Disease - Epilepsy - Drug Treatment for Seizures

Drug Treatment for Seizures

Agent	Mechanism of Action	Dosage	Benefits	Side Effects	Notes
Carbamazepine	Inhibits voltage gated Na+ channels (inhibits action potentials)	600-1200 mg/d	Familiar, inexpensive	Rare blood dyscrasias and hepatitis; diplopia, ataxia common	Slow release available for bid dosing. Narrow therapeutic window*
Ethosuximide	Inhibits T-type calcium channels	250-500 mg/d	Simple to use and dosed qd, bid	Rare blood dyscrasias	Only effective for absence seizures*
Felbamate	Mixed	1200-3600 mg/d	Effective for wide variety of severe seizures	Common aplastic anemia (1 in 40,000) and hepatitis (1 in 80,000)	Common elevated valproic acid and phenytoin levels. Reserved for intractable epilepsy because of risks*
Gabapentin	Unknown	1800-3600 mg/d	No drug interactions	Rare neurotoxicity; no end-organ toxicities	Many pills per day, dosed tid at effective doses. Not protein bound or metabolized*
Lacosamide	Enhancing slow inactivation of voltage gated sodium channels	200-400 mg/d	Available in both oral and iv form	Dizziness, headache, nausea, and diplopia	FDA approved for adjunct treatment for partial epilepsy October 2008*
Lamotrigine	Unknown	100-600 mg/d	Effective for partial and generalized seizures	Common benign rash (1:50-1:500); Rare severe rash - Stevens Johnson (1:40,000)	Rash is more likely with fast titration or with concomitant valproic acid. Dose is higher with enzyme-inducing drugs and lower with valproic acid*
Levetiracetam	Unknown	1000-3000 mg/d	Few drug interactions	Uncommon neurotoxicity, no end-organ toxicities	Well tolerated*
Oxcarbazepine	Inhibits voltage gated Na+ channels (inhibits action potentials)	900-2400 mg/d	Fewer side effects than carbamazepine; dosed bid	Hyponatremia uncommon; neurotoxicity uncommon	No significant induction of most liver enzymes*
Pregabalin	Modulates calcium channels	150-600 mg/d	Few drug interactions	Neurotoxicity, weight gain, peripheral edema, and visual changes are uncommon	FDA schedule V designation*
Phenobarbital	Gamma-aminobutyric acid(A) agonist	90-180 mg/d	Inexpensive, qd dosing	Sedation; hyperactivity in children	Excellent drug if well tolerated
Phenytoin	Inhibits voltage gated Na+ channels (inhibits action potentials)	200-300 mg/d	Familiar	Rare blood dyscrasias and hepatitis; common neurotoxicity, gum hyperplasia, hirsutism, osteoporosis	Narrow therapeutic window*
Rufinamide	Unknown	45 mg/kg·d or 3200 mg/d	Approved for severe epilepsy like that associated with Lennox-Gastaut syndrome	Somnolence or fatigue, coordination abnormalities, dizziness, gait disturbances, and ataxia. Contraindicated in patients with familial short QT syndrome	FDA approved for adjunctive treatment of seizures associated with the Lennox-Gastaut syndrome in children 4 years and older, and adults*
Tiagabine	Inhibits reuptake of GABA	12-56 mg/d	Well tolerated	Uncommon neurotoxicity	Short half-life may require tid or qid dosing in some patients*
Topiramate	Mixed, carbonic anhydrase inhibitor	200-400 mg/d	Effective for partial seizures and Lennox-Gastaut syndrome	Rare nephrolithiasis; common cognitive side effects above 400 mg/d	Not well tolerated above 400 mg/d in many patients*
Valproic acid	Augments production and inhibits metabolism of GABA	750-3000 mg/d	Effective for all partial and generalized seizures	Rare hepatitis (1:40,000); common tremor, weight gain, thrombocytopenia	Hepatitis most common in children on multiple antiepileptic drugs, with mental retardation*
Zonisamide	Unknown	200-400 mg/d	qd dosing is possible because of 60 hr half-life	Rare nephrolithiasis, heat intolerance; uncommon neurotoxicity, metabolic acidosis	Better tolerated bid. The FDA issued an alert regarding the risk of metabolic acidosis in some patients using zonisamide*

bid = twice daily; FDA = Food and Drug Administration; GABA = γ-aminobutyric acid; qid = four times daily; qd = once daily; tid = three times daily.

* The FDA requires a warning label regarding the increased risk of suicidal thoughts and behaviors associated with the use of this drug. The American Epilepsy Society issued a position statement in response to this FDA requirement.