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.
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 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.
- According to Valetgas and others, (2004) "Use of triptans is not associated with increased risk of any ischemic events, including myocardial infarction and stroke, or mortality."
- Diener (Diener 2020) states "In conclusion, the risk of acute coronary syndromes in the treatment of migraine attacks with triptans appears to be extremely low. " Diener still suggests that the newer agents such as Ubrelvy or Lasmiditan, may be safer (in theory).
- According to a recent paper by Okonkwu and Ojha, "the data .. suggests that serious cardiovascular events are quite rare with sumatriptan use". (Okonkwo and Ojha 2020)
|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|
|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
Due to its long half-life, Frova was marketed as effective for menstrual migraines. We find this property to be useful in other migraines as well. Oddly enough, frovatriptan has become far more expensive in recent years (we are writing in 2016), even though generally speaking medications get cheaper as they age. Endo pharmaceuticals, the maker of Frova, has been sued by the FDA for other things (https://www.ftc.gov/news-events/press-releases/2016/03/ftc-sues-endo-pharmaceuticals-inc-others-illegally-blocking-lower). Frovatriptan is now sometimes available at reasonable prices. If not, a reasonable "work around" is to take multiple small doses of sumatriptan, which is priced more reasonably.
Chemical name: Naratriptan
Randomized, double-blind, placebo-controlled trials (Klassen et al. 1997; Mathew et al. 1997) and dose-ranging trials (Havanka et al. 2000) showed efficacy of naratriptan. A meta-analysis of randomized trials showed that naratriptan is better tolerated than rizatriptan, sumatriptan or zolmitriptan. Its efficacy is poorer than rizatriptan and sumatriptan, but comparable to zolmitriptan. It is also less efficacious than eletriptan (Garcia-Ramos et al. 2003). Several randomized, double-blind, placebo-controlled trials found efficacy of this drug in the unusual use as a prophylactic for menstrual migraine (Mannix et al. 2007b; Newman et al. 2001).
Chemical name: Rizatriptan
Chemical name: Sumatriptan
We prescribe sumatriptan often, more so now that it has achieved generic status.
Watch out: In 2008 a combination drug of sumatriptan (85 mg) plus naproxen (500 mg) was marketed as a migraine abortive (Treximet). While reasonably effective, one would wonder why one would choose an expensive new brand name product rather than a far cheaper combination of two generic products (i.e. 1.5 sumatriptan 50+naproxen 500). Efficacy was shown in several randomized, double-blind, placebo-controlled trials (Landy et al. 2007). Another such study was funded by the drugs manufacturer, GlaxoSmithKline and Pozen (Brandes et al. 2007).
Chemical name: Zolmitriptan
Chemical name: Dihydroergotamine (DHE)
Parenteral dihydroergotamine has been used in acute treatment of migraines since 1925 (Tfelt-Hansen and Koehler 2008) and has been used quite consistently since then (Becker et al. 1996; Callaham and Raskin 1986; Scott 1992; Winner et al. 1993). One randomized, double-blind study found similar efficacy of subcutaneous dihydroergotamine and subcutaneous sumatriptan found that migraines were less likely to recur in patients treated with dihydroergotamine than with sumatriptan (Winner et al. 1996). Ergot also has a "level A" strength of evidence for efficacy according to the American Headache Society (Marmura et al, 2015). On the other hand, Vanderpluym et al (2021) felt that the "overall risk of bias" in 15 randomized controlled trials was high.
Chemical name: Dihydroergotamine (DHE) nasal
Several randomized, double-blind, placebo-controlled studies demonstrated the efficacy of dihydroergotamine nasal (Dihydroergotamine Nasal Spray Multicenter Investigators 1995; Ziegler et al. 1994), though one randomized, double-blind, placebo-controlled study found dihydroergotamine nasal to be little better than placebo (Tulunay et al. 1987). A randomized, double-blind, crossover study found dihydroergotamine nasal to be inferior to sumatriptan nasal (Boureau et al. 2000). A crossover study found dihydroergotamine nasal to have slower onset of effect than subcutaneous sumatriptan (Touchon et al. 1996).
Chemical name: Ergotamine / caffeine
Chemical name: Chlorpromazine
A randomized, double-blind, placebo-controlled trial found some efficacy (McEwen et al. 1987). A randomized, double-blind study with no placebo arm found intravenous chlorpromazine and intravenous metoclopramide to have similar efficacy (Cameron et al. 1995). A randomized, double-blind study with no placebo arm found intravenous chlorpromazine and intravenous ketorolac to have similar efficacy (Shrestha et al. 1996). A randomized, unblinded study with no placebo arm premedicated patients with metoclopramide and then compared intravenous chlorpromazine versus intramuscular sumatriptan, and found similar efficacy (Kelly et al. 1997). The Canadian Headache Society states that they "weakly recommend chlorpromazine based on a moderate level of evidence" (Orr, 2015). This drug is not used commonly in the United States, as there is a general dislike of using powerful antipsychotic drugs to treat benign conditions. According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015).
