Guideline sources The following summarized guidelines for the management of migraine are prepared by our editorial team based on guidelines from the Canadian Expert Group on Cannabinoids Use in Chronic Pain (CCP-CEG 2023), the The Scottish Intercollegiate Guidelines Network (SIGN 2022; 2018), the American Academy of Neurology (AAN/AHS 2019), the American Academy of Neurology (AAN 2016; 2012), and the European Federation of Neurological Societies (EFNS 2009). 1 2 3 4 5 6 7 8 9 9 10 11 12 12 13 Definition Migraine is a primary headache disorder characterized by recurrent moderate-to-severe headaches, often accompanied by nausea, vomiting, and/or sensitivity to light and sound. 9 Epidemiology Migraine is due to complex brain network disorder involving the cortex, hypothalamus, thalamus, and brainstem in genetically predisposed individuals. 12 Pathophysiology The overall prevalence of migraine over a 3-month period in the United States adult population is 15.3%, affecting approximately 20.7% of females and 9.7% of males. The global lifetime prevalence of migraines is estimated at 14%. 10 11 Disease course https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 1/10 6/30/23, 1:02 AM Migraine Pathway Disease course The complex interplay between cortex, hypothalamus, thalamus, brainstem involved in modulation of nociceptive signaling results in trigeminovascular system activation, cortical-spreading depression-like event, a slowly propagating wave of neuronal and glial cell depolarization and hyperpolarization causing unilateral, pulsating, moderate to severe intensity headache with or without aura. 9 Prognosis and risk of recurrence Acute migraine therapies (triptans, ergotamines, NSAIDs) are ineffective and account for >50% recurrence of migraine. Approximately 2.2-3.1% of people with episodic migraine progress to chronic migraine at 1-year follow up. 12 13 Guidelines 1. Medical management Management of acute attacks, analgesics: As per SIGN 2022 guidelines, offer aspirin 900 mg as first-line therapy in patients with acute migraine. A Do not use aspirin in doses for migraine during pregnancy. B Show 2 more As per SIGN 2018 guidelines, offer the following analgesics as first-line therapy in patients with acute migraine: aspirin 900 mg ibuprofen 400 mg, increased to 600 mg if ineffective. A As per EFNS 2009 guidelines: Offer the following analgesics for acute management of patients with migraine attacks: Situation Guidance 1,000 mg, PO/IV Acetylsalicylic acid 200-800 mg Ibuprofen 500-1,000 mg Naproxen 50-100 mg Diclofenac, including diclofenac potassium 1,000 mg, PO/suppository Acetaminophen 250/50 mg, PO Acetylsalicylic acid plus caffeine 200-250/50 mg, PO. A Acetaminophen plus caffeine https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 2/10 6/30/23, 1:02 AM Migraine Pathway Consider offering the following analgesics for acute management of patients with migraine attacks: Situation Guidance 1,000 mg, PO/IV Metamizole 1,000 mg, PO Phenazon 200 mg, PO. C Tolfenamic acid Management of acute attacks, triptans: As per SIGN 2022 guidelines, offer triptans (sumatriptan 50-100 mg, or other triptans if sumatriptan fails) as first-line therapy in patients with acute migraine. A Show 3 more As per SIGN 2018 guidelines: Offer triptans as first-line therapy in patients with acute migraine: sumatriptan 50-100 mg as the first choice other triptans if sumatriptan fails. A Consider combination therapy with sumatriptan (50-85 mg) and naproxen (500 mg) for the treatment of patients with acute migraine. C As per EFNS 2009 guidelines, offer the following triptans for acute management of patients with migraine attacks: Situation Guidance 25, 50,100 mg, PO including rapid-release Sumatriptan 25 mg, suppository 10, 20 mg, nasal spray 6 mg subcutaneous 2.5, 5 mg PO including disintegrating form Zolmitriptan 2.5, 5 mg, nasal spray 2.5 mg, PO Naratriptan 10 mg, PO Rizatriptan 12.5 mg, PO Almotriptan 20, 40 mg, PO Eletriptan 2.5 mg, PO. A Frovatriptan https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 3/10 6/30/23, 1:02 AM Migraine Pathway Management of acute attacks (cannabinoids): offer cannabinoid-based medicines as an adjunct treatment for the management of chronic migraine or chronic headache in patients not achieving adequate response with other modalities. B Management of acute attacks, antiemetics: As per SIGN 2022 guidelines: Consider offering the following antiemetics (either as an oral or parenteral formulation depending on presentation and setting) in