Epilepsy - Chronic Management

VERSION: 1.0 CREATED: January 31, 2026 STATUS: Approved

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DIAGNOSIS: Epilepsy - Chronic Management

ICD-10: G40.909 (Epilepsy, unspecified, not intractable, without status epilepticus), G40.309 (Generalized idiopathic epilepsy, not intractable), G40.209 (Localization-related epilepsy, not intractable), G40.109 (Localization-related symptomatic epilepsy, not intractable), G40.A09 (Absence epileptic syndrome, not intractable), G40.B09 (Juvenile myoclonic epilepsy, not intractable)

CPT CODES: 95816 (EEG routine), 95819 (EEG with sleep), 99213-99215 (outpatient E/M), 80201-80299 (therapeutic drug monitoring), 77080 (DEXA), 70553 (MRI brain)

SYNONYMS: Epilepsy chronic management, epilepsy maintenance, epilepsy follow-up, seizure disorder management, long-term epilepsy care, epilepsy outpatient management, seizure maintenance therapy, antiseizure medication management, epilepsy monitoring, controlled epilepsy, well-controlled epilepsy, epilepsy remission monitoring

SCOPE: Long-term outpatient management of adults with established epilepsy diagnosis on stable antiseizure medication (ASM) regimens. Covers routine monitoring, ASM optimization, comorbidity management (depression, anxiety, bone health), women's health and pregnancy planning, driving and employment considerations, ASM withdrawal in seizure-free patients, and bone health. Excludes initial seizure workup (see New Onset Seizure), acute breakthrough seizures (see Breakthrough Seizure), drug-resistant epilepsy requiring surgical evaluation (see Drug-Resistant Epilepsy), and status epilepticus (see SE template).

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

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1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
ASM trough levels (all current ASMs) (CPT 80201-80299)	STAT	STAT	ROUTINE	-	Routine monitoring of adherence and therapeutic dosing; obtain trough level (before morning dose); establish individual therapeutic level when seizure-free	Within therapeutic range; document individual target level when well controlled
CBC with differential (CPT 85025)	-	STAT	ROUTINE	-	Annual monitoring for ASM hematologic effects; carbamazepine (leukopenia, aplastic anemia rare); valproate (thrombocytopenia); felbamate (aplastic anemia)	Normal; WBC <3500 or platelets <100K → evaluate ASM cause
CMP (BMP + LFTs) (CPT 80053)	-	STAT	ROUTINE	-	Annual monitoring of hepatic function (ASM metabolism, hepatotoxicity); renal function (ASM dosing); electrolytes (hyponatremia with carbamazepine/oxcarbazepine)	Normal; hyponatremia → ASM-related SIADH; elevated LFTs → evaluate hepatotoxicity
Sodium (CPT 84295)	STAT	STAT	ROUTINE	-	Carbamazepine, oxcarbazepine, eslicarbazepine cause SIADH; routine monitoring q3-6 months for these agents	135-145 mEq/L; <130 → consider ASM change
Magnesium (CPT 83735)	STAT	STAT	ROUTINE	-	Chronic ASM use may deplete magnesium; hypomagnesemia lowers seizure threshold	>2.0 mg/dL; low → supplement
Pregnancy test (β-hCG) (CPT 84703)	STAT	STAT	ROUTINE	-	Annual screening for women of childbearing potential; before ASM changes; many ASMs are teratogenic	Negative; positive → urgent ASM safety review and OB referral

1B. Extended Workup (Second-line)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Vitamin D, 25-OH (CPT 82306)	-	-	ROUTINE	-	Annual screening for ALL epilepsy patients; enzyme-inducing ASMs (phenytoin, carbamazepine, phenobarbital) and valproate accelerate vitamin D metabolism → osteoporosis and fractures	>30 ng/mL; <20 → supplement 2000-5000 IU/day; recheck 3 months
B12 (CPT 82607) / Folate (CPT 82746)	-	-	ROUTINE	-	Phenytoin and carbamazepine deplete folate; B12 screening in elderly; folate critical for women of childbearing potential (neural tube defect prevention)	Normal; low folate → supplement 1-4 mg/day
Lipid panel (CPT 80061)	-	-	ROUTINE	-	Enzyme-inducing ASMs increase total cholesterol and LDL; cardiovascular risk monitoring	Normal; elevated → statin if indicated; consider switching to non-enzyme-inducing ASM
TSH (CPT 84443)	-	-	ROUTINE	-	Annual thyroid screening; valproate and carbamazepine can affect thyroid function; hypothyroidism increases seizure threshold (protective) but may cause fatigue	Normal
Free (unbound) ASM levels (CPT 80186, 80164)	-	ROUTINE	ROUTINE	-	For protein-bound drugs (phenytoin, valproate) in pregnancy, hypoalbuminemia, renal failure, elderly	Free phenytoin 1-2 mcg/mL; free valproate 5-15 mcg/mL
Ammonia (CPT 82140)	STAT	STAT	ROUTINE	-	Annual or PRN for patients on valproate; encephalopathy can occur with normal LFTs; also check if new confusion/lethargy	<35 μmol/L; elevated → consider carnitine supplementation or valproate dose reduction
DEXA bone density scan referral (CPT 77080)	-	-	ROUTINE	-	Baseline for patients on enzyme-inducing ASMs >2 years; all patients >50; seizure-related falls increase fracture risk	Normal T-score (>-1.0); osteopenia/osteoporosis → treat
Testosterone (total and free) (CPT 84403)	-	-	EXT	-	Enzyme-inducing ASMs increase sex hormone-binding globulin → low free testosterone; may cause sexual dysfunction, depression, fatigue in men	Normal; low → endocrinology referral
Cortisol, AM (CPT 82533)	-	-	EXT	-	Enzyme-inducing ASMs may affect cortisol; evaluate if fatigue is prominent	Normal

