title: Three patients needing high doses of valproic Acid to get therapeutic concentrations.
abstract: Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published. Case 1 received VPA for seizures and schizophrenia and had >50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t = -9.6; df = 6.3, p < 0.001) during the VPA concentrate therapy, possibly due to autoinduction in that formulation. Case 2 had VPA for schizoaffective psychosis with 10 VPA concentrations during an 8-week admission. To maintain a VPA level ≥50 μg/mL, VPA doses increased from 1500 to 4000 mg/day. Case 3 had tuberous sclerosis and epilepsy and was followed up for >4 years with 137 VPA concentrations. To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p < 0.001) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time.
authors.affiliation: Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, KY 40509, USA.
authors.forename: James
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Pharmacy, Eastern State Hospital, Lexington, KY 40511, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: McCollum
authors.affiliation: Apalachee, Inc., Eastside Psychiatric Hospital, Tallahassee, FL 32308, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Ognibene
authors.affiliation: Department of Biostatistics, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Diaz
authors.affiliation: Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, KY 40509, USA ; University of Kentucky Mental Health Research Center, Eastern State Hospital, Lexington, KY 40511, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon