Abstract:Background/Objectives
There have been concerns that clozapine treatment may undermine the capacity of the body to fight infection and increase the vulnerability to contracting COVID-19. This review of recent cohort studies investigated (1) whether people with a severe psychiatric disorder are at increased risk of COVID-19 and complications, (2) the immunological response of clozapine-users who contract COVID-19, and (3) patients’ perspectives on COVID-19 and the pandemic response.
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“…Although incidence rates were higher than reported in previous studies, all cases of mild neutropenia were likely related to infection with COVID-19. 9 This is consistent with evidence that the risks of neutropenia and agranulocytosis are very low after 1 year of treatment. 6,10 In fact, more recent data, including meta-analyses, have challenged the notion that clozapine poses an increased risk of neutropenia compared with conventional antipsychotics.…”
Section: Haematological and Clinical Outcomessupporting
confidence: 87%
“…8 The importance of these recommendations has since been emphasised by recent evidence associating clozapine use with an increased risk of COVID-19 infection which, in some cases, results in clozapine intoxication. 9 Fig. 1Summary of the UK Medicines & Healthcare products Regulatory Agency (MHRA) guidelines for clozapine monitoring frequency (white cell count and absolute neutrophil count) and the emergency 12-weekly monitoring protocol.…”
mentioning
confidence: 99%
“…8 The importance of these recommendations has since been emphasised by recent evidence associating clozapine use with an increased risk of COVID-19 infection which, in some cases, results in clozapine intoxication. 9 Since then, there have been calls for extended monitoring to be implemented in routine practice to help ease restrictions to clozapine use. At present, it is unknown how this policy change influences clinical outcomes in those receiving clozapine treatment.…”
Background
To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.
Aims
To investigate the impact of this temporary policy change on clinical and safety outcomes.
Method
All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.
Results
Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02–28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.
Conclusions
There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.
“…Although incidence rates were higher than reported in previous studies, all cases of mild neutropenia were likely related to infection with COVID-19. 9 This is consistent with evidence that the risks of neutropenia and agranulocytosis are very low after 1 year of treatment. 6,10 In fact, more recent data, including meta-analyses, have challenged the notion that clozapine poses an increased risk of neutropenia compared with conventional antipsychotics.…”
Section: Haematological and Clinical Outcomessupporting
confidence: 87%
“…8 The importance of these recommendations has since been emphasised by recent evidence associating clozapine use with an increased risk of COVID-19 infection which, in some cases, results in clozapine intoxication. 9 Fig. 1Summary of the UK Medicines & Healthcare products Regulatory Agency (MHRA) guidelines for clozapine monitoring frequency (white cell count and absolute neutrophil count) and the emergency 12-weekly monitoring protocol.…”
mentioning
confidence: 99%
“…8 The importance of these recommendations has since been emphasised by recent evidence associating clozapine use with an increased risk of COVID-19 infection which, in some cases, results in clozapine intoxication. 9 Since then, there have been calls for extended monitoring to be implemented in routine practice to help ease restrictions to clozapine use. At present, it is unknown how this policy change influences clinical outcomes in those receiving clozapine treatment.…”
Background
To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.
Aims
To investigate the impact of this temporary policy change on clinical and safety outcomes.
Method
All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.
Results
Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02–28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.
Conclusions
There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.
“…The authors support the previously suggested 9,83 interference of COVID-19 in clozapine metabolism. 91 The main limitation of our study was not determining clozapine plasma concentration after the vaccination. Other limitations were the small sample size and the duration of observation, which might have prevented us from finding other consequences of COVID-19 vaccination.…”
Section: Discussionmentioning
confidence: 93%
“…The authors support the previously suggested 9,83 interference of COVID-19 in clozapine metabolism. 91…”
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.
Key Clinical MessageCOVID‐19 infection may increase the likelihood of neutropenia in patients already on clozapine. In clozapine treated patients experiencing COVID‐19 associated neutropenia, adjunct therapy with lithium can be considered.
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