Seizure Management

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Status Epilepticus

Management of Convulsive Status Epilepticus

Adult emergency pathway: treat ongoing convulsions at 5 minutes, or recurrent convulsions without recovery. Include treatment already given before arrival.

Use this as the emergency entry point: stabilize, give benzodiazepine therapy early, load a second-line ASM if convulsions continue, and escalate promptly if adequately dosed initial treatments fail. The time ranges below are targets, not waiting periods.

ENLS 5.0 Protocol

t₁ = 5 minutes: treat now. t₂ = 30 minutes: lasting injury becomes likely. Refractory status begins when a benzodiazepine and one second-line ASM fail.

Convulsive status: the times are targets, not waiting periods. If the patient does not return toward baseline after the movements stop, get an urgent EEG for nonconvulsive seizures.

0–5 min

Stabilize

ABCs, vitals, seizure onset time
IV access, ECG, finger-stick glucose
Treat hypoglycemia immediately with IV dextrose (or IM glucagon if no IV). Give thiamine before or with glucose when deficiency is suspected; never delay glucose.

5–10 min

Benzodiazepine

Lorazepam 0.1 mg/kg IV, max 4 mg; may repeat once
If no IV: midazolam 10 mg IM for adults; intranasal/buccal alternatives follow age- and weight-based protocol
Diazepam 0.15–0.2 mg/kg IV, max 10 mg

10–30 min

Load ASM

Fosphenytoin 20 mg PE/kg, max 1500 mg PE
Valproate 40 mg/kg, max 3000 mg
Levetiracetam 60 mg/kg, max 4500 mg

If two treatments fail

Refractory SE

Ongoing seizures after adequate benzodiazepine + one second-line ASM
Urgent neurocritical care, airway support, anesthetic infusion and continuous EEG
Do not wait for 30 minutes; treat the cause in parallel

After the movements stop: persistent impaired consciousness can reflect ongoing nonconvulsive seizures. Arrange urgent EEG when the patient does not return toward baseline. The anesthetic pathway above addresses refractory convulsive status; other electrographic patterns require clinical interpretation.

Doses and treatment sequence: ENLS status epilepticus protocol and ESETT trial. Reviewed September 2026; use the local emergency protocol for administration and monitoring.

Clinical details, status definitions, and reference cards

Clinical Reference Cards

Courtesy of Dr. Gena Ghearing

Ictal Interictal Continuum (IIC) Card Management Protocol

Status Epilepticus Pocket Reference Card

When does a seizure become status? t₁ and t₂

The “five minute rule” is not a rule about seizures in general — it is t₁ for convulsive status only. The ILAE 2015 operational definition sets two separate clocks, and they differ by seizure type:

t₁ — the point beyond which the seizure is unlikely to stop on its own. This is when emergency treatment starts.
t₂ — the point beyond which long-term consequences become likely: neuronal injury and death, and altered neuronal networks. This is what you are racing.

Type of status epilepticus	t₁ — treat now	t₂ — risk of lasting injury
Tonic–clonic (convulsive)	5 minutes	30 minutes
Focal with impaired consciousness	10 minutes	> 60 minutes
Absence status	10–15 minutes	Unknown

Use the clocks correctly: these operational estimates vary by seizure type and do not establish a safe waiting period. Clinical deterioration, recurrent seizures without recovery, or uncertain onset requires prompt assessment and treatment. The time associated with injury is less certain in nonconvulsive status.

Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus — Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56(10):1515–23.

Detailed Time-Based Protocol

Phase	Time Range	Intervention & Dosing
Stabilization Phase	0–5 minutes	ABCs (Airway, Breathing, Circulation) Record seizure onset and monitor vitals Establish IV access ECG monitoring Check point-of-care glucose. Below 60 mg/dL, give IV dextrose at once (IM glucagon without IV access); add thiamine before or with glucose when deficiency is suspected, but never delay glucose.
Initial Therapy Phase	5–10 minutes	IV Lorazepam: 0.1 mg/kg, max 4 mg (may repeat once) OR Midazolam 10 mg IM for adults when IV access is not immediately available OR IV Diazepam: 0.15–0.2 mg/kg, max 10 mg (may repeat once)
Second-line Therapy	10–30 minutes	Fosphenytoin 20 mg PE/kg, infuse up to 150 mg PE per minute, maximum 1,500 mg PE; or Phenytoin 20 mg/kg, infuse up to 50 mg per minute. Continuous ECG and blood pressure monitoring. OR IV Valproic Acid: 40 mg/kg, max 3000 mg/dose, single dose OR IV Levetiracetam: 60 mg/kg, max 4500 mg/dose, single dose If none available, consider IV Phenobarbital: 15 mg/kg, single dose
Refractory Therapy	After adequate benzodiazepine + second-line ASM fail; do not wait for 30 minutes	Urgently involve neurocritical care; secure the airway when ongoing convulsions, impaired ventilation, or continuous-infusion therapy requires it Initiate continuous infusion therapy: Use a protocolized continuous infusion such as midazolam or propofol with continuous EEG and cardiorespiratory monitoring; loading, titration, treatment target, and duration must follow the local neurocritical-care protocol Add a second ASM (options: fosphenytoin, valproic acid, levetiracetam, lacosamide, or phenobarbital)
Breakthrough/Recurrence	N/A	Confirm recurrent electrographic seizure activity on raw EEG, reassess confounders and the treatment target, then titrate or change therapy using the local protocol Address underlying cause of seizures If super refractory SE, consider additional continuous infusion: Ketamine may be considered by a neurocritical-care team; dosing, contraindications, and monitoring vary by protocol and evidence base
Additional Therapies	N/A	Ketogenic diet Phenobarbital: 15–20 mg/kg Pentobarbital: 5–15 mg/kg then 0.5–5 mg/kg/h Etiology-directed immunotherapy when autoimmune or inflammatory status is suspected Epilepsy surgery Other rescue approaches such as therapeutic hypothermia or ECT have limited evidence and should be restricted to expert multidisciplinary consideration

Anti-Seizure Medications

Antiseizure medications by mechanism Sodium-channel blockers can aggravate absence and myoclonic seizures and worsen Dravet syndrome.

