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Anticonvulsant drugs

Last updated: August 16, 2021

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Anticonvulsant drugs are classified as either first-generation (classic) agents or second-generation agents. Second-generation anticonvulsants are usually better tolerated and have a broader therapeutic range than classic anticonvulsant drugs. The choice of drug is guided by the type of seizure. First-line treatment for focal seizures includes, e.g., lamotrigine or levetiracetam, while valproate is used for generalized seizures. While all anticonvulsants have dose-dependent side effects on the central nervous system (e.g., somnolence, nausea), select agents also have other side effects (e.g., gingival hyperplasia caused by phenytoin). Anticonvulsants are also used for pain management (e.g., carbamazepine or gabapentin) and as mood stabilizers in bipolar disorders (valproate).

For more information on the treatment of generalized seizures, see treatment of epileptic seizures.

Anticonvulsant drugs inhibit neural activity (↓ neural excitation, ↑ neural inhibition) and increase the seizure threshold by interacting with specific receptors and ion channels.

Overview of anticonvulsant drugs [1]
Classification Agent Indication Mechanism of action Adverse effects Contraindications Interactions

First-generation (classic) anticonvulsants


Carbamazepine [4]

  • Inactivates Na+ channels


  • Inhibition of voltage-gated calcium channels (T-type) in neurons of the thalamus

Phenytoin, fosphenytoin

  • Inactivation of Na+ channels
  • Zero-order elimination (i.e., constant rate of drug eliminated)
  • Cardiorespiratory depression
  • Tolerance and dependence
  • Sedation
  • Induces cytochrome P-450
  • Sedation and dependence (see benzodiazepines)
  • Tolerance
  • Respiratory depression
Second-generation (newer) anticonvulsants


  • Inhibition of voltage-gated Na+channels → glutamate release
  • Hypersensitivity
  • Focal seizures, with or without impairment of consciousness (adjunctive therapy)
  • Not fully understood
  • Blockage of SV2A receptor → GABA and/or glutamate release modulation and inhibition of voltage-gated Ca2+ channels
  • Lethargy, fatigue
  • Nausea
  • Headache
  • Psychiatric symptoms (e.g., personality changes)
  • No significant interactions
Pregabalin (tentative FDA approval)
  • Inhibition of presynaptic P/Q-type Ca2+ channels via action on the α2δ-subunit → Ca2+ intracellular flow → glutamate release [1]
  • Does not bind to GABA receptors despite being a GABA analog
  • None


  • Blockage of voltage-gated Na+
  • GABA
  • Glaucoma
  • Weight loss
  • Kidney stones
  • Cognitive dysfunction (e.g., decreased verbal fluency, cognitive speed, and working memory)
  • Sedation

You can use the following to remember the features of PHENYTOIN: cytochrome P-450 interaction, Hirsutism, Enlarged gums (gingival hyperplasia), Nystagmus, Yellow-browning of skin (melasma), Teratogenicity, Osteomalacia, Interacts with folate, Neuropathy

To remember that the most important side effects of ethoSUXimide are Steven-Johnson syndrome, fatigue, headache, ABdominal upset, and ALLErGies (e.g., urticaria), think of “It sucks that Steven's FATher has given everyone a headache with his ABsurd ALLEGorizations.”

To remember a crucial side effect of vigabatrin, think of “Vision goes away by accident.”

To remember that phenobarbital is first-line treatment for neonates, think of “Phenobarbital is phenomenal for treating babies.”

To remember that the most common side effects of topiramate are speech impairment, weight loss (light), cognitive impairment, sedation, and kidney stones, think of “It leaves you speechless how lightly the cog railway travels through sediments and stones to the top.”


  • Monotherapy should always be the first-line treatment: increase the dosage of the drug to the therapeutic range before initiating combination therapy
  • Combination therapy: drugs from different classes and/or with different pharmacologic modes of action for refractory seizures [7]
  • For more detailed approaches to seizure treatment and epilepsy, see treatment of epileptic seizures.


Pregnancy and breastfeeding

  • Classic anticonvulsants (especially carbamazepine and sodium valproate!) should be avoided if possible → teratogenic effects
  • Newer anticonvulsants: lack of medical data and trials during pregnancy [8]
  • The choice of treatment depends on the type of seizure and which substance enables optimal control of seizures.
  • Approach
    • Optimize seizure control prior to conception.
    • Avoid multiple therapies.
    • Administer the drug at the lowest dose that controls seizures.
    • Monitor plasma drug levels regularly.
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