Migraine headache: Difference between revisions

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Migraine headaches are "a class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms)."<ref>{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=migraine |title=Migraine Disorders |accessdate=2007-11-02 |author=National Library of Medicine |authorlink= |coauthors= |date= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref>
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'''Migraine headaches''' are "a class of disabling primary [[headache]] disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms)."<ref>{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=migraine |title=Migraine Disorders |accessdate=2007-11-02 |author=National Library of Medicine |authorlink= |coauthors= |date= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> Laymen often use the term for any severe headache, especially with nausea and sensitivity to light and sound, but there are specific criteria. Just as the term is overused in some contexts, however, true migraine has different manifestations, is underdiagnosed, and is sometimes preventable as well as treatable.
 
Patients with a diagnosis of migraine are called ''migraneurs''.
 
Since around 2018, studies have suggested that people who get frequent headaches sometimes also have gastrointestinal problems, and conditions such as [[irritable bowel syndrome]] and [[celiac disease]] may be linked to migraines. Treating these digestive conditions may help reduce the frequency and severity of migraines, although more research is needed to understand these connections.


==Classification==
==Classification==
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==Diagnosis==
==Diagnosis==
Migraines are underdiagnosed<ref name="pmid1599358">{{cite journal |author=Lipton RB, Stewart WF, Celentano DD, Reed ML |title=Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis |journal=Arch. Intern. Med. |volume=152 |issue=6 |pages=1273–8 |year=1992 |pmid=1599358 |doi=}}</ref> and misdiagnosed.<ref name="pmid15364670">{{cite journal |author=Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C |title=Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache |journal=Arch. Intern. Med. |volume=164 |issue=16 |pages=1769–72 |year=2004 |pmid=15364670 |doi=10.1001/archinte.164.16.1769}}</ref> The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":
Migraines are underdiagnosed<ref name="pmid1599358">{{cite journal |author=Lipton RB, Stewart WF, Celentano DD, Reed ML |title=Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis |journal=Arch. Intern. Med. |volume=152 |issue=6 |pages=1273–8 |year=1992 |pmid=1599358 |doi=}}</ref> and misdiagnosed.<ref name="pmid15364670">{{cite journal |author=Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C |title=Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache |journal=Arch. Intern. Med. |volume=164 |issue=16 |pages=1769–72 |year=2004 |pmid=15364670 |doi=10.1001/archinte.164.16.1769}}</ref> About a third of headaches that patients report as being migraines are truly migraines<ref name="pmid12011270">{{cite journal |author=Lipton RB, Stewart WF, Liberman JN |title=Self-awareness of migraine: interpreting the labels that headache sufferers apply to their headaches |journal=Neurology |volume=58 |issue=9 Suppl 6 |pages=S21–6 |year=2002 |pmid=12011270 |doi=}}</ref>; while about 90% of headaches that are self-reported not to be migraines are truly not migraines.<ref name="pmid12011270"/> The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":<ref>International  Headache Society. [http://ihs-classification.org/en/02_klassifikation/02_teil1/01.01.00_migraine.html  IHS Classification ICHD-II Migraine headache]</ref><br/>
*5 or more attacks  
*5 or more attacks  
*4 hours to 3 days in duration  
*4 hours to 3 days in duration  
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For migraine with aura, only two attacks are required to justify the diagnosis.
For migraine with aura, only two attacks are required to justify the diagnosis.


The mnemonic POUNDing ('''P'''ulsating, duration of 4-72 h'''O'''urs, '''U'''nilateral, [[N]]ausea, '''D'''isabling) can help diagnose migraine. If 4 of the 5 criteria are met, then the positive [[likelihood-ratio test| likelihood ratio]] for diagnosing migraine is 24.<ref name="pmid16968852">{{cite journal |author=Detsky ME, McDonald DR, Baerlocher MO, Tomlinson GA, McCrory DC, Booth CM |title=Does this patient with headache have a migraine or need neuroimaging? |journal=JAMA |volume=296 |issue=10 |pages=1274–83 |year=2006 |pmid=16968852 |doi=10.1001/jama.296.10.1274}}</ref>
Additional criteria are available.<ref>Ad  Hoc Committee on the Classification of Headache of the National  Institute of Neurological Diseases and Blindness.  [http://jama.ama-assn.org/cgi/reprint/179/9/717 Classification of  headache]. JAMA (1962) 179:717–8</ref>
 
===POUNDing===
The mnemonic POUNDing ('''P'''ulsating, duration of 4-72 h'''O'''urs, '''U'''nilateral, [[N]]ausea, '''D'''isabling) can help diagnose migraine. If 4 of the 5 criteria are met, then the positive [[likelihood ratio]] for diagnosing migraine is 24.<ref name="pmid16968852">{{cite journal |author=Detsky ME, McDonald DR, Baerlocher MO, Tomlinson GA, McCrory DC, Booth CM |title=Does this patient with headache have a migraine or need neuroimaging? |journal=JAMA |volume=296 |issue=10 |pages=1274–83 |year=2006 |pmid=16968852 |doi=10.1001/jama.296.10.1274}}</ref>


The presence of either disability, nausea or sensitivity, can diagnose migraine with<ref name="pmid12913201">{{cite journal |author=Lipton RB, Dodick D, Sadovsky R, ''et al'' |title=A self-administered screener for migraine in primary care: The ID Migraine validation study |journal=Neurology |volume=61 |issue=3 |pages=375-82 |year=2003 |pmid=12913201 |doi=}}</ref>:
===ID Migraine===
The presence of either disability, nausea, or sensitivity to light can diagnose migraine with<ref name="pmid12913201">{{cite journal |author=Lipton RB, Dodick D, Sadovsky R, ''et al'' |title=A self-administered screener for migraine in primary care: The ID Migraine validation study |journal=Neurology |volume=61 |issue=3 |pages=375-82 |year=2003 |pmid=12913201 |doi=}}</ref>:
* [[sensitivity (tests)|sensitivity]] of 81%
* [[sensitivity (tests)|sensitivity]] of 81%
* [[specificity (tests)|specificity]] of 75%
* [[specificity (tests)|specificity]] of 75%
A subsequent [[systematic review]] of ID migraine reported similar results.<ref name="pmid21649653">{{cite journal| author=Cousins G, Hijazze S, Van de Laar FA, Fahey T| title=Diagnostic accuracy of the ID Migraine: a systematic review and meta-analysis. | journal=Headache | year= 2011 | volume= 51 | issue= 7 | pages= 1140-8 | pmid=21649653 | doi=10.1111/j.1526-4610.2011.01916.x | pmc= | url= }} </ref>


==Treatment==
==Treatment==
There are two basic problems in migraine management: treating the acute attack, and preventing migraine in chronic migraneurs.  Some treatment approaches combine preventive approaches with specific preventive measures.
"The addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment" according to a [[randomized controlled trial]]. <ref name="pmid20880898">{{cite journal| author=Holroyd KA, Cottrell CK, O'Donnell FJ, Cordingley GE, Drew JB, Carlson BW et al.| title=Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c4871 | pmid=20880898 | pmc=PMC2947621 | doi=10.1136/bmj.c4871 }} </ref>
===Abortive treatment===
===Abortive treatment===
==== Comparative studies ====
====Non-steroidal anti-inflammatory agents====
A [[randomized controlled trial]] found that high dose acetylsalicylic acid (1000 mg), sumatriptan 50 mg and low dose ibuprofen 400 mg are equally effective at reducing pain to mild or none at two hours; however, sumatriptan was led to more patients being pain free at two hours (37% versus less than 33% for other groups).<ref name="pmid15482357">{{cite journal |author=Diener HC, Bussone G, de Liano H, ''et al'' |title=Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks |journal=Cephalalgia : an international journal of headache |volume=24 |issue=11 |pages=947–54 |year=2004 |pmid=15482357 |doi=10.1111/j.1468-2982.2004.00783.x |issn=}}</ref>  
[[Non-steroidal anti-inflammatory agent]]s (NSAIDs) can help."Oral diclofenac potassium 50 mg is an effective treatment for acute migraine, providing relief from pain and associated symptoms, although only a minority of patients experience pain-free responses" according to a [[meta-analysis]] by the [[Cochrane Collaboration]].<ref name="pmid22336852">{{cite journal| author=Derry S, Rabbie R, Moore  RA| title=Diclofenac with or without an antiemetic for acute migraine  headaches in adults. | journal=Cochrane Database Syst Rev | year= 2012 | volume= 2 | issue= | pages= CD008783 | pmid=22336852 | doi=10.1002/14651858.CD008783.pub2 | pmc= | url= }} </ref>


Another [[randomized controlled trial]], funded by the manufacturer of the study drug, found that a combination of [[sumatriptan]] 85 mg and [[naproxen]] sodium 200 mg was better than either drug alone.<ref name="pmid17405970">{{cite journal |author=Brandes JL, Kudrow D, Stark SR, ''et al'' |title=Sumatriptan-naproxen for acute treatment of migraine: a randomized trial |journal=JAMA |volume=297 |issue=13 |pages=1443-54 |year=2007 |pmid=17405970 |doi=10.1001/jama.297.13.1443}}</ref>
====Serotonin agonists====
High dose [[acetylsalicylic acid]] (1000 mg) may be as effective as [[sumatriptan]], especially if the [[acetylsalicylic acid]] is combined with [[metoclopramide]] to reduce nausea and vomiting, according to a systematic review by the [[Cochrane Collaboration]].<ref name="pmid20393963">{{cite journal| author=Kirthi V, Derry S, Moore RA, McQuay HJ| title=Aspirin with or without an antiemetic for acute migraine headaches in adults. | journal=Cochrane Database Syst Rev | year= 2010 | volume= 4 | issue=  | pages= CD008041 | pmid=20393963
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20393963 | doi=10.1002/14651858.CD008041.pub2 }} </ref> One of the trials in the review reported that high dose [[acetylsalicylic acid]] (1000 mg), [[sumatriptan]] 50 mg and low dose [[ibuprofen]] 400 mg are equally effective at reducing pain to mild or none at two hours according to a [[randomized controlled trial]]; however, sumatriptan was led to more patients being [[pain]] free at two hours (37% versus less than 33% for other groups).<ref name="pmid15482357">{{cite journal |author=Diener HC, Bussone G, de Liano H, ''et al'' |title=Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks |journal=Cephalalgia : an international journal of headache |volume=24 |issue=11 |pages=947–54 |year=2004 |pmid=15482357 |doi=10.1111/j.1468-2982.2004.00783.x |issn=}}</ref>
 
====Dopamine antagonists====
[[Phenothiazine]]s, such as [[prochlorperazine]] 10 mg parenterally and [[chlorpromazine]] 0.04 to 0.1 mg/kg parenterally, are more effective than placebo and more effective than [[metoclopramide]] according to a [[meta-analysis]] of [[randomized controlled trial]]s.<ref name="pmid19496829">{{cite journal| author=Kelly AM, Walcynski T, Gunn B| title=The relative efficacy of phenothiazines for the treatment of acute migraine: a meta-analysis. | journal=Headache | year= 2009 | volume= 49 | issue= 9 | pages= 1324-32 | pmid=19496829 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=19496829 | doi=10.1111/j.1526-4610.2009.01465.x }} </ref> In addition, [[prochlorperazine]] 10 mg intravenously with 12.5 mg [[diphenhydramine]] intravenously may be ''more'' effective than subcutaneous [[sumatriptan]].<ref name="pmid20045576">{{cite journal| author=Kostic MA, Gutierrez FJ, Rieg TS, Moore TS, Gendron RT| title=A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department. | journal=Ann Emerg Med | year= 2010 | volume= 56 | issue= 1 | pages= 1-6 | pmid=20045576 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20045576 | doi=10.1016/j.annemergmed.2009.11.020 }} </ref>
 
====Combination therapy====
High dose [[acetaminophen]] (1000 mg) combined with [[metoclopramide]] is effective and is as effective as oral [[sumatriptan]] 100 mg according to a [[systematic review]] by the [[Cochrane Collaboration]].<ref name="pmid23633349">{{cite journal| author=Derry S, Moore RA| title=Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. | journal=Cochrane Database Syst Rev | year= 2013 | volume= 4 | issue=  | pages= CD008040 | pmid=23633349 | doi=10.1002/14651858.CD008040.pub3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23633349  }} </ref>
 
When using intravenous [[metoclopramide]], a 10 mg dose combined with 25 mg of [[diphenhydramine]] in 50 ml of saline given over 20 minutes may be optimal.<ref name="pmid21227540">{{cite journal| author=Friedman BW, Mulvey L, Esses D, Solorzano C, Paternoster J, Lipton RB et al.| title=Metoclopramide for acute migraine: a dose-finding randomized clinical trial. | journal=Ann Emerg Med | year= 2011 | volume= 57 | issue= 5 | pages= 475-82.e1 | pmid=21227540 | doi=10.1016/j.annemergmed.2010.11.023 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21227540  }} </ref>
 
High dose [[acetylsalicylic acid]] (1000 mg) combined with [[metoclopramide]] is effective according to a [[systematic review]] by the [[Cochrane Collaboration]].<ref  name="pmid20393963"/>
A combination of [[sumatriptan]] 85 mg and [[naproxen]] sodium 200 mg was better than either drug alone according to a [[randomized  controlled trial]]  funded by the manufacturer of the study drug.<ref name="pmid17405970">{{cite journal |author=Brandes JL, Kudrow D, Stark SR, ''et al'' |title=Sumatriptan-naproxen for acute treatment of migraine: a randomized trial |journal=JAMA |volume=297 |issue=13 |pages=1443-54 |year=2007 |pmid=17405970 |doi=10.1001/jama.297.13.1443}}</ref>
 
====Nonpharmacological treatments====
Indirect evidence suggest migraine pain, under certain circumstances, may be worse while laying down.<ref name="pmid19055510">{{cite journal| author=Chou CH, Fuh JL, Hu HH, Wu JC, Wang SJ| title=Throbbing pain is related to Queckenstedt's test effect in migraine patients. | journal=Cephalalgia | year= 2009 | volume= 29 | issue= 3 | pages= 373-8 | pmid=19055510 | doi=10.1111/j.1468-2982.2008.01746.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19055510  }} </ref><ref name="pmid12558761">{{cite journal| author=Doepp F, Schreiber SJ, Dreier JP, Einhäupl KM, Valdueza JM| title=Migraine aggravation caused by cephalic venous congestion. | journal=Headache | year= 2003 | volume= 43 | issue= 2 | pages= 96-8 | pmid=12558761 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12558761  }} </ref>
 
====Corticosteroids====
[[Corticosteroid]]s may help prevent recurrence after abortive treatment according to a [[meta-analysis|meta-analyses]] of [[randomized controlled trial]]s with [[number needed to treat]] of nine<ref name="pmid18541610">{{cite journal |author=Colman I, Friedman BW, Brown MD, ''et al'' |title=Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence |journal=BMJ |volume=336 |issue=7657 |pages=1359–61 |year=2008 |month=June |pmid=18541610 |pmc=2427093 |doi=10.1136/bmj.39566.806725.BE |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=18541610 |issn=}}</ref> or 10<ref name="pmid18976336">{{cite journal |author=Singh A, Alter HJ, Zaia B |title=Does the Addition of Dexamethasone to Standard Therapy for Acute Migraine Headache Decrease the Incidence of Recurrent Headache for Patients Treated in the Emergency Department? A Meta-analysis and Systematic Review of the Literature |journal=Acad Emerg Med |volume= |issue= |pages= |year=2008 |month=October |pmid=18976336 |doi=10.1111/j.1553-2712.2008.00283.x |url= |issn=}}</ref>.
 