Chemical name: Droperidol
One randomized, double-blind, placebo-controlled, dose-ranging trial found droperidol to be efficacious (Silberstein et al. 2003). A randomized, single-blind study with no placebo arm compared intramuscular droperidol with intramuscular meperidine and found similar efficacy (Richman et al. 2002). Vanderpluym et al (2021) reported it to be modestly effective (about .15), similar to the newer drugs for migraine at the top. According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015).
Chemical name: Haloperidol
The Canadian Headache Society states that they "recommend strongly against haloperidol based on a low level of evidence" (Orr, 2015).
Chemical name: Metoclopramide (+ diphenhydramine)
A meta-analysis of randomized, placebo-controlled trials concluded that metoclopramide is efficacious as a migraine abortive (Colman et al. 2004). An interesting randomized, double-blind trial with no placebo arm compared subcutaneous sumatriptan with repeated doses (up to four) of intravenous metoclopramide (20 mg) in which alternate doses of metoclopramide were given with intravenous diphenhydramine 25 mg (Benadryl). The study found similar efficacy of the two approaches (Friedman et al. 2005). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015). According to Vanderpluym et al (2021), various forms of metoclopramide by itself are modestly effective.
The Canadian headache society stated that "We strongly recommend the use of .... metoclopramide, based on a moderate level of evidence," (Orr, 2015). This treatment is sometimes used in US emergency departments (i.e. it has stood up to the test of time).
Chemical name: Prochlorperazine
A randomized, double-blind, placebo-controlled trial demonstrated the efficacy of intravenous prochlorperazine as a migraine abortive (Coppola et al. 1995). A randomized, double-blind, placebo-controlled trial showed intramuscular prochlorperazine to be more efficacious than intramuscular metoclopramide (Jones et al. 1996). Similarly, another trial in the emergency department reported IV prochlorperazine plus 25 mg of diphenydramine (to prevent dyskinesia) was more effective than 1 mg of hydromorphone (Friedman et al, 2017). . A randomized, double-blind, placebo-controlled trial of rectal prochlorperazine demonstrated efficacy (Jones et al. 1994). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015). Vanderpluym et al (2021) compared various forms of this drug and found a risk difference of about 0.3. Compared to the newer agents with RD of about 0.15, this is not too bad.
Other Medications for Migraine (non-triptan, non ergot, non anti-emetic)
butorphanol: This is a rapidly acting opiod. We do not advise using this for migraine due to the high addition risk.
Acetaminophen/aspirin/caffeine combination: This goes under the general name of "excedrin migraine". This is a mildly effective agent, similar to the combination of a "coke" and aspirin.
Chemical name: Magnesium sulfate
A randomized, single-blind, placebo-controlled study found magnesium sulphate 1 g IV over 15 minutes to be efficacious (Demirkaya et al. 2001). A randomized, double-blind, placebo-controlled study found magnesium sulphate to be efficacious for migraine with aura (Bigal et al. 2002). One randomized, double-blind, placebo-controlled trial found intravenous magnesium sulphate to be no more efficacious than placebo as a migraine abortive (Cete et al. 2005). The Canadian Headache Society states that they recommend weakly against the use of magnesium sulfate based on a moderate-quality evidence (Orr, 2015). According to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015). We ourselves think that Magnesium supplements are often helpful for migraine, in a dose of 500 mg orally/day. Also see this page.
Chemical name: Meperidine + promethazine
Chemical name: Methylprednisolone
The Canadian Headache Society states that they "strongly recommend against the use of dexamethasone based on a moderate level of evidence" (Orr, 2015). Dexamethasone and methylprednisoline are both steriods and are closely related. That being said, as of 2016, medrol dose packs are commonly used to treat migraine flare ups.
Chemical name: IV valproate
The Canadian Headache Society states that they "recommend weakly against sodium valproate based on a low level of evidence" (Orr, 2015).
Caffeine, aspirin, acetaminophen. Efficacy of each drug individually was shown in randomized, double-blind, placebo-controlled trials (Smith 1998).
Midrin (isometheptene, dichloralphenazone, acetaminophen).
