Headache: Difference between revisions
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'''Headache''' is defined as | {{TOC|right}} | ||
'''Headache''' is defined as the symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders.<ref>{{MeSH}}</ref> | |||
==Classification== | ==Classification== | ||
Headache type is not stable over time.<ref name="pmid21868455">{{cite journal| author=Merikangas KR, Cui L, Richardson AK, Isler H, Khoromi S, Nakamura E et al.| title=Magnitude, impact, and stability of primary headache subtypes: 30 year prospective Swiss cohort study. | journal=BMJ | year= 2011 | volume= 343 | issue= | pages= d5076 | pmid=21868455 | doi=10.1136/bmj.d5076 | pmc=PMC3161722 | url= }} </ref> | |||
===Primary headaches=== | ===Primary headaches=== | ||
Primary headaches are defined as "conditions in which the primary symptom is headache and the headache cannot be attributed to any known causes."<ref name="title">{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?term=Primary+Headache+Disorders |title=Headache Disorders, Primary |accessdate=2007-12-11 |author=National Library of Medicine |authorlink= |coauthors= |date= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> | Primary headaches are defined as "conditions in which the primary symptom is headache and the headache cannot be attributed to any known causes."<ref name="title">{{cite web |url=http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?term=Primary+Headache+Disorders |title=Headache Disorders, Primary |accessdate=2007-12-11 |author=National Library of Medicine |authorlink= |coauthors= |date= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> | ||
Line 8: | Line 11: | ||
====Migraine headache==== | ====Migraine headache==== | ||
{{main|Migraine headache}} | {{main|Migraine headache}} | ||
;Criteria | |||
Diagnostic criteria developed by the International Headache Society are:<ref>International Headache Society. [http://ihs-classification.org/en/02_klassifikation/02_teil1/01.01.00_migraine.html Migraine headache]</ref><br/> | |||
Migraine ''without'' aura:<br/> | |||
A. At least 5 attacks fulfilling criteria B-D<br/> | |||
B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)<br/> | |||
C. Headache has at least two of the following characteristics: | |||
# unilateral location | |||
# pulsating quality | |||
# moderate or severe [[pain]] intensity | |||
# aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) | |||
D. During headache at least one of the following: | |||
# nausea and/or vomiting | |||
# photophobia and phonophobia | |||
E. Not attributed to another disorder | |||
====Tension headache==== | ====Tension headache==== | ||
{{main|Tension headache}} | |||
====Cluster headache==== | |||
{{main|Cluster headache}} | |||
;Criteria | |||
Diagnostic criteria developed by the International Headache Society are:<ref>International Headache Society. [http://ihs-classification.org/en/02_klassifikation/02_teil1/03.01.00_cluster.html Cluster headache]</ref><br> | |||
A. At least 5 attacks fulfilling criteria B-D <br> | |||
B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated1<br> | |||
C. Headache is accompanied by at least one of the following: | |||
#ipsilateral conjunctival injection and/or lacrimation | |||
#ipsilateral nasal congestion and/or rhinorrhoea | |||
#ipsilateral eyelid oedema | |||
#ipsilateral forehead and facial sweating | |||
#ipsilateral miosis and/or ptosis | |||
#a sense of restlessness or agitation | |||
D. Attacks have a frequency from one every other day to 8 per day<br> | |||
E. Not attributed to another disorder<br> | |||
===Secondary headache=== | ===Secondary headache=== | ||
Secondary headaches are defined as "conditions with headache symptom that can be attributed to a variety of causes including brain vascular disorders; wounds and injuries; infection; drug use or its withdrawal."<ref name="title">{{cite | Secondary headaches are defined as "conditions with headache symptom that can be attributed to a variety of causes including brain vascular disorders; wounds and injuries; infection; drug use or its withdrawal."<ref name="title"/> | ||
====Medication-overuse headache==== | |||
