Chronic Migraine¶
VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Approved
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.
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
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.
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 | - | - |
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
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 | - |
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 |
═══════════════════════════════════════════════════════════ 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 |
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
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