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

Journal article


Shergill, S., Amir Krivoy, Eromona Whiskey, Henrietta Webb-Wilson, Dan Joyce, Derek K. Tracy, Fiona Gaughran, James H. MacCabe and Sukhwinder S. Shergill 2021. Outcomes in treatment-resistant schizophrenia: symptoms, function and clozapine plasma concentrations. Therapeutic Advances in Psychopharmacology. 11. https://doi.org/10.1177/20451253211037179
AuthorsShergill, S., Amir Krivoy, Eromona Whiskey, Henrietta Webb-Wilson, Dan Joyce, Derek K. Tracy, Fiona Gaughran, James H. MacCabe and Sukhwinder S. Shergill
Abstract

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.

KeywordsPsychosis; Clozapine; Norclozapine
Year2021
JournalTherapeutic Advances in Psychopharmacology
Journal citation11
PublisherSAGE
ISSN2045-1253
2045-1261
Digital Object Identifier (DOI)https://doi.org/10.1177/20451253211037179
Official URLhttps://journals.sagepub.com/doi/full/10.1177/20451253211037179
Publication dates
Online16 Oct 2021
Publication process dates
Deposited25 May 2023
Publisher's version
License
Output statusPublished
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