Clozapine Response in Schizophrenia and Hematological Changes

Graham Blackman; Jenny E.L. Lisshammar; Rayyan Zafar; Thomas A. Pollak; Megan Pritchard; Alexis E. Cullen; Jonathan Rogers; Ben Carter; Kira Griffiths; Matthew Nour; Anthony S. David; Philip McGuire; Robert Stewart; James MacCabe

doi:10.1097/JCP.0000000000001329

Clozapine Response in Schizophrenia and Hematological Changes

Graham Blackman, Jenny E.L. Lisshammar, Rayyan Zafar, Thomas A. Pollak, Megan Pritchard, Alexis E. Cullen, Jonathan Rogers, Ben Carter, Kira Griffiths, Matthew Nour, Anthony S. David, Philip McGuire, Robert Stewart, James MacCabe

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

BACKGROUND: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. METHODS: Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as "much," or "very much" improved on the seven-point Clinical Global Impression-Improvement (CGI-I) subscale. RESULTS: In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. IMPLICATIONS: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

Original language	English
Pages (from-to)	19-24
Number of pages	6
Journal	Journal of clinical psychopharmacology
Volume	41
Issue number	1
DOIs	https://doi.org/10.1097/JCP.0000000000001329
Publication status	Published - 1 Jan 2021

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10.1097/JCP.0000000000001329

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@article{3d5cb822dac04b7e950861cbf42a20dc,

title = "Clozapine Response in Schizophrenia and Hematological Changes",

abstract = "BACKGROUND: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. METHODS: Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as {"}much,{"} or {"}very much{"} improved on the seven-point Clinical Global Impression-Improvement (CGI-I) subscale. RESULTS: In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. IMPLICATIONS: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.",

author = "Graham Blackman and Lisshammar, {Jenny E.L.} and Rayyan Zafar and Pollak, {Thomas A.} and Megan Pritchard and Cullen, {Alexis E.} and Jonathan Rogers and Ben Carter and Kira Griffiths and Matthew Nour and David, {Anthony S.} and Philip McGuire and Robert Stewart and James MacCabe",

note = "Funding Information: From the *Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London; †South London and Maudsley NHS Foundation Trust; ‡Central North West London NHS Foundation Trust; §Centre for Neuropsychopharmacology, Imperial College London Trust; ||Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King{\textquoteright}s College London; ¶Division of Psychiatry, University College London; #Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King{\textquoteright}s College London; **Max Planck UCL Centre for Computational Psychiatry and Ageing Research, and ††UCL Institute of Mental Health, University College London, London, United Kingdom. Received May 6, 2020; accepted after revision October 16, 2020. Reprints: Graham Blackman, MBChB, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King{\textquoteright}s College London, 16 De Crespigny Park, London, United Kingdom (e‐mail: [email protected]). G.B. and J.E.L.L. are joint first authors. G.B. is part-funded by a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King{\textquoteright}s College London. R.S. is part-funded by: (i) the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King{\textquoteright}s College London; (ii) a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King's College London; (iii) an NIHR Senior Investigator Award. R.S. declares research funding in the last 5 years from Janssen, Roche, GSK, and Takeda. J.M. is part-funded by (i) the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London; (ii) a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King{\textquoteright}s College London; J.M. has received research funding and travel and accommodation expenses from H Lundbeck. The other authors declare no conflicts of interest. Copyright {\textcopyright} 2020 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000001329 Implications: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response. Publisher Copyright: {\textcopyright} Wolters Kluwer Health, Inc. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jan,

day = "1",

doi = "10.1097/JCP.0000000000001329",

language = "English",

volume = "41",

pages = "19--24",

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T1 - Clozapine Response in Schizophrenia and Hematological Changes

AU - Blackman, Graham

AU - Lisshammar, Jenny E.L.

AU - Zafar, Rayyan

AU - Pollak, Thomas A.

AU - Pritchard, Megan

AU - Cullen, Alexis E.

AU - Rogers, Jonathan

AU - Carter, Ben

AU - Griffiths, Kira

AU - Nour, Matthew

AU - David, Anthony S.

AU - McGuire, Philip

AU - Stewart, Robert

AU - MacCabe, James

N1 - Funding Information: From the *Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London; †South London and Maudsley NHS Foundation Trust; ‡Central North West London NHS Foundation Trust; §Centre for Neuropsychopharmacology, Imperial College London Trust; ||Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London; ¶Division of Psychiatry, University College London; #Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King’s College London; **Max Planck UCL Centre for Computational Psychiatry and Ageing Research, and ††UCL Institute of Mental Health, University College London, London, United Kingdom. Received May 6, 2020; accepted after revision October 16, 2020. Reprints: Graham Blackman, MBChB, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, 16 De Crespigny Park, London, United Kingdom (e‐mail: [email protected]). G.B. and J.E.L.L. are joint first authors. G.B. is part-funded by a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King’s College London. R.S. is part-funded by: (i) the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King’s College London; (ii) a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King's College London; (iii) an NIHR Senior Investigator Award. R.S. declares research funding in the last 5 years from Janssen, Roche, GSK, and Takeda. J.M. is part-funded by (i) the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London; (ii) a Medical Research Council (MRC) Mental Health Data Pathfinder Award to King’s College London; J.M. has received research funding and travel and accommodation expenses from H Lundbeck. The other authors declare no conflicts of interest. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000001329 Implications: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response. Publisher Copyright: © Wolters Kluwer Health, Inc. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - BACKGROUND: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. METHODS: Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as "much," or "very much" improved on the seven-point Clinical Global Impression-Improvement (CGI-I) subscale. RESULTS: In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. IMPLICATIONS: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

AB - BACKGROUND: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. METHODS: Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as "much," or "very much" improved on the seven-point Clinical Global Impression-Improvement (CGI-I) subscale. RESULTS: In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. IMPLICATIONS: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

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DO - 10.1097/JCP.0000000000001329

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C2 - 33347018

AN - SCOPUS:85098925286

SN - 1533-712X

VL - 41

SP - 19

EP - 24

JO - Journal of clinical psychopharmacology

JF - Journal of clinical psychopharmacology

IS - 1

ER -

Clozapine Response in Schizophrenia and Hematological Changes

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