Levetiracetam, from broad-spectrum use to precision prescription: A narrative review and expert opinion. (April 2023)

• Record Type: Journal Article
• Authors: Celdran de Castro, Adriana; Nascimento, Fábio A.; Beltran-Corbellini, Álvaro; Toledano, Rafael; Garcia-Morales, Irene; Gil-Nagel, Antonio; Aledo-Serrano, Ángel
• Is Part Of: Seizure. Volume 107(2023)
• Page Start: 121
• Page End: 131
• Publication Date: 2023-04
• Subjects: antiepileptic drug -- precision medicine -- targeted therapies -- epilepsy -- seizure; AD Alzheimer Disease -- AE Absence epilepsy -- ASM Antiseizure medication -- BZD benzodiazepines -- BRV Brivaracetam -- CBZ Carbamazepine -- CBZ-CR Carbamazepine controlled-release -- EEM Epilepsy with eyelid myoclonia -- EMA European Medicines Agency -- FDA U.S Food and Drug Administration -- FPHE Fosphenitoin -- HR Hazard ratio -- ICH Intracerebral hemorrhage -- IGE Idiopathic generalized epilepsies -- ITT Intention-to-treat -- JME Juvenile Myoclonic Epilepsy -- LG Lennox Gastaut -- LTG Lamotrigine -- LEV Levetiracetam -- MCD Malformation of cortical development -- ME Myoclonic epilepsy -- NPAE neuropsychiatric adverse events -- OXC Oxacarbazepine -- PCDH19-RE PCDH19 related-epilepsy -- PME Progressive Myoclonic Epilepsy -- POLE Photosensitive Occipital Epilepsy -- PP per-protocol -- PHE Phenitoin -- PS Photosensivity -- QoL Quality of life -- RCT Randomized controlled trial -- RR Responder rate -- SAH Subarachnoid hemorrhage -- SE Status Epilepticus -- SeLEAS Self-limited epilepsy with autonomic seizures -- SeLECTS Self-limited epilepsy with centrotemporal spikes -- SF Seizure freedom -- SR Seizure rate -- STXBP1-DEE Syntaxin-binding protein 1developmental and epileptic encephalopathy -- SV Synaptic vesicle -- VPA Valproate -- VPA-XR Valproate extended release -- ZNS Zonisamide; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2023.03.017
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: Levetiracetam broad-spectrum and drug features led to a "one-for-all" overprescription. Levetiracetam seems to be an optimal choice in some clinical scenarios, such as childbearing-aged and pregnant female patients with idiopathic generalized epilepsies and in Alzheimer's and down Syndrome-related epilepsies, as well as in some genetic epilepsies. Levetiracetam is scarcely effective or even harmful in other clinical scenarios, such as in epilepsies related to malformations of cortical development, or patients with variants in PRRT2 or SV2A, as well as SCN8A with gain-of-function. Abstract: Levetiracetam (LEV) is an antiseizure medication (ASM) whose mechanism of action involves the modulation of neurotransmitters release through binding to the synaptic vesicle glycoprotein 2A. It is a broad-spectrum ASM displaying favorable pharmacokinetic and tolerability profiles. Since its introduction in 1999, it has been widely prescribed, becoming the first-line treatment for numerous epilepsy syndromes and clinical scenarios. However, this might have resulted in overuse. Increasing evidence, including the recently published SANAD II trials, suggests that other ASMs are reasonable therapeutic options for generalized and focal epilepsies. Not infrequently, these ASMs show better safety and effectiveness profiles compared to LEV (partially due to the latter's well-known cognitive and behavioral adverse effects, present in up to 20% of patients). Moreover, it has been shown that the underlying etiology of epilepsy is significantly linked to ASMs response in particular scenarios, highlighting the importance of an etiology-based ASM choice. In the case of LEV, it has demonstrated an optimal effectiveness in Alzheimer's disease, Down syndrome, and PCDH19-related epilepsies whereas, in other etiologies such as malformations of cortical development, it may show negligible effects. This narrative review analyzes the current evidence related to the use of LEV for the treatment of seizures. Illustrative clinical scenarios and practical decision-making approaches are also addressed, therefore aiming to define a rational use of this ASM.