Prescription ·Strong evidence ·Reviewed May 2026
Levetiracetam is a broad-spectrum antiepileptic drug used as monotherapy or adjunctive therapy for partial-onset seizures, myoclonic seizures in juvenile myoclonic epilepsy, and primary generalized tonic-clonic seizures. It has a favorable side-effect profile compared to older antiepileptics and does not require routine serum drug level monitoring.
The bottom line
Evidence rating strong. Most-documented uses: broad-spectrum seizure control, favorable drug interaction profile, rapid titration to therapeutic dose. 10 sources indexed (2018–2023), with 2 interaction records on file.
Core mechanism
Binds to synaptic vesicle protein 2A (SV2A) in the brain, modulating neurotransmitter release. Unlike older antiepileptics, it does not act primarily on sodium channels or GABA receptors. By binding SV2A, it reduces excessive synchronous neuronal firing and inhibits burst firing without affecting normal neurotransmission.8
Rapidly and almost completely absorbed; food does not significantly affect bioavailability but may slow absorption rate3
Levetiracetam has minimal enzyme-inducing effects compared to other anticonvulsants, but long-term use may still modestly reduce vitamin D levels. Monitoring is reasonable.
Recommendation: Less vitamin D depletion risk than carbamazepine/phenytoin, but monitoring 25(OH)D levels annually is still recommended for any long-term anticonvulsant.
Levetiracetam can cause irritability, agitation, mood changes, or aggression in some people. Pyridoxine (vitamin B6) has clinical evidence as an adjunct that may reduce levetiracetam-associated behavioral adverse effects, especially when the antiseizure benefit of levetiracetam is otherwise good. Evidence is most developed in children and is mixed enough that this should not be treated as a guaranteed fix.
Recommendation: Ask your prescriber whether vitamin B6 is appropriate if levetiracetam is helping seizures but causing new irritability or mood symptoms. Do not use B6 as a substitute for urgent care if depression, suicidality, severe aggression, or psychosis appears. Avoid chronic high-dose B6 unless supervised because excessive doses can cause neuropathy.
Numbered references. Citations throughout the page link here.
Besag FMC, Vasey MJ, Sen A. Current evidence for adjunct pyridoxine (vitamin B6) for the treatment of behavioral adverse effects associated with levetiracetam: A systematic review. Epilepsy & behavior : E&B. 2023
Jense A, Douville A, Weiss A. The safety of rapid infusion levetiracetam: A systematic review. Pharmacotherapy. 2022
Romoli M, Perucca E, Sen A. Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review. Epilepsy & behavior : E&B. 2020
Rashid M, Rajan AK, Chhabra M et al.. Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies. Seizure. 2020
Watkins AK, Gee ME, Brown JN. Efficacy and safety of levetiracetam for migraine prophylaxis: A systematic review. Journal of clinical pharmacy and therapeutics. 2018
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