1C. Rare/Specialized (Refractory or Atypical)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
HLA-B15:02 / HLA-A31:01 (CPT 81374)	-	-	ROUTINE	-	Before starting carbamazepine/oxcarbazepine in patients of Southeast Asian descent (HLA-B15:02 → SJS/TEN); HLA-A31:01 in Europeans	Negative; positive → avoid carbamazepine/oxcarbazepine
CYP2C19 genotyping (CPT 81225)	-	-	EXT	-	Poor metabolizers accumulate N-desmethylclobazam (active metabolite); excessive sedation on standard clobazam doses	Normal metabolizer; poor → reduce clobazam dose 50%
Carbamazepine-10,11-epoxide level (CPT 80156)	-	-	ROUTINE	-	Active metabolite check when on carbamazepine + valproate (VPA inhibits epoxide hydrolase); toxicity with normal parent level	<9 mcg/mL; elevated → clinical toxicity
Anti-Mullerian hormone (AMH) (CPT 82397)	-	-	EXT	-	Ovarian reserve assessment for women with epilepsy planning pregnancy; valproate associated with polycystic ovarian syndrome (PCOS)	Normal for age; low → fertility referral

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI brain with epilepsy protocol (CPT 70553)	-	-	ROUTINE	-	If never done or done without epilepsy protocol; all patients should have at least one high-quality MRI; repeat if seizure pattern changes	Normal; mesial temporal sclerosis; cortical dysplasia; tumor; vascular malformation	MRI-incompatible implants
EEG (routine) (CPT 95816)	-	URGENT	ROUTINE	-	Baseline if not done; repeat if seizure classification uncertain, new seizure type, or considering ASM withdrawal; includes awake + sleep	Epileptiform discharges; focal vs generalized; EEG normalization (favorable for ASM withdrawal)	None
ECG (12-lead) (CPT 93000)	STAT	STAT	ROUTINE	-	Baseline for QTc-prolonging ASMs (lacosamide → PR prolongation; rufinamide → QT shortening); before ASM changes; annual for lacosamide	Normal; prolonged PR → caution with lacosamide dose increases	None

2B. Extended

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Ambulatory EEG (24-72h) (CPT 95711)	-	-	ROUTINE	-	Capture events if diagnostic uncertainty; quantify interictal discharges; assess for ASM withdrawal candidacy	Seizure activity; interictal discharge frequency	Patient cooperation
DEXA bone density scan (CPT 77080)	-	-	ROUTINE	-	All patients on enzyme-inducing ASMs >2 years; all patients >50 years; any patient with fracture history	Normal T-score; osteopenia/osteoporosis → treat and modify ASM if possible	None
Pelvic ultrasound (CPT 76856)	-	-	EXT	-	Women on valproate with menstrual irregularity; screen for PCOS (valproate-associated)	Normal; polycystic ovaries → endocrinology referral; consider VPA switch	None

2C. Rare/Specialized

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI brain epilepsy protocol (3T) (CPT 70553)	-	-	EXT	-	If prior MRI was 1.5T or non-epilepsy protocol; considering surgical evaluation; unexplained worsening	Subtle lesions missed on standard MRI (FCD, small tumors)	MRI-incompatible implants
Neuropsychological testing (CPT 96132)	-	-	EXT	-	Cognitive complaints; baseline before ASM changes; evaluate ASM cognitive burden; employment/academic concerns	Cognitive profile; identify ASM-related impairment vs baseline	Active seizures may invalidate

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3. TREATMENT

3A. Acute/Emergent (Rescue Medications)

