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'''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|last1=Mutschler|first1=Ernst|title=Arzneimittelwirkungen|language=German|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2013|edition=10|pages=232–5|isbn=978-3-8047-2898-1}}</ref>
'''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|last1=Mutschler|first1=Ernst|title=Arzneimittelwirkungen|language=German|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2013|edition=10|pages=232–5|isbn=978-3-8047-2898-1}}</ref>
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===Treatment of acute symptoms===
===Treatment of acute symptoms===
{{see|Migraine#Management}}
{{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 drug|nonsteroidal anti-inflammatory drugs]] (NSAIDs) or acetaminophen. Opioids are not recommended for treatment of migraines.
Migraine can often be treated with unspecific analgesics such as [[nonsteroidal anti-inflammatory drug]]s (NSAIDs) or [[paracetamol]], with or without [[metoclopramide]]. Examples of specific antimigraine drugs include [[triptans]]<ref name=pharmamotion>[http://pharmamotion.com.ar/serotonin-5ht-receptors-agonists-antagonist/ pharmamotion.com > Serotonin (5-HT): receptors, agonists and antagonists] {{webarchive|url=https://web.archive.org/web/20090915175552/http://pharmamotion.com.ar/serotonin-5ht-receptors-agonists-antagonist/ |date=2009-09-15 }} By Flavio Guzmán, M.D. on 9/08/09</ref> such as [[zolmitriptan]]<ref name="pmid16549032">{{cite journal |vauthors=Morikawa T, Matsuzawa Y, Makita K, Katayama Y |title=Antimigraine drug, zolmitriptan, inhibits high-voltage activated calcium currents in a population of acutely dissociated rat trigeminal sensory neurons |journal=[[Molecular Pain]] |volume=2 |issue= 1|pages=10 |year=2006 |pmid=16549032 |pmc=1434723 |doi=10.1186/1744-8069-2-10 |url=http://www.molecularpain.com/content/2//10}}</ref> and [[ergoline|ergot alkaloids]] such as [[methysergide]].

=== Triptans ===
The triptan drug class includes 1st generation sumatriptan (which has poor bioavailability), and second generation zolmitriptan<ref name=":0">{{Cite journal |last=González-Hernández |first=Abimael |last2=Marichal-Cancino |first2=Bruno A. |last3=MaassenVanDenBrink |first3=Antoinette |last4=Villalón |first4=Carlos M. |date=2018-01-02 |title=Side effects associated with current and prospective antimigraine pharmacotherapies |url=https://doi.org/10.1080/17425255.2018.1416097 |journal=Expert Opinion on Drug Metabolism & Toxicology |volume=14 |issue=1 |pages=25–41 |doi=10.1080/17425255.2018.1416097 |issn=1742-5255 |pmid=29226741}}</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-HT<sub>1B/1D</sub> receptor agonists with some activity at 5-HT<sub>1F</sub>. 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 produce a caution in patients with cardiovascular disease<ref name=":0" />. There is also an increased risk of gastrointestinal adverse events.<ref name=":3">{{Cite journal |last=VanderPluym |first=Juliana H. |last2=Halker Singh |first2=Rashmi B. |last3=Urtecho |first3=Meritxell |last4=Morrow |first4=Allison S. |last5=Nayfeh |first5=Tarek |last6=Torres Roldan |first6=Victor D. |last7=Farah |first7=Magdoleen H. |last8=Hasan |first8=Bashar |last9=Saadi |first9=Samer |last10=Shah |first10=Sahrish |last11=Abd-Rabu |first11=Rami |date=2021-06-15 |title=Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis |url=https://jamanetwork.com/journals/jama/fullarticle/2781052 |journal=JAMA |language=en |volume=325 |issue=23 |pages=2357 |doi=10.1001/jama.2021.7939 |issn=0098-7484 |pmc=PMC8207243 |pmid=34128998}}</ref> Triptans use is limited to less than 10x per month in order to reduce Medication Overuse Headache (MOH)<ref name=":0" />.

