Imitrex vs. Maxalt, Zomig vs. Maxalt, Amerge vs. Relpax, Frova vs. Imitrex, Maxalt vs. Relpax, Zomig vs. Imitrex, Frova vs. Amerge, Imitrex vs. Treximet. Maxalt vs. Frova. Axert vs. Imitrex? How do you know which to choose?
Which triptan is best?
The triptans were created for the acute treatment of migraine. There are 7 triptans available and include Imitrex (Sumatriptan), Maxalt (Rizatriptan), Relpax (Eletriptan), Zomig (Zolmitriptan), Frova (Frovatriptan), Amerge (Naratriptan), Axert (Almotriptan), and Treximet (Sumatriptan/Naproxen).
So what are the best triptans to use? Well let’s back up a little first. The ergot based medications such as DHE (dihydroergotamine) and cafergot (ergotamine + caffeine) have been the oldest and most potent migraine abortive medications used, which are still used today. DHE is still a fantastic option for the acute treatment of migraine. However, the ergots often have more side effects (particularly ergotamine) for patients and eventually the migraine specific triptans were developed for aborting migraine.
Since 1992 (when Sumatriptan first became available), the triptans have been the first and only migraine specific abortive medications available up until 2020 when two new classes of migraine specific abortive medications FINALLY become available. These new abortives include the gepants (Ubrelvy, Nurtec, Zavspret) and ditans (Reyvow), and can be read about in more detail here.
How do the triptans work?
Triptans work by activating (agonist) the serotonin sub-receptor 5-HT1B. The result of activating this receptor is that it helps to constrict (narrow) the dilated inflamed pain-producing meningeal blood vessels which occurs during a migraine attack. The 5-HT1B receptors are also present in the brainstem, and likely play a role in modulating the electrical event of a migraine. Triptans also work by activating (agonist) the serotonin sub-receptor 5-HT1D. The result of activating this receptor is that they stop the trigeminal nerves from releasing a variety of inflammatory proteins around the brain and blood vessels which normally leads to pain during a migraine attack, including CGRP. This receptor also interferes with pain processing between the brainstem and the brain (helps to block this electrical transmission), and it helps to block the nausea and vomiting centers in the brainstem. Triptans help to normalize levels of and decrease the release of a very inflammatory protein released during a migraine called CGRP (calcitonin gene related protein). Triptans also inhibit mast cell degranulation in the dural membranes, which also lessens the sterile inflammation which occurs during a migraine.
WHAT ARE THE SIDE EFFECTS OF TRIPTANS?
Most patients tolerate triptans very well, however, many patients have side effects and discontinue them. So let’s discuss triptans side effects. Just like any medicine, some patients may have more side effects than others. Furthermore, about 30% of patients with migraine may not respond to triptans (triptan non-responder). If side effects do occur, there is some variability between the different types of triptans.
Potential side effects of the triptans include palpitations or racing heart beat, nausea, tingling, numbness or flushing in the face or extremities, drowsiness, fatigue, dizziness, and tightness or pressure in the chest, neck, or jaw. Although the chest pressure is not common, it is usually of a muscular and not a non-cardiac (heart) cause, so it can be scary if you don’t know about this potential side effect. With that said, chest pain could still potentially be a sign of heart attack (myocardial infarction) in patients with vascular risk factors and unknown coronary disease because the triptans do cause some slight vasoconstriction (narrowing) of arteries. So if there is already narrowing in an artery, increasing further narrowing could lead to lack of blood flow to the heart with subsequent heart attack in those at risk.
WHEN SHOULD TRIPTANS NOT BE USED?
Triptans can cause a mild degree of artery constriction (narrowing) due to its activity at the 5-HT1B receptor as discussed above. This could theoretically occur in narrowed arteries from cholesterol build up, such as in the heart. Therefore, triptans should not be used in patients who have coronary artery disease, cerebrovascular disease (stroke), peripheral arterial disease, or uncontrolled risk factors for these diseases (high blood pressure, cholesterol, diabetes, smoking, family history of early heart disease) because chest pain for them could truly represent heart attack. If there is concern for the possibility of underlying cardiovascular disease, a cardiac stress test should be performed prior to triptan prescription.