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Midazolam (Nayzilam)	IN	Seizure cluster rescue; all epilepsy patients should have rescue plan	5 mg single spray :: IN :: once PRN :: 5 mg intranasal into one nostril; may repeat x1 in 10 min; max 10 mg/episode; max 5 episodes/month; prescribe for all patients with history of clusters	Acute narrow-angle glaucoma; severe respiratory depression	Respiratory status; sedation; train caregivers on use	STAT	STAT	ROUTINE	-
Diazepam rectal (Diastat)	PR	Seizure cluster rescue; alternative to intranasal midazolam	10-20 mg based on weight :: PR :: once PRN :: 0.2 mg/kg PR; may repeat x1 in 4-12h; max 2 doses/episode; max 5 episodes/month	Acute narrow-angle glaucoma; severe hepatic impairment	Respiratory status; sedation	STAT	STAT	ROUTINE	-
Diazepam nasal (Valtoco)	IN	Seizure cluster rescue; nasal alternative	5-20 mg based on weight :: IN :: once PRN :: 5, 10, 15, or 20 mg intranasal based on weight; may repeat x1 in 4-12h; max 2 doses/episode	Acute narrow-angle glaucoma	Respiratory status; sedation	STAT	STAT	ROUTINE	-

3B. Symptomatic Treatments

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Sertraline	PO	Depression comorbidity (30-50% of epilepsy patients); does NOT lower seizure threshold; first-line antidepressant in epilepsy	25 mg daily; 50 mg daily; 100 mg daily; 200 mg daily :: PO :: daily :: Start 25 mg daily; increase by 25-50 mg q1-2wk; target 50-200 mg daily; max 200 mg	Concurrent MAOIs	Suicidality monitoring first 4 weeks; serotonin syndrome	-	ROUTINE	ROUTINE	-
Escitalopram	PO	Depression/anxiety comorbidity; well tolerated in epilepsy; does NOT lower seizure threshold	5 mg daily; 10 mg daily; 20 mg daily :: PO :: daily :: Start 5-10 mg daily; increase to 20 mg after 1 week if needed; max 20 mg	Concurrent MAOIs; QT prolongation	QTc if risk factors; suicidality monitoring	-	ROUTINE	ROUTINE	-
Venlafaxine	PO	Depression with comorbid pain syndromes; alternative when SSRIs insufficient; does NOT significantly lower seizure threshold at therapeutic doses	37.5 mg daily; 75 mg daily; 150 mg daily; 225 mg daily :: PO :: daily :: Start 37.5 mg daily (XR); increase by 75 mg q1wk; target 75-225 mg daily; max 225 mg	Uncontrolled hypertension; concurrent MAOIs; abrupt discontinuation	Blood pressure; serotonin syndrome; discontinuation syndrome (taper slowly)	-	ROUTINE	ROUTINE	-
Melatonin	PO	Sleep disturbance (sleep deprivation is major seizure trigger); mild anticonvulsant properties; safe in epilepsy	3 mg qHS; 5 mg qHS; 10 mg qHS :: PO :: QHS :: Start 3 mg 30 min before bed; may increase to 5-10 mg; use extended-release for sleep maintenance	Few contraindications	Daytime sedation; sleep quality	-	ROUTINE	ROUTINE	-
Calcium 600 mg + Vitamin D3 400-800 IU	PO	Bone health for all chronic epilepsy patients; especially enzyme-inducing ASMs	600 mg calcium + 400 IU vitamin D3 BID :: PO :: BID :: 600 mg elemental calcium + 400-800 IU vitamin D3 twice daily with meals; total daily calcium 1000-1200 mg	Hypercalcemia; kidney stones	Serum calcium; vitamin D annually; DEXA q2 years	-	ROUTINE	ROUTINE	-
Folic acid	PO	All women of childbearing potential on ASMs; neural tube defect prevention; folate depletion by enzyme-inducing ASMs	1 mg daily; 4 mg daily :: PO :: daily :: 1 mg daily for all women on ASMs; increase to 4 mg daily at least 3 months before planned conception; continue through first trimester	Few contraindications	Serum folate annually	-	ROUTINE	ROUTINE	-
Alendronate	PO	Osteoporosis (T-score ≤-2.5) or osteopenia with fracture risk in chronic epilepsy patients on enzyme-inducing ASMs	70 mg weekly :: PO :: weekly :: 70 mg PO once weekly; take first thing in morning with full glass water; remain upright 30 min; take on empty stomach	Esophageal abnormalities; inability to sit upright 30 min; hypocalcemia (correct first); CrCl <35	DEXA q2 years; serum calcium; dental exam (osteonecrosis risk with prolonged use); esophageal symptoms	-	-	ROUTINE	-
Lamotrigine dose adjustment (pregnancy)	PO	Lamotrigine levels drop 50-70% during pregnancy due to increased glucuronidation; dose increases typically needed to maintain seizure control	Individualized per levels :: PO :: monthly :: Check lamotrigine level monthly during pregnancy; increase dose to maintain pre-pregnancy level; reduce dose over 2-3 weeks postpartum (levels rebound rapidly)	Stevens-Johnson syndrome risk with rapid dose increases	Monthly lamotrigine levels during pregnancy; postpartum level within 2 weeks of delivery	-	ROUTINE	ROUTINE	-

