Antimigraine drug

{{Short description|Medication intended to reduce the effects or intensity of migraine headache}} {{cs1 config|name-list-style=vanc}} {{Infobox drug class | Image = Zolmitriptan Structure V.1.svg | ImageClass = skin-invert-image | Alt = | Width = 250px | Caption = Zolmitriptan, a common antimigraine medication | Pronounce = | Synonyms =  | Use = Migraine therapy and prevention | ATC_prefix = N02C | Mode_of_action = | Mechanism_of_action = | Biological_target = | Chemical_class =  | Drugs.com = {{Drugs.com|drug-class|antimigraine-agents}} | Consumer_Reports = | medicinenet = | rxlist =  | MeshID = }}

'''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.<ref name="Mutschler">{{cite book| vauthors = Mutschler E |title= Arzneimittelwirkungen|language=German|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2013|edition=10|pages=232–5|isbn=978-3-8047-2898-1}}</ref>

==Treatment of acute symptoms== {{see|Migraine#Management}} 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.

=== Triptans === The triptan drug class includes 1st generation sumatriptan (which has poor bioavailability), and second generation zolmitriptan.<ref name=":0">{{cite journal | vauthors = González-Hernández A, Marichal-Cancino BA, MaassenVanDenBrink A, Villalón CM | title = Side effects associated with current and prospective antimigraine pharmacotherapies | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 14 | issue = 1 | pages = 25–41 | date = January 2018 | pmid = 29226741 | doi = 10.1080/17425255.2018.1416097 | s2cid = 35889312 }}</ref> Due to their safety, efficacy and selectivity, triptans are considered first line agents for abortion of migraines.<ref name=":0" /> 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.<ref name=":0" /> 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.<ref name=":0" /> There is also an increased risk of gastrointestinal adverse events.<ref name=":3">{{cite journal | vauthors = VanderPluym JH, Halker Singh RB, Urtecho M, Morrow AS, Nayfeh T, Torres Roldan VD, Farah MH, Hasan B, Saadi S, Shah S, Abd-Rabu R, Daraz L, Prokop LJ, Murad MH, Wang Z | display-authors = 6 | title = Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis | journal = JAMA | volume = 325 | issue = 23 | pages = 2357–2369 | date = June 2021 | pmid = 34128998 | pmc = 8207243 | doi = 10.1001/jama.2021.7939 }}</ref> Triptans use is limited to less than ten times per month in order to reduce medication overuse headache (MOH).<ref name=":0" />

===Ergot alkaloids=== Ergot alkaloids include ergotamine and dihydroergotamine. This medication class targets the CGRP 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.<ref name=":10">{{cite journal | vauthors = Tfelt-Hansen PC | title = Triptans and ergot alkaloids in the acute treatment of migraine: similarities and differences | journal = Expert Review of Neurotherapeutics | volume = 13 | issue = 9 | pages = 961–963 | date = September 2013 | pmid = 23980649 | doi = 10.1586/14737175.2013.832851 | s2cid = 19114584 | doi-access = free }}</ref> Their lack of selectivity leads to more adverse effects, making them second line compared to triptans.<ref name=":10" /> However, they have been shown to prevent recurrence better than triptans.<ref name=":1">{{cite book | vauthors = Osman N, Worthington I, Lagman-Bartolome A | chapter = General Appendices: Headache in Adults: Self-care Therapy for Common Conditions | title = Compendium of Therapeutics for Minor Ailments | edition = 2nd (CTMA 2) | location = Ottawa, ON | publisher = Canadian Pharmacists Association | isbn = 978-1-894402-96-5 }}</ref> Adverse effects include nausea, vomiting, paresthesia, and ergotism.<ref name=":0" /> Their use is limited to less than ten times per month in order to reduce medication overuse headache (MOH). The oral dosage administrative form is considered less effective than nasal or parenteral forms and has been discontinued in Canada.<ref name=":1" /> Ergotamine is contraindicated during pregnancy.<ref name=":12">{{cite web | vauthors = Lee MJ, Guinn D, Hickenbottom S |date=April 25, 2022 |title=Headache during pregnancy and postpartum |url=https://www.uptodate.com/contents/headache-during-pregnancy-and-postpartum |website=UpToDate}}</ref>

