In the Literature

Landmark publications that define the evidence base for levetiracetam prescribing.

The SANAD II study of the effectiveness and cost-effectiveness of valproate, levetiracetam or lamotrigine for newly diagnosed focal epilepsy

Marson A et al. — The Lancet, 2021

Landmark RCT showing lamotrigine is superior to levetiracetam for focal epilepsy (HR 1.32, p=0.018). Levetiracetam failed to meet non-inferiority criteria.

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT)

Kapur J et al. — New England Journal of Medicine, 2019

Levetiracetam, valproate, and fosphenytoin were equally effective (~50% response) in benzodiazepine-refractory status epilepticus. No superiority for LEV.

Early Identification of Refractory Epilepsy

Kwan P, Brodie MJ. — New England Journal of Medicine, 2000

Seminal study of 470 patients: 47% seizure-free with first drug; only 11% after first drug fails; 4% after two failures. Establishes the critical importance of first drug choice.

Prediction Tools for Psychiatric Adverse Effects After Levetiracetam

Josephson CB et al. — JAMA Neurology, 2019

14.1% of patients on levetiracetam experienced psychiatric symptoms. Depression and behavioural issues were most common.

Mechanisms Underlying Aggressive Behavior Induced by Levetiracetam

Hansen CC et al. — PMC / Frontiers in Neurology, 2018

Detailed mechanistic review of SV2A-mediated aggression. LEV's binding to SV2A disrupts both excitatory and inhibitory neurotransmission, contributing to emotional dysregulation.

False Pharmacoresistance — A True Problem

Bašić S et al. — PMC, 2021

Reviews the concept of false pharmacoresistance — where apparent drug resistance is caused by inappropriate drug choice rather than true refractory epilepsy.

Beyond Seizure Control: A Case Series on Levetiracetam Neuropsychiatric Adverse Effects

Durairaj T et al. — PMC, 2025

16% of patients experienced behavioural side effects; 13.3% experienced depression. Highlights the under-recognition of neuropsychiatric adverse events in clinical practice.

FDA Drug Safety Communication: DRESS with Levetiracetam

US Food and Drug Administration — FDA.gov, 2023

FDA warns of rare but serious Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with levetiracetam and clobazam.