Original ArticleEffect of Adjunctive Lamotrigine Treatment on the Plasma Concentrations of Clozapine, Risperidone and Olanzapine in Patients With Schizophrenia or Bipolar DisorderSpina, Edoardo MD, PhD*†; D'Arrigo, Concetta BSc*; Migliardi, Gaetana Pharm D*; Santoro, Vincenza BSc*; Muscatello, Maria Rosaria MD‡; Micò, Umberto MD‡; D'Amico, Giuseppina MD‡; Perucca, Emilio MD, PhD§Author Information From the *Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina; †IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina; ‡Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina; and §Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, and Institute of Neurology IRCCS C. Mondino Foundation, Pavia, Italy. Correspondence: Prof. Edoardo Spina, 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: October 2006 - Volume 28 - Issue 5 - p 599-602 doi: 10.1097/01.ftd.0000246763.59506.b0 Buy Metrics Abstract The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxy-risperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 ± 7 ng/mL at baseline, 32 ± 7 ng/mL at week 6, and 36 ± 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance. © 2006 Lippincott Williams & Wilkins, Inc.