3C. ASM Optimization (Major ASMs Individually Listed)

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Levetiracetam (Keppra)	PO, IV	Broad-spectrum ASM; first-line for focal and generalized epilepsy; no significant drug interactions; renal elimination	250 mg BID; 500 mg BID; 750 mg BID; 1000 mg BID; 1500 mg BID :: PO :: BID :: Start 250-500 mg BID; increase by 500 mg/day q1-2wk; target 1000-1500 mg BID; max 3000 mg/day; adjust for renal impairment	Hypersensitivity; end-stage renal disease (dose adjust)	Psychiatric effects (irritability, depression, behavioral change in 10-15%); renal function; consider B6 supplementation for behavioral effects	-	ROUTINE	ROUTINE	-
Lamotrigine (Lamictal)	PO	Broad-spectrum ASM; first-line for focal and generalized epilepsy; favorable cognitive and teratogenicity profile; preferred in women of childbearing potential	25 mg daily; 50 mg daily; 100 mg BID; 150 mg BID; 200 mg BID :: PO :: BID :: WITHOUT valproate: Start 25 mg daily x 2wk → 50 mg daily x 2wk → increase by 50 mg/day q1-2wk; target 100-200 mg BID; WITH valproate: Start 25 mg QOD x 2wk → 25 mg daily x 2wk → slow titration (VPA doubles LTG level); max 400 mg/day (200 mg with VPA)	Hypersensitivity; MUST titrate slowly (SJS/TEN risk with rapid titration)	SJS/TEN risk: rash in first 8 weeks → stop immediately and do not rechallenge; lamotrigine levels (especially in pregnancy); drug interactions	-	ROUTINE	ROUTINE	-
Valproate (Depakote)	PO, IV	Broad-spectrum ASM; first-line for generalized epilepsy (JME, absence); effective for multiple seizure types	250 mg BID; 500 mg BID; 750 mg BID; 1000 mg BID :: PO :: BID :: Start 250 mg BID (DR) or 500 mg ER daily; increase by 250-500 mg q1wk; target 500-1000 mg BID; max 60 mg/kg/day	TERATOGENIC — CONTRAINDICATED IN PREGNANCY (neural tube defects 1-2%, neurodevelopmental effects); hepatic disease; urea cycle disorders; mitochondrial disease (POLG mutations)	LFTs, CBC with platelets q3-6 months; ammonia if encephalopathy; weight; hair loss; tremor; PCOS screening in women	-	ROUTINE	ROUTINE	-
Oxcarbazepine (Trileptal)	PO	Focal epilepsy; better tolerated than carbamazepine; fewer drug interactions	150 mg BID; 300 mg BID; 600 mg BID; 900 mg BID :: PO :: BID :: Start 150-300 mg BID; increase by 300 mg/day q1wk; target 600-1200 mg BID; max 2400 mg/day	HLA-B*15:02 positive (SJS risk); hyponatremia	Sodium q1-3 months (SIADH in 2-3%); rash; MHD level if needed	-	ROUTINE	ROUTINE	-
Lacosamide (Vimpat)	PO, IV	Focal epilepsy adjunctive or monotherapy; well tolerated; sodium channel slow inactivation	50 mg BID; 100 mg BID; 150 mg BID; 200 mg BID :: PO :: BID :: Start 50 mg BID; increase by 50 mg/dose weekly; target 100-200 mg BID; max 400 mg/day	Second/third-degree AV block without pacemaker	ECG at baseline and dose changes; PR interval; dizziness; ataxia	-	ROUTINE	ROUTINE	-
Topiramate (Topamax)	PO	Focal and generalized epilepsy; migraine prophylaxis (dual benefit); weight loss effect	25 mg BID; 50 mg BID; 100 mg BID; 200 mg BID :: PO :: BID :: Start 25 mg daily; increase by 25-50 mg q1-2wk; target 100-200 mg BID; max 400 mg/day	Kidney stones; metabolic acidosis; acute narrow-angle glaucoma; TERATOGENIC (cleft lip/palate)	Bicarbonate (metabolic acidosis); cognitive effects ("Dopamax"); kidney stones; weight; word-finding difficulty; pregnancy test	-	ROUTINE	ROUTINE	-
Carbamazepine (Tegretol)	PO	Focal epilepsy; trigeminal neuralgia; effective but many drug interactions (enzyme inducer)	100 mg BID; 200 mg BID; 400 mg BID; 600 mg BID :: PO :: BID :: Start 100-200 mg BID; increase by 200 mg q1wk; target 400-600 mg BID; max 1600 mg/day; use extended-release	HLA-B*15:02 positive; AV block; concurrent MAOIs; bone marrow depression	CBC q3-6 months; LFTs; sodium; carbamazepine level; epoxide level if on VPA; many drug interactions (enzyme inducer)	-	ROUTINE	ROUTINE	-
Brivaracetam (Briviact)	PO, IV	Focal epilepsy; SV2A ligand; may work when levetiracetam failed; fewer psychiatric side effects than LEV	25 mg BID; 50 mg BID; 100 mg BID :: PO :: BID :: Start 25-50 mg BID; may increase to 100 mg BID; max 200 mg/day; no titration required	Hypersensitivity	Psychiatric symptoms (less frequent than LEV); hepatic function	-	ROUTINE	ROUTINE	-
Cenobamate (Xcopri)	PO	Focal epilepsy; high efficacy in drug-resistant cases; dual mechanism	12.5 mg daily; 100 mg daily; 200 mg daily; 400 mg daily :: PO :: daily :: Start 12.5 mg daily; titrate per REMS schedule over 11+ weeks to target 200 mg daily; max 400 mg; SLOW TITRATION MANDATORY	DRESS risk; QT shortening with familial short QT	ECG; DRESS monitoring (rash, fever, eosinophilia); reduce clobazam, phenytoin, phenobarbital doses	-	ROUTINE	ROUTINE	-

