title: Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug.
abstract: Since the serendipitous discovery of its anticonvulsant properties more than 50 years ago, valproic acid has become established as an effective broad-spectrum antiepileptic drug that is particularly useful for the management of generalised epilepsies, for which treatment alternatives are few. However, during the past few years increasing evidence has accumulated that intake of valproic acid during pregnancy is associated with a significant risk of dose-dependent teratogenic effects and impaired postnatal cognitive development in children. Because of these risks, valproic acid should not be used as a first-line drug in women of childbearing potential whenever equally or more effective alternative drugs are available-as in the case of focal epilepsy. In some generalised epilepsy syndromes, such as juvenile myoclonic epilepsy, valproic acid has better documented efficacy than alternative drugs and drug selection should be a shared decision between the clinician and the informed patient based on careful risk-benefit assessment.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: torbjorn.tomson@karolinska.se.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Tomson
authors.affiliation: Epilepsy Centre, Department of Neurophysiology and Experimental Epileptology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neurological Institute "Carlo Besta" Foundation, Milan, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Battino
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; C Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000927:Anticonvulsants / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid