⚠️

DRAFT - Pending Review

This plan requires physician review before clinical use.

Chronic Migraine

VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review

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DIAGNOSIS: Chronic Migraine

ICD-10: G43.709 (Chronic migraine without aura, not intractable), G43.719 (Chronic migraine without aura, intractable), G43.701 (Chronic migraine without aura, not intractable, with status migrainosus), G43.711 (Chronic migraine without aura, intractable, with status migrainosus), G43.909 (Migraine, unspecified, not intractable), G44.40 (Drug-induced headache, not elsewhere classified, not intractable)

CPT CODES: 99213-99215 (Office visit), 64405 (Greater occipital nerve block), 64615 (OnabotulinumtoxinA injection for chronic migraine), 96372 (Therapeutic injection, SC/IM), 96365 (IV infusion, initial), 70553 (MRI brain with and without contrast), 70551 (MRI brain without contrast)

SYNONYMS: Chronic migraine, CM, transformed migraine, chronic daily headache due to migraine, chronic migraine headache, intractable migraine, refractory migraine, chronic migraine without aura, chronic migraine with aura, medication overuse migraine, transformed migraine headache, CDH, chronic daily headache, high-frequency episodic migraine, frequent migraine, daily migraine, persistent migraine, treatment-resistant migraine, difficult-to-treat migraine, CGRP-responsive migraine, botox migraine, preventive migraine management

SCOPE: Comprehensive evaluation and management of chronic migraine in adults (defined as ≥15 headache days/month for >3 months, with migraine features on ≥8 days/month per ICHD-3). Covers preventive pharmacotherapy (oral agents, CGRP monoclonal antibodies, oral CGRP antagonists, onabotulinumtoxinA), acute treatment optimization, medication overuse headache screening and management, comorbidity assessment, and non-pharmacologic interventions. Primary focus on outpatient preventive management with acute/inpatient protocols for status migrainosus and refractory attacks. Excludes episodic migraine with <15 headache days/month (see Migraine template), cluster headache, and other trigeminal autonomic cephalalgias.

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DEFINITIONS: - Chronic Migraine (ICHD-3): Headache occurring on ≥15 days/month for >3 months, with migraine features on ≥8 days/month - Episodic Migraine: <15 headache days per month - Medication Overuse Headache (MOH): Headache ≥15 days/month with regular overuse of acute medications for >3 months (triptans/opioids/combination analgesics ≥10 days/month; simple analgesics ≥15 days/month) - Status Migrainosus: Debilitating migraine attack lasting >72 hours - Refractory Chronic Migraine: Chronic migraine that fails to respond to adequate trials of preventive therapies from at least 2 different pharmacologic classes - High-Frequency Episodic Migraine (HFEM): 8-14 headache days/month; at high risk for transformation to chronic migraine

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DIAGNOSTIC CRITERIA (ICHD-3 1.3):

A. Headache (migraine-like or tension-type-like) on ≥15 days/month for >3 months, fulfilling criteria B and C B. Occurring in a patient who has had at least 5 attacks fulfilling criteria B-D for migraine without aura and/or criteria B and C for migraine with aura C. On ≥8 days/month for >3 months, fulfilling any of the following: 1. Criteria C and D for migraine without aura 2. Criteria B and C for migraine with aura 3. Believed by the patient to be migraine at onset and relieved by a triptan or ergot derivative D. Not better accounted for by another ICHD-3 diagnosis

Note: Chronic migraine with medication overuse should be coded with both G43.7xx AND G44.4x per ICHD-3 recommendations.

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PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
CBC (CPT 85025)	Baseline; rule out anemia contributing to headache; baseline for certain preventives	Normal	STAT	ROUTINE	ROUTINE	-
CMP (CPT 80053)	Electrolytes, renal/hepatic function; baseline before preventive medications	Normal	STAT	ROUTINE	ROUTINE	-
TSH (CPT 84443)	Thyroid dysfunction can cause or worsen chronic headache	Normal (0.4-4.0 mIU/L)	-	ROUTINE	ROUTINE	-
Magnesium (CPT 83735)	Low magnesium associated with increased migraine frequency; many patients deficient	≥1.8 mg/dL	URGENT	ROUTINE	ROUTINE	-
hCG (women of childbearing age) (CPT 84703)	Pregnancy status affects treatment selection (many preventives contraindicated)	Document status	STAT	STAT	ROUTINE	-
LFTs (CPT 80076)	Baseline before topiramate, valproate; screen for hepatotoxicity from chronic analgesics	Normal	URGENT	ROUTINE	ROUTINE	-

1B. Extended Workup (Second-line)

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
ESR (CPT 85652) / CRP (CPT 86140)	If inflammatory or secondary cause suspected; age >50 with new headache	Normal	URGENT	ROUTINE	ROUTINE	-
Vitamin D, 25-hydroxy (CPT 82306)	Deficiency associated with increased migraine frequency and severity	>30 ng/mL	-	ROUTINE	ROUTINE	-
Ferritin (CPT 82728)	Iron deficiency associated with migraine; rule out occult deficiency	>50 ng/mL	-	ROUTINE	ROUTINE	-
Lipid panel (CPT 80061)	Cardiovascular risk assessment; migraine with aura increases stroke risk	Optimal per guidelines	-	-	ROUTINE	-
Hemoglobin A1c (CPT 83036)	Metabolic syndrome screening; comorbidity	<5.7%	-	-	ROUTINE	-
Urine drug screen (CPT 80307)	If opioid overuse or substance use suspected	Document	-	ROUTINE	ROUTINE	-

