title: Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder.
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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy. espina@unime.it
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.forename: Concetta
authors.initials: C
authors.lastname: D'Arrigo
authors.forename: Gaetana
authors.initials: G
authors.lastname: Migliardi
authors.forename: Vincenza
authors.initials: V
authors.lastname: Santoro
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Muscatello
authors.forename: Umberto
authors.initials: U
authors.lastname: Micò
authors.forename: Giuseppina
authors.initials: G
authors.lastname: D'Amico
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D003024:Clozapine / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D018967:Risperidone / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D014227:Triazines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D014227:Triazines; D001569:Benzodiazepines; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine; D000077213:Lamotrigine