Pharmacokinetic considerations in antipsychotic augmentation strategies: How to combine risperidone with low-potency antipsychotics

Michael Paulzen, Georgios Schoretsanitis*, Benedikt Stegmann, Christoph Hiemke, Gerhard Gruender, Koen R. J. Schruers, Sebastian Walther, Sarah E. Lammertz, Ekkehard Haen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

Objectives: To investigate in vivo the effect of low-potency antipsychotics on metabolism of risperidone (RIS).

Methods: A therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-OH-RIS of 1584 patients was analyzed. Five groups were compared; a risperidone group (n = 842) and four co-medication groups; a group co-medicated with chlorprothixene (n = 67), a group with levomepromazine (n = 32), a group with melperone (n = 46), a group with pipamperone (n = 63) and a group with prothipendyl (n = 24). Plasma concentrations, dose-adjusted plasma concentrations (C/D) of RIS, 9-OH-RIS and active moiety (RIS + 9-OH-RIS; AM) as well as the metabolic ratios (9-OH-RIS/RIS; MR) were computed.

Results: Differences in plasma concentrations were detected for AM and RIS. Pairwise comparisons revealed significant findings; RIS plasma concentrations were higher in co-medication groups than in monotherapy group. Chlorprothixene-and prothipendyl-medicated patients demonstrated no other differences. In the levomepromazine and melperone group plasma and C/D concentrations of AM and RIS were higher, while MRs were lower. For pipamperone, differences included higher C/D values of RIS and lower MRs.

Conclusions: Alterations of risperidone metabolism suggest pharmacokinetic interactions for levomepromazine and melperone. In the pipamperone-group, lower MRs as well as higher plasma and C/D levels of RIS suggest potential interactions. (C) 2017 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)101-106
Number of pages6
JournalProgress in Neuro-Psychopharmacology & Biological Psychiatry
Volume76
DOIs
Publication statusPublished - 2 Jun 2017

Keywords

  • Antipsychotics
  • Risperidone
  • Psychopharmacology
  • Pharmacokinetics
  • Therapeutic drug monitoring
  • CYTOCHROME-P450 2D6
  • LEVOMEPROMAZINE
  • SCHIZOPHRENIA
  • MELPERONE
  • METABOLISM
  • CYP2D6
  • 9-HYDROXYRISPERIDONE
  • HALOPERIDOL
  • QUETIAPINE
  • INHIBITOR

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