3D. Women's Health / Pregnancy Planning

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Folic acid (preconception)	PO	Neural tube defect prevention for ALL women of childbearing potential on ASMs; start before conception	4 mg daily :: PO :: daily :: 4 mg daily starting at least 3 months before planned conception; continue through first trimester; 1 mg daily maintenance otherwise	None	Few	Serum folate; neural tube screening ultrasound	-	-	ROUTINE	-
Levonorgestrel IUD (Mirena/Liletta)	IUD	Reliable contraception for women on enzyme-inducing ASMs; NOT affected by enzyme induction (unlike oral contraceptives)	N/A — device placement :: IUD :: once :: Place levonorgestrel IUD for reliable contraception; efficacy NOT reduced by enzyme-inducing ASMs; preferred over oral contraceptives for women on phenytoin, carbamazepine, phenobarbital, topiramate >200 mg	PID; uterine anomaly; pregnancy	Placement confirmation; string check annually	-	-	ROUTINE	-
Copper IUD (Paragard)	IUD	Non-hormonal contraception; alternative when hormonal methods not desired; NOT affected by ASMs	N/A — device placement :: IUD :: once :: Place copper IUD; completely unaffected by ASM interactions; non-hormonal option	Same as hormonal IUD	Same as hormonal IUD; heavier menses	-	-	ROUTINE	-
Vitamin K (neonatal prophylaxis)	IM	Neonates born to mothers on enzyme-inducing ASMs at increased risk of hemorrhagic disease of newborn	1 mg IM at birth :: IM :: once :: 1 mg vitamin K IM to neonate at delivery; standard of care but especially critical with maternal enzyme-inducing ASMs	None	None needed beyond standard neonatal care	-	ROUTINE	-	-

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4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	ED	HOSP	OPD	ICU
Neurology follow-up every 3-6 months for seizure-free patients; every 1-3 months during ASM changes or if not well controlled	-	ROUTINE	ROUTINE	-
Comprehensive epilepsy center referral if seizures persist despite two or more appropriately chosen ASMs (meets ILAE definition of drug-resistant epilepsy)	-	URGENT	ROUTINE	-
Psychiatry referral for depression or anxiety screening positive (PHQ-9 ≥10 or GAD-7 ≥10); psychiatric comorbidities affect seizure control and quality of life	-	ROUTINE	ROUTINE	-
Reproductive endocrinology or OB/GYN referral for preconception counseling in women of childbearing potential; ASM teratogenicity review and optimization before pregnancy	-	-	ROUTINE	-
Neuropsychological testing referral for cognitive complaints potentially related to ASMs; baseline assessment before surgery evaluation or ASM changes	-	-	ROUTINE	-
Endocrinology referral for metabolic bone disease (osteoporosis on DEXA); PCOS in women on valproate; testosterone deficiency in men on enzyme-inducing ASMs	-	-	ROUTINE	-
Social work for disability documentation, vocational rehabilitation, insurance assistance, and community support services	-	ROUTINE	ROUTINE	-
Driving evaluation by state DMV and neurology documentation of seizure-free interval per state requirements; commercial driving restrictions per federal DOT regulations	-	-	ROUTINE	-
Ophthalmology referral for patients on vigabatrin (visual field testing q3 months) or any patient with visual complaints	-	-	ROUTINE	-

4B. Patient Instructions

Recommendation	ED	HOSP	OPD
Take ASMs at the same time every day; use pill organizers and phone alarms; missing even one dose increases seizure risk — contact neurologist if unable to afford or obtain medications	ROUTINE	ROUTINE	ROUTINE
Maintain consistent sleep schedule with 7-9 hours nightly; sleep deprivation is the strongest modifiable seizure trigger; avoid shift work if possible	-	ROUTINE	ROUTINE
Do not stop ASMs abruptly; sudden discontinuation can trigger status epilepticus even in well-controlled patients — always taper under neurologist guidance	ROUTINE	ROUTINE	ROUTINE
Return to ED immediately if seizure lasts >5 minutes, multiple seizures without recovery, seizure in water, significant injury during seizure, or first seizure in pregnancy	STAT	STAT	ROUTINE
Do not drive until seizure-free for state-mandated period (typically 3-12 months); report seizures to neurologist for driving documentation; commercial driving has stricter federal requirements	-	ROUTINE	ROUTINE
Women of childbearing potential: use reliable contraception (IUD preferred over oral contraceptives if on enzyme-inducing ASMs); notify neurologist BEFORE planning pregnancy for medication optimization	-	ROUTINE	ROUTINE
Inform all prescribing doctors and pharmacists about epilepsy and ASMs before starting new medications; many drugs interact with ASMs (antibiotics, antidepressants, pain medications)	-	ROUTINE	ROUTINE
Avoid excessive alcohol (alcohol withdrawal and binge drinking lower seizure threshold); if consuming alcohol, limit to 1 drink maximum with food	-	ROUTINE	ROUTINE
Carry medical alert identification (bracelet or app) with epilepsy diagnosis and medications listed	-	ROUTINE	ROUTINE

4C. Lifestyle & Prevention

Recommendation	ED	HOSP	OPD
Regular aerobic exercise (30 minutes, 5 days/week) improves seizure control, mood, and cardiovascular health; no restriction on exercise type unless frequent tonic/drop seizures (avoid swimming alone, climbing)	-	ROUTINE	ROUTINE
Stress reduction through regular exercise, mindfulness, cognitive behavioral therapy; chronic stress is an independent seizure trigger	-	-	ROUTINE
Weight management: topiramate and zonisamide may help with weight loss; valproate and pregabalin may cause weight gain — consider when selecting ASMs	-	-	ROUTINE
Bone health: weight-bearing exercise, calcium and vitamin D supplementation, DEXA screening, and bisphosphonate if osteoporotic — especially critical for patients on enzyme-inducing ASMs	-	-	ROUTINE
Home safety: shower instead of baths, avoid locked bathroom doors, use stove guards, microwave preferred over stovetop, carpeted floors reduce injury risk during falls	-	ROUTINE	ROUTINE
SUDEP awareness: discuss SUDEP risk openly; optimizing seizure control is the best prevention; nocturnal supervision and seizure detection devices reduce risk	-	ROUTINE	ROUTINE

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5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Psychogenic non-epileptic seizures (PNES)	Waxing/waning; eyes closed; pelvic thrusting; asynchronous limb movements; duration >2 min; lack of postictal confusion; may coexist with epilepsy	Video-EEG monitoring; postictal prolactin (normal in PNES)
Syncope (vasovagal, cardiac)	Triggered by standing, heat, emotion; brief convulsive movements possible (convulsive syncope); rapid recovery	ECG; tilt table; Holter; echocardiogram
Cardiac arrhythmia	Sudden LOC without warning; palpitations; family history of sudden cardiac death	ECG; Holter; event monitor; cardiac MRI
Sleep disorders (narcolepsy, parasomnia)	Episodes during sleep; cataplexy; sleep paralysis; REM behavior disorder	Polysomnography; MSLT
Panic attacks	Anxiety; hyperventilation; palpitations; derealization; preserved consciousness; gradual onset	EEG (normal during events); psychiatric evaluation
Transient ischemic attack	Focal neurologic deficit; vascular risk factors; abrupt onset; negative symptoms (weakness, numbness) vs positive (seizure movements)	MRI/DWI; MRA; carotid imaging
Migraine with aura	Visual aura (positive phenomena spreading over minutes); headache follows; duration 5-60 min	Clinical history; EEG during episodes (normal)