Triptans are also considered to be contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction) due to theoretical concerns of vasoconstriction potentially causing stroke. This contraindication has historically also included hemiplegic migraine and basilar migraine (now called migraine with brainstem aura). When the triptan studies were done previously, they excluded patients with these forms of migraine due to the ongoing vascular theory of migraine at that time. The vascular theory of migraine assumed that vasoconstriction and lack of blood flow was the cause of aura and neurologic features with migraine. So the thinking was that if you cause further vasoconstriction with a triptan, you may cause stroke. However, we now know that these phenomenon are primarily of an electrical basis and not a vascular basis. Therefore many specialists have gotten more liberal with the use of triptans in patients with hemiplegic or basilar migraine, and there have been a number of case series and case reports of these patients using triptans without any problems. However, larger confirmatory studies would be preferable.
Patients that can not use triptans due to side effects, or if they have any of these medical contraindications noted above, should consider one of the newer types of migraine abortive medications available with either the gepants (Ubrelvy, Nurtec, Zavspret), ditans (Reyvow) or neuromodulatory devices. Ubrelvy, Nurtec, Zavspret and Reyvow are not triptans. These newer options often have a much lower side effect profile, can be taken in the setting of these medical contraindications to triptans mentioned above, and work by an entirely different mechanism of action.
It is also important to know that triptans can cause medication overuse headache (rebound headache) if used consistently greater than 10 days per month on average. The result is that the headache continues to worsen in frequency and/or severity. This also happens with NSAIDs, over the counter pain meds, and other types of as-needed pain medications. The phenomenon of rebound headache is discussed in much greater detail here. Notably, the gepants (Ubrelvy, Nurtec, Zavspret) do not cause rebound headache. If triptans, or any migraine abortive medication, is having to be used at this high frequency, a preventive migraine treatment should be used until the migraine and headache frequency is significantly improved consistently for several months. This can be done with a variety of medications which may also include the CGRP monoclonal antibody (mAb) treatments (Aimovig, Ajovy, Emgality, Vyepti), Botox, natural supplements, herbals and vitamins, or neuromodulatory devices.
WHAT IS THE BEST TRIPTAN TO USE?
Triptans are all similar in mechanism of action in how they work. So, it is not necessarily that one is better than another and some people may respond better to one versus another. However, there are many differences between the triptans drugs which allow them to be tailored and fine-tuned towards different types of migraine characteristics, as discussed below. This is a very important clinical point that is almost always overlooked by most physicians prescribing these medications if they are not headache specialists.
Tailoring triptans to specific migraine characteristics can make a dramatic difference in its effectiveness since triptans are not all one in the same medication. The information below can be discussed with your doctor to hopefully get a better response to your triptan therapy.
LIST OF TRIPTANS:
-Sumatriptan: oral, subcutaneous injection, needle-less subcutaneous injection, nasal spray, breath-powered intranasal delivery system
-Zolmitriptan: oral, orally dissolvable tablet, nasal spray
-Rizatriptan: oral, orally dissolvable tablet
-Almotriptan: oral
-Eletriptan: oral
-Sumatriptan/Naproxen: oral
-Frovatriptan: oral
-Naratriptan: oral
GROUP 1 TRIPTANS:
-Faster onset of action, higher potency (thus can have higher side effect potential), tend to have a higher 24-hour migraine recurrence
-Sumatriptan, Sumatriptan/Naproxen, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan
GROUP 2 TRIPTANS:
-Slower onset of action, lower potency (thus often have lower side effect potential), lower 24-hour migraine recurrence since the duration of action is longer:
-Frovatriptan, Naratriptan
FINE-TUNING YOUR TRIPTAN CHOICE:(Remember the mnemonic CORN, and this will help to narrow down the best triptan to consider):
Contraindications
Onset to peak pain
Recurrence of migraine after treatment
Nausea and vomiting severity
Contraindications:
This is not an exhaustive list, but are the most common. Your doctor should be well aware of when triptans should not be used.
