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Jackson J, McCollum B, Ognibene J, et al. Three patients needing high doses of valproic Acid to get therapeutic concentrations. Case Rep Psychiatry. 2015;2015:542862doi: 10.1155/2015/542862.
Jackson, J., McCollum, B., Ognibene, J., Diaz, F. J., & de Leon, J. (2015). Three patients needing high doses of valproic Acid to get therapeutic concentrations. Case reports in psychiatry, 2015542862. https://doi.org/10.1155/2015/542862
Jackson, James, et al. "Three patients needing high doses of valproic Acid to get therapeutic concentrations." Case reports in psychiatry vol. 2015 (2015): 542862. doi: https://doi.org/10.1155/2015/542862
Jackson J, McCollum B, Ognibene J, Diaz FJ, de Leon J. Three patients needing high doses of valproic Acid to get therapeutic concentrations. Case Rep Psychiatry. 2015;2015:542862. doi: 10.1155/2015/542862. Epub 2015 Apr 27. PMID: 26000191; PMCID: PMC4427013.
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Case Rep Psychiatry. 2015;2015:542862. doi: 10.1155/2015/542862. Epub 2015 Apr 27.

Three patients needing high doses of valproic Acid to get therapeutic concentrations.

Case reports in psychiatry

James Jackson, Betsy McCollum, Judy Ognibene, Francisco J Diaz, Jose de Leon

Affiliations

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

PMID: 26000191 PMCID: PMC4427013 DOI: 10.1155/2015/542862

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.

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