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6. MONITORING PARAMETERS

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
ASM trough levels	Each OPD visit; 2 weeks after dose change; with breakthrough seizures	Individual therapeutic level	Adjust dose; assess adherence; check drug interactions	STAT	STAT	ROUTINE	-
CBC with differential	Baseline; q6 months first year; annually	WBC >3500; platelets >100K	Low counts → evaluate ASM cause; felbamate: any cytopenia → stop	-	ROUTINE	ROUTINE	-
CMP (LFTs, renal function)	Baseline; q6 months first year; annually	Normal ALT/AST; normal creatinine	LFTs >3x ULN → evaluate; adjust renally-cleared ASMs	-	ROUTINE	ROUTINE	-
Sodium	Baseline; q3 months for OXC/CBZ/ESL; annually otherwise	135-145 mEq/L	<130 → fluid restrict; consider ASM change; <125 → urgent correction	STAT	ROUTINE	ROUTINE	-
Vitamin D, 25-OH	Annually	>30 ng/mL	Deficient → supplement 2000-5000 IU/day; recheck 3 months	-	-	ROUTINE	-
DEXA bone density	Baseline if >2 years on enzyme-inducing ASMs or >50; q2 years	T-score >-1.0	Osteopenia → supplement + exercise; osteoporosis → bisphosphonate	-	-	ROUTINE	-
Seizure frequency (diary)	Every visit	Seizure-free or decreasing	Persistent seizures → optimize ASM; refer for DRE evaluation	-	ROUTINE	ROUTINE	-
PHQ-9 (depression screening)	Every visit	<5	≥10 → psychiatry referral; evaluate ASM contribution	-	-	ROUTINE	-
Pregnancy test	Annually for women of childbearing potential; before ASM changes	Negative	Positive → urgent ASM safety review; OB referral	-	ROUTINE	ROUTINE	-
ECG	Baseline for lacosamide; annually if on QT-affecting ASMs	Normal PR; normal QTc	PR >220 ms → reduce lacosamide; QT shortening → evaluate	STAT	ROUTINE	ROUTINE	-
Weight	Every visit	Stable	Significant gain (VPA, pregabalin) → dietary counseling; consider ASM with weight-neutral or loss profile	-	ROUTINE	ROUTINE	-
Lipid panel	Annually for enzyme-inducing ASMs	Normal	Elevated → statin; consider ASM switch	-	-	ROUTINE	-

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7. DISPOSITION CRITERIA

Disposition	Criteria
Routine outpatient follow-up (q6 months)	Well-controlled seizures (seizure-free >6 months); stable ASM doses; no side effects; labs stable
More frequent follow-up (q1-3 months)	Recent ASM change; not yet seizure-free; new comorbidity; pregnancy planning; first year of treatment
Admit to hospital	Breakthrough seizure cluster; ASM toxicity requiring monitoring; inability to take oral medications; seizure-related injury
Admit to EMU	Presurgical evaluation; diagnostic uncertainty (epileptic vs PNES); seizure classification needed
Refer to comprehensive epilepsy center	Meets DRE criteria (failed 2+ ASMs); candidate for surgical evaluation; complex ASM management
ASM withdrawal consideration	Seizure-free ≥2 years; normal EEG; MRI normal or stable; patient preference after risk-benefit discussion; recurrence risk ~35% overall (higher with abnormal EEG, known lesion, JME)

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8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
Lamotrigine and levetiracetam first-line for focal epilepsy; valproate first-line for generalized	Class I evidence (RCTs)	Marson et al. Lancet 2021 (SANAD II)
Valproate should be avoided in women of childbearing potential due to teratogenicity and neurodevelopmental effects	Class I evidence; Regulatory guidance	Tomson et al. Lancet Neurol 2018 (EURAP)
ASM withdrawal after 2+ seizure-free years: ~35% recurrence risk; abnormal EEG and known etiology increase risk	Class I evidence (systematic review)	Lamberink et al. Lancet Neurol 2017
Depression and anxiety highly prevalent in epilepsy; SSRIs safe and do not worsen seizures	Class II evidence; Guideline	Mula et al. Epilepsia 2017
SUDEP risk reduction: optimize seizure control, nocturnal supervision, avoid prone sleeping	AAN Practice Guideline	Harden et al. Neurology 2017
Enzyme-inducing ASMs reduce bone mineral density; screening and supplementation recommended	Class II evidence	Vestergaard. Acta Neurol Scand 2005
Enzyme-inducing ASMs reduce oral contraceptive efficacy; IUDs recommended	Class III evidence; Guideline	Reimers. Seizure 2015
Lamotrigine levels decrease 50-70% during pregnancy; monthly monitoring recommended	Class II evidence	Pennell et al. Neurology 2008
Refer drug-resistant epilepsy for surgical evaluation; surgery superior to continued medical therapy for mesial TLE	Class I evidence (RCT)	Wiebe et al. NEJM 2001
Seizure diary improves seizure reporting accuracy and patient engagement	Expert consensus	Expert consensus; standard clinical practice