the treatment of patients with acute migraine, including patients presenting with migraine-associated symptoms of nausea or vomiting: metoclopramide 10 mg prochlorperazine 10 mg can be considered. C Do not use metoclopramide regularly due to the risk of extrapyramidal side effects. D As per EFNS 2009 guidelines, consider offering the following antiemetics for acute management of patients with migraine attacks: metoclopramide: 10-20 mg, PO; 20 mg, suppository; 10 mg, IM/IV/subcutaneous domperidon: 20-30 mg, PO. C Management of acute attacks, addressing medication overuse: As per SIGN 2022 guidelines, inform patients about the risk of developing medication overuse headache when starting acute treatment. B Show 2 more As per SIGN 2018 guidelines: Inform patients about the risk of developing medication-overuse headache when starting acute treatment. B Address medication overuse in patients overusing acute treatment. A 2. Specific circumstances Pediatric and adolescent patients (diagnosis): Diagnose a specific headache type (primary, secondary, or other headache syndrome) when evaluating pediatric and adolescent patients with headache. B Elicit the following when evaluating pediatric and adolescent patients with headache in order to improve diagnostic accuracy for migraine and appropriately counsel the patient: premonitory and aura symptoms headache semiology (onset, location, quality, severity, frequency, duration, aggravating and alleviating factors) associated symptoms (nausea, vomiting, phonophobia and photophobia) pain-related disability. B Pediatric and adolescent patients (screening for comorbidities): Screen pediatric and adolescent patients with migraine for mood and anxiety disorders because of the increased risk of headache persistence. B https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 4/10 6/30/23, 1:02 AM Migraine Pathway Discuss management options for comorbid mood and anxiety disorders in pediatric and adolescent patients with migraine. B Pediatric and adolescent patients, counseling on prevention: As per AHS/AAN 2019 guidelines, counsel patients and families that lifestyle and behavioral factors may influence headache frequency. B Show 2 more As per AHS/AAN 2019 guidelines, counsel patients and their families about migraine-healthy habits, including lifestyle modification, and identification/disproving/resolution of migraine triggers/aggravating factors and avoidance of medication overuse. B Pediatric and adolescent patients (pharmacologic prophylaxis): inform patients and caregivers that the majority of preventative treatment for migraine in pediatric and adolescent patients are not superior to placebo. B Show 8 more Pediatric and adolescent patients (counseling on acute treatment): make collaborative agreements with patients and their families on individualized treatment goals. B Show 4 more Pediatric and adolescent patients (management of acute attacks): offer ibuprofen oral solution 10 mg/kg as the initial treatment to reduce pain in pediatric and adolescent patients with migraine. B Show 9 more Pediatric and adolescent patients (monitoring): Consider counseling patients and their families to maintain a headache diary to monitor their response to treatments. C Consider referring pediatric and adolescent patients with hemiplegic migraine or migraine with brainstem aura not responding to other treatment to a headache specialist to find effective treatment. C Patients with menstrual migraine: offer triptans in patients with acute migraine associated with menstruation. A Show 2 more 3. Preventative measures Migraine prophylaxis, first-line agents: As per SIGN 2022 guidelines: Offer propranolol (80-160 mg daily) as first-line prophylactic therapy in patients with episodic or chronic migraine. A Offer topiramate (50-100 mg daily) as prophylactic therapy in patients with episodic or chronic migraine. Counsel female patients who may become pregnant regarding the associated risks of topiramate during pregnancy, the need to use effective contraception, and the need to seek further advice on migraine prophylaxis if pregnant or planning a pregnancy. A https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 5/10 6/30/23, 1:02 AM Migraine Pathway As per SIGN 2018 guidelines: Offer propranolol 80-160 mg daily as first-line prophylactic treatment in patients with episodic or chronic migraine. A Offer topiramate 50-100 mg daily as a prophylactic treatment in patients with episodic or chronic migraine. A As per AAN 2016 guidelines: Offer onabotulinumtoxin A injection to increase headache-free days in patients with chronic migraine. A Consider offering onabotulinumtoxin A injection to improve health-related quality of life in patients with chronic migraine. C As per AAN 2012 guidelines, offer the following agents as the first choice for migraine prophylaxis: Situation Guidance Divalproex sodium Antiepileptic drugs Sodium valproate Topiramate Metoprolol -blockers Propranolol Timolol Frovatriptan for short-term prevention of menstrual migraine. A Triptans As per EFNS 2009 guidelines, offer the following agents as the first choice for migraine prophylaxis: Situation Guidance Metoprolol 50-200 mg -blockers Propranolol 40-240 mg Flunarizine 5-10 mg CCBs Valproic acid 500-1,800 mg Antiepileptic drugs Topiramate 25-100 mg. A Migraine prophylaxis, second-line agents: As per SIGN 2022 guidelines, consider offering the following agents as prophylactic therapy in patients with episodic or chronic migraine: amitriptyline 25-150 mg at night https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 6/10 6/30/23, 1:02 AM Migraine Pathway candesartan 16 mg daily sodium valproate 400-1,500 mg daily flunarizine 10 mg daily. C Show 2 more As per SIGN 2018 guidelines, consider offering the following agents as prophylactic therapy in patients with episodic or chronic migraine amitriptyline 25-150 mg at night candesartan 16 mg daily sodium valproate 400-1,500 mg daily. C Show 3 more As per AAN 2012 guidelines, offer the following agents as the second choice for migraine prophylaxis: Situation Guidance Amitriptyline Antidepressants Venlafaxine Atenolol -blockers Nadolol Naratriptan Triptans Zolmitriptan for short-term prevention of menstrual migraine. B As per EFNS 2009 guidelines, offer the following agents as the second choice for migraine prophylaxis: amitriptyline 50-150 mg venlafaxine 75-150 mg naproxen 2 250-500 mg petasites 2 75 mg bisoprolol 5-10 mg. B Migraine prophylaxis, third-line agents: As per SIGN 2022 guidelines, do not use botulinum toxin A injections as prophylactic therapy in patients with episodic migraine. D Show 5 more As per AAN 2012 guidelines, offer the following agents as the third choice for migraine prophylaxis: Situation Guidance Lisinopril ACEIs https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 7/10 6/30/23, 1:02 AM Migraine Pathway Candesartan ARBs Clonidine Alpha-agonists Guanfacine Carbamazepine Antiepileptic drugs Nebivolol -blockers Pindolol. B As per EFNS 2009 guidelines, offer the following agents as the third choice for migraine prophylaxis: acetylsalicylic acid 300 mg gabapentin 1,200-1,600 mg magnesium 24 mmol tanacetum parthenium 3 6.25 mg riboflavin 400 mg coenzyme Q10 300 mg candesartan 16 mg lisinopril 20 mg methysergide 4-12 mg. B Migraine prophylaxis, agents with no evidence for benefit: As per SIGN 2022 guidelines, do not use gabapentin as prophylactic therapy in patients with episodic or chronic migraine. D As per AAN 2012 guidelines, do not use the following agents for migraine prophylaxis: lamotrigine D clomipramine. D Show 2 more Clinical findings Symptoms Past medical history Fatigue Migraine-type headache Headache and nausea Headache and vomiting Headache with aura Low mood Neck pain One-sided headache Phonophobia https://web.pathway.md/diseases/recEYiKvmxqyw7w0k 8/10 6/30/23, 1:02 AM Migraine Pathway Photophobia Pulsatile headache Sleeping disorder Throbbing headache Neurological exam Acute or recurrent ataxia References 1. S D Silberstein, S Holland, F Freitag et al. 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. Neurology. 2012 Apr 24;78 17 1337 45. Open 2. S Evers, J Afra, A Frese et al. EFNS guideline on the drug treatment of migraine revised report of an EFNS task force. Eur J Neurol. 2009 Sep;16 9 968 81. Open 3. Scottish Intercollegiate Guidelines Network. SIGN 155 Pharmacological management of migraine. SIGN. 2022 Sep. Open 4. Oskoui M, Pringsheim T, Holler-Managan Y et al. Practice guideline update summary: Acute treatment of migraine in children and adolescents Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2019 Sep 10;93 11 487 499. Open 5. Oskoui M, Pringsheim T, Billinghurst L et al. Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2019 Sep 10;93 11 500 509. Open 6. Scottish Intercollegiate Guidelines Network. Pharmacological management of migraine: A national clinical guideline. SIGN. 2018 Feb;Publication no. 155. Open 7. Simpson DM, Hallett M, Ashman EJ et al. 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