Sodium channel
- phenytoin
- carbamazepine
- oxcarbazepine
- eslicarbazepine
- lamotrigine
- rufinamide
- zonisamide
- topiramate
Slow sodium inactivation
- lacosamide (distinct from the fast-inactivation drugs)
Calcium channel
- ethosuximide (T‑type)
- valproate (T‑type)
- gabapentin
- pregabalin (both bind the α2δ subunit)
GABA enhancement
- benzodiazepines
- clobazam
- phenobarbital
- primidone
- tiagabine (blocks GABA reuptake)
- vigabatrin (inhibits GABA transaminase)
SV2A binding
- levetiracetam
- brivaracetam (also blocks sodium channels)
AMPA antagonist
- perampanel (the only marketed AMPA antagonist)
Multiple or other
- valproate
- topiramate
- felbamate (also NMDA)
- cenobamate (sodium channel and GABA‑A)
- cannabidiol
Disease-specific
- everolimus (mTOR inhibitor; tuberous sclerosis complex)
- ganaxolone (extrasynaptic GABA‑A; CDKL5 deficiency disorder)
- fenfluramine (serotonin; Dravet syndrome)

Each drug is listed by its main mechanism; several act in more than one way. Board Review has an interactive map of where each drug acts.

This rapid reference includes abbreviated adult epilepsy dosing, common adverse effects, and laboratory intervals when applicable. Some entries are syndrome-specific, adjunctive, rescue, or off-label uses rather than interchangeable maintenance regimens.