=== Ditans === 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.<ref name=":2">{{cite journal | vauthors = Yang CP, Liang CS, Chang CM, Yang CC, Shih PH, Yau YC, Tang KT, Wang SJ | display-authors = 6 | title = Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis | journal = JAMA Network Open | volume = 4 | issue = 10 | pages = e2128544 | date = October 2021 | pmid = 34633423 | pmc = 8506232 | doi = 10.1001/jamanetworkopen.2021.28544 }}</ref> Lasmiditan has been suggested to have less pain relief when compared to the triptans at the 2 hour mark post taking the medication. Lasmiditan was shown to have higher adverse events (dizziness, fatigue and nausea) than the triptans or another novel medication class, CGRP antagonists.<ref name=":2" /> However, they could be an option for patients with cardiovascular risks due to their lack of vasoconstriction .<ref name=":2" /> Due to risk of dizziness, those who take lasmiditan should avoid driving 8 hours after taking.<ref name=":3" /> Another ditan that was ultimately not marketed is alniditan.

=== Gepants === {{see also|Calcitonin gene-related peptide receptor antagonist}} 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.<ref name=":2" /> 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.<ref name=":2" /> They are well tolerated with fewer adverse effects compared to triptans .<ref name=":2" />

=== NSAIDS === 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.<ref name=":11">{{cite web | vauthors = Schwedt TJ, Garza MI |date=April 25, 2022 |title=Acute treatment of migraine in adults |url=https://www.uptodate.com/contents/acute-treatment-of-migraine-in-adults |website=UpToDate}}</ref> 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.<ref name=":12" /> Combination therapy of an NSAID with a triptan can be used when either medication is insufficient alone for migraine relief or recurrence .<ref name=":1" /> Long term NSAID use has risks including nephrotoxicity and cardiotoxicity, and long term acetaminophen use is associated with hepatoxicity.<ref name=":3" /> If warranted, an antiemetic can be used in combination with an NSAID.<ref name=":11" />

=== Opioids === 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.<ref name=":3" /> In addition, their strength of efficacy has shown to be low or insufficient for pain relief of migraines.<ref name=":3" /> Importantly, there is also risk of addiction and opioid use disorder.<ref name=":3" />

== Prevention == {{see|Migraine#Prevention}} 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.

=== Serotonin antagonists === Non-selective serotonin receptor antagonists like methysergide, pizotifen, and cyproheptadine are used to prevent migraines.<ref name="SegelckeMesslinger2017">{{cite journal | vauthors = Segelcke D, Messlinger K | title = Putative role of 5-HT2B receptors in migraine pathophysiology | journal = Cephalalgia | volume = 37 | issue = 4 | pages = 365–371 | date = April 2017 | pmid = 27127104 | doi = 10.1177/0333102416646760 | url =https://open.fau.de/bitstreams/a6fb0554-f9da-4cc6-9a08-80f55dfb3d47/download | doi-access = free }}</ref> Their antimigraine effects may be due specifically to serotonin 5-HT2B receptor blockade.<ref name="SegelckeMesslinger2017" />

===Beta blockers=== Beta blockers have been deemed effective options for the prevention of migraines. In particular, metoprolol, timolol and propranolol have the most strength of efficacy.<ref name=":4">{{cite web | vauthors = Schwedt TJ, Garza MI |date=March 11, 2022 |title=Preventative treatment of episodic migraine in adults |url= https://www.uptodate.com/contents/preventive-treatment-of-episodic-migraine-in-adults |access-date=April 17, 2022 |website=Up to Date}}</ref> The timeframe to effectiveness in generally within 3 months.<ref name=":4" /> Patients with cardiovascular risk factors should avoid the use of beta blockers for migraine prevention.<ref name=":4" />

=== Antidepressants === Antidepressants are suggested to be both efficacious and tolerable in the treatment of migraine prevention for both migraine frequency and migraine index.<ref name=":7">{{cite journal | vauthors = Xu XM, Yang C, Liu Y, Dong MX, Zou DZ, Wei YD | title = Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis | journal = European Journal of Neurology | volume = 24 | issue = 8 | pages = 1022–1031 | date = August 2017 | pmid = 28557171 | doi = 10.1111/ene.13320 | s2cid = 4572477 }}</ref> The exact mechanism of action is unknown but seems to be related to serotonin's impact on migraine.<ref name=":7" /> In particular, amitryptyline (a tricyclic antidepressant) has the most evidence to suggest its efficacy.<ref name=":7" /> Selective serotonin reuptake inhibitors (SSRIs) as well Serotonin–norepinephrine reuptake inhibitors (SNRIs) are likely effective as well, but more studies are required in order to provide more evidence.<ref name=":7" /> Adverse events of antidepressants can include fatigue, nausea, drowsiness, dizziness, dry mouth, GI upset and weakness.<ref name=":7" /> Sedation is also common.<ref name=":4" />

