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Changes in Brain Glutamate on Switching to Clozapine in Treatment Resistant Schizophrenia

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)662-671
Number of pages10
JournalSchizophrenia Bulletin
Issue number3
Accepted/In press30 Sep 2020
Published1 May 2021

Bibliographical note

Funding Information: This work was funded by the Medical Research Council, UK, Grant MR/L003988/1 to A.E. This study presents independent research funded in part by the National Institute for Health Research (NIHR), Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London. Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


  • Clozapine MRS R2 28Sept20

    Clozapine_MRS_R2_28Sept20.docx, 184 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:30 Sep 2020

King's Authors


It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P =. 01) but not in the ACC (n = 24, F = 0.02, P =. 59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r =. 42, P =. 04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.

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