What is Levetiracetam?
A comprehensive overview of levetiracetam — from its discovery to its mechanism of action and approved clinical uses.
History & Development
Levetiracetam (brand names: Keppra, Keppra XR, Elepsia XR, Spritam) was first approved by the FDA in 1999 as adjunctive therapy for partial-onset seizures in adults. It was developed by UCB Pharma and represented a novel class of antiepileptic drug with a unique mechanism of action distinct from all prior agents. Over the following two decades, its indications were expanded to include myoclonic seizures and primary generalised tonic-clonic seizures, and it became one of the most widely prescribed antiepileptic drugs globally.
Mechanism of Action
Levetiracetam exerts its antiepileptic effects by binding to synaptic vesicle protein 2A (SV2A), a glycoprotein found in presynaptic vesicles throughout the brain. SV2A plays a critical role in vesicular priming — the process by which neurotransmitter-filled vesicles are prepared for release. By binding SV2A, levetiracetam inhibits this priming step, reducing the rate of neurotransmitter release from presynaptic terminals.
Important: The same SV2A mechanism that reduces excitatory neurotransmission also affects inhibitory (GABAergic) neurotransmission. This dual effect on both excitatory and inhibitory circuits is believed to contribute to the neuropsychiatric side effects — particularly aggression and irritability — observed in 10–20% of patients. [Hansen et al., PMC 2018]
Pharmacokinetics
| Parameter | Value |
|---|---|
| Bioavailability | ~100% (oral) |
| Time to peak (Tmax) | 1–1.3 hours |
| Protein binding | <10% — minimal drug interactions |
| Half-life | 6–8 hours (adults); longer in elderly/renal impairment |
| Metabolism | Enzymatic hydrolysis in blood — not hepatic CYP450 |
| Elimination | Primarily renal (66% unchanged) |
| Dose adjustment | Required in renal impairment |
Approved Indications
Focal (Partial) Seizures
Adjunctive therapy in adults and children ≥1 month. SANAD II (2021) now shows lamotrigine is superior for focal epilepsy as monotherapy.
Myoclonic Seizures
Adjunctive therapy for myoclonic seizures in adults and adolescents ≥12 years with juvenile myoclonic epilepsy.
Primary Generalised Tonic-Clonic
Adjunctive therapy in adults and children ≥6 years. Sodium valproate remains preferred first-line for most generalised epilepsies.