| Antimigraine drug | |
|---|---|
| Drug class | |
 Zolmitriptan, a common antimigraine medication | |
| Class identifiers | |
| Use | Migraine therapy and prevention |
| ATC code | N02C |
| Clinical data | |
| Drugs.com | Drug Classes |
| Legal status | |
| In Wikidata | |
Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks. [1]
Examples of specific antimigraine drug classes include triptans (first line option), ergot alkaloids, ditans and gepants. Migraines can also be treated with unspecific analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen. Opioids are not recommended for treatment of migraines.
The triptan drug class includes 1st generation sumatriptan (which has poor bioavailability), and second generation zolmitriptan. [2] Due to their safety, efficacy and selectivity, triptans are considered first line agents for abortion of migraines. [2] These medications are selective 5-HT1B/1D receptor agonists with some activity at 5-HT1F. They produce an antimigraine effect by vasoconstriction of the vessels in the brain, as well as inhibiting trigeminal CGRP release and pain transmission. [2] They are normally well tolerated but the vasoconstrictor effects can lead to problematic side effects such as nausea, dizziness and chest discomfort, and therefore require caution in patients with cardiovascular disease. [2] There is also an increased risk of gastrointestinal adverse events. [3] Triptans use is limited to less than ten times per month in order to reduce Medication Overuse Headache (MOH). [2]
Ergot alkaloids include ergotamine and dihydroergotamine. This medication class targets the GCRP receptor pathway due to their likeness to serotonin, dopamine and noradrenaline. They show activity at serotonin 5-HT1-2, dopamine D2-like and alpha1/alpha2-adrenoreceptors. [4] Their lack of selectivity leads to more adverse effects, making them second line compared to triptans. [4] However, they have been shown to prevent recurrence better than triptans. [5] Adverse effects include nausea, vomiting, paresthesia, and ergotism. [2] Their use is limited to less than ten times per month in order to reduce medication overuse headaches (MOH's). The oral dosage administrative form is considered less effective than nasal or parenteral forms and has been discontinued in Canada. [5] Ergotamine is contraindicated during pregnancy. [6]
Ditans (eg. lasmiditan) are a new group of anti migraine drugs which were developed due some of the concerns with the 1st line triptans (eg. adverse effects, concern with use in cardiovascular disease, use of less than 10x per month to reduce MOH). Ditans are 5-HT1F receptors agonists. [7] Lasmiditan has been suggested to have less pain relief when compared to the triptans at the 2 hour mark post taking the medication. Lasmitan was shown to have higher adverse events (dizziness, fatigue and nausea) than the triptans or another novel medication class, GCRP antagonists. [7] However, they could be an option for patients with cardiovascular risks due to their lack of vasoconstriction . [7] Due to risk of dizziness, those who take lasmiditan should avoid driving 8 hours after taking. [3]
Gepants (eg. rimegepant, ubrogepant, and atogepant) are also a new group of anti migraine drugs, along with ditans. They are calcitonin gene-related peptide (CGRP) receptor antagonists. [7] Gepants have been suggested to have less pain relief at 2 hours compared to triptans. Similar to ditans, they offer another therapy option that does not include vasoconstriction, thus may be suitable for those with cardiovascular risk factors. [7] They are well tolerated with fewer adverse effects compared to triptans . [7]
NSAIDS are a nonspecific medication used for abortion of migraines due to their analgesic properties. They can be used for mild to moderate migraines, but are less effective against severe migraines. [8] Similar to the triptans and ergots alkaloids, their use should be limited to less than 10x per month to reduce MOH. Acetaminophen is an analgesic that can also be used, but NSAIDS should be tried first due to their anti-inflammatory properties. However, acetaminophen would be considered first line in pregnant patients. [6] Combination therapy of an NSAID with a triptan can be used when either medication is insufficient alone for migraine relief or recurrence . [5] Long term NSAID use has risks including nephrotoxicity and cardiotoxicity, and long term acetaminophen use is associated with hepatoxicity. [3] If warranted, an antiemetic can be used in combination with an NSAID. [8]
Opioids are not recommended for treatment of acute migraines due to their significant side effect profile, including twice the risk of medication overuse headache when compared to NSAIDS, acetaminophen or triptans. [3] In addition, their strength of efficacy has showed to be low or insufficient for pain relief of migraines. [3] Importantly, there is also risk of addiction and opioid use disorder. [3]
For patients who require preventive therapy with symptoms such as more than 4 migraines per month or migraines lasting longer than 12 hours, first-line drugs for the prevention of migraine attacks include beta blockers, antidepressants, and anti convulsants.