=== Ergots Alkaloids ===
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-HT<sub>1-2</sub>, dopamine D2-like and alpha1/alpha2-adrenoreceptors<ref name=":10">{{Cite journal |last=Tfelt-Hansen |first=Peer C |date=2013-09-01 |title=Triptans and ergot alkaloids in the acute treatment of migraine: similarities and differences |url=https://doi.org/10.1586/14737175.2013.832851 |journal=Expert Review of Neurotherapeutics |volume=13 |issue=9 |pages=961–963 |doi=10.1586/14737175.2013.832851 |issn=1473-7175}}</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">Osman, N., Worthington, I., Lagman-Bartolome, A. General Appendices: Headache in Adults: Self-care Therapy for Common Conditions In: Compendium of Therapeutics for Minor Ailments, 2nd edition (CTMA 2). Ottawa, ON: Canadian Pharmacists Association. <nowiki>https://www-e-therapeutics-ca.uml.idm.oclc.org/search</nowiki> Accessed Nov 20, 2021</ref>. Adverse effects include nausea, vomiting, paresthesia, and ergotism<ref name=":0" />. Their use is limited to less than 10x per month in order to reduce MOH. The oral dosage administrative form is considered less effective than nasal or parental forms and has been discontinued in Canada<ref name=":1" />. Ergotamine is contraindicated during pregnancy<ref>{{Cite web |last=Lee, Guinn & Hickenbottom |first=Men-Jean, Debra & Susan |date=April 25, 2022 |title=Headache during pregnancy and postpartum |url=https://www-uptodate-com.uml.idm.oclc.org/contents/headache-during-pregnancy-and-postpartum?sectionName=Acute%20migraine%20treatment&search=acute%20migraine&topicRef=3347&anchor=H3&source=see_link#H3 |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-HT<sub>1F</sub> receptors agonists <ref name=":2">{{Cite journal |last=Yang |first=Chun-Pai |last2=Liang |first2=Chih-Sung |last3=Chang |first3=Ching-Mao |last4=Yang |first4=Cheng-Chia |last5=Shih |first5=Po-Hsuan |last6=Yau |first6=Yun-Chain |last7=Tang |first7=Kuo-Tung |last8=Wang |first8=Shuu-Jiun |date=2021-10-11 |title=Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis |url=https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784777 |journal=JAMA Network Open |language=en |volume=4 |issue=10 |pages=e2128544 |doi=10.1001/jamanetworkopen.2021.28544 |issn=2574-3805 |pmc=PMC8506232 |pmid=34633423}}</ref>. 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<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" />.

=== Gepants ===
Gepants (eg. rimegepant and ubrogepant) 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 |last=Schwedt & Garza |first=Todd & Ivan |date=April 25, 2022 |title=Acute treatment of migraine in adults |url=https://www-uptodate-com.uml.idm.oclc.org/contents/acute-treatment-of-migraine-in-adults?search=acute%20migraine&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 |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 and ASA should be selecting first due to their anti inflammatory properties. 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 MOH headache when compared to NSAIDS, acetaminophen or triptans<ref name=":3" />.In addition, their strength of efficacy has showed 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===
===Prevention===
{{see|Migraine#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.
First-line drugs for the prevention of migraine attacks include the [[beta blocker]]s [[propranolol]], [[metoprolol]] and [[bisoprolol]], the antiepileptics [[valproic acid]] and [[topiramate]], as well as [[flunarizine]]. Less well evidenced is the use of [[amitriptyline]], [[venlafaxine]], ''[[Petasites albus]]'' extract, [[riboflavin]] (vitamin B<sub>2</sub>), [[magnesium]], [[coenzyme Q10|coenzyme Q<sub>10</sub>]], [[gabapentin]], [[acetylsalicylic acid]], and [[naproxen]].<ref name="Mutschler" />