This combination product for migraine has been taken off the market because two ingredients (isometheptene, dichloralphenazone) are no longer FDA approved. Practically, we do not think there is a reasonable substitute. We do not think one should substitute chloral hydrate (which has the same issues as dichloralphenazone). We are simply not sure if there is a substitute for isometheptene. Perhaps caffeine. A somewhat similar drug that is still FDA approved is fioricet (caffeine, butabarbital, acetoaminophen). It is controlled due to the butabarbital. More about the Midrin situation can be found here:
Nonsteroidal antiinflammatory agents include aspirin, naproxen, ibuprofen, and an immense number of other pain relievers. They share several features -- they are generally not addictive, they generally irritate the stomach, and they occasionally are associated with increased blood pressure and worsening of kidney function. Many of these are "OTC" or over the counter agents. Recently there have been a few that seem particularly suitable for migraine treatment.
We generally first suggest patients try the simple OTC NSAID's such as aspirin (500 mg). This includes some combination products such as "Excedrin migraine". If this is not enough, then we often suggest indomethacin (indocin), with care not to take it very often because of stomach irritation.
Cambia (diclofenac 50mg) -- a powder that is dissolved in your liquid of choice. Again, very powerful. The Candian headache society disagrees saying that "based on low-quality evidence, we recommend weakly against the use of diclofenac" (Orr, 2015). This adverse recommendation is routinely contradicted by our patients who say that Cambia works very well. We think it is especially helpful in hemiplegic migraine. According to the American Headache society, the evidence for efficacy is level A (Marmura et al, 2015). Cambia is a very expensive ground-up version of an old cheap drug, with the brand name of Volteran, which comes in 25 mg tablets. Some patients just use the generic diclofenac. Of course, it doesn't come in a powder this way. One would wonder why diclofenac works so well when other NSAID's don't seem to work as well. Presumably they all do the same thing.
Naproxen was studied in randomized, double-blind, placebo-controlled trials (Andersson et al. 1989). The trial showed that naproxen diminished headache severity at 2 hrs., though it did not improve the attack overall. A double-blind, parallel group study found naproxen and ergotamine to have similar efficacy (Treves et al. 1992). The typical dose is 500 or 550. According to the American Headache society, the evidence for efficacy is level A (Marmura et al, 2015).
Ketoprofen (Orudis) 100 mg has, according to the American Headache society, evidence for efficacy at level B (Marmura et al, 2015).
Ketorolac (Toradol). The Canadian headache society stated that " We strongly recommend the use of ... ketorolac, based on a low level of evidence". (Orr, 2015) Our take on this is that all of the nonsteroidals do the same thing, and they should all work. See commentary below about ketorolac administered as a nasal spray.
The American Headache Society had no comments about the Cox-2 NSAID's (such as Celebrex) for migraine (Marmura, 2015). We have not encountered their use at all in our patients in Chicago. One would think that they would work too, perhaps with less stomach upset, but perhaps with more cardiovasacular risk than the non-selective NSAIDs.
Newer nonsteroidal agents that can be used as abortives in migraine include
Ketorolac: SPRIX (nasal spray form of ketorolac, https://www.sprix.com/Home.aspx) . According to the American Headache society, the evidence for efficacy is level C negative (Marmura et al, 2015). This would suggest that it is not effective. On the other hand, ketorolac IV or IM (30-60 mg) is, according to the American Headache society, the evidence for efficacy is level B (Marmura et al, 2015). So as of 2015, it would seem that Sprix is not effective, but IV or IM ketorolac is effective. This is hard to follow. Rao e tal (2016), found intranasal ketorolac more effective than sumatriptan. So to summarize, there is mixed evidence. Nasal ketorolac is not in general use as of 2021, so probably it is not effective. On the other hand, intramuscular ketorolac is still used. We would think that the nasal administration is less reliable than IM or IV.
The combination of indomethacin, prochlorperazine and caffeine suppositories was shown to be comparable to sumatriptan in a randomized, double-blind, parallel group trial (Sandrini et al. 2007), and was shown to be more efficacious than sumatriptan in a randomized, double-blind, crossover trial (Di Monda et al. 2003). This formulation is not generally available.
Most neurologists are very reluctant to prescribe opiates for Migraine because there is a strong tendency to develop addiction. These include butorphanol IM, Codeine 30, Meperidine (demerol) IM 75, Methadone IM 10, Tramadol IV 100. According to the American Headache society, the evidence for efficacy is level C (Marmura et al, 2015). Strangely, missing from this list provided by the American Headache Society, is oxocodone, which we feel is used very commonly. It is certainly addictive as well. There are many other opiates -- addiction is the problem common to all of them. We think in most situations, it is best to avoid them.