Skip to main content
Kent Academic Repository

Outcomes in treatment-resistant schizophrenia: symptoms, function and clozapine plasma concentrations

Krivoy, Amir, Whiskey, Eromona, Webb-Wilson, Henrietta, Joyce, Dan, Tracy, Derek K., Gaughran, Fiona, MacCabe, James H., Shergill, Sukhwinder S. (2021) Outcomes in treatment-resistant schizophrenia: symptoms, function and clozapine plasma concentrations. Therapeutic Advances in Psychopharmacology, 11 . pp. 1-9. ISSN 2045-1253. (doi:10.1177/20451253211037179) (KAR id:97159)


Background: Clozapine is the only medication licenced for treating patients with treatment-refractory schizophrenia. However, there are no evidence-based guidelines as to the optimal plasma level of clozapine to aim for, and their association with clinical and functional outcome.

Objective: We assessed the relationship between clinical and functional outcome measures and blood concentrations of clozapine among patients with treatment-refractory psychosis.

Methods: Data were reviewed in 82 patients with treatment-refractory psychosis admitted to a specialised tertiary-level service and treated with clozapine. Analysis focussed on the relationship between clozapine and norclozapine plasma concentrations and the patient’s clinical symptoms and functional status.

Results: Clinical symptom improvement was positively correlated with norclozapine plasma concentrations and inversely correlated with clozapine to norclozapine plasma concentrations ratio. Clozapine concentrations showed a bimodal association with clinical improvement (peaks around 350 and 660 ng/ml). Clinical symptom improvement correlated with functional outcomes, although there was no significant correlation between the latter and clozapine or norclozapine plasma concentrations.

Conclusion: Clozapine treatment was associated with optimal clinical improvement at two different peak plasma concentrations around 350 and 650 ng/ml. Clinical improvement was associated with functional outcome; however, functionality was not directly associated with clozapine concentrations. A subset of patients may require higher clozapine plasma concentrations to achieve clinical improvement.

Item Type: Article
DOI/Identification number: 10.1177/20451253211037179
Uncontrolled keywords: psychosis, clozapine, norclozapine
Subjects: R Medicine
Divisions: Divisions > Division of Natural Sciences > Kent and Medway Medical School
Depositing User: Rachael Heller
Date Deposited: 28 Sep 2022 08:33 UTC
Last Modified: 29 Sep 2022 09:40 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Shergill, Sukhwinder S..

Creator's ORCID:
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.