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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 first-generation anticonvulsants [1]

Overview
Agent	Indication	Mechanism of action	Adverse effects	Contraindications	Interactions
Valproate	First-line long-term treatment for tonic-clonic generalized seizures Partial (focal) seizures Absence epilepsy Treatment of established status epilepticus [2] Myoclonic seizures Migraine prophylaxis Bipolar disorder	Inhibits GABA transaminase → ↑ GABA → ↓ neuronal excitability Inactivates Na⁺ channels and Ca²⁺ channels	Gastrointestinal upset Tremor Alopecia Pancreatitis Weight gain Teratogenicity Especially neural tube defects (contraindicated in women of childbearing age/pregnancy) ) See pharmacotherapy during pregnancy Hepatotoxicity (usually occurs during the first 6 months of treatment): LFT should be regularly performed in people taking valproate [3] Cytochrome P450 inhibition [4] Rash Dizziness Sedation Ataxia Thrombocytopenia (may manifest as easy bruising) Agranulocytosis	Pregnancy (especially valproate and carbamazepine)	Cytochrome P450 inhibition
Carbamazepine [5]	First-line treatment for focal seizures First-line treatment of trigeminal neuralgia Second-line treatment for generalized tonic-clonic seizures	Inactivates Na⁺ channels	Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) Rash Hyponatremia, hyperhydration, and edema (due to SIADH) DRESS syndrome Blood count abnormalities (e.g., agranulocytosis, aplastic anemia) Teratogenicity during the first trimester (cleft lip/palate, spina bifida) (see pharmacotherapy during pregnancy) Folate depletion Diplopia Ataxia Hepatotoxicity Stevens-Johnson syndrome Induces cytochrome P450 Dizziness Sedation		Strong induction of cytochrome P450
Ethosuximide	First-line for absence seizures	Inhibition of voltage-gatedcalcium channels (T-type) in neurons of the thalamus	Gastrointestinal symptoms Allergic skin reactions (urticaria, Stevens-Johnson syndrome) Pancytopenia Fatigue Headache Myopia Sedation Dizziness		Increases serum levels of phenytoin
Phenytoin, fosphenytoin	Tonic-clonic seizures Only rarely used for long-term treatment of focal seizures Treatment of established status epilepticus[2]	Inactivation of Na⁺ channels Zero-order elimination (i.e., constant rate of drug eliminated)	Hirsutism Hyperpigmentation of skin (melasma) Gingival hyperplasia Nystagmus Osteopenia Megaloblastic anemia due to ↓ folate absorption Peripheral neuropathy Stevens-Johnson syndrome Drug-induced lupus erythematosus DRESS syndrome Intoxication: sedation, diplopia, ataxia, arrhythmias Induction of cytochrome P-450 enzymes Teratogenic: fetal hydantoin syndrome Hypothyroidism [6] Sedation Dizziness Rash Hepatotoxicity		Induction of cytochrome P450
Phenobarbital	First-line treatment in neonates Tonic-clonic generalized seizures Focal seizures Status epilepticus	GABA_Aagonist → ↑ GABA action	Cardiorespiratory depression Tolerance and dependence Sedation Induces cytochrome P-450		Induction of cytochrome P450
Benzodiazepines	First-line for status epilepticus Second-line treatment for eclampsia	Indirect GABA_A agonist → ↑ GABA action	Sedation and dependence (see benzodiazepines) Tolerance Respiratory depression		Alcohol, opioids, sedatives: ↑ CNS depression

Overview of second-generation anticonvulsants [1]

Overview
Agent		Indication	Mechanism of action	Adverse effects	Contraindications	Interactions
Lamotrigine		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	Inhibition of voltage-gated Na⁺channels → ↓ glutamate release	Rash, exfoliative dermatitis, or rarely, Stevens-Johnson syndrome (slow titration is necessary to prevent skin and mucous membrane reactions) Hemophagocytic lymphohistiocytosis Rarely hepatotoxic or nephrotoxic Blurry vision Gastrointestinal symptoms Sedation Dizziness DRESS Syndrome	Hypersensitivity	Coadministration of carbamazepine, phenobarbital, phenytoin → ↑ clearance
Tiagabine		Focal seizures, with or without impairment of consciousness (adjunctive therapy)	Inhibits GABA reuptake → ↑ GABA	Dizziness Gastrointestinal upset: nausea, vomiting, diarrhea Insomnia Drowsiness Weight changes
Levetiracetam		First-line treatment for long-term therapy of focal seizures Generalized seizures	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) Sedation Dizziness		No significant interactions
Gabapentinoids	Pregabalin (tentative FDA approval)	Drug combination for long-term treatment of focal seizures Neuropathic pain Neuralgia after herpes infection Generalized anxiety disorder	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	Somnolence Nausea Ataxia Impaired vision Weight gain		No significant interactions
Gabapentinoids	Gabapentin	Second-line treatment for focal seizures Postherpetic neuralgia Peripheral (poly)neuropathy		Dry mouth Somnolence, nausea Ataxia Dizziness Weight gain		Morphine: ↑ concentrations of gabapentin
Vigabatrin		Refractory focal seizures (adjunctive therapy) Monotherapy for infantile spasms (West syndrome)	Inhibits GABA transaminase irreversibly → ↑ GABA	Irreversible vision loss	None	Decreases serum levels of phenytoin
Topiramate		Focal and generalized tonic-clonic epileptic seizures Migraine prophylaxis Idiopathic intracranial hypertension	Blockage of voltage-gated Na⁺ channels ↑ GABA	Angle-closure glaucoma Weight loss Kidney stones Cognitive dysfunction (e.g., decreased verbal fluency, cognitive speed, and working memory) Sedation Dizziness Mood disturbance, depression Paresthesia	None	Decreases efficacy of oral contraceptives

Video thumbnail Mechanism of action: anticonvulsant drugs

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.”

References:[1][7]

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 [8]
For more detailed approaches to seizure treatment and epilepsy, see treatment of epileptic seizures.

References:[7][8]

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 [9]
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.