A more recent [[randomized controlled trial]] found insignificant benefit, but the study was small and the magnitude of the benefit was similar to the prior [[meta-analysis meta-analyses]].<ref name="pmid19846269">{{cite journal| author=Fiesseler FW, Shih R, Szucs P, Silverman ME, Eskin B, Clement M et al.| title=Steroids for migraine headaches: a randomized double-blind, two-armed, placebo-controlled trial. | journal=J Emerg Med | year= 2011 | volume= 40 | issue= 4 | pages= 463-8 | pmid=19846269 | doi=10.1016/j.jemermed.2009.08.022 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19846269  }} </ref>
 
====Investigational treatments====
[[Telcagepant]] (MK-0974), an oral antagonist of [[calcitonin gene-related peptide]] receptor, may be as effective as [[zolmitriptan]] but with less [[drug toxicity]] according to a [[randomized controlled trial]].<ref name="pmid19036425">{{cite journal |author=Ho TW, Ferrari MD, Dodick DW, ''et al'' |title=Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial |journal=Lancet |volume=372 |issue=9656 |pages=2115–23 |year=2008 |month=December |pmid=19036425 |doi=10.1016/S0140-6736(08)61626-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61626-8 |issn=}}</ref>
 
"Sublingual feverfew/ginger appears safe and effective as a first-line abortive treatment" according to a [[randomized controlled trial]].<ref name="pmid21631494">{{cite journal| author=Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R| title=A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™ M) in the treatment of migraine. | journal=Headache | year= 2011 | volume= 51 | issue= 7 | pages= 1078-86 | pmid=21631494 | doi=10.1111/j.1526-4610.2011.01910.x | pmc= | url= }} </ref>


===Preventive treatment===
===Preventive treatment===
The antiepileptic drug topiramate can reduce the frequency of migraine attacks.<ref name="pmid14982912">{{cite journal |author=Brandes JL, Saper JR, Diamond M, ''et al'' |title=Topiramate for migraine prevention: a randomized controlled trial |journal=JAMA |volume=291 |issue=8 |pages=965–73 |year=2004 |pmid=14982912 |doi=10.1001/jama.291.8.965 |issn=}}</ref>
[[Clinical practice guideline]]s address preventive treatment.<ref>Silberstein et al. (2012) [http://www.neurology.org/content/78/17/1337.full 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]</ref>
 
Perhaps a third of patients meet consensus criteria for preventive treatment.<ref name="pmid17261680">{{cite journal |author=Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF |title=Migraine prevalence, disease burden, and the need for preventive therapy |journal=Neurology |volume=68 |issue=5 |pages=343–9 |year=2007 |pmid=17261680 |doi=10.1212/01.wnl.0000252808.97649.21 |issn=}}</ref>
 
[[Systematic review]]s addresse options.<ref name="pmid23592242">{{cite journal| author=Shamliyan TA, Choi JY, Ramakrishnan R, Miller JB, Wang SY, Taylor FR et al.| title=Preventive pharmacologic treatments for episodic migraine in adults. | journal=J Gen Intern Med | year= 2013 | volume= 28 | issue= 9 | pages= 1225-37 | pmid=23592242 | doi=10.1007/s11606-013-2433-1 | pmc=PMC3744311 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23592242 }} </ref><ref name="pmid20159899">{{cite journal|  author=Pringsheim T, Davenport WJ, Becker WJ| title=Prophylaxis of  migraine headache. | journal=CMAJ | year= 2010 | volume= 182 | issue= 7 |  pages= E269-76 | pmid=20159899
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20159899 | doi=10.1503/cmaj.081657 | pmc=PMC2855933 }} </ref>
 
====Tricyclic antidepressants====
[[Tricyclic antidepressant]]s may be effective and may be more effective than [[second-generation antidepressant]]s according to a [[systematic review]].<ref name="pmid20961988">{{cite journal| author=Jackson JL, Shimeall W, Sessums L, Dezee KJ, Becher D, Diemer M et al.| title=Tricyclic antidepressants and headaches: systematic review and meta-analysis. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c5222 | pmid=20961988 | doi=10.1136/bmj.c5222 | pmc=PMC2958257 | url= }} </ref>
 
====Adrenergic beta-antagonists====
Placebo is as effective as adding the [[adrenergic beta-antagonist]] drug [[propanolol]] to patients not adequately controlled on [[topiramate]].In a [[randomized controlled trial]], both groups reduced their days with migraine by half.<ref name="pmid22377815">{{cite journal| author=Silberstein SD, Dodick DW, Lindblad AS, Holroyd K, Harrington M, Mathew NT et al.| title=Randomized, placebo-controlled trial of propranolol added to topiramate in chronic migraine. | journal=Neurology | year= 2012 | volume= 78 | issue= 13 | pages= 976-84 | pmid=22377815 | doi=10.1212/WNL.0b013e31824d5846 | pmc=PMC3310312 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22377815  }} </ref>
 
====Angiotensin inhibition====
[[Angiotensin-converting enzyme inhibitor]] and [[angiotensin II receptor antagonist]] medications may reduce attacks according to a [[systematic review]].<ref name="pmid23592242">{{cite journal| author=Shamliyan TA, Choi JY, Ramakrishnan R, Miller JB, Wang SY, Taylor FR et al.| title=Preventive pharmacologic treatments for episodic migraine in adults. | journal=J Gen Intern Med | year= 2013 | volume= 28 | issue= 9 | pages= 1225-37 | pmid=23592242 | doi=10.1007/s11606-013-2433-1 | pmc=PMC3744311 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23592242 }} </ref>
 
====Anticonvulsants====
The [[anticonvulsant]] drug [[topiramate]] can increase response among patients with [[migraine]] according to  a [[randomized controlled trial]].<ref name="pmid14982912">{{cite journal |author=Brandes JL, Saper JR, Diamond M, ''et al'' |title=Topiramate for migraine prevention: a randomized controlled trial |journal=JAMA |volume=291 |issue=8 |pages=965–73 |year=2004 |pmid=14982912 |doi=10.1001/jama.291.8.965 |issn=}}</ref>> The [[relative benefit increase]] was 113.0%. For patients at similar risk to those in this study (23.0% had response), this leads to an [[absolute benefit increase]] of 26%. 3.8 patients must be treated for one to benefit ([[number needed to treat]] = 3.8). [http://sumsearch.org/calc/calc.shtml?calc_rx_rates.shtml?eer=49.0&cer=23.0 Click here] to adjust these results for patients at higher or lower risk of response.
 
