An international study to investigate and optimise the safety of discontinuing valproate in young men and women with epilepsy: Protocol

• DOI: 10.1371/journal.pone.0306226
• Publication Date: 2024-08-29T19:37:06Z
• Authors: Gashirai K. Mbizvo; Glen P. Martin; Matthew Sperrin; Laura J. Bonnett; Pieta Schofield; Iain Buchan; Gregory Y. H. Lip; Anthony G. Marson
• Keywords: Valproic Acid/adverse effects; Male; Adult; Anticonvulsants/adverse effects; Epilepsy; Levetiracetam; Adolescent; Science; Valproic Acid; Q; R; Middle Aged; Lamotrigine; Study Protocol; Young Adult; Levetiracetam/therapeutic use; Medicine; Humans; Female; Anticonvulsants; Lamotrigine/adverse effects; Epilepsy/drug therapy; Retrospective Studies

Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk men's offspring, prompting recommendations restrict everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called "target trial") using retrospective observational data. The data be drawn from ~250m mainly US patients TriNetX repository ~60m UK Clinical Practice Research Datalink (CPRD). These scanned individuals 16-54 years epilepsy on who either continued, switched lamotrigine or levetiracetam, discontinued between 2014-2024, creating four groups. Randomisation these groups emulated baseline confounder adjustment g-methods. Mortality outcomes assessed compared over 1-10 years, employing time-to-first-event recurrent events analyses. A causal prediction model developed aid predicting safest alternative antiseizure medications. Together, findings optimise informed decision-making about selection, providing immediate vital information patients, clinicians regulators.