1C. Rare/Specialized

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Homocysteine (CPT 83090)	Elevated levels associated with migraine with aura; vascular risk	Normal	-	-	EXT	-
ANA (CPT 86235)	If CNS vasculitis or autoimmune cause suspected	Negative	-	EXT	EXT	-
Antiphospholipid antibodies (CPT 86147, 86235)	Recurrent migraine with aura, young stroke risk	Negative	-	-	EXT	-
Prolactin (CPT 84146)	If pituitary pathology suspected	Normal	-	-	EXT	-
Lumbar puncture (CPT 62270)	Suspected IIH (papilledema), SAH, or infectious etiology	See LP section	URGENT	URGENT	-	-

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRI brain without contrast (CPT 70551)	New chronic migraine diagnosis; change in headache pattern; refractory to treatment	Normal; rule out structural lesion, white matter disease, Chiari malformation	MRI-incompatible devices	URGENT	ROUTINE	ROUTINE	-

2B. Extended

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRI brain with and without contrast (CPT 70553)	If mass, infection, inflammation, or meningeal enhancement suspected	Rule out enhancing lesion	Contrast allergy, renal disease (eGFR <30)	-	ROUTINE	ROUTINE	-
MRA head (CPT 70544)	Suspected vasculopathy; RCVS; dissection	Normal vasculature	MRI-incompatible devices, contrast allergy if contrast-enhanced, renal disease (eGFR <30)	URGENT	ROUTINE	ROUTINE	-
MRV head (CPT 70546)	Suspected cerebral venous thrombosis; papilledema	Patent venous sinuses	MRI-incompatible devices, contrast allergy if contrast-enhanced, renal disease (eGFR <30)	URGENT	URGENT	ROUTINE	-
CT head without contrast (CPT 70450)	Thunderclap headache; worst headache of life; focal deficits; altered mental status	Rule out hemorrhage, mass	None in emergency	STAT	URGENT	-	-
ECG (CPT 93000)	Prior to DHE, triptan, or QT-prolonging medications	Normal QTc (<470 ms female, <450 ms male), no ischemia	None	STAT	STAT	ROUTINE	-

2C. Specialized

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRI cervical spine (CPT 72141)	Cervicogenic component suspected; occipital neuralgia	Rule out Chiari, structural pathology	MRI-incompatible devices	-	EXT	ROUTINE	-
Polysomnography (CPT 95810)	Suspected sleep apnea contributing to chronic headache	AHI <5 (normal)	None	-	-	ROUTINE	-
Ophthalmologic exam with fundoscopy	Papilledema suspected; visual symptoms	Normal optic disc; no papilledema	None	URGENT	URGENT	ROUTINE	-

LUMBAR PUNCTURE (CPT 62270)

Indication: Suspected IIH (papilledema, visual obscurations, pulsatile tinnitus), thunderclap headache with negative CT (SAH), suspected meningitis, new daily persistent headache evaluation

Timing: URGENT after CT excludes mass effect

Study	Rationale	Target Finding	ED	HOSP	OPD	ICU
Opening pressure	IIH diagnosis; elevated ICP	10-20 cm H2O (>25 cm H2O suggests IIH)	STAT	STAT	-	-
Cell count (tubes 1 and 4) (CPT 89051)	Infection, SAH	WBC <5; RBC 0 or clearing	STAT	STAT	-	-
Protein (CPT 84157)	Infection, inflammation	15-45 mg/dL	STAT	STAT	-	-
Glucose (CPT 82945)	Infection	>60% serum glucose	STAT	STAT	-	-
Xanthochromia	SAH if CT negative	Negative	STAT	STAT	-	-

Contraindications: Mass lesion with mass effect on imaging, coagulopathy (INR >1.5, platelets <50K), skin infection at puncture site

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3. TREATMENT

3A. Acute Treatment - Mild-Moderate Attacks (Limit Total Acute Medication Days)

CRITICAL: In chronic migraine, acute medication use must be strictly limited to prevent/treat medication overuse headache. Triptans ≤9 days/month, NSAIDs ≤14 days/month, combination analgesics ≤10 days/month. Track on headache diary.

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Ibuprofen	PO	Mild-moderate migraine attack	400-800 mg :: PO :: once :: 400-800 mg PO once; limit to ≤14 days/month; max 2400 mg/day	Renal disease, GI bleeding, aspirin-exacerbated respiratory disease	Renal function; medication days/month	-	ROUTINE	ROUTINE	-
Naproxen sodium	PO	Mild-moderate migraine attack	500-825 mg :: PO :: once :: 500-825 mg PO once; limit to ≤14 days/month	Renal disease, GI bleeding, aspirin-exacerbated respiratory disease	Renal function; medication days/month	-	ROUTINE	ROUTINE	-
Acetaminophen	PO	Mild attack; NSAID contraindicated	1000 mg :: PO :: once :: 1000 mg PO once; max 3000 mg/day; limit to ≤14 days/month	Hepatic disease, chronic alcohol use	LFTs if frequent use; medication days/month	-	ROUTINE	ROUTINE	-

3B. Acute Treatment - Moderate-Severe Attacks (Triptans and Gepants)

CAUTION: Serotonin syndrome risk when combining triptans with SNRIs (venlafaxine), SSRIs, or other serotonergic agents. Monitor for agitation, hyperthermia, clonus, hyperreflexia. Risk is generally low but clinically relevant.

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Sumatriptan SC	SC	Moderate-severe migraine; rapid relief needed	6 mg :: SC :: once :: 6 mg SC once; may repeat in 2h; max 12 mg/24h; limit ≤9 days/month	CAD, stroke/TIA, uncontrolled HTN, hemiplegic migraine, MAOIs, pregnancy	Chest tightness, BP; medication days/month; serotonin syndrome signs if on SNRI/SSRI	STAT	STAT	-	-
Sumatriptan PO	PO	Moderate-severe migraine	50-100 mg :: PO :: once :: 50-100 mg PO once; may repeat in 2h; max 200 mg/24h; limit ≤9 days/month	CAD, stroke/TIA, uncontrolled HTN, hemiplegic migraine, MAOIs, pregnancy	Chest tightness, BP; medication days/month; serotonin syndrome signs if on SNRI/SSRI	-	ROUTINE	ROUTINE	-
Rizatriptan	PO	Moderate-severe migraine	5-10 mg :: PO :: once :: 5-10 mg PO (ODT available); may repeat in 2h; max 30 mg/24h; limit ≤9 days/month; use 5 mg if on propranolol	CAD, stroke/TIA, uncontrolled HTN, hemiplegic migraine, MAOIs, pregnancy; reduce dose with propranolol	Chest tightness, BP; medication days/month; serotonin syndrome signs if on SNRI/SSRI	-	ROUTINE	ROUTINE	-
Eletriptan	PO	Moderate-severe migraine; high efficacy	40 mg :: PO :: once :: 40 mg PO once; may repeat in 2h; max 80 mg/24h; limit ≤9 days/month	CAD, stroke/TIA, uncontrolled HTN, hemiplegic migraine, MAOIs, pregnancy; severe hepatic impairment	Chest tightness, BP; medication days/month; serotonin syndrome signs if on SNRI/SSRI	-	ROUTINE	ROUTINE	-
Ubrogepant	PO	Moderate-severe migraine; CV contraindications to triptans; lower MOH risk	50-100 mg :: PO :: once :: 50-100 mg PO once; may repeat in 2h; max 200 mg/24h	Strong CYP3A4 inhibitors; severe hepatic/renal impairment	LFTs periodically; may have lower MOH risk	-	ROUTINE	ROUTINE	-
Rimegepant (acute)	PO	Moderate-severe migraine; dual acute/preventive use; lower MOH risk	75 mg :: PO :: once :: 75 mg PO ODT once daily PRN; do not exceed 1 dose/day	Strong CYP3A4 inhibitors; severe hepatic impairment	LFTs periodically; may have lower MOH risk	-	ROUTINE	ROUTINE	-
Zavegepant nasal	IN	Moderate-severe migraine; need non-oral route	10 mg :: IN :: once :: 10 mg intranasal once; do not repeat in 24h	Hypersensitivity	Nasal irritation; LFTs periodically	-	ROUTINE	ROUTINE	-

3C. Acute Treatment - Status Migrainosus / Refractory (ED/Inpatient)

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IV fluids (NS or LR)	IV	Dehydration; volume repletion	1000 mL :: IV :: bolus :: NS or LR 1L bolus then 75-125 mL/hr maintenance	Heart failure, volume overload	I/O, electrolytes	STAT	STAT	-	-
Prochlorperazine IV	IV	First-line ED migraine treatment; antiemetic + analgesic	10 mg :: IV :: once :: 10 mg IV slow push over 5-10 min; may repeat x1 in 30 min; give with diphenhydramine	QT prolongation, Parkinson's disease, seizure disorder	QTc, akathisia, dystonia	STAT	STAT	-	-
Metoclopramide IV	IV	Alternative to prochlorperazine; migraine + nausea	10-20 mg :: IV :: once :: 10-20 mg IV over 15-30 min; may repeat x1 in 30 min; give with diphenhydramine	QT prolongation, Parkinson's, seizure disorder	QTc, akathisia, dystonia	STAT	STAT	-	-
Diphenhydramine IV	IV	Akathisia prophylaxis with dopamine antagonists	25-50 mg :: IV :: once :: 25-50 mg IV push (give with prochlorperazine or metoclopramide)	Narrow-angle glaucoma, urinary retention	Sedation	STAT	STAT	-	-
Ketorolac IV	IV	Adjunctive analgesic; anti-inflammatory	30 mg :: IV :: once :: 30 mg IV once (15 mg if age >65 or CrCl <50); max 5 days total	Renal disease, GI bleeding, anticoagulation, recent bypass surgery	Renal function, GI symptoms	STAT	STAT	-	-
Dexamethasone IV	IV	Reduce headache recurrence; refractory migraine	10 mg :: IV :: once :: 10 mg IV once (reduces 72h recurrence by ~25%)	Active infection, uncontrolled diabetes	Glucose, insomnia	URGENT	URGENT	-	-
Magnesium sulfate IV	IV	Adjunctive; low magnesium associated with migraine; migraine with aura	2 g :: IV :: once :: 2 g IV over 20-30 min	Renal failure (CrCl <20), myasthenia gravis, heart block	Mg levels, DTRs, respiratory status	URGENT	URGENT	-	-
Valproate sodium IV	IV	Refractory to first-line; status migrainosus	500-1000 mg :: IV :: once :: 500-1000 mg IV over 15-30 min; may repeat in 8h	Pregnancy (teratogen), hepatic disease, mitochondrial disease, pancreatitis	Ammonia, LFTs, platelets	URGENT	URGENT	-	-
Dihydroergotamine (DHE) IV	IV	Refractory status migrainosus; prolonged migraine	1 mg :: IV :: q8h :: Premedicate: metoclopramide 10 mg IV + diphenhydramine 25 mg IV 30 min prior; Test dose: 0.5 mg IV over 1 min; If tolerated: 0.5-1 mg IV q8h x 3-5 days	CAD, CVA, uncontrolled HTN, peripheral vascular disease, pregnancy, triptan within 24h, ergot allergy, CYP3A4 inhibitors	BP q4h, chest pain, nausea, extremity perfusion	URGENT	STAT	-	-

3D. Preventive Therapies - Oral First-Line Agents

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Topiramate	PO	First-line oral preventive; Level A evidence; weight-neutral/loss	25 mg :: PO :: daily :: Start 25 mg QHS; increase by 25 mg/week; target 50-100 mg BID; max 200 mg/day	Baseline BMP (bicarbonate), pregnancy test	Nephrolithiasis, pregnancy (teratogen - cleft palate), metabolic acidosis, glaucoma (acute angle-closure)	Bicarbonate q3-6mo, cognitive effects, paresthesias, weight, renal function	-	ROUTINE	ROUTINE	-
Amitriptyline	PO	First-line; comorbid insomnia, depression, or tension-type features	10-25 mg :: PO :: QHS :: Start 10-25 mg QHS; increase by 10-25 mg q1-2 weeks; target 50-150 mg QHS	Baseline ECG if >40 years or cardiac history	Cardiac arrhythmia, recent MI, narrow-angle glaucoma, urinary retention, MAOIs	QTc (ECG), anticholinergic effects, weight, sedation	-	ROUTINE	ROUTINE	-
Propranolol	PO	First-line; comorbid anxiety, hypertension, or essential tremor	40 mg :: PO :: BID :: Start 40 mg BID; increase every 1-2 weeks; target 80-240 mg/day in divided doses	Baseline HR, BP	Asthma/severe COPD, bradycardia (<60), heart block (2nd/3rd degree), decompensated HF, depression (relative)	HR, BP, fatigue, exercise tolerance, depression screening	-	ROUTINE	ROUTINE	-
Venlafaxine XR	PO	First-line; comorbid depression, anxiety, or fibromyalgia	37.5 mg :: PO :: daily :: Start 37.5 mg daily x 1 week; increase to 75 mg daily; target 75-150 mg daily; max 225 mg/day	Baseline BP	Uncontrolled HTN, MAOIs, narrow-angle glaucoma; serotonin syndrome risk with triptans (monitor closely)	BP (dose-dependent HTN), serotonin syndrome signs (agitation, hyperthermia, clonus), withdrawal if abrupt discontinuation	-	ROUTINE	ROUTINE	-
Valproate/Divalproex	PO	First-line; Level A evidence; may benefit comorbid bipolar disorder	250 mg :: PO :: BID :: Start 250 mg BID or 500 mg ER QHS; increase to 500-1000 mg/day; max 1500 mg/day	Baseline LFTs, CBC, pregnancy test (mandatory)	Pregnancy (neural tube defects - ABSOLUTE), hepatic disease, mitochondrial disease, pancreatitis	LFTs, ammonia, CBC, weight q3-6mo; mandatory contraception counseling in women	-	ROUTINE	ROUTINE	-
Candesartan	PO	First-line; comorbid hypertension; Level B evidence	8 mg :: PO :: daily :: Start 8 mg daily; increase to 16 mg daily after 4 weeks	Baseline BMP, BP	Pregnancy, bilateral renal artery stenosis, hyperkalemia	BP, potassium, renal function	-	-	ROUTINE	-
Metoprolol succinate	PO	Alternative beta-blocker; comorbid hypertension	25-50 mg :: PO :: daily :: Start 25-50 mg daily; target 100-200 mg daily	Baseline HR, BP	Asthma/severe COPD, bradycardia (<60), heart block (2nd/3rd degree), decompensated HF, depression (relative)	HR, BP, fatigue	-	ROUTINE	ROUTINE	-

3E. Preventive Therapies - CGRP Monoclonal Antibodies

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Erenumab (Aimovig)	SC	Chronic migraine prevention; may use as first-line or after oral failure; only CGRP receptor antibody	70 mg :: SC :: monthly :: 70 mg SC monthly; may increase to 140 mg SC monthly if inadequate response after 3 months	Screen for constipation history, HTN	Hypersensitivity; caution with severe constipation (can cause serious constipation), uncontrolled HTN	BP (may increase), constipation (can be severe), injection site reactions; reassess efficacy at 3 months	-	-	ROUTINE	-
Fremanezumab (Ajovy)	SC	Chronic migraine prevention; monthly or quarterly dosing option	225 mg :: SC :: monthly :: 225 mg SC monthly OR 675 mg SC quarterly (three 225 mg injections)	None specific	Hypersensitivity	Injection site reactions; reassess efficacy at 3 months	-	-	ROUTINE	-
Galcanezumab (Emgality)	SC	Chronic migraine prevention; also approved for episodic cluster headache	240 mg :: SC :: loading :: 240 mg SC loading dose (two 120 mg injections), then 120 mg SC monthly	None specific	Hypersensitivity	Injection site reactions; reassess efficacy at 3 months	-	-	ROUTINE	-
Eptinezumab (Vyepti)	IV	Chronic migraine prevention; rapid onset (may work within days); IV formulation for clinic/infusion center	100 mg :: IV :: quarterly :: 100 mg IV q3 months; may increase to 300 mg IV q3 months if inadequate response	IV access; infusion center scheduling	Hypersensitivity	Infusion reactions (nasopharyngitis, hypersensitivity); reassess efficacy at 3-6 months	-	ROUTINE	ROUTINE	-

3F. Preventive Therapies - Oral CGRP Antagonists (Gepants)

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Atogepant (Qulipta)	PO	Chronic migraine prevention; oral alternative to CGRP mAbs; only gepant FDA-approved for chronic migraine prevention	60 mg :: PO :: daily :: 60 mg PO daily (approved dose for chronic migraine); reduce to 10 mg daily with strong CYP3A4 inhibitors; avoid with strong CYP3A4 inducers	Baseline LFTs	Severe hepatic impairment (Child-Pugh C); strong CYP3A4 inducers; end-stage renal disease	LFTs q3-6 months; weight (may cause weight loss); constipation	-	-	ROUTINE	-
Rimegepant (Nurtec ODT)	PO	Dual-purpose: acute and preventive treatment; chronic migraine prevention	75 mg :: PO :: every other day :: 75 mg PO ODT every other day for prevention; may also use PRN for acute attacks (75 mg, max once daily)	Baseline LFTs	Strong CYP3A4 inhibitors (ketoconazole, itraconazole); severe hepatic impairment	LFTs q3-6 months; monitor for dyspnea (rare)	-	-	ROUTINE	-

3G. Preventive Therapies - OnabotulinumtoxinA and Procedures

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
OnabotulinumtoxinA (Botox) (CPT 64615, J0585)	IM	Chronic migraine ONLY (≥15 HA days/month); Level A evidence; FDA-approved for chronic migraine	155 units :: IM :: q12 weeks :: 155-195 units IM across 31-39 injection sites q12 weeks; PREEMPT protocol: 7 head/neck muscle groups (frontalis, corrugator, procerus, temporalis, occipitalis, cervical paraspinal, trapezius); 5 units per site	Confirm chronic migraine diagnosis (≥15 days/month); document medication overuse status; NOT approved for episodic migraine	Active infection at injection sites, myasthenia gravis, Lambert-Eaton syndrome, known hypersensitivity to botulinum toxin	Injection site pain, neck pain, eyelid ptosis (1-2%); assess response at 2nd-3rd cycle (minimum 2 cycles before declaring failure); document headache days reduction	-	-	ROUTINE	-
Greater occipital nerve block (CPT 64405)	SC/IM	Adjunctive; bridging therapy; acute relief during preventive initiation	2-3 mL :: SC :: bilateral :: Lidocaine 2% or bupivacaine 0.25% (2-3 mL per side) with optional dexamethasone 4 mg or methylprednisolone 40 mg; bilateral GON block	Identify occipital nerves; patient consent	Local anesthetic allergy, infection at injection site, anticoagulation (relative)	Local pain, transient numbness; assess response in 30-60 min; may repeat q4-12 weeks	-	ROUTINE	ROUTINE	-
Sphenopalatine ganglion (SPG) block	IN	Refractory chronic migraine; adjunctive procedure	0.3 mL :: IN :: bilateral :: Lidocaine 4% or bupivacaine 0.5% via SPG applicator (e.g., SphenoCath, Tx360); bilateral	Identify nasal anatomy	Nasal pathology, anticoagulation, local anesthetic allergy	Throat numbness, transient epistaxis; assess response; series of treatments often needed	-	ROUTINE	ROUTINE	-

3H. Preventive Therapies - Nutraceuticals and Supplements

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Magnesium oxide	PO	Adjunctive preventive; Level B evidence; low side effect profile	400-600 mg :: PO :: daily :: 400-600 mg PO daily; use chelated form (glycinate or citrate) if GI intolerance	None	Renal failure (CrCl <30)	Diarrhea (dose-limiting); check serum Mg if symptoms	-	ROUTINE	ROUTINE	-
Riboflavin (Vitamin B2)	PO	Adjunctive preventive; Level B evidence; nutraceutical	400 mg :: PO :: daily :: 400 mg PO daily; may take 3 months for full effect	None	None significant	Bright yellow urine (benign); minimal side effects	-	-	ROUTINE	-
Coenzyme Q10 (CoQ10)	PO	Adjunctive preventive; Level C evidence; nutraceutical	100 mg :: PO :: TID :: 100 mg PO TID (300 mg/day total); may take 3 months for full effect	None	Caution with warfarin (may reduce INR)	GI upset; monitor INR if on warfarin	-	-	ROUTINE	-
Butterbur (Petasites)	PO	Preventive; Level A evidence (AAN recommendation withdrawn due to hepatotoxicity concerns - use with caution)	75 mg :: PO :: BID :: 75 mg PO BID of PA-free extract only; NOT recommended without PA-free verification	Verify PA-free (pyrrolizidine alkaloid-free) extract	Hepatotoxicity risk with non-PA-free products; ragweed allergy; pregnancy	LFTs if prolonged use; USE WITH CAUTION - AAN withdrew recommendation due to safety concerns	-	-	EXT	-

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4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	Indication	ED	HOSP	OPD	ICU
Headache specialist / Neurology referral	All chronic migraine patients; coordination of preventive therapy	URGENT	ROUTINE	ROUTINE	-
Behavioral health / Psychology referral	CBT for headache; biofeedback training; comorbid anxiety/depression; coping strategies	-	ROUTINE	ROUTINE	-
Psychiatry referral	Comorbid depression/anxiety requiring pharmacotherapy; suicidal ideation	-	URGENT	ROUTINE	-
Pain psychology / Biofeedback specialist	Non-pharmacologic headache management; relaxation training; stress management	-	-	ROUTINE	-
Physical therapy	Cervicogenic component; neck/shoulder tension; postural issues; trigger point therapy	-	ROUTINE	ROUTINE	-
Sleep medicine	Suspected sleep apnea, insomnia, or sleep disorder contributing to chronic headache	-	-	ROUTINE	-
Ophthalmology	Papilledema, visual symptoms, suspected IIH	URGENT	URGENT	ROUTINE	-
Reproductive endocrinology / OB-GYN	Menstrual migraine management; contraception counseling with migraine; pregnancy planning	-	-	ROUTINE	-
Interventional pain / Neuromodulation	Refractory chronic migraine; consideration for nerve stimulation devices	-	-	ROUTINE	-

4B. Patient/Family Instructions

Recommendation	ED	HOSP	OPD
Chronic migraine is a neurological condition that requires long-term management	ROUTINE	ROUTINE	ROUTINE
Keep daily headache diary: frequency, severity, triggers, medications used (acute medication days are CRITICAL to track)	ROUTINE	ROUTINE	ROUTINE
STRICTLY limit acute medication use: triptans ≤9 days/month, NSAIDs ≤14 days/month, combination analgesics ≤10 days/month	ROUTINE	ROUTINE	ROUTINE
Preventive medications take 4-8 weeks to show benefit; give each an adequate trial (2-3 months at target dose)	-	ROUTINE	ROUTINE
CGRP injections are administered monthly or quarterly; most patients see improvement by month 3	-	-	ROUTINE
Botox treatments are given every 12 weeks; minimum 2 cycles needed before assessing efficacy	-	-	ROUTINE
Identify and avoid personal migraine triggers (e.g., certain foods, stress, weather, hormonal changes)	ROUTINE	ROUTINE	ROUTINE
Return to ED if: worst headache of life, fever with headache, neurologic deficits, altered mental status, seizure	ROUTINE	ROUTINE	ROUTINE
Follow up with headache specialist/neurologist in 4-6 weeks for preventive initiation and q3 months thereafter	-	ROUTINE	ROUTINE
Do NOT stop preventive medications abruptly without physician guidance	-	ROUTINE	ROUTINE

4C. Lifestyle & Non-Pharmacologic Interventions

Recommendation	ED	HOSP	OPD
Regular sleep schedule (7-8 hours); avoid oversleeping and sleep deprivation	-	ROUTINE	ROUTINE
Regular aerobic exercise (150 min/week; 30 min, 5 days/week); builds gradually	-	ROUTINE	ROUTINE
Stress management: cognitive behavioral therapy (CBT) for headache, mindfulness-based stress reduction (MBSR), progressive muscle relaxation	-	ROUTINE	ROUTINE
Biofeedback training (thermal or EMG biofeedback; Level A evidence for migraine prevention)	-	-	ROUTINE
Stay well-hydrated (64+ oz water daily); avoid dehydration triggers	ROUTINE	ROUTINE	ROUTINE
Consistent meal schedule (avoid skipping meals); limit or avoid alcohol, aged cheese, MSG, processed meats, nitrates	-	ROUTINE	ROUTINE
Limit caffeine to consistent moderate intake (<200 mg/day); avoid abrupt caffeine withdrawal	-	ROUTINE	ROUTINE
Consider neuromodulation devices (FDA-cleared): sTMS (SpringTMS), eTNS (Cefaly), nVNS (gammaCore), REN (Nerivio)	-	-	ROUTINE
Acupuncture (Level A evidence from Cochrane reviews; may be used adjunctively)	-	-	ROUTINE
Yoga and tai chi (emerging evidence for headache frequency reduction)	-	-	ROUTINE

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═══════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Medication overuse headache (MOH)	Chronic daily headache with frequent acute medication use (≥10-15 days/month); may coexist with chronic migraine	Medication diary; detoxification trial; headache frequency may improve with withdrawal
Chronic tension-type headache	Bilateral, pressing/tightening, mild-moderate intensity; NO nausea/vomiting; no more than one of photo/phonophobia	Clinical history; typically lacks migraine features
New daily persistent headache (NDPH)	Distinct remembered onset date; daily and unremitting from onset; no prior chronic headache	Clinical history; MRI brain; may need LP
Hemicrania continua	Continuous strictly unilateral headache with autonomic features; responds absolutely to indomethacin	Indomethacin trial (complete response diagnostic)
Idiopathic intracranial hypertension (IIH)	Papilledema, visual obscurations, pulsatile tinnitus; worse with Valsalva; typically young obese females	Fundoscopy, LP with elevated OP (>25 cm H2O), MRI/MRV
Cerebral venous thrombosis	Progressive headache, seizures, focal deficits; risk factors (OCP, pregnancy, coagulopathy)	MRV/CTV; D-dimer
Giant cell arteritis	Age >50, new headache, jaw claudication, scalp tenderness, visual symptoms, elevated inflammatory markers	ESR/CRP, temporal artery biopsy
Intracranial neoplasm	Progressive headache worse in morning/with Valsalva; focal neurologic deficits; seizures	MRI brain with contrast
Low CSF pressure headache (SIH)	Orthostatic headache (worse upright, better supine); may have subdural collections	MRI brain (pachymeningeal enhancement, brain sagging); LP with low OP
Cervicogenic headache	Unilateral, starts in neck/occipital region; triggered by neck movement/posture; reduced cervical ROM	Cervical exam, cervical imaging; diagnostic nerve block
Sleep apnea-related headache	Morning headache; daytime somnolence; snoring; obesity	Polysomnography
Temporomandibular disorder (TMD)	Temporomandibular pain; jaw clicking; worsened by chewing	TMJ exam; dental evaluation

6. MONITORING PARAMETERS

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Headache days per month	Monthly (diary)	<15 days/month; ideally ≥50% reduction	Adjust preventive strategy; reassess diagnosis	-	Daily	ROUTINE	-
Migraine days per month	Monthly (diary)	≥50% reduction from baseline	Escalate preventive; consider combination therapy	-	Daily	ROUTINE	-
Acute medication days per month	Monthly (diary)	Triptans ≤9, NSAIDs ≤14, total ≤10-14	Address MOH; counsel on limits; adjust plan	-	Daily	ROUTINE	-
MIDAS (Migraine Disability Assessment)	q3 months	Improving score; target grade I-II	Adjust treatment; consider additional interventions	-	-	ROUTINE	-
HIT-6 (Headache Impact Test)	q3 months	Score <50 (little/no impact)	Escalate treatment if ≥60 (severe impact)	-	-	ROUTINE	-
PHQ-9 (depression screening)	q3-6 months	<5 (minimal)	Refer behavioral health; consider antidepressant	-	ROUTINE	ROUTINE	-
GAD-7 (anxiety screening)	q3-6 months	<5 (minimal)	Refer behavioral health; consider anxiolytic preventive	-	ROUTINE	ROUTINE	-
Pain scale (0-10)	Per assessment	Improving trend; functional improvement	Escalate acute or preventive treatment	STAT	q4h	Each visit	-
Vital signs (HR, BP)	Per assessment	Normal; monitor for beta-blocker/venlafaxine effects	Adjust medication doses	STAT	q4h	Each visit	-
ECG (if on QT-prolonging agents or DHE)	Before administration	Normal QTc (<470 ms F, <450 ms M)	Avoid vasoactive/QT-prolonging drugs	STAT	STAT	As needed	-
Labs per preventive agent	q3-6 months	Per agent (LFTs for topiramate/valproate; bicarbonate for topiramate; BP for venlafaxine)	Adjust dose or switch agent	-	-	ROUTINE	-
Weight	Each visit	Stable or improving	Address if significant gain (valproate) or loss (topiramate)	-	-	ROUTINE	-

7. DISPOSITION CRITERIA

Disposition	Criteria
Discharge from ED	Acute attack relieved; able to tolerate PO; no red flags; headache diary provided; outpatient follow-up arranged within 2-4 weeks
Admit to hospital	Status migrainosus unresponsive to ED treatment (>72h); need for IV DHE protocol; inability to tolerate PO; severe dehydration; concern for secondary headache requiring inpatient workup; psychiatric comorbidity requiring stabilization
ICU admission	Rare; suspected intracranial pathology; hemodynamic instability during treatment; severe adverse drug reaction
Discharge from hospital	Pain controlled on oral medications; tolerating PO; ambulatory; preventive medication initiated or optimized; outpatient follow-up arranged
Outpatient follow-up	New diagnosis: 4-6 weeks; During preventive titration: q4-6 weeks; Stable on preventive: q3-6 months; On Botox: q12 weeks; On CGRP mAb: reassess at 3 months then q3-6 months

8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
ICHD-3 criteria for chronic migraine (1.3)	Expert Consensus	Headache Classification Committee of the International Headache Society. Cephalalgia 2018;38(1):1-211 PubMed
Topiramate effective for chronic migraine prevention	Class I, Level A	Silberstein SD et al. Headache 2007;47(2):170-180 PubMed
OnabotulinumtoxinA for chronic migraine (PREEMPT trial)	Class I, Level A	Dodick DW et al. Headache 2010;50(6):921-936 PubMed
OnabotulinumtoxinA PREEMPT-2 results	Class I, Level A	Aurora SK et al. Cephalalgia 2010;30(7):804-814 PubMed
Erenumab for chronic migraine prevention	Class I, Level A	Tepper SJ et al. Lancet Neurol 2017;16(6):425-434 PubMed
Fremanezumab for chronic migraine (HALO-CM)	Class I, Level A	Silberstein SD et al. N Engl J Med 2017;377(22):2113-2122 PubMed
Galcanezumab for chronic migraine (REGAIN)	Class I, Level A	Detke HC et al. Neurology 2018;91(24):e2211-e2221 PubMed
Eptinezumab for chronic migraine (PROMISE-2)	Class I, Level A	Lipton RB et al. Neurology 2020;94(13):e1365-e1377 PubMed
Atogepant for chronic migraine prevention (PROGRESS)	Class I, Level A	Pozo-Rosich P et al. Lancet 2023;402(10404):775-785 PubMed
Rimegepant for migraine prevention	Class I, Level A	Croop R et al. Lancet 2021;397(10268):51-60 PubMed
AAN/AHS practice guideline update on migraine prevention	Expert Consensus	Silberstein SD et al. Neurology 2012;78(17):1337-1345 PubMed
AHS consensus statement on CGRP mAbs in migraine	Expert Consensus	American Headache Society. Headache 2019;59(1):1-18 PubMed
Behavioral treatments for migraine (biofeedback, CBT, relaxation)	Class I, Level A	Penzien DB et al. Neurology 2005;64(10):2010-2015 PubMed
Prochlorperazine/metoclopramide for acute migraine	Class I, Level A	Friedman BW et al. Ann Emerg Med 2008;52(4):399-406 PubMed
Dexamethasone reduces migraine recurrence	Class I, Level A	Singh A et al. Acad Emerg Med 2008;15(12):1223-1233 PubMed
DHE for refractory status migrainosus	Class II, Level B	Raskin NH. Neurology 1986;36(7):995-997 PubMed
Riboflavin for migraine prevention	Class II, Level B	Schoenen J et al. Neurology 1998;50(2):466-470 PubMed
Magnesium for migraine prevention	Class II, Level B	Peikert A et al. Cephalalgia 1996;16(4):257-263 PubMed
Ubrogepant for acute migraine (ACHIEVE-I and ACHIEVE-II)	Class I, Level A	Dodick DW et al. JAMA 2019;322(24):2489-2496 PubMed
Acupuncture for migraine prevention (Cochrane review)	Class I, Level A	Linde K et al. Cochrane Database Syst Rev 2016;(6):CD001218 PubMed
Beta-blockers (propranolol) for migraine prevention	Class I, Level A	Linde K et al. Cochrane Database Syst Rev 2004;(2):CD003225 PubMed
Medication overuse headache criteria and management	Expert Consensus	Diener HC et al. Nat Rev Neurol 2016;12(10):575-583 PubMed
Candesartan for migraine prevention	Class II, Level B	Stovner LJ et al. JAMA 2014;311(11):1091-1099 PubMed
Neuromodulation devices for migraine (sTMS, eTNS, nVNS)	Class II, Level B	Starling AJ et al. Headache 2018;58(S1):187-196 PubMed

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CLINICAL DECISION SUPPORT NOTES

• Chronic migraine is defined as ≥15 headache days/month for >3 months with migraine features on ≥8 days; differentiate from episodic migraine (<15 days/month)
• Up to 50-80% of chronic migraine patients have comorbid medication overuse headache (MOH); ALWAYS screen for acute medication frequency
• Patients with MOH may need detoxification before or concurrent with preventive initiation; some preventives (e.g., topiramate, CGRP mAbs) may work even with ongoing overuse
• CGRP-targeted therapies (mAbs and oral gepants) represent a paradigm shift: mechanism-specific, well-tolerated, may be used first-line in appropriate patients
• OnabotulinumtoxinA (Botox) is ONLY approved for chronic migraine (≥15 days/month), NOT episodic migraine; requires minimum 2 treatment cycles before assessing efficacy
• Atogepant (Qulipta) is the only oral CGRP antagonist (gepant) with specific FDA approval for chronic migraine prevention (60 mg daily)
• Rimegepant offers dual-use: 75 mg every other day for prevention AND 75 mg as needed for acute treatment
• Oral preventives should be titrated slowly and given 2-3 months at target dose before declaring failure; most patients need trials of multiple agents
• Combination preventive therapy may be necessary for refractory patients (e.g., oral agent + CGRP mAb + Botox)
• Non-pharmacologic approaches (CBT, biofeedback, exercise, stress management) are evidence-based and should be recommended to ALL patients
• Neuromodulation devices (Cefaly, gammaCore, SpringTMS, Nerivio) are FDA-cleared options with favorable safety profiles
• Address comorbidities: depression (50%), anxiety (50%), sleep disorders (40%), obesity - treatment of comorbidities may improve headache
• Pregnancy planning requires careful medication review: discontinue teratogens (topiramate, valproate), gepants; CGRP mAbs should be stopped (limited safety data); consider nerve blocks, magnesium, biofeedback
• Goal of treatment: reduce headache frequency by ≥50%, reduce disability (MIDAS/HIT-6), optimize acute treatment, minimize medication overuse, improve quality of life
• Serotonin syndrome risk: When combining triptans with SNRIs (venlafaxine) or SSRIs, monitor for agitation, hyperthermia, clonus, hyperreflexia, and diaphoresis; risk is generally low but clinically relevant per FDA advisory

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CHANGE LOG

v1.1 (January 30, 2026) - Expanded all cross-references to standalone content per C1/C2/C3/C4 (naproxen, sumatriptan PO, rizatriptan, eletriptan, metoprolol contraindications; MRA/MRV contraindications) - Added ICU to frontmatter setting field for consistency with table columns per S1 - Added ECG OPD coverage (ROUTINE) for outpatient triptan/preventive initiation per S2/R3 - Added LFTs ED coverage (URGENT) for status migrainosus patients needing IV valproate per R7 - Added serotonin syndrome warning to Section 3B header and individual triptan monitoring fields per R4 - Added serotonin syndrome interaction note to venlafaxine XR entry in Section 3D per R4 - Added serotonin syndrome note to Clinical Decision Support Notes per R4 - Updated butterbur indication text to explicitly note AAN recommendation withdrawal per M3 - Added PubMed citation links to all 24 references in Section 8 per R5 - Version incremented from 1.0 to 1.1

v1.0 (January 30, 2026) - Initial template creation for Chronic Migraine - Comprehensive preventive pharmacotherapy: oral agents (topiramate, amitriptyline, propranolol, venlafaxine, valproate, candesartan) - CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) with individual dosing - Oral CGRP antagonists (atogepant, rimegepant) with dual-use detail - OnabotulinumtoxinA (Botox) PREEMPT protocol - Procedural interventions (GON block, SPG block) - Nutraceutical preventives (magnesium, riboflavin, CoQ10, butterbur with safety warning) - Acute treatment optimization with MOH prevention limits - Status migrainosus / refractory treatment protocols (ED/inpatient) - Non-pharmacologic interventions including neuromodulation devices - Comorbidity screening (depression, anxiety, sleep, MOH) - 24 evidence references with author/journal/year format