====Botulinum toxin====
[[Botulinum toxin]] may have small benefit according to a [[meta-analysis]]<ref name="pmid22535858">{{cite journal| author=Jackson JL, Kuriyama A, Hayashino Y| title=Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. | journal=JAMA | year= 2012 | volume= 307 | issue= 16 | pages= 1736-45 | pmid=22535858 | doi=10.1001/jama.2012.505 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22535858  }} </ref> that included the PREEMPT 1<ref name="pmid20647170">{{cite journal| author=Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB et al.| title=OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. | journal=Cephalalgia | year= 2010 | volume= 30 | issue= 7 | pages= 793-803 | pmid=20647170 | doi=10.1177/0333102410364676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20647170  }} </ref> and PREEMPT 2<ref name="pmid20647171">{{cite journal| author=Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB et al.| title=OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. | journal=Cephalalgia | year= 2010 | volume= 30 | issue= 7 | pages= 804-14 | pmid=20647171 | doi=10.1177/0333102410364677 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20647171  }} </ref> trials. These trials also showed improvement in the quality of life.<ref name="pmid21956721">{{cite journal| author=Lipton RB, Varon SF, Grosberg B, McAllister PJ, Freitag F, Aurora SK et al.| title=OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine. | journal=Neurology | year= 2011 | volume= 77 | issue= 15 | pages= 1465-72 | pmid=21956721 | doi=10.1212/WNL.0b013e318232ab65 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21956721  }} </ref> However, these studies have been criticized for inability to blind the participants and most subjects having medication overuse headache.<ref name="pmid21111904">{{cite journal| author=Olesen J, Tfelt-Hansen P| title=Licence for Botox in so-called chronic migraine. | journal=Lancet | year= 2010 | volume= 376 | issue= 9755 | pages= 1825-6; discussion 1826 | pmid=21111904 | doi=10.1016/S0140-6736(10)62165-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21111904  }} </ref>
 
The long term [[drug toxicity]] of botulinum toxin is uncertain.<ref name="pmid16785106">{{cite journal| author=Abbruzzese G, Berardelli A| title=Neurophysiological effects of botulinum toxin type A. | journal=Neurotox Res | year= 2006 | volume= 9 | issue= 2-3 | pages= 109-14 | pmid=16785106 | doi= | pmc= | url= }} </ref><ref name="pmid10479034">{{cite journal| author=Erdal J, Ostergaard L, Fuglsang-Frederiksen A, Werdelin L, Dalager T, Sjö O et al.| title=Long-term botulinum toxin treatment of cervical dystonia--EMG changes in injected and noninjected muscles. | journal=Clin Neurophysiol | year= 1999 | volume= 110 | issue= 9 | pages= 1650-4 | pmid=10479034 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10479034  }} </ref><ref name="pmid22359151">{{cite journal| author=Colosimo C, Tiple D, Berardelli A| title=Efficacy and Safety of Long-term Botulinum Toxin Treatment in Craniocervical Dystonia: A Systematic Review. | journal=Neurotox Res | year= 2012 | volume=  | issue=  | pages=  | pmid=22359151 | doi=10.1007/s12640-012-9314-y | pmc= | url= }} </ref>
 
====Investigational agents====
Standards for the conducts of trials of preventive medications have been proposed by the Task Force of the International Headache Society Clinical Trials Subcommittee.<ref name="pmid18294250">{{cite journal| author=Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J et al.| title=Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. | journal=Cephalalgia | year= 2008 | volume= 28 | issue= 5 | pages= 484-95 | pmid=18294250 | doi=10.1111/j.1468-2982.2008.01555.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18294250  }} </ref>
 
==Prognosis==
Migraines with auras in mid-life may be associated with [[stroke]]<ref name="pmid19861375">{{cite journal| author=Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T| title=Migraine and cardiovascular disease: systematic review and meta-analysis. | journal=BMJ | year= 2009 | volume= 339 | issue=  | pages= b3914 | pmid=19861375
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19861375 | doi=10.1136/bmj.b3914 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> and brain infarcts on [[magnetic resonance imaging]]<ref>{{Cite journal
| doi = 10.1001/jama.2009.932
| volume = 301
| issue = 24
| pages = 2563-2570
| last = Scher
| first = Ann I.
| coauthors = Larus S. Gudmundsson, Sigurdur Sigurdsson, Anna Ghambaryan, Thor Aspelund, Guthny Eiriksdottir, Mark A. van Buchem, Vilmundur Gudnason, Lenore J. Launer
| title = Migraine Headache in Middle Age and Late-Life Brain Infarcts
| journal = JAMA
| accessdate = 2009-06-24
| date = 2009-06-24
| url = http://jama.ama-assn.org/cgi/content/abstract/301/24/2563
}}</ref>.


==References==
==References==
<references/>
{{reflist}}[[Category:Suggestion Bot Tag]]
 
[[Category:Health Sciences Workgroup]]
[[Category:CZ Live]]

Latest revision as of 11:00, 19 September 2024

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Migraine headaches are "a class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms)."[1] Laymen often use the term for any severe headache, especially with nausea and sensitivity to light and sound, but there are specific criteria. Just as the term is overused in some contexts, however, true migraine has different manifestations, is underdiagnosed, and is sometimes preventable as well as treatable.