=== Anticonvulsants === Both sodium valproate and divalproex sodium have been established as efficacious for migraine prophylaxis.<ref>{{cite journal |author4-link=David W. Dodick | vauthors = Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E | title = Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society | journal = Neurology | volume = 78 | issue = 17 | pages = 1337–1345 | date = April 2012 | pmid = 22529202 | pmc = 3335452 | doi = 10.1212/WNL.0b013e3182535d20 }}</ref> They are well tolerated short term, but should be monitored during long term therapy because of risks of pancreatitis, liver failure and teratogenicity.<ref>{{cite journal | vauthors = Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E | title = Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society | journal = Neurology | volume = 78 | issue = 17 | pages = 1337–1345 | date = April 2012 | pmid = 22529202 | pmc = 3335452 | doi = 10.1212/WNL.0b013e3182535d20 }}</ref> 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.<ref name=":4" /> Topiramate is another anticonvulsant with therapeutic efficacy in migraine prophylaxis.<ref name=":6">{{cite journal | vauthors = Linde M, Mulleners WM, Chronicle EP, McCrory DC | title = Topiramate for the prophylaxis of episodic migraine in adults | journal = The Cochrane Database of Systematic Reviews | issue = 6 | article-number = CD010610 | date = June 2013 | volume = 2016 | pmid = 23797676 | doi = 10.1002/14651858.CD010610 | pmc = 7388931 | collaboration = Cochrane Pain, Palliative and Supportive Care Group }}</ref> It is a safe medication but should be used in caution in females of childbearing ages because it is suggested to cause birth defects.<ref name=":6" />

=== Calcitonin gene receptor peptide (CGRP) antagonists === CGRP antagonists can be used for both acute migraine treatment as well as prophylactically.<ref name=":8">{{cite journal | vauthors = Urits I, Jones MR, Gress K, Charipova K, Fiocchi J, Kaye AD, Viswanath O | title = CGRP Antagonists for the Treatment of Chronic Migraines: a Comprehensive Review | journal = Current Pain and Headache Reports | volume = 23 | issue = 5 | page = 29 | date = March 2019 | pmid = 30874961 | doi = 10.1007/s11916-019-0768-y | s2cid = 78092916 }}</ref> CGRP is a neuropeptide which is thought to induce migraines via vasodilation of cranial arteries.<ref name=":8" /> CGRP can also release inflammatory agents and cause nervous system sensitization.<ref name=":8" /> It is theorized that by antagonizing the CGRP receptor of the trigeminal ganglia, lowered CGRP is released and less migraine occurs.<ref name=":8" /> Erenumab is a highly selective human monoclonal antibody which is a promising new development in migraine treatment.<ref name=":8" /> It has low risk of hepatoxicity like gepants can have, due to being mostly eliminated via proteolysis.<ref>{{cite journal | vauthors = Szkutnik-Fiedler D | title = Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of New Anti-Migraine Drugs-Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies | journal = Pharmaceutics | volume = 12 | issue = 12 | page = 1180 | date = December 2020 | pmid = 33287305 | doi = 10.3390/pharmaceutics12121180 | pmc = 7761673 | doi-access = free }}</ref>

=== Melatonin === 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.<ref name=":5">{{cite journal | vauthors = Long R, Zhu Y, Zhou S | title = Therapeutic role of melatonin in migraine prophylaxis: A systematic review | journal = Medicine | volume = 98 | issue = 3 | article-number = e14099 | date = January 2019 | pmid = 30653130 | pmc = 6370052 | doi = 10.1097/MD.0000000000014099 }}</ref> Melatonin has a good safety profile but there have been rare instances of serious side effects.<ref name=":5" /> More studies are needed in order to suggest the therapeutic use of melatonin for prophylaxis of migraine.<ref name=":5" />

== Prophylaxis in pediatric patients == There is not a strong degree of evidence for the use of anti migraine drugs prophylactically in children and adolescence.<ref name=":92">{{cite journal | vauthors = Locher C, Kossowsky J, Koechlin H, Lam TL, Barthel J, Berde CB, Gaab J, Schwarzer G, Linde K, Meissner K | display-authors = 6 | title = Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis | journal = JAMA Pediatrics | volume = 174 | issue = 4 | pages = 341–349 | date = April 2020 | pmid = 32040139 | pmc = 7042942 | doi = 10.1001/jamapediatrics.2019.5856 }}</ref> It is highly important to consider risk vs benefit when considering their use in the paediatric population.<ref name=":92"/>

== References == {{Reflist}}

Category:Antimigraine drugs