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Antiepileptic (Antiseizure) Drugs — Classification & Uses

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Seizure Classification (ILAE)

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Classification of Antiepileptic Drugs

I. By Chemical Class / Drug Families

1. Hydantoins

• Phenytoin (diphenylhydantoin)
• Fosphenytoin (prodrug of phenytoin)

2. Barbiturates

• Phenobarbital
• Primidone (metabolized to phenobarbital)
• Mephobarbital

3. Iminostilbenes (Dibenzazepines)

• Carbamazepine
• Oxcarbazepine
• Eslicarbazepine

4. Succinimides

• Ethosuximide
• Methsuximide

5. Benzodiazepines

• Diazepam, Lorazepam (IV — status epilepticus)
• Clonazepam, Clobazam (chronic use)
• Midazolam

6. Valproic Acid (Valproate)

• Sodium valproate / valproic acid / divalproex sodium

7. Newer / Second-generation Drugs

• Lamotrigine — phenyltriazine
• Levetiracetam — pyrrolidine
• Topiramate — sulfamate-substituted monosaccharide
• Gabapentin — structural GABA analogue
• Pregabalin — structural GABA analogue
• Zonisamide — sulfonamide benzisoxazole
• Lacosamide — functionalized amino acid
• Vigabatrin — GABA analogue
• Tiagabine — nipecotic acid derivative
• Felbamate
• Perampanel
• Brivaracetam
• Rufinamide
• Stiripentol

8. Carbonic Anhydrase Inhibitors

• Acetazolamide (adjunct, especially menstrual seizures)

9. Others

• Cannabidiol (Epidiolex) — Dravet/Lennox-Gastaut
• Fenfluramine — Dravet syndrome
• Everolimus — TSC-related seizures
• ACTH / Corticosteroids — infantile spasms

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II. By Mechanism of Action

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Uses of Major Antiepileptic Drugs

1. Phenytoin

• Drug of choice (older): Focal seizures, focal-to-bilateral tonic-clonic seizures
• IV (fosphenytoin): Status epilepticus (2nd line after benzodiazepines)
• Also used: Trigeminal neuralgia, cardiac arrhythmias (class IB)
• Not used in: Absence seizures (may worsen)

2. Carbamazepine

• Drug of choice: Focal seizures, focal-to-bilateral tonic-clonic seizures
• Also: Trigeminal neuralgia (DOC), bipolar disorder (mood stabilizer), diabetic neuropathy
• Not used in: Absence, myoclonic seizures (may worsen)

3. Valproic Acid (Valproate)

• Broad-spectrum — drug of choice for:
  • Generalized tonic-clonic seizures
  • Absence seizures
  • Myoclonic seizures (including JME)
  • Mixed seizure disorders
• Also used: Bipolar disorder, migraine prophylaxis
• Avoid in: Pregnancy (teratogenic — neural tube defects), liver disease

4. Ethosuximide

• Drug of choice: Typical absence seizures (petit mal) — especially in children
• Not effective: Focal seizures or tonic-clonic seizures
• If absence + tonic-clonic coexist: Use valproate instead

5. Phenobarbital

• Drug of choice in neonatal seizures
• Used in febrile convulsions (prophylaxis)
• Broad-spectrum but causes sedation; now second-line for most seizures
• Cheap and widely available in low-resource settings

6. Benzodiazepines

7. Lamotrigine

• Broad-spectrum; effective in focal seizures, generalized tonic-clonic, absence, atypical absence, atonic, JME
• Drug of choice in women of childbearing age (relatively safer in pregnancy)
• Preferred in Lennox-Gastaut syndrome (adjunct)
• Risk: Stevens-Johnson syndrome (especially if titrated rapidly or combined with valproate)

8. Levetiracetam

• Very broad-spectrum: focal seizures, generalized tonic-clonic, myoclonic, absence
• Increasingly used as first-line (monotherapy and adjunct)
• Good safety profile; minimal drug interactions
• Main SE: behavioral/psychiatric effects (irritability, aggression)
• Available IV — used in status epilepticus

9. Topiramate

• Broad-spectrum: focal, generalized tonic-clonic, Lennox-Gastaut, JME, infantile spasms, Dravet
• Also approved: Migraine prophylaxis, obesity
• SE: cognitive slowing, word-finding difficulty ("dopamax"), weight loss, kidney stones, metabolic acidosis, glaucoma

10. Gabapentin & Pregabalin

• Gabapentin: Adjunct for focal seizures; also used in neuropathic pain, postherpetic neuralgia
• Pregabalin: Adjunct for focal seizures; also anxiety, fibromyalgia, neuropathic pain
• Neither is useful for generalized seizures

11. Zonisamide

• Broad-spectrum: focal seizures, generalized tonic-clonic, myoclonic
• Also used adjunctively in infantile spasms
• SE: cognitive effects, weight loss, oligohidrosis (children), kidney stones

12. Lacosamide

• Adjunct for focal seizures
• Unique MOA: enhances slow inactivation of Na⁺ channels
• Also IV formulation available

13. Vigabatrin

• Drug of choice: Infantile spasms (especially due to tuberous sclerosis)
• Adjunct for refractory focal seizures
• Serious SE: irreversible visual field defects (limits use)

14. Tiagabine

• Adjunct for focal seizures
• Rarely used due to narrow spectrum and risk of non-convulsive status epilepticus

15. Acetazolamide

• Adjunct; especially for catamenial epilepsy (menstrual seizure exacerbations)
• Tolerance develops rapidly; not suitable for chronic therapy

16. Cannabidiol (CBD / Epidiolex)

• Approved for: Dravet syndrome, Lennox-Gastaut syndrome, TSC-related seizures
• Mechanism: uncertain (not via cannabinoid receptors at therapeutic doses)

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Drug Selection by Seizure Type (Summary Table)

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Important Non-Epilepsy Uses

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