Changes in immunoglobulin levels during clozapine treatment in schizophrenia.

Antipsychotic Observational Psychosis Treatment-resistance

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 18 05 2023
revised: 20 09 2023
accepted: 06 10 2023
pubmed: 14 10 2023
medline: 14 10 2023
entrez: 13 10 2023
Statut: ppublish

Résumé

Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored. This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS). IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03). The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Sections du résumé

BACKGROUND AND HYPOTHESIS OBJECTIVE
Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored.
DESIGN METHODS
This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS).
RESULTS RESULTS
IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: β = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03).
CONCLUSIONS CONCLUSIONS
The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Identifiants

DOI: 10.1016/j.bbi.2023.10.001 PMID: 37832895
pubmed: 37832895
pii: S0889-1591(23)00301-X
doi: 10.1016/j.bbi.2023.10.001
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

223-228

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Kira Griffiths (K)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

Maria Ruiz Mellado (MR)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

Raymond Chung (R)

Department of Social Genetic and Developmental Psychiatry, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

John Lally (J)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK; Department of Psychiatry, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Department of Psychiatry, Mater Misericordiae University Hospital, Dublin, Ireland.

Grant McQueen (G)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

Kyra-Verena Sendt (KV)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

Amy Gillespie (A)

Department of Psychiatry, University of Oxford, UK.

Muhammad Ibrahim (M)

Department of Immunobiology, Faculty of Life Sciences and Medicine, King's College London, UK.

Alex Richter (A)

Institute of Immunology and Immunotherapy, University of Birmingham, UK.

Adrian Shields (A)

Institute of Immunology and Immunotherapy, University of Birmingham, UK.

Mark Ponsford (M)

Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK; Henry Wellcome Building, School of Medicine, Cardiff University, Cardiff, UK.

Stephen Jolles (S)

Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK.

John Hodsoll (J)

Department of Biostatistics and Health Informatics, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

Thomas A Pollak (TA)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

Rachel Upthegrove (R)

Institute for Mental Health, University of Birmingham, UK; Early Intervention Service, Birmingham Womens and Childrens NHS Foundation Trust, UK.

Alice Egerton (A)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK.

James H MacCabe (JH)

Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, UK. Electronic address: james.maccabe@kcl.ac.uk.

Classifications MeSH