Original ArticleEffect of Valproate on Olanzapine Plasma Concentrations in Patients With Bipolar or Schizoaffective DisorderSpina, Edoardo MD, PhD*; D'Arrigo, Concetta BSc*; Santoro, Vincenza BSc*; Muscatello, Maria Rosaria MD†; Pandolfo, Gianluca MD†; Zoccali, Rocco MD†; Diaz, Francisco J PhD‡; Leon, Jose de MD§Author Information From the *Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina and IRCCS Centro Neurolesi “Bonino-Pulejo”; †Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Messina, Italy; ‡Department of Statistics, Universidad Nacional, Medellin, Colombia; and §UK Mental Health Research Center at Eastern State Hospital, Lexington, KY. Received for publication June 2, 2009; accepted September 9, 2009. Correspondence: Prof. Edoardo Spina, MD, PhD, Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Policlinico Universitario di Messina, Via Consolare Valeria, 98125 Messina, Italy (e-mail: [email protected]). Therapeutic Drug Monitoring: December 2009 - Volume 31 - Issue 6 - p 758-763 doi: 10.1097/FTD.0b013e3181c0590e Buy Metrics Abstract The effect of valproate on the steady-state plasma concentrations of olanzapine was investigated in 18 patients with bipolar or schizoaffective disorder. Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate coadministration, mean plasma olanzapine concentrations decreased significantly from 32.9 ± 9.7 ng/mL at baseline to 27.4 ± 9.8 ng/mL at week 2 (P = 0.02), and to 26.9 ± 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma olanzapine concentrations. Valproate coadministration with olanzapine was well tolerated and no patient showed a worsening of his or her psychopathological condition. These findings indicate that valproate, at doses of up to 2000 mg/d, is associated with a minimal, presumably not clinically significant, decrease in plasma olanzapine concentrations, possibly as a result of induction of olanzapine metabolism. New studies are needed to confirm that valproate could have mild inductive effects. © 2009 Lippincott Williams & Wilkins, Inc.