-Known vascular disease (coronary artery disease, peripheral vascular disease, history of stroke)
-Vascular risk factors (poorly controlled hypertension, hyperlipidemia, diabetes, smoking, premature family history of coronary artery disease (men less than age 55, women less than age 65), postmenopausal women, etc.
-Kidney or liver failure
-Prinz-Metal angina
Onset to migraine peak pain:
-Group 1 triptan (quicker onset) is generally much more useful than a Group 2 triptan (slower onset).
-A subcutaneous injection or nasal spray triptan will typically be more effective than an oral triptan if the patient wakes with migraine already ongoing (waking migraine), or if the Mmigraine hits its peak pain level within 30 minutes (fast onset).
Return of migraine after treatment:
-If migraine recurrence occurs within 24 hours (for example it goes away with the triptan, but keeps returning later in the day or the next day), or the migraine is usually multiple consecutive days long (such as menstrual migraine):
-Combine the 1st dose of the triptan with an NSAID (such as Naproxen)
-Use a group 2 triptan (Naratriptan vs. Frovatriptan)
Nausea and vomiting severity:
-If nausea and vomiting occur early in the attack, or are severe to where it is hard to keep a pill down without vomiting it back up:
-A subcutaneous injection or nasal spray triptan should be used.
-Of note, dissolvable triptan tablets are still absorbed by the gastrointestinal tract, not sublingually. So, vomiting will still make this route ineffective, similar to a regular pill.
TRIPTAN PEARLS IN FURTHER FINE-TUNING TRIPTAN CHOICES:
Sumatriptan:
-Highest potency (in subcutaneous form) and quickest onset (subcutaneous > nasal spray) of triptans
-Greatest flexibility is dosing route options
Rizatriptan:
-Fastest onset of oral triptans
-Greatest likelihood of 2h pain-free and sustained pain-free response
-Propranolol increases its serum concentration, so 5mg per dose should be if used together
Zolmitriptan:
-Most likely to treat persistent headache when 1st dose fails
Almotriptan:
-The group 1 triptan with the least side effects
Eletriptan:
-Highest potential for drug interactions. Decrease dosage with CYP3A4 drugs such as macrolides, fungal, HIV, etc.
Naratriptan:
-The “gentle triptan” with the least side effects given its slower onset of action
-Low 24 hour migraine recurrence rate
-Good choice to give shortly prior to an expected and known migraine trigger (menstruation, air travel, etc.)
-Does not have monoamine oxidase metabolism, so it can be given with MAOI (as can Eletriptan and Frovatriptan)
Frovatriptan:
-Low side effect potential given its slower onset of action
-Longest half life
-Low 24 hour migraine recurrence rate
-Good choice to give shortly prior to an expected and known migraine trigger (menstruation, air travel, etc.)
Can You Combine a Triptan and a Gepant in the same day?
Yes, you can use a triptan and an abortive gepant such as Nurtec, Ubrelvy, or Zavspret in the same day. Migraine patients like to have, and should have, a war chest to use if the first medicine fails. The gepants fit in nicely to this scenario in that they can be used together with a triptan.
Just a reminder though that you can not combine triptans and DHE (dihydroergotamine) in the same 24 hours.
CONCLUSIONS:
The triptans were and have been a game changer for millions of migraine patients in aborting migraine attacks. Using the highest available triptan dose is also generally recommended to see the full effect. We see many patients who have “failed triptans”, but on further history they were put on very low doses (such as 25 mg sumatriptan, when 100 mg is the standard dose). Even so, about 30% of migraineurs do not respond to triptans, only 1/3rd are pain-free at 2 hours, and only 17-25% remain pain-free at 24 hours. Therefore, although the majority respond well to triptans, not everyone does. Luckily, there are other medication options including two brand new classes of migraine abortive medications (gepants, ditans), and these are detailed here.
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