title: Valproate as monotherapy for juvenile myoclonic epilepsy: dose-effect study.
abstract: Sodium valproate enteric-coated tablets were used in this double-blind, randomized, cross-over study of 16 patients with juvenile myoclonic epilepsy comparing 1000 mg and 2000 mg VPA daily in b.i.d. administration with 6 months of observation on each dose. Myoclonic, absence, and generalized tonic-clonic seizures were registered separately. Subjective side-effects were monitored, and a computerized neuropsychologic test battery was performed on each dose. There was no significant difference in seizure frequency between the two doses. Only 25% of the patients were seizure free throughout the study despite concentrations well within the normally proposed therapeutic range for VPA. During the higher dose, 37.5% of the patients had an improved seizure control, but 25% of the patients had an increase in seizure frequency compared to the lower dose. However, there was no correlation between VPA concentrations and subjective side-effects or neuropsychologic test results. Our observations point out the possibility that the common strategy of increasing plasma levels in difficult-to-treat patients until side effects occur should perhaps be reconsidered, but this suggestion needs further confirmation.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Sundqvist
authors.forename: T
authors.initials: T
authors.lastname: Tomson
authors.forename: B
authors.initials: B
authors.lastname: Lundkvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D019540:Area Under Curve; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004831:Epilepsies, Myoclonic / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000517:prevention & control; D012894:Sleep Stages / Q000187:drug effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid