Management of Seizures

1. Classification of Seizures (ILAE 2017)

• Katzung's Basic and Clinical Pharmacology, 16e

2. General Principles of Chronic Treatment

• Monotherapy first: The majority of patients (~2/3) achieve adequate control with a single agent. Combination therapy is reserved for failures with two or more appropriate monotherapy trials.
• Pharmacoresistance: Patients failing two or more adequate trials are considered drug-resistant. Consider epilepsy surgery evaluation, neuromodulation, or dietary therapy.
• Treat the seizure type, not just the diagnosis: Drug choice depends on the seizure type or epilepsy syndrome.
• Avoid driving and hazardous activities until seizures are controlled. Reporting requirements vary by jurisdiction. - Goldman-Cecil Medicine

3. Antiseizure Drug (ASD) Selection

Focal (Partial) Seizures

• Lamotrigine - well tolerated; mood-stabilizing; risk of Stevens-Johnson syndrome with rapid titration (especially if added to valproate)
• Carbamazepine - start 200 mg twice daily; risks: diplopia, benign leukopenia, SIADH, rare aplastic anemia
• Levetiracetam - no drug-drug interactions; ideal in elderly and polypharmacy; adverse effects include irritability and psychiatric symptoms
• Oxcarbazepine, lacosamide, zonisamide - alternative options

• Topiramate - useful for focal and generalized; causes psychomotor slowing, cognitive effects; avoid in renal stones
• Phenytoin - once/twice daily dosing advantage; nonlinear kinetics (narrow therapeutic index); long-term cosmetic effects (hirsutism, gingival hypertrophy, coarsening of features) and osteoporosis; avoided in young patients on long-term therapy
• Cenobamate - recently approved; shown to significantly improve control after failure of up to 3 medications

Generalized Seizures (Tonic-Clonic)

• Lamotrigine
• Valproic acid (sodium valproate) - highly effective but avoid in women of childbearing age (teratogen, neural tube defects, hyperandrogenism); monitor LFTs and CBC; avoid in liver disease, thrombocytopenia
• Levetiracetam

Absence Seizures

• Ethosuximide - drug of choice for pure absence
• Valproate - especially if mixed with other generalized seizure types
• Lamotrigine - alternative

Myoclonic Seizures

• Valproate, Levetiracetam, Clonazepam

Special Syndromes

• Dravet syndrome: Valproate, clobazam; avoid sodium channel blockers (lamotrigine, carbamazepine)
• Lennox-Gastaut: Valproate, lamotrigine, rufinamide, clobazam
• Infantile spasms (West syndrome): ACTH, vigabatrin (especially for tuberous sclerosis)
• GLUT1 deficiency: Ketogenic diet is first-line

Drug monitoring: Serum levels are guidelines only. Dose decisions should be based on seizure control and side effects, not levels alone. More frequent monitoring in pregnancy, elderly, hepatic/renal impairment, and polypharmacy. - Textbook of Family Medicine, 9e

4. Non-Pharmacologic Management

Epilepsy Surgery

• Best option for drug-resistant focal epilepsy with identifiable focus
• Temporal lobe resection: 64% long-term seizure freedom
• Parieto-occipital resection: 46%; Frontal lobe: 27%
• Overall ~65% achieve sustained seizure freedom long-term

Neurostimulation

• Vagus Nerve Stimulator (VNS): Implanted device; open-loop stimulation; approved for drug-refractory focal seizures; useful in Lennox-Gastaut
• Responsive Neurostimulator (RNS): Closed-loop; detects abnormal EEG and delivers counter-stimulation
• Deep Brain Stimulation (DBS): Bilateral anterior thalamic nuclei stimulation; approved as adjunct for focal seizures; median ~75% seizure reduction across devices

Dietary Therapy

• Ketogenic diet: High fat, low carbohydrate; especially effective in myoclonic epilepsies, infantile spasms, Dravet, tuberous sclerosis, and GLUT1 deficiency - Katzung's Basic and Clinical Pharmacology, 16e

