Antibody deficiency in patients taking clozapine

Ponsford, Mark; Jolles, Stephen

doi:10.1136/bmj.l483

Cited by 5 publications

(6 citation statements)

References 12 publications

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“…However, the role of depressed WCC function in clozapine-induced infections is not clear; for example, death from pneumonia is reported to have occurred in the absence of a neutropenia (Taylor et al, 2009). Other immunomodulatory effects of clozapine have also been shown (Roge et al, 2012), and evidence is now emerging on the effect of clozapine on immunoglobulins and the role antibody deficiency plays in clozapine-induced infection (Jolles et al, 2014;Lozano et al, 2016;Ponsford and Jolles, 2019;Ponsford et al, 2018). Antibody replacement therapy may successfully reduce risk of infection (Ponsford et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Incident infection during the first year of treatment – A comparison of clozapine and paliperidone palmitate long-acting injection

et al. 2022

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Background: To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI). Method: A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services. Results: The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; p = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15–15.76, p = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related. Conclusion: Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.

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Section: Discussionmentioning

confidence: 99%

Incident infection during the first year of treatment – A comparison of clozapine and paliperidone palmitate long-acting injection

et al. 2022

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“…Postulated mechanisms include sialorrhoea, sedation, agranulocytosis, and aspiration. We recently reported an association between clozapine therapy in schizophrenia and hypogammaglobulinemia (12, 13), greater than that reported following rituximab and methotrexate therapy in rheumatoid arthritis (14). To better define the clinical and immunologic abnormalities associated with clozapine use we performed a retrospective case review of patients assessed at the Immunology Centre for Wales (ICW).…”

Section: Introductionmentioning

confidence: 86%

Clinical and laboratory characteristics of clozapine treated schizophrenia patients referred to a national immunodeficiency clinic reveals a B-cell signature resembling CVID

Ponsford

Steven

Bramhall

et al. 2019

Preprint

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Purpose: An association between antibody deficiency and clozapine use in individuals with Schizophrenia has recently been reported. We hypothesized that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns. Methods: Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunologic features for individuals with diagnosis of schizophrenia-like illness. Results: 1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizo-affective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B-cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT. Conclusion: Our findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency CVID, however appears reversible upon drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.

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“…Off‐target effects of SGAs at the thromboxane A2 receptor (TBXA2R) and platelet‐activating factor receptor (PTAFR) have been implicated in increased pneumonia prevalence, 20 as TBXA2R and PTAFR mediate capillary permeability at the alveolar level, which if compromised can lead to alveoli oedema–a recognised risk factor as well as symptom of pneumonia 21 . There is also emerging evidence to suggest that clozapine can impede immunoglobulin function 22–26 …”

Section: Introductionmentioning

confidence: 99%

“…21 There is also emerging evidence to suggest that clozapine can impede immunoglobulin function. [22][23][24][25][26] Few studies have examined risk differences between individual antipsychotics 23,24,27 or association with pneumonia-related death. In this study, we have examined the association of specific antipsychotic exposure to overall pneumonia-related mortality, and performed sub-analysis by pneumonia type-pneumonia can manifest due to pathogenic infection or aspiration of substances, 21 and it is important to understand if there is differential risk with antipsychotic use between pneumonia types.…”

Section: Introductionmentioning

confidence: 99%

A case–control study of antipsychotic use and pneumonia‐related mortality in the United Kingdom

Copeland

Wallman

Morgan

et al. 2023

Acta Psychiatr Scand

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Background and aim There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia‐related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia‐related death with specific antipsychotic exposure. Method Deaths analysed were those reported to a UK‐based drug‐related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case–control study with cases defined as pneumonia‐related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post‐mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders. Results There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia‐related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15–1·55]; prescribed AOR 1·28 [95% CI 1·11–1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77–1·47]; prescribed AOR 0·91 [95% CI 0·71–1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22–1·82]; prescribed AOR 1·44 [95% CI 1·18–1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07–1·66]; prescribed AOR 1·28 [95% CI 1·01–1·64]). Conclusion Olanzapine and quetiapine were found to increase the risk of pneumonia‐related death in this NPSAD sample to a clinically important extent.

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Antibody deficiency in patients taking clozapine

Cited by 5 publications

References 12 publications

Incident infection during the first year of treatment – A comparison of clozapine and paliperidone palmitate long-acting injection

Incident infection during the first year of treatment – A comparison of clozapine and paliperidone palmitate long-acting injection

Clinical and laboratory characteristics of clozapine treated schizophrenia patients referred to a national immunodeficiency clinic reveals a B-cell signature resembling CVID

A case–control study of antipsychotic use and pneumonia‐related mortality in the United Kingdom

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