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CHANGE LOG

v1.0 (January 31, 2026) - Initial template creation - Comprehensive chronic epilepsy management covering routine monitoring, ASM optimization, comorbidity management, women's health, bone health, and lifestyle - Major ASMs individually listed with complete prescribing information - Women's health section including pregnancy planning, contraception, and ASM teratogenicity

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APPENDIX A: ASM Therapeutic Level Ranges

ASM	Therapeutic Range	Key Notes
Carbamazepine	4-12 mcg/mL	Check epoxide with VPA; enzyme inducer
Clobazam	30-300 ng/mL	N-desmethylclobazam 300-3000 ng/mL
Eslicarbazepine	3-35 mcg/mL (as licarbazepine)	Monitor sodium
Lacosamide	1-10 mcg/mL	PR interval monitoring
Lamotrigine	2.5-15 mcg/mL	Drops 50-70% in pregnancy; doubled by VPA
Levetiracetam	12-46 mcg/mL	Wide therapeutic index; renal dosing
Oxcarbazepine (MHD)	3-35 mcg/mL	Monitor sodium (SIADH)
Phenobarbital	15-40 mcg/mL	Enzyme inducer; sedation
Phenytoin (total)	10-20 mcg/mL	Nonlinear kinetics; check free level
Phenytoin (free)	1-2 mcg/mL	Use in low albumin, renal failure, pregnancy
Topiramate	5-20 mcg/mL	Metabolic acidosis; cognitive effects
Valproate (total)	50-100 mcg/mL	Check free level if low albumin; teratogenic
Valproate (free)	5-15 mcg/mL	Active fraction
Zonisamide	10-40 mcg/mL	Long half-life (63h)
Brivaracetam	0.2-2.0 mcg/mL	Clinical response is primary guide
Cenobamate	Not well established	Dose by clinical response; slow titration

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APPENDIX B: ASM Teratogenicity Risk

ASM	Teratogenicity Risk	Major Malformation Rate	Key Risks	Recommendation
Valproate	HIGHEST RISK	9-11%	Neural tube defects (1-2%); neurodevelopmental impairment (30-40%); lower IQ	AVOID in women of childbearing potential unless no alternative
Topiramate	HIGH	4-9%	Cleft lip/palate (3x baseline risk); SGA infants	Avoid if possible; folic acid 4 mg
Phenobarbital	HIGH	5-7%	Cardiac defects; cleft palate; cognitive effects	Avoid in pregnancy
Phenytoin	MODERATE	3-7%	Fetal hydantoin syndrome; cardiac defects; cleft palate	Avoid if possible
Carbamazepine	MODERATE	3-5%	Neural tube defects (0.5-1%); cardiac defects	Acceptable if no alternative; folic acid 4 mg
Oxcarbazepine	LOW-MODERATE	2-3%	Limited data; extrapolated from CBZ	Acceptable option
Lamotrigine	LOW	2-3%	Cleft palate (slightly elevated at >200 mg/dose)	PREFERRED in pregnancy; monitor levels monthly
Levetiracetam	LOW	1-2%	No consistent pattern; favorable data	PREFERRED in pregnancy
Lacosamide	INSUFFICIENT DATA	Unknown	Limited pregnancy registry data	Use with caution
Brivaracetam	INSUFFICIENT DATA	Unknown	Very limited pregnancy data	Use with caution

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APPENDIX C: ASM Withdrawal Protocol

Eligibility criteria for ASM withdrawal: - Seizure-free ≥2 years (≥5 years preferred for lower recurrence risk) - Normal or normalized EEG (abnormal EEG doubles recurrence risk) - Normal MRI or stable known lesion - Not juvenile myoclonic epilepsy (lifelong treatment typically needed) - Patient informed of recurrence risk and driving implications - Patient preference after shared decision-making

Withdrawal protocol: 1. Taper one ASM at a time (if on polytherapy) 2. Reduce by 25% of dose every 2-4 weeks 3. Total taper period: 2-6 months depending on ASM and dose 4. Monitor with EEG before and during taper 5. Stop driving during taper and for state-mandated period after last dose 6. If seizure recurs → restart ASM at last effective dose; typically regain control

Recurrence risk factors: - Abnormal EEG before withdrawal: 2x risk - Known structural lesion: 2x risk - Juvenile myoclonic epilepsy: >90% recurrence - Longer seizure-free period: lower risk - Monotherapy at withdrawal: lower risk than polytherapy