Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

The clozapine to norclozapine ratio: a narrative review of the clinical utility to minimize metabolic risk and enhance clozapine efficacy

Research output: Contribution to journalReviewResearchpeer-review

  1. Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. An update on the drug safety of treating erectile dysfunction

    Research output: Contribution to journalReviewResearchpeer-review

  3. Cardiovascular safety and benefits of GLP-1 receptor agonists

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra-high risk for psychosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Kenya A Costa-Dookhan
  • Sri Mahavir Agarwal
  • Araba Chintoh
  • Veronica N Tran
  • Nicolette Stogios
  • Bjørn H Ebdrup
  • Sanjeev Sockalingam
  • Tarek K Rajji
  • Gary J Remington
  • Dan Siskind
  • Margaret K Hahn
View graph of relations

Introduction: Clozapine remains the most effective antipsychotic for treatment-refractory schizophrenia. However, ~40% of the patients respond insufficiently to clozapine. Clozapine's effects, both beneficial and adverse, have been proposed to be partially attributable to its main metabolite, N-desmethylclozapine (NDMC). However, the relation of the clozapine to norclozapine ratio (CLZ:NDMC; optimally defined as ~2) to clinical response and metabolic outcomes is not clear.Areas covered: This narrative review comprehensively examines the clinical utility of the CLZ:NDMC ratio to reduce metabolic risk and increase treatment efficacy. The association of the CLZ:NDMC ratio with changes in psychopathology, cognitive functioning, and cardiometabolic burden will be explored, as well as adjunctive treatments and their effects.Expert opinion: The literature suggests a positive association between the CLZ:NDMC ratio and better cardiometabolic outcomes. Conversely, the CLZ:NDMC ratio appears inversely associated with better cognitive functioning but less consistently with other psychiatric domains. The CLZ:NDMC ratio may be useful for predicting and monitoring cardiometabolic adverse effects and optimizing potential cognitive benefits of clozapine. Future studies are required to replicate these findings, which if substantiated, would encourage examination of adjunctive treatments aiming to alter the CLZ:NDMC ratio to best meet the needs of the individual patient, thereby broadening clozapine's clinical utility.

Original languageEnglish
JournalExpert Opinion on Drug Safety
Volume19
Issue number1
Pages (from-to)43-57
Number of pages15
ISSN1474-0338
DOIs
Publication statusPublished - Jan 2020

    Research areas

  • Antipsychotic Agents/administration & dosage, Clozapine/administration & dosage, Cognition/drug effects, Drug Monitoring/methods, Humans, Schizophrenia/drug therapy

ID: 59086612