Medication-overuse headache has also been called rebound headache, drug-induced headache, medication-misuse headache. According to the International Classification of Headache Disorders, 2nd Edition (ICHD-II)—-Revision of Criteria for 8.2 Medication-Overuse Headache, criteria are:<ref name="pmid25112307">{{cite journal| author=Kristoffersen ES, Straand J, Vetvik KG, Benth JS, Russell MB, Lundqvist C| title=Brief intervention for medication-overuse headache in primary care. The BIMOH study: a double-blind pragmatic cluster randomised parallel controlled trial. | journal=J Neurol Neurosurg Psychiatry | year= 2014 | volume= | issue= | pages= | pmid=25112307 | doi=10.1136/jnnp-2014-308548 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25112307 }} </ref><ref name="pmid15910572">{{cite journal| author=Silberstein SD, Olesen J, Bousser MG, Diener HC, Dodick D, First M et al.| title=The International Classification of Headache Disorders, 2nd Edition (ICHD-II)--revision of criteria for 8.2 Medication-overuse headache. | journal=Cephalalgia | year= 2005 | volume= 25 | issue= 6 | pages= 460-5 | pmid=15910572 | doi=10.1111/j.1468-2982.2005.00878.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15910572 }} </ref> | |||
* "Headache present on ≥15 days/month." | |||
* "Regular overuse for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache." | |||
** "Simple analgesics on >15 days/month on a regular basis for >3 months." | |||
** "Ergotamine, triptans, opioids or combination analgesics on >10 days/month on a regular basis for >3 months." | |||
** "Any combination of ergotamine, triptans, analgesics and/or opioids >15 days/month on a regular basis for >3 months without overuse of any single class alone." | |||
* Headache has developed or markedly worsened during medication overuse. | |||
The role of overuse of medications for treating migraine (triptans, analgesics, ergots) and their withdrawal as a cause of headache has been successfully<ref name="pmid25112307">{{cite journal| author=Kristoffersen ES, Straand J, Vetvik KG, Benth JS, Russell MB, Lundqvist C| title=Brief intervention for medication-overuse headache in primary care. The BIMOH study: a double-blind pragmatic cluster randomised parallel controlled trial. | journal=J Neurol Neurosurg Psychiatry | year= 2014 | volume= | issue= | pages= | pmid=25112307 | doi=10.1136/jnnp-2014-308548 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25112307 }} </ref> and unsuccessfully<ref name="pmid17475943">{{cite journal |author=Bøe MG, Mygland A, Salvesen R |title=Prednisolone does not reduce withdrawal headache: a randomized, double-blind study |journal=Neurology |volume=69 |issue=1 |pages=26–31 |year=2007 |pmid=17475943 |doi=10.1212/01.wnl.0000263652.46222.e8 |issn=}}</ref> demonstrated in trials. | |||
Medication-overuse headache is suggested if the sum of the answers to the following Severity of Dependence Scale<ref name="pmid19279030">{{cite journal| author=Grande RB, Aaseth K, Saltyte Benth J, Gulbrandsen P, Russell MB, Lundqvist C| title=The Severity of Dependence Scale detects people with medication overuse: the Akershus study of chronic headache. | journal=J Neurol Neurosurg Psychiatry | year= 2009 | volume= 80 | issue= 7 | pages= 784-9 | pmid=19279030 | doi=10.1136/jnnp.2008.168864 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19279030 }} </ref> are ≥5 for women and ≥4 for men:<ref name="pmid25112307"/> | |||
# "Do you think your use of headache medication was out of control? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)" | |||
# "Did the prospect of missing a dose make you anxious or worried? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)" | |||
# "Did you worry about your use of your headache medication? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)" | |||
# "Did you wish you could stop? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)" | |||
# "How difficult would you find it to stop or go without your headache medication? (not difficult=0, quite difficult=1, very difficult=2, impossible=3" | |||
==Diagnosis== | ==Diagnosis== | ||
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* headache aggravated by exertion or a valsalva-like maneuver | * headache aggravated by exertion or a valsalva-like maneuver | ||
* headache with vomiting | * headache with vomiting | ||
Possible subarchnoid hemorrhage: nontraumatic headache that peaked within 1 hour and: | |||
* age ≥40, neck pain or stiffness | |||
* limited neck flexion | |||
* witnessed loss of consciousness | |||
* onset during exertion | |||
* thunderclap headache (instantly peaking pain) | |||
<ref>Perry JJ, Stiell IG, Sivilotti MA, et al. [ CLinical decision rules to rule out subarachnoid hemorrhage for acute headache]. JAMA. 2013 Sep 25;310(12):1248–55.</ref> | |||
CT scan should also be considered in the following settings: | CT scan should also be considered in the following settings: | ||
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* New-onset or change in chronic headaches. Prevalence of significant pathology is 32%.<ref name="pmid16968852"/> This compares to a prevalence of significant pathology of 1% for patients with chronic headaches referred to a neurologist.<ref name="pmid15606567">{{cite journal |author=Sempere AP, Porta-Etessam J, Medrano V, ''et al'' |title=Neuroimaging in the evaluation of patients with non-acute headache |journal=Cephalalgia |volume=25 |issue=1 |pages=30–5 |year=2005 |pmid=15606567 |doi=10.1111/j.1468-2982.2004.00798.x |issn=}}</ref> Presumably the prevalence would be lower in primary care. | * New-onset or change in chronic headaches. Prevalence of significant pathology is 32%.<ref name="pmid16968852"/> This compares to a prevalence of significant pathology of 1% for patients with chronic headaches referred to a neurologist.<ref name="pmid15606567">{{cite journal |author=Sempere AP, Porta-Etessam J, Medrano V, ''et al'' |title=Neuroimaging in the evaluation of patients with non-acute headache |journal=Cephalalgia |volume=25 |issue=1 |pages=30–5 |year=2005 |pmid=15606567 |doi=10.1111/j.1468-2982.2004.00798.x |issn=}}</ref> Presumably the prevalence would be lower in primary care. | ||
* Patients with [[human immunodeficiency virus]]. This is based on a [[clinical practice guideline]].<ref name="pmid11782746">{{cite journal |author= |title=Clinical policy: critical issues in the evaluation and management of patients presenting to the emergency department with acute headache |journal=Ann Emerg Med |volume=39 |issue=1 |pages=108–22 |year=2002 |pmid=11782746 |doi= |issn=|url=http://www.acep.org/WorkArea/showcontent.aspx?id=8802}}</ref> | * Patients with [[human immunodeficiency virus]]. This is based on a [[clinical practice guideline]].<ref name="pmid11782746">{{cite journal |author= |title=Clinical policy: critical issues in the evaluation and management of patients presenting to the emergency department with acute headache |journal=Ann Emerg Med |volume=39 |issue=1 |pages=108–22 |year=2002 |pmid=11782746 |doi= |issn=|url=http://www.acep.org/WorkArea/showcontent.aspx?id=8802}}</ref> | ||
==Treatment== | |||
[[phenothiazine|Prochlorperazine]] is better than [[phenothiazine|promethazine]] in relieving nonspecific, benign headaches according to a [[randomized controlled trial]].<ref name="pmid18534808">{{cite journal |author=Callan JE, Kostic MA, Bachrach EA, Rieg TS |title=Prochlorperazine vs. promethazine for headache treatment in the emergency department: a randomized controlled trial |journal=J Emerg Med |volume=35 |issue=3 |pages=247–53 |year=2008 |month=October |pmid=18534808 |doi=10.1016/j.jemermed.2007.09.047 |url=http://linkinghub.elsevier.com/retrieve/pii/S0736-4679(08)00104-2 |issn=}}</ref> | |||
After relief has been achieved, recurrence may be similarly affected by oral [[sumatriptan]] and oral [[naproxen]].<ref name="pmid20303198">{{cite journal| author=Friedman BW, Solorzano C, Esses D, Xia S, Hochberg M, Dua N et al.| title=Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan. | journal=Ann Emerg Med | year= 2010 | volume= 56 | issue= 1 | pages= 7-17 | pmid=20303198 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20303198 | doi=10.1016/j.annemergmed.2010.02.005 | pmc=PMC2902611 }} </ref> | |||
===Migraine headache=== | |||
{{main|Migraine headache}} | |||
===Tension headache=== | |||
{{main|Tension headache}} | |||
===Medication-overuse headache=== | |||
A trial found the following counseling that lasted about 9 minutes to be effective:<ref name="pmid25112307">{{cite journal| author=Kristoffersen ES, Straand J, Vetvik KG, Benth JS, Russell MB, Lundqvist C| title=Brief intervention for medication-overuse headache in primary care. The BIMOH study: a double-blind pragmatic cluster randomised parallel controlled trial. | journal=J Neurol Neurosurg Psychiatry | year= 2014 | volume= | issue= | pages= | pmid=25112307 | doi=10.1136/jnnp-2014-308548 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25112307 }} </ref> | |||
* Patients are given information about medication-overuse headache | |||
* "Patients received feedback on their SDS score and risk of medication-induced headache. " | |||
* "With a consultation in an empathic and collaborative manner, the BI aimed towards achieving a decision by the patient that he/she would cut down the offending medication, an agreement about how the GP could support and a concrete plan. " | |||
* "Explicit recommendations were reduction in headache medication towards ‘safe levels’, and information about possible difficulties and gains including that MOH usually ‘gets worse before it improves’ 1–2 weeks after withdrawal." | |||
==Prognosis== | |||
Most chronic headaches are tension-type headache, although migraine may coexist.<ref name="pmid19279030"/> Almost half have medication overuse.<ref name="pmid19279030"/> | |||
==References== | ==References== | ||
<references/> | <references/>[[Category:Suggestion Bot Tag]] |
Latest revision as of 12:00, 26 August 2024
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Headache is defined as the symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders.[1]
Classification
Headache type is not stable over time.[2]
Primary headaches
Primary headaches are defined as "conditions in which the primary symptom is headache and the headache cannot be attributed to any known causes."[3]
Migraine headache
- Criteria
Diagnostic criteria developed by the International Headache Society are:[4]
Migraine without aura:
A. At least 5 attacks fulfilling criteria B-D
B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
C. Headache has at least two of the following characteristics:
- unilateral location
- pulsating quality
- moderate or severe pain intensity
- aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)
D. During headache at least one of the following:
- nausea and/or vomiting
- photophobia and phonophobia
E. Not attributed to another disorder
Tension headache
Cluster headache
- Criteria
Diagnostic criteria developed by the International Headache Society are:[5]
A. At least 5 attacks fulfilling criteria B-D
B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated1
C. Headache is accompanied by at least one of the following:
- ipsilateral conjunctival injection and/or lacrimation
- ipsilateral nasal congestion and/or rhinorrhoea
- ipsilateral eyelid oedema
- ipsilateral forehead and facial sweating
- ipsilateral miosis and/or ptosis
- a sense of restlessness or agitation
D. Attacks have a frequency from one every other day to 8 per day
E. Not attributed to another disorder
Secondary headache
Secondary headaches are defined as "conditions with headache symptom that can be attributed to a variety of causes including brain vascular disorders; wounds and injuries; infection; drug use or its withdrawal."[3]
Medication-overuse headache
Medication-overuse headache has also been called rebound headache, drug-induced headache, medication-misuse headache. According to the International Classification of Headache Disorders, 2nd Edition (ICHD-II)—-Revision of Criteria for 8.2 Medication-Overuse Headache, criteria are:[6][7]
- "Headache present on ≥15 days/month."
- "Regular overuse for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache."
- "Simple analgesics on >15 days/month on a regular basis for >3 months."
- "Ergotamine, triptans, opioids or combination analgesics on >10 days/month on a regular basis for >3 months."
- "Any combination of ergotamine, triptans, analgesics and/or opioids >15 days/month on a regular basis for >3 months without overuse of any single class alone."
- Headache has developed or markedly worsened during medication overuse.
The role of overuse of medications for treating migraine (triptans, analgesics, ergots) and their withdrawal as a cause of headache has been successfully[6] and unsuccessfully[8] demonstrated in trials.
Medication-overuse headache is suggested if the sum of the answers to the following Severity of Dependence Scale[9] are ≥5 for women and ≥4 for men:[6]
- "Do you think your use of headache medication was out of control? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)"
- "Did the prospect of missing a dose make you anxious or worried? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)"
- "Did you worry about your use of your headache medication? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)"
- "Did you wish you could stop? (never/almost never=0, sometimes=1, often=2, always/nearly always=3)"
- "How difficult would you find it to stop or go without your headache medication? (not difficult=0, quite difficult=1, very difficult=2, impossible=3"
Diagnosis
X-ray computed tomography (CT Scan) should be considered if one of the following is present:[10]
- cluster-type headache
- abnormal findings on neurologic examination
- undefined headache (ie, not cluster, migraine, or tension-type)
- headache with aura
- headache aggravated by exertion or a valsalva-like maneuver
- headache with vomiting
Possible subarchnoid hemorrhage: nontraumatic headache that peaked within 1 hour and:
- age ≥40, neck pain or stiffness
- limited neck flexion
- witnessed loss of consciousness
- onset during exertion
- thunderclap headache (instantly peaking pain)
CT scan should also be considered in the following settings:
- Acute thunderclap headache. Prevalence of significant pathology is 40%[10]
- New-onset or change in chronic headaches. Prevalence of significant pathology is 32%.[10] This compares to a prevalence of significant pathology of 1% for patients with chronic headaches referred to a neurologist.[12] Presumably the prevalence would be lower in primary care.
- Patients with human immunodeficiency virus. This is based on a clinical practice guideline.[13]
Treatment
Prochlorperazine is better than promethazine in relieving nonspecific, benign headaches according to a randomized controlled trial.[14]
After relief has been achieved, recurrence may be similarly affected by oral sumatriptan and oral naproxen.[15]
Migraine headache
Tension headache
Medication-overuse headache
A trial found the following counseling that lasted about 9 minutes to be effective:[6]
- Patients are given information about medication-overuse headache
- "Patients received feedback on their SDS score and risk of medication-induced headache. "
- "With a consultation in an empathic and collaborative manner, the BI aimed towards achieving a decision by the patient that he/she would cut down the offending medication, an agreement about how the GP could support and a concrete plan. "
- "Explicit recommendations were reduction in headache medication towards ‘safe levels’, and information about possible difficulties and gains including that MOH usually ‘gets worse before it improves’ 1–2 weeks after withdrawal."
Prognosis
Most chronic headaches are tension-type headache, although migraine may coexist.[9] Almost half have medication overuse.[9]
References
- ↑ Anonymous (2024), Headache (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Merikangas KR, Cui L, Richardson AK, Isler H, Khoromi S, Nakamura E et al. (2011). "Magnitude, impact, and stability of primary headache subtypes: 30 year prospective Swiss cohort study.". BMJ 343: d5076. DOI:10.1136/bmj.d5076. PMID 21868455. PMC PMC3161722. Research Blogging.
- ↑ 3.0 3.1 National Library of Medicine. Headache Disorders, Primary. Retrieved on 2007-12-11.
- ↑ International Headache Society. Migraine headache
- ↑ International Headache Society. Cluster headache
- ↑ 6.0 6.1 6.2 6.3 Kristoffersen ES, Straand J, Vetvik KG, Benth JS, Russell MB, Lundqvist C (2014). "Brief intervention for medication-overuse headache in primary care. The BIMOH study: a double-blind pragmatic cluster randomised parallel controlled trial.". J Neurol Neurosurg Psychiatry. DOI:10.1136/jnnp-2014-308548. PMID 25112307. Research Blogging.
- ↑ Silberstein SD, Olesen J, Bousser MG, Diener HC, Dodick D, First M et al. (2005). "The International Classification of Headache Disorders, 2nd Edition (ICHD-II)--revision of criteria for 8.2 Medication-overuse headache.". Cephalalgia 25 (6): 460-5. DOI:10.1111/j.1468-2982.2005.00878.x. PMID 15910572. Research Blogging.
- ↑ Bøe MG, Mygland A, Salvesen R (2007). "Prednisolone does not reduce withdrawal headache: a randomized, double-blind study". Neurology 69 (1): 26–31. DOI:10.1212/01.wnl.0000263652.46222.e8. PMID 17475943. Research Blogging.
- ↑ 9.0 9.1 9.2 Grande RB, Aaseth K, Saltyte Benth J, Gulbrandsen P, Russell MB, Lundqvist C (2009). "The Severity of Dependence Scale detects people with medication overuse: the Akershus study of chronic headache.". J Neurol Neurosurg Psychiatry 80 (7): 784-9. DOI:10.1136/jnnp.2008.168864. PMID 19279030. Research Blogging.
- ↑ 10.0 10.1 10.2 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.
- ↑ Perry JJ, Stiell IG, Sivilotti MA, et al. [ CLinical decision rules to rule out subarachnoid hemorrhage for acute headache]. JAMA. 2013 Sep 25;310(12):1248–55.
- ↑ Sempere AP, Porta-Etessam J, Medrano V, et al (2005). "Neuroimaging in the evaluation of patients with non-acute headache". Cephalalgia 25 (1): 30–5. DOI:10.1111/j.1468-2982.2004.00798.x. PMID 15606567. Research Blogging.
- ↑ (2002) "Clinical policy: critical issues in the evaluation and management of patients presenting to the emergency department with acute headache". Ann Emerg Med 39 (1): 108–22. PMID 11782746. [e]
- ↑ Callan JE, Kostic MA, Bachrach EA, Rieg TS (October 2008). "Prochlorperazine vs. promethazine for headache treatment in the emergency department: a randomized controlled trial". J Emerg Med 35 (3): 247–53. DOI:10.1016/j.jemermed.2007.09.047. PMID 18534808. Research Blogging.
- ↑ Friedman BW, Solorzano C, Esses D, Xia S, Hochberg M, Dua N et al. (2010). "Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan.". Ann Emerg Med 56 (1): 7-17. DOI:10.1016/j.annemergmed.2010.02.005. PMID 20303198. PMC PMC2902611. Research Blogging.