Neurology · Topic 11 of 22

Seizures & Antiseizure Medications

Neurology · seizures

Seizures & Antiseizure Medications

After a first seizure, look for a provoking cause, image and get an EEG — and start an antiseizure drug only when recurrence risk justifies it.

Key numbers

Epilepsy: 2 unprovoked seizures2 seizures > 24 h apart

First unprovoked seizure: individualize starting a drug21–45% recur in 2 yr

Phenytoin level 10–20 mcg/mL10–20 mcg/mL

Seizure over 5 minutes: give IV benzodiazepine> 5 min

01 · Defined byEpilepsy: 2 unprovoked seizures

Epilepsy = at least 2 unprovoked seizures more than 24 hours apart, or 1 unprovoked seizure with a recurrence risk of at least 60% over 10 years, or a diagnosed epilepsy syndrome (ILAE).

02 · Don't confuseProvoked seizure: treat the cause, not epilepsy

A provoked (acute symptomatic) seizure occurs within 1 week of stroke, TBI, anoxia or neurosurgery, or with CNS infection, severe metabolic derangement, intoxication or withdrawal — correct the cause; long-term antiseizure drugs are usually unnecessary.

03 · The numberPhenytoin level 10–20 mcg/mL

Therapeutic total phenytoin is 10–20 mcg/mL (free 1–2 mcg/mL); with hypoalbuminemia, kidney or liver disease, order a free (unbound) level because the total level underestimates active drug.

What it is

Core idea

Phenytoin has saturable (zero-order) metabolismPhenytoin metabolism (CYP2C9) saturates in the upper range, so small dose increases or CYP inhibitors can raise levels disproportionately — adjust in small steps and recheck levels.

Presentation

What you'll see

Tongue bite and postictal confusion favor seizureAfter loss of consciousness, a bitten tongue, incontinence or prolonged confusion suggests seizure; brief myoclonic jerks also occur with syncope or ventricular arrhythmia, so get an ECG.

Diagnosis & monitoring

Work-up

Dose to seizure control, not to the levelThe right dose is the lowest that stops seizures without adverse effects; levels are guides — check them for suspected toxicity, nonadherence, breakthrough seizures or a new interacting drug.

Do right now

In this order

First moves

Seizure over 5 minutes: give IV benzodiazepine> 5 min

→

Tongue bite and postictal confusion favor seizure

→

First seizure: neuroimaging, EEG, glucose and electrolytes

→

Provoked seizure: treat the cause, not epilepsy

→

First unprovoked seizure: individualize starting a drug21–45% recur in 2 yr

Why each step

Seizure over 5 minutes: give IV benzodiazepineA seizure lasting more than 5 minutes needs drug termination: IV lorazepam 0.1 mg/kg (max 4 mg per dose, may repeat once), then a longer-acting second agent (fosphenytoin, levetiracetam or valproate) — see Status Epilepticus.

First seizure: neuroimaging, EEG, glucose and electrolytesEvaluate a new-onset seizure with brain imaging (CT now, MRI to follow if CT is negative), an EEG, and labs — glucose, sodium, calcium, magnesium, phosphate, renal and liver tests.

Provoked seizure: treat the cause, not epilepsyA provoked (acute symptomatic) seizure occurs within 1 week of stroke, TBI, anoxia or neurosurgery, or with CNS infection, severe metabolic derangement, intoxication or withdrawal — correct the cause; long-term antiseizure drugs are usually unnecessary.

First unprovoked seizure: individualize starting a drugAfter a first unprovoked seizure, recurrence risk is 21–45% over 2 years; immediate treatment lowers 2-year recurrence but not long-term remission, so most patients start an antiseizure drug after a second seizure.

Management

Orders

Fosphenytoin no faster than 150 mg PE/minLoad fosphenytoin 15–20 mg PE/kg IV no faster than 150 mg PE/min with continuous ECG and blood pressure monitoring — rapid infusion causes severe hypotension and arrhythmias.

Valproate: hepatotoxicity, pancreatitis, hyperammonemiaValproate (level 50–100 mcg/mL) carries boxed warnings for hepatotoxicity, pancreatitis and fetal harm; it can cause hyperammonemic encephalopathy, so check ammonia in a confused patient taking it.

Carbamazepine: screen HLA-B*1502, watch sodiumBefore carbamazepine, screen patients of Asian ancestry for HLA-B*1502 (SJS/TEN risk); it causes SIADH-type hyponatremia (as does oxcarbazepine) and carries a boxed warning for aplastic anemia and agranulocytosis.

Levetiracetam: renal dosing, mood and behavior effectsLevetiracetam has few drug interactions and is dosed by creatinine clearance; watch for irritability, mood change, behavioral abnormalities and psychosis.

Red flags & don'ts

Avoid harm

Phenytoin toxicity: nystagmus, then ataxia, then lethargy complicationPhenytoin toxicity rises with level: lateral-gaze nystagmus usually near 20 mcg/mL, ataxia near 30 mcg/mL, dysarthria and lethargy above 40 mcg/mL — individual thresholds vary widely.

Carbapenems drop valproate to subtherapeutic levels interactionCarbapenems (meropenem, imipenem, ertapenem) can drop valproate levels below therapeutic and cause breakthrough seizures — choose another antibiotic or bridge with a different antiseizure drug.

Phenytoin, carbamazepine, phenobarbital induce CYP450 interactionPhenytoin, carbamazepine and phenobarbital induce CYP450 and lower levels of oral contraceptives, anticoagulants, antiretrovirals, chemotherapy and other antiseizure drugs; long-term use also lowers vitamin D.

Valproate doubles lamotrigine levels — titrate slowly interactionValproate more than doubles lamotrigine levels; combined use or fast titration raises the risk of lamotrigine's boxed-warning rash (Stevens-Johnson syndrome), so follow the slower titration schedule.

Epileptic seizure or functional (psychogenic) seizure?

Commonly confused

Movements	Tonic phase, then clonic phase
Duration	Usually remits within minutes
Eyes	No active resistance
Afterward	Postictal confusion; tongue bite, incontinence
Best test	EEG (a normal EEG does not exclude it)

Teach & follow up

Patient education

Avoid valproate when pregnancy is possibleAvoid valproate in patients who could become pregnant (neural tube defects, lower IQ); give folic acid to all of childbearing potential on antiseizure drugs — lamotrigine carries lower teratogenic risk.

More detail

Reference

Show 5 reference facts

Counsel no driving, swimming alone, climbing, power tools or tub bathing until seizures are controlled; most US states allow driving after 6–12 months seizure-free, and a few require physician reporting.

Drug-resistant epilepsy (failure of 2 adequate antiseizure drug trials) warrants referral to an epilepsy center for surgery evaluation; tapering may be considered after at least 2 seizure-free years.

After a first seizure, a routine EEG shows epileptiform abnormalities in about 23% and imaging is significantly abnormal in about 10%; a normal EEG does not exclude epilepsy.

Alcohol withdrawal seizures are not treated with antiseizure drugs — treating the withdrawal syndrome, usually with a benzodiazepine, prevents them.

Seizure prophylaxis after significant TBI lowers early (first-week) seizures but not later epilepsy and is stopped after 1 week unless seizures occur.

Pearl

A provoked seizure needs its cause fixed, not a lifelong antiseizure drug.

Sources · Merck Manual Professional — Seizure Disorders (Mar 2026) · Merck Manual Professional — Antiseizure Medications (Mar 2026) · Krumholz A et al. Evidence-based guideline: Management of an unprovoked first seizure in adults (AAN/AES). Neurology 2015;84:1705–1713 · Krumholz A et al. Practice parameter: Evaluating an apparent unprovoked first seizure in adults (AAN/AES). Neurology 2007;69:1996–2007 · Fisher RS et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55:475–482 · Beghi E et al. Recommendation for a definition of acute symptomatic seizure (ILAE). Epilepsia 2010;51:671–675 · Dilantin (extended phenytoin sodium) prescribing information — DailyMed · Cerebyx (fosphenytoin sodium) injection prescribing information — DailyMed · Depakote (divalproex sodium) prescribing information — DailyMed (rev. 3/2026) · Tegretol (carbamazepine) prescribing information — DailyMed · Lamictal (lamotrigine) prescribing information — DailyMed · Keppra (levetiracetam) prescribing information — DailyMed · American Epilepsy Society — Proposed Algorithm for Convulsive Status Epilepticus (2016 guideline chart) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).