Patients with a diagnosis of migraine are called migraneurs.

Since around 2018, studies have suggested that people who get frequent headaches sometimes also have gastrointestinal problems, and conditions such as irritable bowel syndrome and celiac disease may be linked to migraines. Treating these digestive conditions may help reduce the frequency and severity of migraines, although more research is needed to understand these connections.

Classification

  • Common migraine (without aura)
  • Classic migraine (with aura or neurological symptoms)

Diagnosis

Migraines are underdiagnosed[2] and misdiagnosed.[3] About a third of headaches that patients report as being migraines are truly migraines[4]; while about 90% of headaches that are self-reported not to be migraines are truly not migraines.[4] The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":[5]

  • 5 or more attacks
  • 4 hours to 3 days in duration
  • 2 or more of - unilateral location, pulsating quality, moderate to severe pain, aggravation by or avoidance of routine physical activity
  • 1 or more accompanying symptoms - nausea and/or vomiting, photophobia, phonophobia

For migraine with aura, only two attacks are required to justify the diagnosis.

Additional criteria are available.[6]

POUNDing

The mnemonic POUNDing (Pulsating, duration of 4-72 hOurs, Unilateral, Nausea, Disabling) can help diagnose migraine. If 4 of the 5 criteria are met, then the positive likelihood ratio for diagnosing migraine is 24.[7]

ID Migraine

The presence of either disability, nausea, or sensitivity to light can diagnose migraine with[8]:

A subsequent systematic review of ID migraine reported similar results.[9]

Treatment

There are two basic problems in migraine management: treating the acute attack, and preventing migraine in chronic migraneurs. Some treatment approaches combine preventive approaches with specific preventive measures. "The addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment" according to a randomized controlled trial. [10]

Abortive treatment

Non-steroidal anti-inflammatory agents

Non-steroidal anti-inflammatory agents (NSAIDs) can help."Oral diclofenac potassium 50 mg is an effective treatment for acute migraine, providing relief from pain and associated symptoms, although only a minority of patients experience pain-free responses" according to a meta-analysis by the Cochrane Collaboration.[11]

Serotonin agonists

High dose acetylsalicylic acid (1000 mg) may be as effective as sumatriptan, especially if the acetylsalicylic acid is combined with metoclopramide to reduce nausea and vomiting, according to a systematic review by the Cochrane Collaboration.[12] One of the trials in the review reported that high dose acetylsalicylic acid (1000 mg), sumatriptan 50 mg and low dose ibuprofen 400 mg are equally effective at reducing pain to mild or none at two hours according to a randomized controlled trial; however, sumatriptan was led to more patients being pain free at two hours (37% versus less than 33% for other groups).[13]

Dopamine antagonists

Phenothiazines, such as prochlorperazine 10 mg parenterally and chlorpromazine 0.04 to 0.1 mg/kg parenterally, are more effective than placebo and more effective than metoclopramide according to a meta-analysis of randomized controlled trials.[14] In addition, prochlorperazine 10 mg intravenously with 12.5 mg diphenhydramine intravenously may be more effective than subcutaneous sumatriptan.[15]

Combination therapy

High dose acetaminophen (1000 mg) combined with metoclopramide is effective and is as effective as oral sumatriptan 100 mg according to a systematic review by the Cochrane Collaboration.[16]

When using intravenous metoclopramide, a 10 mg dose combined with 25 mg of diphenhydramine in 50 ml of saline given over 20 minutes may be optimal.[17]

High dose acetylsalicylic acid (1000 mg) combined with metoclopramide is effective according to a systematic review by the Cochrane Collaboration.[12] A combination of sumatriptan 85 mg and naproxen sodium 200 mg was better than either drug alone according to a randomized controlled trial funded by the manufacturer of the study drug.[18]

Nonpharmacological treatments

Indirect evidence suggest migraine pain, under certain circumstances, may be worse while laying down.[19][20]

Corticosteroids

Corticosteroids may help prevent recurrence after abortive treatment according to a meta-analyses of randomized controlled trials with number needed to treat of nine[21] or 10[22].

A more recent randomized controlled trial found insignificant benefit, but the study was small and the magnitude of the benefit was similar to the prior meta-analysis meta-analyses.[23]

Investigational treatments

Telcagepant (MK-0974), an oral antagonist of calcitonin gene-related peptide receptor, may be as effective as zolmitriptan but with less drug toxicity according to a randomized controlled trial.[24]

"Sublingual feverfew/ginger appears safe and effective as a first-line abortive treatment" according to a randomized controlled trial.[25]

Preventive treatment

Clinical practice guidelines address preventive treatment.[26]

Perhaps a third of patients meet consensus criteria for preventive treatment.[27]

Systematic reviews addresse options.[28][29]

Tricyclic antidepressants

Tricyclic antidepressants may be effective and may be more effective than second-generation antidepressants according to a systematic review.[30]

Adrenergic beta-antagonists

Placebo is as effective as adding the adrenergic beta-antagonist drug propanolol to patients not adequately controlled on topiramate.In a randomized controlled trial, both groups reduced their days with migraine by half.[31]

Angiotensin inhibition

Angiotensin-converting enzyme inhibitor and angiotensin II receptor antagonist medications may reduce attacks according to a systematic review.[28]

Anticonvulsants

The anticonvulsant drug topiramate can increase response among patients with migraine according to a randomized controlled trial.[32]> The relative benefit increase was 113.0%. For patients at similar risk to those in this study (23.0% had response), this leads to an absolute benefit increase of 26%. 3.8 patients must be treated for one to benefit (number needed to treat = 3.8). Click here to adjust these results for patients at higher or lower risk of response.