=== 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 |last=Schwedt |first=Todd |date=March 11, 2022 |title=Preventative treatment of episodic migraine in adults |url=https://www-uptodate-com.uml.idm.oclc.org/contents/preventive-treatment-of-episodic-migraine-in-adults?search=preventive%20treatment%20of%20migraine%20in%20adults&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 |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 |last=Xu |first=X.-M. |last2=Yang |first2=C. |last3=Liu |first3=Y. |last4=Dong |first4=M.-X. |last5=Zou |first5=D.-Z. |last6=Wei |first6=Y.-D. |date=2017-05-29 |title=Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis |url=https://doi-org.uml.idm.oclc.org/10.1111/ene.13320 |journal=European Journal of Neurology |language=en |volume=24 |issue=8 |pages=1022–1031 |doi=10.1111/ene.13320 |issn=1351-5101}}</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" />. Serotonin selective 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<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 |last=Silberstein |first=S.D. |last2=Holland |first2=S. |last3=Freitag |first3=F. |last4=Dodick |first4=D.W. |last5=Argoff |first5=C. |last6=Ashman |first6=E. |date=2012-04-24 |title=Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: Table 1: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society |url=https://www.neurology.org/lookup/doi/10.1212/WNL.0b013e3182535d20 |journal=Neurology |language=en |volume=78 |issue=17 |pages=1337–1345 |doi=10.1212/WNL.0b013e3182535d20 |issn=0028-3878 |pmc=PMC3335452 |pmid=22529202}}</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 |last=Silberstein |first=S.D. |last2=Holland |first2=S. |last3=Freitag |first3=F. |last4=Dodick |first4=D.W. |last5=Argoff |first5=C. |last6=Ashman |first6=E. |date=2012-04-24 |title=Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: Table 1: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society |url=https://www.neurology.org/lookup/doi/10.1212/WNL.0b013e3182535d20 |journal=Neurology |language=en |volume=78 |issue=17 |pages=1337–1345 |doi=10.1212/WNL.0b013e3182535d20 |issn=0028-3878 |pmc=PMC3335452 |pmid=22529202}}</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 |last=Linde |first=Mattias |last2=Mulleners |first2=Wim M |last3=Chronicle |first3=Edward P |last4=McCrory |first4=Douglas C |date=2013-06-24 |editor-last=Cochrane Pain, Palliative and Supportive Care Group |title=Topiramate for the prophylaxis of episodic migraine in adults |url=https://doi.wiley.com/10.1002/14651858.CD010610 |journal=Cochrane Database of Systematic Reviews |language=en |doi=10.1002/14651858.CD010610}}</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 |last=Urits |first=Ivan |last2=Jones |first2=Mark R. |last3=Gress |first3=Kyle |last4=Charipova |first4=Karina |last5=Fiocchi |first5=Jacob |last6=Kaye |first6=Alan D. |last7=Viswanath |first7=Omar |date=2019-03-14 |title=CGRP Antagonists for the Treatment of Chronic Migraines: a Comprehensive Review |url=https://doi.org/10.1007/s11916-019-0768-y |journal=Current Pain and Headache Reports |language=en |volume=23 |issue=5 |pages=29 |doi=10.1007/s11916-019-0768-y |issn=1534-3081}}</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 |last=Szkutnik-Fiedler |first=Danuta |date=2020-12-03 |title=Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies |url=https://www.mdpi.com/1999-4923/12/12/1180 |journal=Pharmaceutics |language=en |volume=12 |issue=12 |pages=1180 |doi=10.3390/pharmaceutics12121180 |issn=1999-4923}}</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 |last=Long |first=Rujin |last2=Zhu |first2=Yousheng |last3=Zhou |first3=Shusheng |date=2019 |title=Therapeutic role of melatonin in migraine prophylaxis: A systematic review |url=https://journals.lww.com/00005792-201901180-00045 |journal=Medicine |language=en |volume=98 |issue=3 |pages=e14099 |doi=10.1097/MD.0000000000014099 |issn=0025-7974 |pmc=PMC6370052 |pmid=30653130}}</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" />.

== Migraine 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=":9">{{Cite journal |last=Locher |first=Cosima |last2=Kossowsky |first2=Joe |last3=Koechlin |first3=Helen |last4=Lam |first4=Thanh Lan |last5=Barthel |first5=Johannes |last6=Berde |first6=Charles B |last7=Gaab |first7=Jens |last8=Schwarzer |first8=Guido |last9=Linde |first9=Klaus |last10=Meissner |first10=Karin |date=2020-04-01 |title=Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis |url=https://jamanetwork.com/journals/jamapediatrics/fullarticle/2760572 |journal=JAMA Pediatrics |language=en |volume=174 |issue=4 |pages=341 |doi=10.1001/jamapediatrics.2019.5856 |issn=2168-6203 |pmc=PMC7042942 |pmid=32040139}}</ref>

<ref name=":9" />


==References==
==References==

Revision as of 01:21, 26 April 2022

Antimigraine drug
Drug class
Zolmitriptan, a common antimigraine medication
Class identifiers
UseMigraine therapy and prevention
ATC codeN02C
Clinical data
Drugs.comDrug 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

Treatment of acute symptoms

Further information: 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[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 produce a 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 10x per month in order to reduce Medication Overuse Headache (MOH)[2].

Ergots Alkaloids

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 10x per month in order to reduce MOH. The oral dosage administrative form is considered less effective than nasal or parental forms and has been discontinued in Canada[5]. Ergotamine is contraindicated during pregnancy[6].

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 [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

Gepants (eg. rimegepant and ubrogepant) 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

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 and ASA should be selecting first due to their anti inflammatory properties. 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

Opioids are not recommended for treatment of acute migraines due to their significant side effect profile, including twice the risk of MOH 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].

Prevention

Further information: 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.

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[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

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]. Serotonin selective 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].

Anticonvulsants

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].

Calcitonin Gene Receptor Peptide (CGRP) Antagonists

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].

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[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].

Migraine Prophylaxis in Pediatric Patients

There is not a strong degree of evidence for the use of anti migraine drugs prophylactically in children and adolescence[17]

[17]

References

  1. ^ Mutschler, Ernst (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 232–5. ISBN 978-3-8047-2898-1.
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