Medication	Mechanism / Target	Abbreviated Adult Epilepsy Dosing	Common Side Effects	Common Laboratory Reference Range*
Acetazolamide	Carbonic anhydrase inhibitor	Oral: 375–1000 mg/day (divided doses)	Paresthesias, fatigue, taste alteration, acidosis, kidney stones	N/A
Brivaracetam	SV2A ligand — higher affinity and more selective than levetiracetam	Oral or IV: 50–200 mg/day (in 2 divided doses)	Drowsiness, dizziness, fatigue, irritability	N/A
Carbamazepine	Sodium channel blockade (fast inactivation)	Oral: 800–1200 mg/day (in 2–4 divided doses; range ~400–1600 mg)	Dizziness, drowsiness, diplopia, ataxia, hyponatremia, leukopenia; serious rash including SJS/TEN (HLA-B15:02 screening recommended before initiation for patients with ancestry in populations where HLA-B15:02 is common; consider HLA-A*31:01 risk according to ancestry and local guidance)	4–12 µg/mL
Cannabidiol (Dravet, LGS, or TSC-associated seizures)	Not fully defined — GPR55 antagonism, TRPV1 desensitisation, adenosine reuptake inhibition. Not a CB1 agonist	Oral: target 10 mg/kg/day for Dravet/LGS (maximum 20 mg/kg/day); target 25 mg/kg/day for TSC, divided BID	Diarrhea, fatigue, decreased appetite, somnolence; raised transaminases, especially with valproate (check liver tests before and during treatment)	N/A
Cenobamate	Dual: inhibits the persistent sodium current and positively modulates GABA-A at a non-benzodiazepine site	Oral: 200 mg/day (after gradual titration; max 400 mg/day)	Dizziness, somnolence, fatigue, headache, nausea; DRESS with fast titration; shortens the QT interval (contraindicated in familial short-QT syndrome)	No established therapeutic target
Clobazam (adjunct for LGS)	1,5-benzodiazepine — positive allosteric GABA-A modulator (the other benzodiazepines used for seizures are 1,4-benzodiazepines)	Oral: 10–40 mg/day (usually divided BID)	Sedation, drowsiness, drooling	Clobazam 30–300 ng/mL; N-desmethylclobazam 300–3000 ng/mL
Clorazepate	Benzodiazepine prodrug → nordiazepam; positive allosteric GABA-A modulator	Oral: 15–90 mg/day (divided doses)	Drowsiness, dizziness, fatigue, ataxia	N/A
Clonazepam (rarely used long-term)	Benzodiazepine — positive allosteric GABA-A modulator	Initial dose should not exceed 1.5 mg/day divided TID; titrate individually. Labeled maximum 20 mg/day.	Sedation, drowsiness, cognitive impairment, tolerance	N/A
Diazepam	Benzodiazepine — positive allosteric GABA-A modulator	Oral: 4–40 mg/day (divided doses). IV or IM for status epilepticus (labeled adjunct): 5–10 mg, IV preferred, repeated at 10–15 minute intervals to a maximum of 30 mg (the protocol above uses 0.15–0.2 mg/kg, maximum 10 mg). Rectal gel or nasal spray (Valtoco) for seizure clusters: 0.2 mg/kg at 12 years and older (0.3 mg/kg at 6–11 years, 0.5 mg/kg at 2–5 years), rounded to the unit dose; a second dose may follow 4–12 hours later.	Sedation, fatigue, ataxia, muscle weakness; venous thrombosis and phlebitis at the IV injection site; somnolence after the rectal gel	N/A
Eslicarbazepine acetate	Prodrug → eslicarbazepine; sodium channel blockade, stabilizing the inactivated state	Oral: 800–1600 mg/day (usually once daily)	Dizziness, headache, diplopia, somnolence	N/A
Ethosuximide	T-type calcium channel blockade in thalamocortical relay neurons	Oral: start 500 mg/day and titrate; doses above 1500 mg/day require strict medical supervision (absence seizures)	Nausea, vomiting, lethargy, headache, weight loss	40–100 µg/mL
Everolimus (TSC associated seizures)	mTOR inhibitor — targets the pathway disrupted in tuberous sclerosis	Oral: Titrated to trough 5–15 ng/mL	Stomatitis, infections, rash, fatigue	5–15 ng/mL
Felbamate (rarely used – toxicity)	NMDA receptor blockade (channel block, favoring GluN2B-containing receptors), plus sodium channel blockade and GABA-A potentiation	Oral: 1200–3600 mg/day (divided TID–QID)	Sedation, nausea, vomiting, risk of aplastic anemia/liver failure	N/A
Fenfluramine	Serotonin release and 5-HT receptor agonism (notably 5-HT2C), with sigma-1 receptor modulation	Oral solution: 0.1 mg/kg BID initially; up to 0.35 mg/kg BID (maximum 26 mg/day). Lower maximum with stiripentol plus clobazam.	Decreased appetite, somnolence, diarrhea, fatigue; boxed warning requires echocardiographic monitoring for valvular heart disease and pulmonary arterial hypertension	No established therapeutic target
Fosphenytoin (parenteral only)	Water-soluble prodrug of phenytoin; voltage-dependent sodium channel blockade. Dosed in phenytoin sodium equivalents (PE): 1.5 mg fosphenytoin = 1 mg PE	IV for generalized tonic–clonic status epilepticus: loading 15–20 mg PE/kg at 100–150 mg PE/min. Non-emergent loading: 10–20 mg PE/kg IV or IM; maintenance 4–6 mg PE/kg/day in divided doses. Also labeled for seizures during neurosurgery and as a short-term substitute for oral phenytoin. Infusion must not exceed 150 mg PE/min (boxed warning).	Pruritus, nystagmus, dizziness, somnolence, ataxia; hypotension and cardiac arrhythmias with rapid infusion (cardiac monitoring during and after the infusion)	As phenytoin: total 10–20 µg/mL, unbound 1–2 µg/mL; do not measure until conversion is complete (about 2 h after an IV infusion, 4 h after IM)
Gabapentin (adjunctive therapy for focal seizures)	Binds the alpha-2-delta subunit of voltage-gated calcium channels. Despite the name, not a GABA agonist	Oral: 900–3600 mg/day (divided TID)	Dizziness, somnolence, peripheral edema, ataxia	N/A
Ganaxolone (CDKL5 deficiency)	Neuroactive steroid — positive allosteric modulator of synaptic and extrasynaptic GABA-A receptors	Oral: Titrated to 600 mg TID (1800 mg/day)	Somnolence, pyrexia, salivary hypersecretion	N/A
Lacosamide	Enhances slow inactivation of sodium channels — a different action from the classic fast-inactivation blockers	Oral or IV: 200–400 mg/day divided BID; 600 mg/day was not more effective and caused more adverse reactions in trials	Dizziness, headache, nausea, diplopia; PR prolongation and AV block (ECG when there is cardiac disease or other PR-prolonging drugs)	10–20 µg/mL
Lamotrigine	Sodium channel blockade with inhibition of glutamate release	Oral: 100–400 mg/day in 2 divided doses, reached by slow titration. Valproate roughly halves the dose needed and enzyme inducers raise it, so use the matching titration schedule.	Rash, including Stevens–Johnson syndrome (more likely with fast titration or valproate), dizziness, diplopia, headache	3–15 µg/mL
Levetiracetam	Binds synaptic vesicle protein SV2A, modulating neurotransmitter release	Oral or IV: 1000–3000 mg/day divided BID; adjust for renal function	Drowsiness, dizziness, irritability, behavioral changes	10–40 µg/mL
Lorazepam	Benzodiazepine — positive allosteric GABA-A modulator; no active metabolite	Oral: 2–6 mg/day (divided doses). IV for status epilepticus (labeled): 4 mg slowly at 2 mg/min; one further 4 mg dose after 10–15 minutes if seizures continue (the protocol above uses 0.1 mg/kg, maximum 4 mg). The injection is also labeled for IM use.	Sedation, dizziness, weakness, unsteadiness; with the injection, CNS and respiratory depression	N/A
Methsuximide	Succinimide — T-type calcium channel blockade	Oral: 300–1200 mg/day	Nausea, vomiting, dizziness, drowsiness	10–40 µg/mL (as N-desmethylmethsuximide)
Midazolam	Benzodiazepine — positive allosteric GABA-A modulator; short acting	Nasal spray (Nayzilam) for seizure clusters, 12 years and older: 5 mg into one nostril; one further 5 mg into the other nostril after 10 minutes if there is no response (maximum 2 doses per cluster). IV or IM injection: labeled for sedation; the 10 mg IM dose for status epilepticus in the protocol above follows the AES 2016 guideline (RAMPART trial) rather than the label.	Somnolence, headache, nasal discomfort, throat irritation, rhinorrhea; with the injection, respiratory depression and apnea	N/A
Oxcarbazepine	Prodrug → licarbazepine (MHD); sodium channel blockade	Oral: 600–2400 mg/day (divided BID)	Dizziness, sedation, hyponatremia	3–35 µg/mL (MHD)
Perampanel	Selective non-competitive AMPA receptor antagonist	Oral: 8–12 mg/day (once daily at bedtime)	Dizziness, somnolence, hostility, irritability, falls	No established therapeutic target
Phenobarbital	Barbiturate — prolongs GABA-A chloride channel opening; inhibits glutamate responses at higher concentrations	Oral or IV: 60–200 mg/day (usually once at bedtime)	Sedation, cognitive impairment, ataxia, dependence	10–40 µg/mL
Phenytoin	Use- and voltage-dependent sodium channel blockade (fast inactivation)	Oral or IV: 300–400 mg/day (divided BID; ~5–7 mg/kg/day to maintain level 10–20 µg/mL)	Nystagmus, ataxia, gingival hyperplasia, hirsutism, sedation	Total 10–20 µg/mL; free concentration is often more informative with low albumin, renal failure, pregnancy, or interacting drugs
Primidone (rarely used)	Metabolised to phenobarbital and PEMA, both active; GABA-A modulation	Oral: 750–1500 mg/day (divided BID–TID)	Sedation, ataxia, nausea, dizziness	N/A
Pregabalin (adjunctive therapy for focal seizures)	Binds the alpha-2-delta subunit of voltage-gated calcium channels	Oral: 150–600 mg/day (divided BID)	Dizziness, somnolence, weight gain, peripheral edema	N/A
Rufinamide (rare, LGS)	Prolongs the inactivated state of sodium channels	Oral with food: start 400–800 mg/day divided BID; titrate to a maximum of 3200 mg/day	Dizziness, fatigue, nausea, vomiting	N/A
Stiripentol (rare, Dravet)	Positive allosteric GABA-A modulator; also inhibits CYP, raising clobazam and norclobazam levels	Oral: 50 mg/kg/day divided BID or TID (maximum 3000 mg/day), used with clobazam for Dravet syndrome in the labeled population	Drowsiness, ataxia, loss of appetite	N/A
Tiagabine (rarely used)	Blocks the GAT-1 GABA reuptake transporter	Oral: 32–56 mg/day (divided BID–QID)	Dizziness, nervousness, fatigue, tremor	N/A
Topiramate	Multiple: sodium channels, GABA-A potentiation, AMPA/kainate antagonism, carbonic anhydrase inhibition	Oral: 100–400 mg/day (divided BID)	Cognitive slowing and word-finding difficulty, weight loss, paresthesias, kidney stones, metabolic acidosis; rarely acute angle-closure glaucoma	5–20 µg/mL
Valproate / Divalproex Sodium	Broad and not fully established: sodium channels, increased GABA turnover, histone deacetylase inhibition (no T-type calcium effect in thalamic neurons)	Oral (DR/ER) or IV: 1000–3000 mg/day (divided BID–TID; ~15–60 mg/kg/day)	GI upset, tremor, weight gain, hair loss, hepatotoxicity, thrombocytopenia, hyperammonemia, pancreatitis; the most teratogenic ASM (see Pregnancy)	50–125 µg/mL
Vigabatrin (restricted use; REMS)	Irreversible GABA-transaminase inhibitor, raising brain GABA	For refractory focal seizures: start 1000 mg/day divided BID; titrate to recommended 3000 mg/day	Permanent visual field loss (boxed warning; vision monitoring under the REMS), sedation, irritability	N/A
Zonisamide	Sodium channels and T-type calcium channels, with weak carbonic anhydrase inhibition	Oral: 100–400 mg/day (once daily or divided BID)	Dizziness, somnolence, loss of appetite, weight loss	10–40 µg/mL

*Laboratory ranges vary by assay and are not universal treatment targets. Clinical response, toxicity, sample timing, baseline concentration, interactions, protein binding, and free drug levels may matter more than a population interval. Doses are abbreviated educational examples; verify whether each use is labeled, adjunctive, syndrome-specific, or off-label.

Medication table for rapid educational reference only. Verify indication, formulation, interactions, organ-function adjustments, pregnancy considerations, titration, and current prescribing information before use.

Drug-Resistant Epilepsy

From drug resistance to treatment options Refer as soon as two appropriate medications have failed; a third medication rarely brings freedom from seizures.

1Two ASM trials failTolerated, appropriately chosen and adequately dosed, alone or combined
2Refer to an epilepsy centerConfirm the diagnosis, epilepsy type and adherence
3Presurgical evaluation and SEEGVideo-EEG in the EMU · epilepsy-protocol MRI · neuropsychology · PET, SPECT or MEG as needed · stereo EEG when noninvasive data do not agree
4Choose a treatmentResection or laser ablation for a localized onset · VNS, RNS or DBS · corpus callosotomy for drop attacks · dietary therapy · trials

Step 3: presurgical evaluation and SEEG

The aim is to find the epileptogenic zone, the cortex whose removal or disconnection stops the seizures, and to map the function around it. No test shows it directly. Each test defines a different zone, the team infers the epileptogenic zone from where they overlap, and it is only proven when the patient is seizure-free after surgery (Rosenow & Lüders 2001).

From the noninvasive workup to a treatment decision. The more the tests agree, the better the chance of seizure freedom.

Zone	What it is	Main test
Seizure-onset zone	Where recorded seizures begin	Ictal scalp or intracranial EEG
Irritative zone	Where interictal spikes arise; often larger than the onset zone	EEG, MEG
Symptomatogenic zone	Cortex that produces the first symptoms; it can lie away from the onset	Video of the seizures (semiology)
Epileptogenic lesion	The structural abnormality	Epilepsy-protocol MRI
Functional deficit zone	Cortex that works abnormally between seizures	Examination, neuropsychology, FDG-PET
Eloquent cortex	Cortex that must be spared, such as language and motor areas	Functional MRI, Wada test, electrical stimulation mapping

Stereo EEG (SEEG)

When the noninvasive results disagree, show no lesion, suggest a deep or bilateral onset, or point to cortex near language or motor areas, the team states a hypothesis about where seizures start and how they spread, and tests it with depth electrodes. Each lead passes through a small drill hole along a trajectory planned on MRI and vascular imaging to avoid vessels, and is placed with a stereotactic frame or robot. About a dozen leads is typical: 902 electrodes in 76 implantations in one series (van der Loo 2017).

What it records. A typical electrode (DIXI Microdeep) is 0.8 mm across and carries 5 to 18 contacts, 2 mm long and 1.5 mm apart, numbered from the deepest; other makes differ slightly. One lead can sample a deep target and the cortex it passes through, and both hemispheres can be sampled in one implant.
In the monitoring unit, ASMs are reduced to record habitual seizures, and electrical stimulation through pairs of contacts maps function and can reproduce the patient’s aura or seizure.
Compared with subdural grids and strips, SEEG needs no craniotomy and reaches sulcal depths, the insula, the cingulate and the mesial temporal structures. Grids cover a continuous area of surface cortex, which helps functional mapping of the convexity.
Safety. In a meta-analysis, pooled rates were 1.3% for any complication, 1.0% for hemorrhage and 0.8% for infection, each estimated separately (Mullin 2016); one center reported major complications after 2.6% of implantations (van der Loo 2017).
What comes next: resection, laser ablation, radiofrequency thermocoagulation through the SEEG contacts, or responsive neurostimulation leads placed at the onset zones when they cannot be removed.
Lead names record side, internal target and external entry region. At Mount Sinai, LHplT is the left lead from the hippocampus to the lateral temporal cortex; see the SEEG lead naming reference.

A coronal slice through the hippocampal bodies, seen from the front with the patient’s left on the right. Original schematic, not a patient implant.

Explore implants in 3D in the Epilepsy Brain Atlas. Each example opens with its leads and contacts on a template brain.

Standard left implantThe eight named leads of the clinical team’s standard left-sided placement Left mesial temporalTemporal, insular, orbitofrontal and cingulate sampling Right insulo-opercularTransopercular and oblique insular leads Right frontal–cingulateMedial frontal and cingulate network Left laser ablationOccipital approach with an illustrative ablation zone Neuromodulation targetsAnterior and centromedian thalamus, pulvinar, hippocampal RNS SEEG lead namingSide, internal region, external region; the team’s standard and published examples

Therapy Category	Description/Details
Definition	Drug-resistant epilepsy (DRE) is defined by failure of two tolerated, appropriately chosen and adequately used ASM schedules—whether alone or in combination—to achieve sustained seizure freedom. Referral to a comprehensive epilepsy center should occur promptly so the diagnosis, adherence barriers, epilepsy type, imaging, surgical candidacy, devices, dietary therapy, and psychosocial needs can be reviewed; referral does not commit a patient to surgery.
Surgical Options	Resection (lesionectomy, lobar or multilobar resection, hemispherectomy in catastrophic cases) or MRI-guided laser interstitial thermal therapy for a well-localized onset; corpus callosotomy may reduce drop attacks. In the randomized trial of temporal lobe surgery (patients aged 16 and older), 58% were free of seizures impairing awareness at 1 year, against 8% who continued medication (Wiebe 2001).
Neuromodulation Techniques	VNS (FDA 1997; since 2017 labeled for focal seizures from age 4, and also used off label for generalized epilepsies such as Lennox–Gastaut syndrome): mean seizure frequency fell 28% with high stimulation vs 15% with low stimulation at 3 months (Handforth 1998). In a registry of 5,554 patients, responders (at least 50% fewer seizures) rose from 49% at 0–4 months to 63% at 24–48 months, and about 8% became seizure-free (Englot 2016). RNS (FDA 2013; adults with one or two seizure foci): mean seizure frequency fell 37.9% vs 17.3% with sham in the 12-week blinded period (Morrell 2011). In open-label follow-up the median reduction was 75% at 9 years, and 18% had at least one year free of seizures (Nair 2020). DBS (FDA 2018; adults whose focal seizures have failed three or more ASMs): bilateral stimulation of the anterior nucleus of the thalamus gave a median 40.4% reduction vs 14.5% with sham at the end of the blinded phase (Fisher 2010). Open-label median reductions were 41% at 1 year and 69% at 5 years (Salanova 2015), and 75% at 7 years (Salanova 2021). All three are palliative: the benefit grows over years and seizure freedom is uncommon. Diathermy is contraindicated with each device, and MRI is possible only under the manufacturer's conditions for the implanted system.
Dietary & Other Therapies	Ketogenic diet, or a less restrictive version such as the modified Atkins diet or low glycemic index treatment, in children and adults; it is the treatment of choice for GLUT1 deficiency and pyruvate dehydrogenase deficiency. Syndrome-specific medications: cannabidiol (Lennox–Gastaut, Dravet, tuberous sclerosis), fenfluramine (Dravet, Lennox–Gastaut), stiripentol (Dravet), everolimus (tuberous sclerosis) and ganaxolone (CDKL5 deficiency). Immunotherapy when an autoimmune cause is suspected, and clinical trials.
References	Definition: ILAE task force (Kwan 2010). VNS: AAN guideline update (Morris 2013). Device indications from the FDA approvals and the manufacturers' labeling; trial results as linked above.

