The disquietude of clozapine continuation during the COVID‐19 pandemic

The coronavirus disease (COVID-19) pandemic has posed numerous challenges to the world. Patients who suffer from a mental health condition are more likely to become infected with COVID-19 because they may have difficulties in following precautionary measures, needing regular contact with a health facility for psychological monitoring and a reduction in health care support during the pandemic. The risk of infection is also increased because of comorbidities and/or psychotropic medication side effects. In a recent systematic review of sixteen studies conducted in seven nations, higher COVID-19 mortality was seen in people with mental disorders. Therefore, individuals with psychiatric disorders should be considered as high-risk for severe COVID-19 complications and encourage to take substantive preventive strategies. Clozapine is an important medicine in the treatment of resistant schizophrenia. Although effective, clozapine has a wide range of significant side effects that some of them are irritating such as sedation, dizziness, gastrointestinal symptoms, sialorrhea, benign fever etc. Some of them are life threatening such as seizures, heart adverse effects, pneumonia, hepatic failure, pancreatitis, respiratory failure, agranulocytosis, and sudden death. Many side effects overlap with COVID-19 symptoms such as fever, flu-like symptoms, and myalgia that is seen with neutropenic sepsis (Table 1). 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. It is consistent with previous studies showing clozapine is associated with higher rates of infection and pneumonia than those on other antipsychotics. 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. Persons on clozapine are at risk for cardiovascular events and death due to the presence of comorbid medical disorders. 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. 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%. Fever in patients who take clozapine is related to varied causes from a benign fever to serious condition such as neutropenic sepsis. 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. Diabetes is a common side effect, and it raises the risk of COVID-19 infection and related complications. Blood glucose monitoring is particularly crucial. A cumulative 10% risk of seizures after 3.8 years of clozapine treatment has been recognised. COVID-19 infection has been linked to a variety of neurological symptoms, including headache, dizziness, myalgia and anosmia, encephalopathy, encephalitis, necrotizing hemorrhagic encephalopathy, stroke, epileptic seizures, rhabdomyolysis, and Guillain-Barre syndrome. COVID-19 infection increases the risk of thromboembolism and raises the risk of deep venous thrombosis and pulmonary embolism. Venous thromboembolism is a rare clozapine adverse effect, although smoking, weight gain, and cardiovascular disease all enhance the risk. 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. Azithromycin causes neutropenia, which is also a common clozapine side effect. 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. 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 Received: 21 September 2021 Revised: 22 November 2021 Accepted: 20 December 2021