The medications discussed here are the migraine [1] medications which are used to treat individual migraine [1] attacks (See this post [2]). They can be divided into broad categories: Analgesics, NSAIDs, Triptans [3], ergot derivatives, Gepants, Anti-emetics, Cannabinoids and Opioids.
** We included cannabinoids since people are interested in them, but they should not be recommended for migraine. Opioids, given their risks, should be a last resort.
** Neuromodulation devices can be used to treat migraine attacks and are reviewed in another section [4]
** Lasmiditan will not be marketed in Canada.
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The simple analgesics
| Examples (generics) | Acetaminophen Paracetamol |
| Examples (brand names) | Tylenol |
| How does it work? | Acetaminophen blocks the production of prostaglandins which are natural substances in the body that cause pain. It is not considered an anti-inflammatory [5] medication. |
| Is this a good option for migraine? | It may work for mild migraine attacks but is rarely sufficient. |
| Are there risks? | Taken regularly (15 days per month or more), acetaminophen can cause medication overuse headaches. High doses of acetaminophen can cause liver damage. |
| Are there side effects [6]? | Acetaminophen is usually well tolerated. High doses on a regular basis may cause tinnitus |
| Comments and interesting facts | Acetaminophen comes from nature! Components related to acetaminophen are found in the cinchona bark. |
The non-steroidal anti-inflammatory drugs or NSAIDs
| Examples (generics) | ibuprofen, naproxen, acetylsalicylic acid, diclofenac, ketorolac, nabumetone, mefenamic acid |
| Examples (brand names) | Advil, Motrin, Aleve, Aspirin, Toradol, Cambia, Voltaren, Ponstan |
| How do they work? | NSAIDs block the enzyme COX that produces inflammatory substances but also molecules involved in blood clotting and gastric function. |
| Are they good options for migraine? | Yes. NSAIDs are the first-line option for migraine attacks. |
| Are there risks? | NSAIDs can irritate the stomach and cause ulcers and bleeds. They can also increase blood pressure and have been associated with a risk of heart disease (though the risk is very small). They should be avoided or used cautiously in people with kidney disease. |
| Are there side effects? | Stomachupset, some people report sleepiness |
| Comments and interesting facts | The response to NSAIDs may vary. One person may respond to ibuprofen better than naproxen or the reverse. NSAIDs also have different durations of action. Ibuprofen is taken every 4-6 hours, Naproxen lasts longer and can be taken every 12 hours. |
| More interesting facts | Aspirin comes from the willow bark. White willow was used in antiquity for its anti-fever properties. If you use natural products, remember that white willow (salix alba) is like aspirin. |
Triptans
| Examples (generics) | There are seven triptans [7] in Canada: Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan [8], zolmitriptan |
| Brand names | Axert, Amerge, Frova, Maxalt, Relpax, Imitrex, Zomig |
| How do they work? | Triptans act on the serotonin receptors. We know now that they also block the release of CGRP. |
| Are they a good option for migraine? | Triptans are an option if NSAIDs fail to control migraine attacks. Although they can be life changing, some people do not seem to be helped by triptans [7]. As responses can vary, it is important to try a few different ones before abandoning triptans. |
| Are there risks? | Triptans constrict blood vessels and should not be used in people with a history of stroke or heart disease. Triptans should not be used for specific migraine types like hemiplegic migraine [9] and basilar migraine. They can be used for migraine with a typical aura [10]. Some triptan may be used during pregnancy after a careful discussion of risks and benefits. |
| Are there side effects? | Side effects [6] may limit the use of triptans even if they are effective. Fatigue, nausea, chest pressure, and an increase in headache have been reported. |
| Comments and interesting facts | Triptans are not painkillers. They are used only for migraine and a few related less common headache types. When the first triptan was commercialized in 1992, results were so impressive that many psychiatric theories of migraine were put into question. |
Gepants
| Generic names | Ubrogepant Rimegepant (expected in Canada in 2024) |
| Brand names | Ubrelvy Nurtec |
| How do they work? | Gepants block the CGRP receptor |
| Are they a good option for migraine? | Gepants were designed for migraine treatment in line with the CGRP blockade concept, they are specific. |
| Are there risks? | Gepants do not constrict blood vessels. Gepants are metabolized by the liver and may interact with other medications. Gepants cannot be taken by pregnant women. |
| Are there side effects? | The main side effect reported in clinical trials is nausea. They appear to be better tolerated than triptans |
| Comments and interesting facts | Gepants are also used for migraine prevention, therefore they do not induce medication overuse headache. |
Ergot derivatives
| Examples (generics) | Ergotamine, dihydroergotamine (DHE) [11] |
| Examples (brand names) | Cafergot, Migranal (DHE nasal spray) |
| How do they work? | Ergot derivatives act on serotonin receptors, but are a bit different than the triptans. |
| Are they a good option for migraine? | Ergotamine and DHE should not be used as first or even second-line therapy. They have more side effects and risks than triptans. They should be prescribed by experienced physicians. DHE has the advantage of not causing a medication overuse headache. |
| Are there risks? | Ergot derivatives have more effect on arteries and veins than triptans. They should never be used in people with any vascular disease and they must be avoided in pregnancy. |
| Are there side effects? | Nausea, vomiting, diarrhea, leg cramps, and high blood pressure [12] have been reported. |
| Comments and interesting facts | Ergotamine was inspired by rye ergot (Claviceps purpurea), a fungus that grows on rye. (See this post [13]) |
Anti-emetics (for nausea and vomiting)
| Examples (generics) | Dimenhydrinate, odansetron, chlorpromazine, metoclopramide |
| Examples (brand names) | Gravol, Zofran, Stemetil, Maxeran, Metonia |
| How do they work? | Anti-emetics act through different mechanisms. Some act on dopamine, others on serotonin. |
| Are they a good option for migraine? | Anti-emetics may decrease the nausea and vomiting associated with migraine and allow other medications such as NSAIDs or triptans to be taken and not thrown up. |
| Are there risks? | Some anti-emetics acting on dopamine can produce spasms and restlessness, and heart rhythm issues. |
| Are there side effects? | Sleepiness |
| Comments and interesting facts | Anti-emetics acting on dopamine are used in the intra-venous form in the emergency department to treat refractory migraine attacks (status migrainosus). The oral forms do not have this effect. |
Opioids
| Examples (generics) | Codeine, hydromorphone, morphine, oxycodone, tramadol, burprenorphine |
| Examples (brand names) | Statex, Dilaudid, Supeudol, Oxycocet, Zytram, Butrans |
| How do they work? | Opioids act on the morphine receptors in our brain to block pain. There are different receptors (mu, kappa, and delta) with different effects |
| Are they a good option for migraine? | NO. Opioids should be avoided in people with migraine since they carry a high risk of causing chronic migraine [14] and medication overuse headache. Only physicians experienced in the management of headache should prescribe opioids to people with migraine. |
| Are there risks? | There are risks including worsening migraine, addiction, and respiratory failure. |
| Are there side effects? | Constipation, sedation, myoclonus (spasms or jumpy muscles). |
| Comments and interesting facts | Opioids seem to decrease the effectiveness of migraine preventives and neuromodulation devices |
Cannabinoides
| Examples | Many products exist in a legally commercialized form in Canada. They can be inhaled or ingested. The THC/CBD content varies significantly. |
| How do they work? | THC acts on our cannabinoid receptors. CBD is a very complex substance acting on different networks. |
| Are they a good option for migraine? | NO. Cannabinoids are not recommended to treat migraine attacks. There is very little if any evidence to support their effectiveness and safety. |
| Are there risks? | There are risks including chronification, addiction, cyclical vomiting syndrome, stroke and respiratory failure. |
| Are there side effects? | Drowsiness, rebound anxiety, nausea, dizziness [15]. |
| Comments and interesting facts | Cannabinoids are often considered safe by the public but they have risks and contra-indications. Their use should be discussed with an experienced health care provider. |
The combinations: Fiorinal, Excedrin migraine, Tylenol #2, #3
Many combination products are sold over-the-counter (without a prescription) in Canada. Most will combine acetaminophen or aspirin with caffeine [16] and sometimes a low dose of codeine.
Fiorinal, used frequently for migraine management in the 1980s, contains barbiturates, and anxiolytics that may help through a calming effect, but can be addictive.
Combination analgesics may be perceived as very benign drugs, but caffeine [16], opiates [17] and barbiturates all have risks and side effects that should be taken into account. The risk of medication overuse headache is quite high with these compounds.
For people with migraine who experience a partial benefit with NSAIDs and/or triptans alone, combining the two medications may lead to more effective migraine treatment. In Canada, there is a product available by prescription that combines sumatriptan [8] and naproxen in a single pill. For more information on this approach see here.
REFERENCES
Mayans L, Walling A. Acute Migraine [1] Headache: Treatment Strategies. Am Fam Physician. 2018; 97(4):243-51.
Worthington I, Pringsheim T, Gawel MJ, Gladstone J, Cooper P, Dilli E, et al. Canadian Headache Society Guideline: acute drug therapy [18] for migraine headache. Can J Neurol Sci. 2013; 40(5 Suppl 3):S1-s80.
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