Drug	Mechanism of Action
Benzodiazepines, Phenobarbital	↑ GABA A action
Levetiracetam	Inhibits vesicle fusion by binding SV2A proteins
Valproic Acid	Blocks Na+ channels & blocks GABA transaminase
Ethosuximide	Blocks thalamic T-type Ca2+ channels
Phenytoin, Carbamazepine	Blocks Na+ channels
Gabapentin	Blocks Ca2+ channels

First-generation anticonvulsants

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Carbamazepine

• First-line treatment for focal seizures
• First-line treatment of trigeminal neuralgia
• Second-line treatment for generalized tonic-clonic seizures

Mnemonic

CBZ = Cranial nerve pain, Bipolar disorder, and seiZures

Valproate (Valproic Acid)

Indication

• First-line long-term treatment for tonic-clonic generalized seizures
• Partial (focal) seizures
• Absence epilepsy
• Treatment of established status epilepticus
• Myoclonic seizures
• Migraine prophylaxis
• Bipolar disorder

Tip

Used as both as an anticonvulsant and a mood stabilizer.

Mechanism of action

• Inhibits GABA transaminase → ↑ GABA → ↓ neuronal excitability
• Inactivates Na⁺ channels and Ca²⁺ channels

Adverse effects

• Tremor
• Alopecia
• Teratogenicity
  • Impairs folate metabolism, leading to neural tube defects (contraindicated in women of childbearing age/pregnancy)

Phenytoin

Adverse effects

1. Phenytoin toxicity is mainly characterized by CNS manifestations. Its effect on the cerebellum and vestibular system can cause ataxia and nystagmus.
2. Long-term therapy with phenytoin may cause gingival hyperplasia, coarsening of the facial features, and hirsutism.
3. Phenytoin interferes with the metabolism of folic acid and may cause megaloblastic anemia.
4. Phenytoin induces the P450 cytochrome oxidase system. It increases the metabolism—and therefore decreases the blood level—of many medications.
5. If taken during pregnancy, phenytoin may cause fetal hydantoin syndrome.

Second-generation anticonvulsants

Lamotrigine

Indication

• First-line treatment for long-term therapy of focal seizures
• Second-line treatment for generalized seizures and absence seizures
• Mood stabilizer for treatment of bipolar disorder

Mnemonic

Use lamotrigine when your patients feel less like a lion and more like a lamb. Lamotr-itch-gine can cause itchy rashes.

Mechanism of action

• Inhibition of voltage-gated Na⁺ channels → ↓ glutamate release

Adverse effects

• Rash, exfoliative dermatitis, Stevens-Johnson syndrome (slow titration is necessary to prevent skin and mucous membrane reactions)
• Hemophagocytic lymphohistiocytosis

Gabapentinoids

• Pregabalin
  • Drug combination for long-term treatment of focal seizures
  • Neuropathic pain
  • Neuralgia after herpes infection
• Gabapentin
  • Second-line treatment for focal seizures
  • Postherpetic neuralgia
  • Peripheral (poly)neuropathy

Mechanism of action

• Inhibition of presynaptic P/Q-type Ca²⁺ channels via action on the α2δ-subunit → ↓ Ca²⁺ intracellular flow → ↓ glutamate release

Topiramate

Indications

• Focal and generalized tonic-clonic epileptic seizures
• Migraine prophylaxis
• Idiopathic intracranial hypertension

Mechanism of action

• Blockage of voltage-gated Na+ channels
• ↑ GABA

Pregnancy and breastfeeding

• Classic anticonvulsants (especially carbamazepine and sodium valproate!) should be avoided if possible → teratogenic effects