Migraine abortives

Marcello Cherchi M.D. Ph.D., Chicago IL and Timothy C. Hain, MD, Chicago IL

Page last modified: September 13, 2021

Migraine abortives are medications taken after a headache starts, in an attempt to prevent it from progressing. They are different from prophylactic drugs (taken daily). A recent large meta-analysis of migraine abortives was that of Vanderplum et al (2021). We have added their comments as appropriate below.

The following incomplete list includes medications, discussed in the medical literature, and each of which has been asked about by patients in our practice in Chicago at some point. The list contains some comments regarding our prescribing practices, but we do not endorse any particular drugs. When applicable, we have added in the recommendations of review articles concerning abortives, such as that by Orr et al (2015) and Vanderpluym et al (2021), although in some instances these recommendations violate clinical experience and common sense.

This list implies that "migraine" is a monolithic disease where the best treatment can be elucidated by evidence, such as a double-blind placebo controlled trial. Actually, genetic studies suggest that there are many genetic variants associated with the collection of symptoms called "migraine", and a "splitter" could reasonably argue that these are all different diseases. Logically then, medications might work better in genetic subvariants, and the clinical evidence should be looked at as dubious, as it presumes that "migraine" is a disease. In our opinion, clinical experience can help the astute clinician pick medications that are more likely to be effective for variants of "migraine", but often the treatment process involves trial/error.

New drugs:

Recently FDA approved is Lasmiditan (Reyvow).

This is another 5HT drug, working on 5HT1-F. It was developed by Lilly. This is likely a "cleaner" Triptan like drug. It will probably work in patients who respond to Triptans, but might have less side effects. Interestingly, dizziness is a very common side effect (16-18%). We would not call this a "break-through" drug, and in fact, since sumatriptan is presently cheap, this will probably have the net effect of increasing the cost of migraine care, as it will replace a cheap drug that works rather well, with an expensive drug that works slightly better. See Kuca et al (2018) for more about efficacy.

As this drug is newly approved, we think best to wait till it is better understood rather than starting it right now (i.e. in 9/2020). Often the more interesting side effects are not known until the first 100,000 people give this a try. There is a discount card for Commercial insured patients. It comes in three strengths -- 50, 100, 200. The recommended # appears to be 8 tablets. Although there are 3 strengths, the prescribing information says no more than 1 dose in 24 hours. This seems a bit odd, as if you take a 200, that would be 4 of the 50's. Well anyway.

According to Vanderpluym's et al's meta-analysis, this drug works with "significant improvement", but also there were "significantly increased risk" of various adverse events. So unsurprisingly, this drug seems somewhat similar to triptans, as it also is a serotonin (5HT) receptor drug. With respect to improvement, the risk difference for "pain relief" (more is better) was roughly 0.15. Other drugs have higher pain relief scores.

Oral CGRP inhibitors (Gepants)

According to Vanderpluym et al (2021), "Compared with placebo, rimegepant(3RCTs;oralandsub- lingual) and ubrogepant(3RCTs;oral) were associated with significant improvement in pain freedom and pain relief at 2 hours (moderate to high SOE) and sustained pain freedom at 1 day and at 1 week (low to high SOE). Ubrogepant was associated withsignificantly more adverse event srelated to ear,nose,and throat symptoms." Our clinical experience with these drugs has been that they seem to be fairly effective, and low side effect. They appear to be a reasonable alternative to Triptans (see below).

Triptans

Triptans are the prototype migraine abortive drug. At this writing, this category includes sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan and eletriptan. These drugs are all group-1 agents. These drugs are 5HT-1B and 1D (serotonin) receptor agonists. Some also affect 5HT-1F (see above). Serotonin does a lot of things in the body and there are many receptors, presently ranging from 5HT1-7. The table below contains an overview of the timing of these drugs. Tmax is the time when the effect peaks. T 1/2 tells you (approximately) how long the effect lasts. As a general rule, it takes 5 half-lives for a drug to be completely eliminated -- thus this varies from about 10 hours to 5 days. The Canadian Headache Society states that they recommend sumatriptan (one of these) based on a "moderate level of evidence" (Orr, 2015). This is reasonable and we think the recommendation applies to almost all triptans. Triptans have good evidence (level A) for effectiveness according to the American Headache Society (Marmura et al, 2015).

While the triptans are fairly clean, there has been some concern about the risk of cardiac side effects. The evidence as of 2021 is that the risk is low.

Compound Dose Tmax T 1/2 Generic cost/usual rx intending to last 30 days
Rizatriptan (Maxalt) 5-10 1 2-2.5 24.52/18, 25.82/18
Eletriptan (Relpax) 20-40 1-1.25 4-7 86.50/6, 82.53/6
Sumatriptan (Imitrex) 100 2.5 2-2.5 22.09/9
Zolmitriptan (zomig) 2.5 2.5 3 48.06/6
Almotriptan (Axert) 12.5 2.5 3.6 70.96/6
Naratriptan (Amerge) 2.5 2-3 5-6 26.03/9
Frovatriptan (Frova) 2.5 2-4 25 This has gone down !
(modified from Matthew and Loder, 2005) -- Cost data from NMPP (Jan 2018)

Considering cost, the self-pay charge ranges PER PILL from roughly $1.50 (Rizatriptan -- Maxalt), to the nose-bleed price of about $10. These are old medications, many of whom are no longer patent protected. Most of our patients without the best insurance coverage use sumatriptan or rizatriptan. Those with good insurance, tend to use frovatriptan.

Cost quoted for brand named versions of these medications is usually astounding -- roughly 10 times the cost of the generic versions. So when your pharmacy says that you saved 1000's of dollars on your triptan, this is how they come up with this figure. One would hope that nobody really pays these gigantic prices and that they are mostly just for show -- sort of like mark downs in department stores. Certain entities (like Medicare) can't negotiate prices of drugs due to the wisdom of our federal government, so they pay the full freight.

Similar medications to the triptans, including ergot drugs, are also priced in nose-bleed territory, some of which are amazingly expensive.

Chemical name: Almotriptan

Chemical name: Eletriptan

Chemical name: Frovatriptan

Chemical name: Naratriptan

Chemical name: Rizatriptan

Chemical name: Sumatriptan

Chemical name: Zolmitriptan

Ergot derivatives

Chemical name: Dihydroergotamine (DHE)