5. Status Epilepticus (SE)

• Generalized tonic-clonic seizures: continuous for ≥5 minutes (diagnosis) / neurologic consequences after ≥30 minutes
• Focal impaired awareness seizures: ≥10 minutes / consequences after ≥60 minutes

Step-by-Step Management Protocol

• Position patient to maximize ventilation and prevent aspiration
• Immobilize C-spine if trauma suspected
• Oxygen by mask; suction secretions; nasopharyngeal airway if tongue obstructs
• Monitor: HR, BP, RR, SpO2; treat hyperthermia
• IV/IO access; send: electrolytes, glucose, Ca²⁺, Mg²⁺, renal/liver function, CBC, ASD levels, urine toxicology
• Correct metabolic abnormalities

Phase 1 - Early SE (0-10 min): Benzodiazepines (First-Line)

Delays >10 minutes are associated with higher mortality, longer seizure duration, and more complications.

• Give a second dose only after 5 minutes of continued seizure activity
• If seizure persists 5 minutes after second dose, administer a third benzodiazepine and proceed to second-line agent

Phase 2 - Established SE (10-30 min): Second-Line Agents (~45% efficacy)

Phase 3 - Refractory SE (>30 min, failed above): ICU Management

• Goal: EEG burst suppression
• Intubation is required; use propofol or ketamine as sedative induction agents (have intrinsic antiepileptic activity); prefer succinylcholine (short-acting NMB) to allow ongoing seizure monitoring
• Therapeutic hypothermia is not beneficial in SE

Nonconvulsive SE (NCSE)

• Reported in 12-24% of cardiac arrest survivors
• Continuous EEG monitoring is recommended in comatose patients (especially with neuromuscular blockade/hypothermia)
• EEG findings reliably predict neurologic outcome post-cardiac arrest - Rosen's Emergency Medicine

6. Special Considerations

First Seizure

• Treatment after a first unprovoked seizure is debated
• Higher recurrence risk with: EEG abnormalities, prior neurologic injury, focal seizure onset, family history
• Many clinicians defer treatment after a single seizure given comparable adverse effect risk vs. recurrence risk - Textbook of Family Medicine, 9e

Seizure-Provoking Medications to Avoid

Pregnancy

• Valproate is strongly teratogenic - avoid if possible
• Lamotrigine and levetiracetam are preferred but require dose adjustment (increased clearance)
• Folic acid supplementation is essential

Traumatic Brain Injury (TBI)

• Phenytoin reduces early seizures (first 7 days) but not late seizures; no improvement in outcome shown
• Preferred prophylaxis (if used): Levetiracetam 500 mg BID x 7 days
• No routine prophylaxis recommended beyond 7 days

Intracerebral Hemorrhage (ICH)

• Prophylactic anticonvulsants are associated with worse neurologic outcomes; not recommended routinely - Rosen's Emergency Medicine

Recent Evidence (2025-2026)

• A 2026 AAN Practice Guideline (PMID 41370742) specifically addresses functional (psychogenic) seizures - a distinct entity from epileptic seizures requiring behavioral/psychological management rather than ASDs.
• A 2025 Cochrane review (PMID 40990160) found that self-management and behavioral interventions for adults with epilepsy can improve quality of life alongside pharmacotherapy.
• A 2025 Cochrane meta-analysis (PMID 41070722) identified key prognostic factors predicting unprovoked seizure recurrence after a first seizure, informing decisions on when to start treatment.

1. Classify seizure type before selecting therapy
2. Monotherapy first; switch drugs rather than combining early on
3. Levetiracetam and lamotrigine are widely preferred first-line agents due to favorable side-effect and interaction profiles
4. Status epilepticus: benzodiazepines → levetiracetam/fosphenytoin/valproate → ICU with continuous infusions
5. Consider surgery, neurostimulation, or ketogenic diet for drug-resistant epilepsy
6. Valproate is highly effective but carries significant risks in women of childbearing age and in liver disease