Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder

Edoardo Spina, Concetta D'Arrigo, Gaetana Migliardi, Vincenza Santoro, Maria Rosaria Muscatello, Umberto Micò, Giuseppina D'Amico, Emilio Perucca

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)599-602
Number of pages4
JournalTherapeutic Drug Monitoring
Volume28
Issue number5
DOIs
Publication statusPublished - Oct 2006

Fingerprint

olanzapine
Risperidone
Clozapine
Bipolar Disorder
Schizophrenia
Plasmas
norclozapine
Therapeutics
Pharmacokinetics
Metabolites
Antipsychotic Agents
lamotrigine

Keywords

  • Clozapine
  • Drug interaction
  • Lamotrigine
  • Olanzapine
  • Pharmacokinetics
  • Risperidone

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

Cite this

Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder. / Spina, Edoardo; D'Arrigo, Concetta; Migliardi, Gaetana; Santoro, Vincenza; Muscatello, Maria Rosaria; Micò, Umberto; D'Amico, Giuseppina; Perucca, Emilio.

In: Therapeutic Drug Monitoring, Vol. 28, No. 5, 10.2006, p. 599-602.

Research output: Contribution to journalArticle

Spina, Edoardo ; D'Arrigo, Concetta ; Migliardi, Gaetana ; Santoro, Vincenza ; Muscatello, Maria Rosaria ; Micò, Umberto ; D'Amico, Giuseppina ; Perucca, Emilio. / Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder. In: Therapeutic Drug Monitoring. 2006 ; Vol. 28, No. 5. pp. 599-602.
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N2 - 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.

AB - 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.

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