Botulinum toxin

Botulinum toxin may have small benefit according to a meta-analysis[33] that included the PREEMPT 1[34] and PREEMPT 2[35] trials. These trials also showed improvement in the quality of life.[36] However, these studies have been criticized for inability to blind the participants and most subjects having medication overuse headache.[37]

The long term drug toxicity of botulinum toxin is uncertain.[38][39][40]

Investigational agents

Standards for the conducts of trials of preventive medications have been proposed by the Task Force of the International Headache Society Clinical Trials Subcommittee.[41]

Prognosis

Migraines with auras in mid-life may be associated with stroke[42] and brain infarcts on magnetic resonance imaging[43].

References

  1. National Library of Medicine. Migraine Disorders. Retrieved on 2007-11-02.
  2. Lipton RB, Stewart WF, Celentano DD, Reed ML (1992). "Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis". Arch. Intern. Med. 152 (6): 1273–8. PMID 1599358[e]
  3. Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C (2004). "Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache". Arch. Intern. Med. 164 (16): 1769–72. DOI:10.1001/archinte.164.16.1769. PMID 15364670. Research Blogging.
  4. 4.0 4.1 Lipton RB, Stewart WF, Liberman JN (2002). "Self-awareness of migraine: interpreting the labels that headache sufferers apply to their headaches". Neurology 58 (9 Suppl 6): S21–6. PMID 12011270[e]
  5. International Headache Society. IHS Classification ICHD-II Migraine headache
  6. Ad Hoc Committee on the Classification of Headache of the National Institute of Neurological Diseases and Blindness. Classification of headache. JAMA (1962) 179:717–8
  7. Detsky ME, McDonald DR, Baerlocher MO, Tomlinson GA, McCrory DC, Booth CM (2006). "Does this patient with headache have a migraine or need neuroimaging?". JAMA 296 (10): 1274–83. DOI:10.1001/jama.296.10.1274. PMID 16968852. Research Blogging.
  8. Lipton RB, Dodick D, Sadovsky R, et al (2003). "A self-administered screener for migraine in primary care: The ID Migraine validation study". Neurology 61 (3): 375-82. PMID 12913201[e]
  9. Cousins G, Hijazze S, Van de Laar FA, Fahey T (2011). "Diagnostic accuracy of the ID Migraine: a systematic review and meta-analysis.". Headache 51 (7): 1140-8. DOI:10.1111/j.1526-4610.2011.01916.x. PMID 21649653. Research Blogging.
  10. Holroyd KA, Cottrell CK, O'Donnell FJ, Cordingley GE, Drew JB, Carlson BW et al. (2010). "Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial.". BMJ 341: c4871. DOI:10.1136/bmj.c4871. PMID 20880898. PMC PMC2947621. Research Blogging.
  11. Derry S, Rabbie R, Moore RA (2012). "Diclofenac with or without an antiemetic for acute migraine headaches in adults.". Cochrane Database Syst Rev 2: CD008783. DOI:10.1002/14651858.CD008783.pub2. PMID 22336852. Research Blogging.
  12. 12.0 12.1 Kirthi V, Derry S, Moore RA, McQuay HJ (2010). "Aspirin with or without an antiemetic for acute migraine headaches in adults.". Cochrane Database Syst Rev 4: CD008041. DOI:10.1002/14651858.CD008041.pub2. PMID 20393963. Research Blogging.
  13. Diener HC, Bussone G, de Liano H, et al (2004). "Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks". Cephalalgia : an international journal of headache 24 (11): 947–54. DOI:10.1111/j.1468-2982.2004.00783.x. PMID 15482357. Research Blogging.
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  16. Derry S, Moore RA (2013). "Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.". Cochrane Database Syst Rev 4: CD008040. DOI:10.1002/14651858.CD008040.pub3. PMID 23633349. Research Blogging.
  17. Friedman BW, Mulvey L, Esses D, Solorzano C, Paternoster J, Lipton RB et al. (2011). "Metoclopramide for acute migraine: a dose-finding randomized clinical trial.". Ann Emerg Med 57 (5): 475-82.e1. DOI:10.1016/j.annemergmed.2010.11.023. PMID 21227540. Research Blogging.
  18. Brandes JL, Kudrow D, Stark SR, et al (2007). "Sumatriptan-naproxen for acute treatment of migraine: a randomized trial". JAMA 297 (13): 1443-54. DOI:10.1001/jama.297.13.1443. PMID 17405970. Research Blogging.
  19. Chou CH, Fuh JL, Hu HH, Wu JC, Wang SJ (2009). "Throbbing pain is related to Queckenstedt's test effect in migraine patients.". Cephalalgia 29 (3): 373-8. DOI:10.1111/j.1468-2982.2008.01746.x. PMID 19055510. Research Blogging.
  20. Doepp F, Schreiber SJ, Dreier JP, Einhäupl KM, Valdueza JM (2003). "Migraine aggravation caused by cephalic venous congestion.". Headache 43 (2): 96-8. PMID 12558761[e]
  21. Colman I, Friedman BW, Brown MD, et al (June 2008). "Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence". BMJ 336 (7657): 1359–61. DOI:10.1136/bmj.39566.806725.BE. PMID 18541610. PMC 2427093. Research Blogging.
  22. Singh A, Alter HJ, Zaia B (October 2008). "Does the Addition of Dexamethasone to Standard Therapy for Acute Migraine Headache Decrease the Incidence of Recurrent Headache for Patients Treated in the Emergency Department? A Meta-analysis and Systematic Review of the Literature". Acad Emerg Med. DOI:10.1111/j.1553-2712.2008.00283.x. PMID 18976336. Research Blogging.
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  24. Ho TW, Ferrari MD, Dodick DW, et al (December 2008). "Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial". Lancet 372 (9656): 2115–23. DOI:10.1016/S0140-6736(08)61626-8. PMID 19036425. Research Blogging.
  25. Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R (2011). "A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™ M) in the treatment of migraine.". Headache 51 (7): 1078-86. DOI:10.1111/j.1526-4610.2011.01910.x. PMID 21631494. Research Blogging.
  26. Silberstein et al. (2012) 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
  27. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF (2007). "Migraine prevalence, disease burden, and the need for preventive therapy". Neurology 68 (5): 343–9. DOI:10.1212/01.wnl.0000252808.97649.21. PMID 17261680. Research Blogging.
  28. 28.0 28.1 Shamliyan TA, Choi JY, Ramakrishnan R, Miller JB, Wang SY, Taylor FR et al. (2013). "Preventive pharmacologic treatments for episodic migraine in adults.". J Gen Intern Med 28 (9): 1225-37. DOI:10.1007/s11606-013-2433-1. PMID 23592242. PMC PMC3744311. Research Blogging.
  29. Pringsheim T, Davenport WJ, Becker WJ (2010). "Prophylaxis of migraine headache.". CMAJ 182 (7): E269-76. DOI:10.1503/cmaj.081657. PMID 20159899. PMC PMC2855933. Research Blogging.
  30. Jackson JL, Shimeall W, Sessums L, Dezee KJ, Becher D, Diemer M et al. (2010). "Tricyclic antidepressants and headaches: systematic review and meta-analysis.". BMJ 341: c5222. DOI:10.1136/bmj.c5222. PMID 20961988. PMC PMC2958257. Research Blogging.
  31. Silberstein SD, Dodick DW, Lindblad AS, Holroyd K, Harrington M, Mathew NT et al. (2012). "Randomized, placebo-controlled trial of propranolol added to topiramate in chronic migraine.". Neurology 78 (13): 976-84. DOI:10.1212/WNL.0b013e31824d5846. PMID 22377815. PMC PMC3310312. Research Blogging.
  32. Brandes JL, Saper JR, Diamond M, et al (2004). "Topiramate for migraine prevention: a randomized controlled trial". JAMA 291 (8): 965–73. DOI:10.1001/jama.291.8.965. PMID 14982912. Research Blogging.
  33. Jackson JL, Kuriyama A, Hayashino Y (2012). "Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis.". JAMA 307 (16): 1736-45. DOI:10.1001/jama.2012.505. PMID 22535858. Research Blogging.
  34. Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB et al. (2010). "OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial.". Cephalalgia 30 (7): 793-803. DOI:10.1177/0333102410364676. PMID 20647170. Research Blogging.
  35. Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB et al. (2010). "OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial.". Cephalalgia 30 (7): 804-14. DOI:10.1177/0333102410364677. PMID 20647171. Research Blogging.
  36. Lipton RB, Varon SF, Grosberg B, McAllister PJ, Freitag F, Aurora SK et al. (2011). "OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine.". Neurology 77 (15): 1465-72. DOI:10.1212/WNL.0b013e318232ab65. PMID 21956721. Research Blogging.
  37. Olesen J, Tfelt-Hansen P (2010). "Licence for Botox in so-called chronic migraine.". Lancet 376 (9755): 1825-6; discussion 1826. DOI:10.1016/S0140-6736(10)62165-4. PMID 21111904. Research Blogging.
  38. Abbruzzese G, Berardelli A (2006). "Neurophysiological effects of botulinum toxin type A.". Neurotox Res 9 (2-3): 109-14. PMID 16785106[e]
  39. Erdal J, Ostergaard L, Fuglsang-Frederiksen A, Werdelin L, Dalager T, Sjö O et al. (1999). "Long-term botulinum toxin treatment of cervical dystonia--EMG changes in injected and noninjected muscles.". Clin Neurophysiol 110 (9): 1650-4. PMID 10479034[e]
  40. Colosimo C, Tiple D, Berardelli A (2012). "Efficacy and Safety of Long-term Botulinum Toxin Treatment in Craniocervical Dystonia: A Systematic Review.". Neurotox Res. DOI:10.1007/s12640-012-9314-y. PMID 22359151. Research Blogging.
  41. Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J et al. (2008). "Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults.". Cephalalgia 28 (5): 484-95. DOI:10.1111/j.1468-2982.2008.01555.x. PMID 18294250. Research Blogging.
  42. Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T (2009). "Migraine and cardiovascular disease: systematic review and meta-analysis.". BMJ 339: b3914. DOI:10.1136/bmj.b3914. PMID 19861375. Research Blogging.
  43. Scher, Ann I.; Larus S. Gudmundsson, Sigurdur Sigurdsson, Anna Ghambaryan, Thor Aspelund, Guthny Eiriksdottir, Mark A. van Buchem, Vilmundur Gudnason, Lenore J. Launer (2009-06-24). "Migraine Headache in Middle Age and Late-Life Brain Infarcts". JAMA 301 (24): 2563-2570. DOI:10.1001/jama.2009.932. Retrieved on 2009-06-24. Research Blogging.