Beta blockers have been deemed effective options for the prevention of migraines. In particular, metoprolol, timolol and propranolol have the most strength of efficacy. [9] The timeframe to effectiveness in generally within 3 months. [9] Patients with cardiovascular risk factors should avoid the use of beta blockers for migraine prevention. [9]
Antidepressants are suggested to be both efficacious and tolerable in the treatment of migraine prevention for both migraine frequency and migraine index. [10] The exact mechanism of action is unknown but seems to be related to serotonin's impact on migraine. [10] In particular, amitryptyline (a tricyclic antidepressant) has the most evidence to suggest its efficacy. [10] Selective serotonin re-uptake inhibitors as well as serotonin and norepinephrine re-uptake inhibitors are likely effective as well, but more studies are required in order to provide more evidence. [10] Adverse events of antidepressants can include fatigue, nausea, drowsiness, dizziness, dry mouth, GI upset and weakness. [10] Sedation is also common. [9]
Both sodium valproate and divalproex sodium have been established as efficacious for migraine prophylaxis. [11] They are well tolerated short term, but should be monitored during long term therapy because of risks of pancreatitis, liver failure and teratogenicity. [12] Valproate should not be used in females of childbearing age because studies suggest that children exposed to valproate in the prenatal period are associated with having lower IQ scores. [9] Topiramate is another anticonvulsant with therapeutic efficacy in migraine prophylaxis. [13] It is a safe medication but should be used in caution in females of childbearing ages because it is suggested to cause birth defects. [13]
CGRP antagonists can be used for both acute migraine treatment as well as prophylactically. [14] CGRP is a neuropeptide which is thought to induce migraines via vasodilation of cranial arteries. [14] CGRP can also release inflammatory agents and cause nervous system sensitization. [14] It is theorized that by antagonizing the CGRP receptor of the trigeminal ganglia, lowered CGRP is released and less migraine occurs. [14] Erenumab is a highly selective human monoclonal antibody which is a promising new development in migraine treatment. [14] It has low risk of hepatoxicity like gepants can have, due to being mostly eliminated via proteolysis. [15]
There have been some studies suggesting the benefit of using melatonin for prophylaxis of migraine, however, there is a lack of strength of evidence due to a low number of studies as well as conflicting results. [16] Melatonin has a good safety profile but there have been rare instances of serious side effects. [16] More studies are needed in order to suggest the therapeutic use of melatonin for prophylaxis of migraine. [16]
There is not a strong degree of evidence for the use of anti migraine drugs prophylactically in children and adolescence. [17] It is highly important to consider risk vs benefit when considering their use in the paediatric population. [17]
Migraine is a genetically influenced complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea and light and sound sensitivity. Other characterizing symptoms may include nausea, vomiting, cognitive dysfunction, allodynia, and dizziness. Exacerbation of headache symptoms during physical activity is another distinguishing feature. Up to one-third of migraine sufferers experience aura: a premonitory period of sensory disturbance widely accepted to be caused by cortical spreading depression at the onset of a migraine attack. Although primarily considered to be a headache disorder, migraine is highly heterogenous in its clinical presentation and is better thought of as a spectrum disease rather than a distinct clinical entity. Disease burden can range from episodic discrete attacks, consisting of as little as several lifetime attacks, to chronic disease.
A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, can be very painful and are a common cause of chronic daily headache. They typically occur in patients with an underlying headache disorder such as migraine or tension-type headache that "transforms" over time from an episodic condition to chronic daily headache due to excessive intake of acute headache relief medications. MOH is a serious, disabling and well-characterized disorder, which represents a worldwide problem and is now considered the third-most prevalent type of headache. The proportion of patients in the population with Chronic Daily Headache (CDH) who overuse acute medications ranges from 18% to 33%. The prevalence of medication overuse headache (MOH) varies depending on the population studied and diagnostic criteria used. However, it is estimated that MOH affects approximately 1-2% of the general population, but its relative frequency is much higher in secondary and tertiary care.
Sumatriptan, sold under the brand name Imitrex among others, is a medication used to treat migraine headaches and cluster headaches. It is taken orally, intranasally, or by subcutaneous injection. Therapeutic effects generally occur within three hours.
Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.
Rizatriptan, sold under the brand name Maxalt among others, is a medication used for the treatment of migraine headaches. It is taken by mouth. It can also be applied on the tongue. It is a serotonin (5-HT) 1B/1D receptor agonist (triptan).
Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. Nausea is a common side effect.
Caffeine/ergotamine is the proprietary name of a medication consisting of ergotamine tartrate and caffeine. This combination is used for the treatment of headaches, such as migraine headache.
Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the market in the United States and Canada due to adverse effects. It is taken by mouth.
Agomelatine, sold under the brand names Valdoxan and Thymanax, among others, is an atypical antidepressant most commonly used to treat major depressive disorder and generalized anxiety disorder. One review found that it is as effective as other antidepressants with similar discontinuation rates overall but fewer discontinuations due to side effects. Another review also found it was similarly effective to many other antidepressants.
Almotriptan is a triptan medication discovered and developed by Almirall for the treatment of heavy migraine headache.
Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second-generation triptan medication intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc.
Pizotifen (INN) or pizotyline (USAN), trade name Sandomigran, is a benzocycloheptene-based drug used as a medicine, primarily as a preventive to reduce the frequency of recurrent migraine headaches.
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
Naratriptan (trade names include Amerge) is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. It is a selective 5-HT1 receptor subtype agonist.
Preventive treatment of migraine can be an important component of migraine management. Such treatments can take many forms, including everything from surgery, taking certain drugs or nutritional supplements, to lifestyle alterations such as increased exercise and avoidance of migraine triggers.
Lasmiditan, sold under the brand name Reyvow, is a medication used for the acute treatment of migraine with or without aura in adults. It is not useful for prevention. It is taken by mouth.
Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as antagonists of the calcitonin gene-related peptide receptor (CGRPR).
Migraine treatment may be either prophylactic (preventive) or abortive (rescue). Prevention is better than cure, so the ideal treatment goal is to prevent migraine attacks. Because migraine is an exceedingly complex condition, there are various preventive treatments which have their effect by disrupting different links in the chain of events that occur during a migraine attack. As rescue treatments also target and disrupt different processes occurring during migraine, these are summarized, with their relative merits and demerits.
Donitriptan (INN) is a triptan drug which was investigated as an antimigraine agent but ultimately was never marketed. It acts as a high-affinity, high-efficacy/near-full agonist of the 5-HT1B and 5-HT1D receptors, and is among the most potent of the triptan series of drugs. Donitriptan was being developed in France by bioMérieux-Pierre Fabre and made it to phase II clinical trials in Europe before development was discontinued.
Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent migraines in adults. It is given by injection under the skin.
Major chemical drug groups – based upon the Anatomical Therapeutic Chemical Classification System | |
|---|---|
| gastrointestinal tract / metabolism (A) | |
| blood and blood forming organs (B) | |
| cardiovascular system (C) | |
| skin (D) | |
| genitourinary system (G) | |
| endocrine system (H) | |
| infections and infestations (J, P, QI) | |
| malignant disease (L01–L02) | |
| immune disease (L03–L04) | |
| muscles, bones, and joints (M) | |
| brain and nervous system (N) |
|
| respiratory system (R) | |
| sensory organs (S) | |
| other ATC (V) | |
