2.5, 5 mg                   10 mg                                same

     Maxalt

     rizatriptan    30 min              10 mg                        30 mg                                2-3 hours

     Axert

     Almotriptan  30 min              6.25, 12.5 mg          25 mg                                4 hours

     Relpax

     Eletriptan     30 min              20, 40 mg                80 mg                                4 hours

     Amerge

     naratriptan   1-2 hr                2.5 mg                      5 mg                                    6 hours

     Frova

     Frovatriptan 1-2 hr                2.5 mg                      5 mg                                   26 hours 

Triptans, SSRI/SNRI drugs and Serotonin Syndrome.

The FDA has applied a warning to all triptans since they came out , first as sumatriptan in 1991, of rare development of Serotonin Syndrome for Migraine patients who chronically took SSRI/SNRI drugs and one of the triptans. The FDA has never changed this warning. All over America, everyday neurologists’ office are faxed a letter from the pharmacist of a patient for whom he has ordered a triptan, listing the warning.

What have US migraine experts said about using triptans and SSRI and SNRI drugs?

In a recent review, most physician migraine experts did not recommend that triptans and SSRIs or SNRIs be discontinued unless symptoms arise.

What is Serotonin Syndrome?

The symptoms of serotonin syndrome are restlessness, hallucination, loss of coordination, tachycardia, changes in blood pressure, fever, nausea, vomiting, or diarrhea.  The risk is estimated to be less than 0.03% of patients and life-threatening events are less than 0.002%.

Who figured out the truth about using SSRI and SNRI drugs with triptans?

Dr. Randy Evans, a headache neurologist in Houston, was the man who investigated the problem and figured it out.  Dr. Randy Evans found that the FDA warning was wrong.

Triptans block the release of 5HT 1D receptors which are part of the migraine cycle, thus stopping the release of the inflammatory neurochemicals Neurokinin A, Substance P, and CGRP which cause the migraine headache.

Dr. Evans obtained information about the triptans utilizing the Freedom of Information Act and was able to find that the 5HT receptor active in triptan/SSRI/SNRI relationships was not a 1D receptor.

Because of this, there is little risk of triptans setting off the serotonin syndrome when given conjointly with SSRIs or SNRIs.

Want to learn more about Serotonin Syndrome? Read my article on my website, www.doctormigraine.com. Please click here to read.

Read my Big Book on Migraine Here.

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All the best.

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Britt Talley Daniel MD