Clinical correlates of early onset antipsychotic treatment resistance

Daniela Fonseca de Freitas; Deborah Agbedjro; Giouliana Kadra-Scalzo; Emma Francis; Isobel Ridler; Megan Pritchard; Hitesh Shetty; Aviv Segev; Cecilia Casetta; Sophie E. Smart; Anna Morris; Johnny Downs; Søren Rahn Christensen; Nikolaj Bak; Bruce J. Kinon; Daniel Stahl; Richard D. Hayes; James H. MacCabe

doi:10.1177/02698811221132537

Clinical correlates of early onset antipsychotic treatment resistance

Daniela Fonseca de Freitas^*, Deborah Agbedjro, Giouliana Kadra-Scalzo, Emma Francis, Isobel Ridler, Megan Pritchard, Hitesh Shetty, Aviv Segev, Cecilia Casetta, Sophie E. Smart, Anna Morris, Johnny Downs, Søren Rahn Christensen, Nikolaj Bak, Bruce J. Kinon, Daniel Stahl, Richard D. Hayes, James H. MacCabe

^*Corresponding author for this work

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

4 Citations (Scopus)

Abstract

Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS. Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Original language	English
Pages (from-to)	1226-1233
Number of pages	8
Journal	Journal of Psychopharmacology
Volume	36
Issue number	11
DOIs	https://doi.org/10.1177/02698811221132537
Publication status	Published - 1 Nov 2022

Keywords

antipsychotic agents
clozapine
Psychotic disorders
schizophrenia
treatment refractory

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10.1177/02698811221132537

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Fonseca de Freitas, D., Agbedjro, D., Kadra-Scalzo, G., Francis, E., Ridler, I., Pritchard, M., Shetty, H., Segev, A., Casetta, C., Smart, S. E., Morris, A., Downs, J., Christensen, S. R., Bak, N., Kinon, B. J., Stahl, D., Hayes, R. D., & MacCabe, J. H. (2022). Clinical correlates of early onset antipsychotic treatment resistance. Journal of Psychopharmacology, 36(11), 1226-1233. https://doi.org/10.1177/02698811221132537

@article{d49197cb3ec24f54ae2090c6a80ef438,

title = "Clinical correlates of early onset antipsychotic treatment resistance",

abstract = "Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS. Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.",

keywords = "antipsychotic agents, clozapine, Psychotic disorders, schizophrenia, treatment refractory",

author = "{Fonseca de Freitas}, Daniela and Deborah Agbedjro and Giouliana Kadra-Scalzo and Emma Francis and Isobel Ridler and Megan Pritchard and Hitesh Shetty and Aviv Segev and Cecilia Casetta and Smart, {Sophie E.} and Anna Morris and Johnny Downs and Christensen, {S{\o}ren Rahn} and Nikolaj Bak and Kinon, {Bruce J.} and Daniel Stahl and Hayes, {Richard D.} and MacCabe, {James H.}",

note = "Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Company Ltd. for work unrelated to the analysis reported here. SRC, NB and BK were employees of Lundbeck at the time of the study. JHM received research funding for this study from H. Lundbeck A/S. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by a researcher-initiated grant to JHM from H. Lundbeck A/S, as part of STRATA, a large multi-centre research collaborative program led by JHM, funded by the Medical Research Council (Grant number MR/L011794). This work utilised the Clinical Record Interactive Search (CRIS) platform funded and developed by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. DFdF, DA, GKS, EF, IR, MP, HS, DS, RDH and JHM received salary support from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. JD is supported by a NIHR Clinician Science Fellowship award (CS-2018-18-ST2-014), a Medical Research Council (MRC) Clinical Research Training Fellowship (MR/L017105/1) and a Psychiatry Research Trust Peggy Pollak Research Fellowship in Developmental Psychiatry. The views expressed are those of the authors and not those of the NHS, the NIHR, the Department of Health and Social Care, or H. Lundbeck S/A. Publisher Copyright: {\textcopyright} The Author(s) 2022.",

year = "2022",

month = nov,

day = "1",

doi = "10.1177/02698811221132537",

language = "English",

volume = "36",

pages = "1226--1233",

journal = "Journal of Psychopharmacology",

issn = "0269-8811",

publisher = "Sage Publications",

number = "11",

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Fonseca de Freitas, D , Agbedjro, D , Kadra-Scalzo, G , Francis, E , Ridler, I , Pritchard, M, Shetty, H, Segev, A, Casetta, C, Smart, SE, Morris, A , Downs, J, Christensen, SR, Bak, N, Kinon, BJ, Stahl, D , Hayes, RD & MacCabe, JH 2022, 'Clinical correlates of early onset antipsychotic treatment resistance', Journal of Psychopharmacology, vol. 36, no. 11, pp. 1226-1233. https://doi.org/10.1177/02698811221132537

TY - JOUR

T1 - Clinical correlates of early onset antipsychotic treatment resistance

AU - Fonseca de Freitas, Daniela

AU - Agbedjro, Deborah

AU - Kadra-Scalzo, Giouliana

AU - Francis, Emma

AU - Ridler, Isobel

AU - Pritchard, Megan

AU - Shetty, Hitesh

AU - Segev, Aviv

AU - Casetta, Cecilia

AU - Smart, Sophie E.

AU - Morris, Anna

AU - Downs, Johnny

AU - Christensen, Søren Rahn

AU - Bak, Nikolaj

AU - Kinon, Bruce J.

AU - Stahl, Daniel

AU - Hayes, Richard D.

AU - MacCabe, James H.

N1 - Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Company Ltd. for work unrelated to the analysis reported here. SRC, NB and BK were employees of Lundbeck at the time of the study. JHM received research funding for this study from H. Lundbeck A/S. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by a researcher-initiated grant to JHM from H. Lundbeck A/S, as part of STRATA, a large multi-centre research collaborative program led by JHM, funded by the Medical Research Council (Grant number MR/L011794). This work utilised the Clinical Record Interactive Search (CRIS) platform funded and developed by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. DFdF, DA, GKS, EF, IR, MP, HS, DS, RDH and JHM received salary support from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. JD is supported by a NIHR Clinician Science Fellowship award (CS-2018-18-ST2-014), a Medical Research Council (MRC) Clinical Research Training Fellowship (MR/L017105/1) and a Psychiatry Research Trust Peggy Pollak Research Fellowship in Developmental Psychiatry. The views expressed are those of the authors and not those of the NHS, the NIHR, the Department of Health and Social Care, or H. Lundbeck S/A. Publisher Copyright: © The Author(s) 2022.

PY - 2022/11/1

Y1 - 2022/11/1

N2 - Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS. Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

AB - Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS. Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

KW - antipsychotic agents

KW - clozapine

KW - Psychotic disorders

KW - schizophrenia

KW - treatment refractory

UR - http://www.scopus.com/inward/record.url?scp=85140646912&partnerID=8YFLogxK

U2 - 10.1177/02698811221132537

DO - 10.1177/02698811221132537

M3 - Article

C2 - 36268751

AN - SCOPUS:85140646912

SN - 0269-8811

VL - 36

SP - 1226

EP - 1233

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

IS - 11

ER -

Clinical correlates of early onset antipsychotic treatment resistance

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