Challenges in Prescribing Clozapine in the Era of COVID-19: A Review Focused on Immunological Implications

Jeong, Seong Hoon; Kim, Yong Sik

doi:10.9758/cpn.2021.19.3.411

Cited by 11 publications

(11 citation statements)

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“…These inflammatory states can aggravate morbidity from COVID-19 infection, and the immunosuppressive effects of clozapine may decrease the defensive capacity of the host. 36 In addition to our main objective, our search also found some interesting results regarding clozapine and COVID-19 vaccination. One study including 139 patients showed that clozapine blood levels have significantly increased after the second COVID-19 vaccination and changes in WBC count were limited to mild granulocytopenia, moderate granulocytopenia, and leukocytopenia.…”

Section: Resultsmentioning

confidence: 87%

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Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Moga

Teodorescu

Dragan³

et al. 2022

American Journal of Therapeutics

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Background: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. Areas of Uncertainty:In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection?Data Sources: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis.Therapeutic Advances: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients.Results: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia.Conclusions: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.

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Section: Resultsmentioning

confidence: 87%

“…These inflammatory states can aggravate morbidity from COVID-19 infection, and the immunosuppressive effects of clozapine may decrease the defensive capacity of the host. 36…”

Section: Resultsmentioning

confidence: 99%

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Moga

Teodorescu

Dragan³

et al. 2022

American Journal of Therapeutics

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“…First, the immunosuppressive effect of clozapine may render a patient more susceptible to COVID-19 (de Leon et al ., 2020). Second, clozapine may exacerbate inflammation and increase the risk of cytokine storms (Jeong and Kim, 2021). Third, since the released cytokines impede the synthesis and action of cytochrome P450 enzymes, clozapine concentrations may soar, leading to sudden toxicity (Cranshaw and Harikumar, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…What is more unsettling is that the elevated ANC might indicate an over-activated cytokine network. Since clozapine has a significant effect on the cytokine network, there is concern that it may increase the likelihood of a cytokine storm, potentially worsening the prognosis (Roge et al ., 2012; Jeong and Kim, 2021). Fortunately, a recent review concluded that there is insufficient evidence that clozapine leads to a worse outcome (Giles et al ., 2023).…”

Section: Discussionmentioning

confidence: 99%

Change in absolute neutrophil count after COVID-19 infection in patients using clozapine versus other antipsychotics

Jeong,

Lee,

Kim

et al. 2024

International Clinical Psychopharmacology

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It was reported that patients who contracted COVID-19 while taking clozapine exhibited a distinct hematological response. However, the absence of control groups made it difficult to attribute it to clozapine. The changes in absolute neutrophil counts (ANCs) during the 4 weeks after COVID-19 infection were compared between the two groups of patients with severe mental illnesses (SMIs) (49 patients using clozapine and 54 using other antipsychotics) using generalized additive modeling. Although the pattern of a transient drop in ANC followed by gradual recovery could be demonstrated in both groups, it was more pronounced in the clozapine group (P = 0.00025). Nevertheless, overall ANC remained at a higher level in the clozapine group. The results suggested potential interaction between clozapine and COVID-19 at the level of hematological dynamics. However, it did not necessarily indicate that such interaction is inevitably harmful or dangerous. It was more of a concern that some patients using other antipsychotics exhibited decreased ANC, which did not easily recover. Traditionally, clinicians have been concerned about the worsening of hematological side effects in clozapine patients after COVID-19 infection. However, the obtained result highlighted the necessity of hematological monitoring in patients using any type of antipsychotics for SMIs.

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“…However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol (initiation, titration, and monitoring), and side effects in patients with COVID-19 infection. 10,11 During the pandemic, studies have shown difficulties in the administration of long-acting injectable antipsychotics (LAIs) 12,13 as well as the unfavorable effects of switching from LAIs to oral antipsychotics. 14 Accumulating evidence indicates that antipsychotics may have a protective effect against SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection

Moga

Petric

Miron

et al. 2023

American Journal of Therapeutics

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Background: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 . Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients.Study Question: The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters. Study Design:We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics.Measures and outcomes: The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine.

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Challenges in Prescribing Clozapine in the Era of COVID-19: A Review Focused on Immunological Implications

Cited by 11 publications

References 100 publications

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Change in absolute neutrophil count after COVID-19 infection in patients using clozapine versus other antipsychotics

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection

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