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Case Reports in Psychiatry
Volume 2015 (2015), Article ID 542862, 12 pages
Case Report

Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

1Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, KY 40509, USA
2Pharmacy, Eastern State Hospital, Lexington, KY 40511, USA
3Apalachee, Inc., Eastside Psychiatric Hospital, Tallahassee, FL 32308, USA
4Department of Biostatistics, The University of Kansas Medical Center, Kansas City, KS 66160, USA
5University of Kentucky Mental Health Research Center, Eastern State Hospital, Lexington, KY 40511, USA

Received 28 February 2015; Accepted 8 April 2015

Academic Editor: Liliana Dell’Osso

Copyright © 2015 James Jackson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 (; df = 6.3, ) 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; ) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time.