key: cord-0819686-93yt87mz authors: Shoib, Sheikh; Bharati‐Sinha, Vidya; Javed, Sana; Gürcan, Ahmet; Gürcan, Gamze; Das, Soumitra; Chandradasa, Miyuru; Saeed, Fahimeh title: The disquietude of clozapine continuation during the COVID‐19 pandemic date: 2022-02-07 journal: Health Sci Rep DOI: 10.1002/hsr2.506 sha: 4e13e5afd947fa324ae38e0cd47e09f647f18f67 doc_id: 819686 cord_uid: 93yt87mz nan COVID-19 symptoms such as fever, flu-like symptoms, and myalgia that is seen with neutropenic sepsis (Table 1) . 5, 6 Further, in a study conducted in the United Kingdom among 6309 persons with schizophrenia, it was found that individuals on clozapine had an increased risk of COVID-19 infection compared with those who were on other antipsychotics. 7 It is consistent with previous studies showing clozapine is associated with higher rates of infection and pneumonia than those on other antipsychotics. 8, 9 It is thought that the higher incidence of pneumonia is likely due to sialorrhea. As a result, it raises the risk of pneumonia with COVID-19 infection. 10 Persons on clozapine are at risk for cardiovascular events and death due to the presence of comorbid medical disorders. 11 Diabetes and cardiovascular disease are common comorbidities that enhance the risk. Myocarditis, pericarditis, and cardiomyopathy could be consequence of both COVID-19 and clozapine. These adverse cardiac events appear with highly variable symptoms from a flu-like initiation to chest pain, shortness of breath, fever, tachypnea, and sudden death. Serial MB isoenzyme of creatine phosphokinase (CPK-MB), C-reactive protein (CRP), troponin test, and ECG is advised in order to determine any sign which refers to a cardiac event. 12, 13 Clozapine-induced cardiac complications may be missed and delayed presenting to services due to the similarity with the symptomatology of the COVID-19. A delay could lead to serious consequences such as clozapine-induced myocarditis has an estimated mortality of more than 20%. 14 Fever in patients who take clozapine is related to varied causes from a benign fever to serious condition such as neutropenic sepsis. 3 To reduce the risks of concealing COVID-19 symptoms, it is advisable to avoid paracetamol treatment for clozapine fever. To avoid neutropenic sepsis, a white blood cells (WBC) count with absolute neutrophil count monitoring is required. It will help to distinguish between neutropenic sepsis and COVID-19 infection if symptoms appear. Vitamin D supplementation is necessary to reduce the risk of pneumonia, and smoking cessation should be promoted. 15 Diabetes is a common side effect, and it raises the risk of COVID-19 infection and related complications. Blood glucose monitoring is particularly crucial. 3 A cumulative 10% risk of seizures after 3.8 years of clozapine treatment has been recognised. 16 18 Venous thromboembolism is a rare clozapine adverse effect, although smoking, weight gain, and cardiovascular disease all enhance the risk. 19 When a person on clozapine contracts COVID-19, it is likely that neurological and vascular complications become more likely than the general population. Many medicines are used off-label for the treatment of COVID-19. Chloroquine, hydroxychloroquine, azithromycin, lopinavir/ritonavir, ribavirin, remdesivir, and tocilizumab are the most used medications. Each of these substances distinctly interacts with psychotropic drugs. With clozapine, atazanavir, lopinavir/ritonavir, and QT prolongation can occur, necessitating strict monitoring. 20 Azithromycin causes neutropenia, which is also a common clozapine side effect. 21 Clozapine has been reported to increase ribavirin blood levels due to pharmacokinetic interactions, which increases the risk of bone marrow suppression and necessitates comprehensive blood count monitoring. 15 Ribavirin produces serious adverse effects, including depression, aggressiveness, and suicide ideation. Due to a reduction in metabolism in response to inflammatory reactions, COVID-19 infection enhances the probability Covid-19, and mental health: a transformational opportunity to apply an evidence-based approach to clinical practice and research. Evid Based Ment Health Association between mental health disorders and mortality among patients with COVID-19 in 7 countries: a systematic review and meta-analysis Unique effects of clozapine: a pharmacological perspective Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine. Therapeutic Advances in Drug Safety COVID-19: current understanding of its pathophysiology, clinical presentation, and treatment The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder Clozapine treatment and risk of COVID-19 infection: retrospective cohort study Antipsychotic re-exposure and recurrent pneumonia in schizophrenia: a nested case-control study Second-generation antipsychotic medications and risk of pneumonia in schizophrenia Aspiration pneumonia due to clozapine-induced sialorrhea diabetes mellitus, cardiovascular risk and mortality: results of a 21-year naturalistic study in patients with schizophrenia and schizoaffective disorder Clozapine-related sudden pericarditis in a patient taking long acting aripiprazole and valproate: a case report Update on the adverse effects of clozapine: focus on myocarditis Potentially fatal outcomes associated with clozapine Evidence regarding vitamin D and risk of COVID-19 and its severity Carod-Artal FJ. Neurological complications of coronavirus and COVID-19. Complicaciones neurol ogicas por coronavirus y COVID-19 Incidence of venous thromboembolism in hospitalized patients with COVID-19 Clozapine associated pulmonary embolism: systematic review Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents Drug interactions of clinical significance Clozapine: an updated overview of pharmacogenetic biomarkers, risks, and safety-particularities in the context of COVID-19 Review and management of clozapine side effects Antipsychotic-induced immune dysfunction: a consideration for COVID-19 risk Elevated clozapine levels and toxic effects after SARS-CoV-2 vaccination Clozapine-associated secondary antibody deficiency Clozapine treated patients and COVID-19: ensuring continued care through collaboration Community mental health care delivery during the COVID-19 pandemic: practical strategies for improving care for people with serious mental illness Consensus statement on the use of clozapine during the COVID-19 pandemic Outcomes for schizophrenia patients with clozapine treatment: how good does it get? Suicide and genetic biomarkers: toward personalized tailored-treatment with lithium and clozapine Safety and efficacy of combined clozapine-azathioprine treatment in a case of resistant schizophrenia associated with Behçet's disease: a 2-year follow-up