Neuromodulation devices: where they sit

A front view, so the patient's left is on the right of the drawing. Choose a device for its parts, its target, the trial results and when it stimulates; point at or tab to a part for what it is.

What the devices look like

Original drawings for teaching, not photographs or patient films. The hardware is drawn to scale within each picture from the manufacturers' published dimensions, except that the leads are shortened and the vagus nerve coils and the DBS tip are also shown enlarged. The films show typical placements. The numbers on each picture match the list below it.

Women's Health & Hormones

Sex hormones and antiseizure medications act on each other in both directions, and the questions change across a lifetime: the menstrual cycle, contraception, planning and carrying a pregnancy, breastfeeding, gender-affirming hormones and menopause. Most people with epilepsy who plan a pregnancy have a healthy one. Do not stop an antiseizure medication abruptly because of pregnancy.

Most of the evidence comes from cisgender women, so this topic says “women”. The same principles apply to anyone who menstruates, can become pregnant or takes sex hormones, including transgender and nonbinary people.

Across the lifespan

What to think about at each stage. Each theme is covered below.

How hormones, seizures and ASMs interact

Estrogen tends to excite neurons and progesterone to calm them, through its metabolite allopregnanolone at the GABA-A receptor. Seizures cluster when estrogen is high relative to progesterone. Separately, many ASMs change hormone levels, and hormones change ASM levels.

Point at or tab to an arrow for its explanation.

Catamenial epilepsy

Catamenial epilepsy is a cyclical worsening of seizures tied to the menstrual cycle. Herzog's working definition is a twofold or greater rise in the average daily seizure frequency in one phase of the cycle (Herzog 1997). In 87 women with focal epilepsy who charted three cycles, 39% met it in at least two of the three (Herzog 2004).

Schematic hormone curves on a 28-day cycle. Day 1 is the first day of bleeding; days before the next bleed are counted back, so ovulation is day −14.

Pattern	Days	Seizures rise against	Why
C1 perimenstrual	−3 to +3	Follicular and luteal days	Progesterone and allopregnanolone fall before menses
C2 periovulatory	10 to −13	Follicular and luteal days	The preovulatory estrogen surge, not yet opposed by progesterone
C3 luteal, in inadequate luteal-phase cycles	10 to +3	Follicular days (4 to 9)	Estrogen rises at midcycle but progesterone stays low

Making the diagnosis. Ask for a diary of seizures and bleeding days over two or three cycles. A midluteal (day 22) progesterone below 5 ng/mL marks an inadequate luteal phase. The calculator applies Herzog's comparisons to one charted cycle.

Enter seizure counts from one cycle. The day counts adjust to the cycle length; the ovulatory phase absorbs the difference.

Treatment

Optimize the everyday ASM first. The options below all rest on small or uncontrolled studies. A Cochrane review found only four randomized trials that met its criteria (treatment for at least 12 weeks), all of progesterone or norethisterone (Maguire 2021).

Option	Evidence
Clobazam around menses, 20–30 mg daily for about 10 days	Double-blind crossover in 18 women: clobazam preferred by 14 (Feely 1982). Needs predictable cycles; clobazam may make hormonal contraception less effective.
Acetazolamide, intermittent or daily	Retrospective survey of 20 women: 40% reported at least 50% fewer seizures (Lim 2001).
A temporary rise in the usual ASM dose over the vulnerable days	Common practice; not tested in trials.
Progesterone lozenges, 200 mg three times daily on days 14–25, then tapered over days 26–28	NIH trial, 294 women: no benefit overall. Post hoc, women whose seizures at least tripled perimenstrually responded more often: 37.8% vs 11.1% on placebo (Herzog 2012).
Suppressing the cycle: depot medroxyprogesterone, continuous hormonal contraception, GnRH analogues	Uncontrolled series only; for example, of 14 women with uncontrolled seizures given medroxyprogesterone, the 11 analyzed had 30% fewer seizures a month (Mattson 1984). Consider interactions and bone health.

Contraception

An unplanned pregnancy carries more risk with epilepsy, which is on the CDC's list of such conditions, and a switch away from valproate or topiramate takes months to plan. Choose a method that the ASM does not weaken.

US Medical Eligibility Criteria for Contraceptive Use, 2024 (CDC summary chart).

Enzyme inducers. The CDC names phenytoin, carbamazepine, barbiturates, primidone, topiramate and oxcarbazepine. Eslicarbazepine, cenobamate, rufinamide, felbamate, clobazam, perampanel at 12 mg/day and topiramate above 200 mg/day can make hormonal contraception less effective, according to their labeling. Intrauterine devices and depot medroxyprogesterone are unaffected.
Lamotrigine works in both directions. Combined pills more than halved lamotrigine levels (13 vs 28 µmol/L; Sabers 2003), and levels rose by a median 27% in the hormone-free week (Contin 2006). Progestin-only methods did not change lamotrigine (Reimers 2005). Lamotrigine lowered levonorgestrel by 19% without evidence of ovulation (Sidhu 2006).
Emergency contraception on an enzyme inducer, or within 4 weeks of stopping one: offer a copper IUD. If that is not possible, levonorgestrel 3 mg can be considered, with unknown effectiveness; ulipristal is not recommended (FSRH).
Valproate requires highly effective contraception under the European and UK pregnancy prevention programmes, which now also cover topiramate (EU from 2023, UK from June 2024).

Planning a pregnancy

Fertility is usually normal. Women with epilepsy trying to conceive became pregnant within 12 months as often as controls (60.7% vs 60.2%), and 81.5% of pregnancies in each group ended in a live birth (WEPOD, Pennell 2018).
Choose the ASM before conception. The 2024 guideline asks for ASMs and doses that optimize both seizure control and fetal outcome at the earliest opportunity before conception. Consider lamotrigine, levetiracetam or oxcarbazepine; avoid valproate when clinically feasible. Never stop a drug abruptly.
Aim for seizure control first. Seizure freedom for at least 9 months before pregnancy is probably associated with an 84–92% chance of staying seizure-free during it (AAN/AES 2009).
Folic acid: the AAN/AES/SMFM guideline asks for at least 0.4 mg daily before conception and through pregnancy (Level B); RCOG advises 5 mg daily for all women with epilepsy from before conception through the first trimester. The best dose is uncertain. Children whose mothers took periconceptional folate had a mean IQ of 108 against 101 (NEAD, Meador 2013), and MONEAD found no sign of harm at higher doses (Meador 2025).
Record a baseline level of each ASM while seizures are controlled; it is the target for the pregnancy.
Enroll in a pregnancy registry such as the North American AED Pregnancy Registry.

During pregnancy

Convulsive seizures are the main danger to mother and baby, so the guideline's first priority is to minimize them (Level A). Death during the delivery hospitalization was 80 per 100,000 deliveries in women with epilepsy against 6 per 100,000 in women without, and preeclampsia, preterm labor and stillbirth were modestly more common (MacDonald 2015). In the UK, SUDEP caused 11 of 14 epilepsy-related maternal deaths in 2006–08 (Edey 2014).

Malformations and development

Risk Level	Medications	Notes
High Risk	Valproate; also phenobarbital and topiramate when clinically feasible alternatives exist	Valproate has a dose-dependent risk of major malformations (neural tube, cardiac) and lowers IQ and raises autism risk. The guideline says to avoid it when clinically feasible, to avoid phenobarbital (cardiac malformations) and phenobarbital and topiramate (oral clefts), and to avoid valproate and topiramate to reduce babies born small for gestational age.
Intermediate	Carbamazepine, Phenytoin	Risk varies by medication and dose; carbamazepine above 700 mg/day carried more than twice the odds of levetiracetam. Use the fewest medications and lowest effective doses compatible with seizure control.
Lowest Risk	Lamotrigine, Levetiracetam, Oxcarbazepine	The 2024 guideline says to consider these to minimize major congenital malformations (Level A). No medication is universally safest for every epilepsy.

Major malformations with each monotherapy in the EURAP registry, with 95% intervals from the counts (Tomson 2018). The general-population rate is about 2.4–2.9%.

ASM	Lower dose	Middle dose	Higher dose
Valproate	≤650 mg: 6.3%	651–1450 mg: 11.3%	>1450 mg: 25.2%
Phenobarbital	≤80 mg: 2.7%	81–130 mg: 6.2%	>130 mg: 11.7%
Carbamazepine	≤700 mg: 4.5%	—	>700 mg: 7.2%
Lamotrigine	≤325 mg: 2.5%	—	>325 mg: 4.3%

Malformation rate by daily dose at conception, EURAP 2018. Dose dependence was significant for all four.

IQ. At age 6, mean IQ after valproate exposure was 97, against 105 for carbamazepine and 108 for lamotrigine and phenytoin, falling with valproate dose (NEAD, Meador 2013).
Autism. Among children of mothers with epilepsy, autism by age 8 was 10.5% after valproate, 6.2% after topiramate, 4.1% after lamotrigine and 4.2% unexposed. After adjustment, only valproate raised the risk (hazard ratio 2.67; Hernández-Díaz 2024).
Lamotrigine and levetiracetam. In MONEAD, where most mothers with epilepsy took one or both, their children's language and verbal scores matched those of children of healthy women at age 2 (Meador 2021), 3 (Meador 2023) and 6, although higher exposure was linked to lower scores in secondary analyses (Meador 2025). The guideline recommends developmental screening for every exposed child.

Levels and seizures

Clearance rises through pregnancy and falls back within weeks of delivery. In MONEAD, 23% of pregnant women had more seizures that impaired awareness, about the same as nonpregnant women with epilepsy (25%), but the pregnant women's doses were changed more than twice as often (74% vs 31%; Pennell 2020). Monitoring and adjusting doses is part of why.

Top: a schematic from published magnitudes; individual courses vary. With lamotrigine, seizures worsened when the level fell below 65% of the individual's target (Pennell 2008). Bottom: Pennell 2022.

Check levels against the prepregnancy baseline through pregnancy, guided by each drug's pharmacokinetics; many centers check lamotrigine, levetiracetam and oxcarbazepine monthly. Raise the dose when the level falls or seizures return (guideline, Level B).
Be cautious about removing or replacing an ASM that controls tonic–clonic seizures once a woman is already pregnant (Level B).
In labor, continue ASMs. Treat a convulsive seizure promptly with the institution's pregnancy-aware protocol, and consider eclampsia.

Delivery and after

Lower any dose raised in pregnancy. Plan the reduction before delivery and review it within 10 days of birth (RCOG 2016). Watch for dizziness, double vision and unsteadiness as clearance returns.
Protect sleep. Night feeds can be shared, for example with expressed milk.
Handle the baby safely: change and feed on the floor or a low surface, use a very shallow baby bath, and do not bathe the baby alone.
Screen for depression. Peripartum depression affected 26.7% of women with epilepsy against 18.9% without, and anxiety 22.4% against 14.8% (Bjørk 2015).
Vitamin K. Newborns receive intramuscular vitamin K routinely; RCOG specifically advises it after exposure to enzyme inducers. Evidence is insufficient to support giving the mother vitamin K before delivery (AAN/AES 2009).

Breastfeeding

Breastfeeding is encouraged. In NEAD, children who were breastfed had an IQ 4 points higher at age 6 than those who were not (Meador 2014). In MONEAD about half of infant blood levels were too low to measure; the median infant level was 28.9% of the mother's for lamotrigine and 5.3% for levetiracetam (Birnbaum 2020). Watch for sedation and poor feeding with phenobarbital, primidone and benzodiazepines.

Bone and reproductive health

Valproate and polycystic ovary features. In a 12-month randomized comparison, new features of polycystic ovary syndrome (hyperandrogenism or ovulatory dysfunction) appeared in 54% on valproate and 38% on lamotrigine, and the full syndrome in 9% vs 2%; the difference was largest when valproate started before age 26 (Morrell 2008). Features improved after switching to lamotrigine (Isojärvi 1998).
Anovulatory cycles. Over three cycles, 10.9% of cycles were anovulatory in controls, 14.3% in focal epilepsy and 27.1% in generalized epilepsy; women taking valproate, or within 3 years of taking it, were most affected (Morrell 2002).
Enzyme inducers and sex hormones. Carbamazepine, phenytoin and phenobarbital raise SHBG and lower bioactive testosterone and estradiol, which can cause menstrual disorders in women and reduced sexual function in men (Isojärvi 2005).
Bone. Enzyme inducers and valproate are associated with lower bone density and more fractures (odds ratio 1.38 for enzyme inducers; Vestergaard 2004). NICE advises considering vitamin D and calcium for people at risk. The timing of bone density scans is expert opinion, for example after 5 years of treatment or at menopause.

Gender-affirming hormone therapy

Evidence is thin. The only cohort of people with a seizure history had 34 people: 21 on masculinizing and 13 on feminizing therapy. More had seizures only before starting hormones than only after (18 vs 6), and feminizing therapy made no significant difference (Blackman 2025). In a US inpatient database of 4,765 transgender women, feminizing hormones were not associated with seizures during hospitalization (Reddy 2026). Single case reports describe seizures increasing after estradiol was started. The rest is extrapolated from contraception and menopause data, so plan changes with the endocrinologist and follow the individual closely.

Interactions that matter when someone on an ASM starts or changes gender-affirming hormones (Alick-Lindstrom 2025; WPATH SOC8).

Before and after a change: keep a seizure diary; check lamotrigine and other relevant ASM levels; on an enzyme inducer, check hormone levels and consider a non-inducing ASM.
Estrogen choice: WPATH advises against ethinyl estradiol and favors transdermal estradiol for people over 45 or with a past venous thromboembolism. Hormone levels are usually checked every 3 months in the first year.
Bone, fertility and mood: ASMs and GnRH agonists can both lower bone density. Discuss fertility preservation before starting. Screen for depression and suicidality: in a clinic cohort of transgender and gender-diverse people with epilepsy, 68% reported suicidal ideation and 29% had functional seizures (Byrnes 2025).

Perimenopause and menopause

Seizures often worsen in perimenopause, when estrogen swings high relative to progesterone, especially in women with a catamenial pattern. After menopause the picture is mixed, and a past catamenial pattern predicted improvement (Harden 1999). Menopause came earlier in women with more seizures: at a mean 46.7 years with frequent seizures against 49.9 years with infrequent ones (Harden 2003).

Top: Harden 1999. Bottom: Harden 2006.

Hormone therapy. Conjugated estrogens with medroxyprogesterone worsened seizures in a dose-related way; the two women on lamotrigine had levels 25–30% lower. No study has tested the regimens used today in women with epilepsy. Transdermal estradiol with micronized progesterone may have a better safety profile, based on general-population observational data (Smith 2026); choose the regimen with the women's health specialist. Check lamotrigine levels when hormone therapy starts or stops.
Bone. In the Women's Health Initiative, postmenopausal women taking ASMs had more fractures (hazard ratio 1.44; 1.36 for enzyme inducers; Carbone 2010). Review vitamin D, calcium, falls and bone density.

Primary guidance: AAN/AES/SMFM practice guideline on teratogenesis, perinatal and neurodevelopmental outcomes after in-utero ASM exposure (Pack 2024); US Medical Eligibility Criteria for Contraceptive Use (CDC 2024); RCOG Green-top Guideline 68. This topic supports counseling and does not replace individualized neurology, obstetric, endocrine and maternal-fetal-medicine care.

Historical registry data (2006–2012)

Do not use this older table as a current counseling calculator. It reproduces selected results from 2006–2012 publications with different enrollment, comparator, dose, and outcome methods. Current counseling should use the 2024 AAN/AES/SMFM guideline and the latest pregnancy-registry publications. The historical data remain useful for illustrating dose dependence and why estimates differ among registries.

Medication	NAAPR (Hernandez-Diaz 2012)	UK Register (Morrow 2006)	EURAP (Tomson 2011)
Lamotrigine	2.0%	3.2%	2.0% (<300mg) 4.5% (≥300mg)
Levetiracetam	2.4%	0% (small sample)	-
Carbamazepine	3.0%	2.2%	3.4% (<400mg) 8.7% (≥1000mg)
Phenytoin	2.9%	3.7%	-
Valproate	9.3%	6.2%	5.6% (<700mg) 24.2% (≥1500mg)
Topiramate	4.2%	7.1%	-
Phenobarbital	5.5%	-	5.4% (<150mg) 13.7% (≥150mg)
Unexposed / Control	1.1%	3.5%	-

Seizure Management

Status Epilepticus