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

Abstract

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.

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

“…The same review found that SARS-CoV-2 infected and clozapine-treated patients show a temporary reduction in neutrophils' count; however, vaccination studies did not indicate severe adverse effects. The authors support the previously suggested 9,83 interference of COVID-19 in clozapine metabolism. 91…”

“…Data suggested that TRS patients on clozapine treatment are at no greater risk of developing neutropenia or agranulocytosis if contracting COVID-19 than the noninfected population and that only a mild, transient drop in ANC is to be expected. 9,83…”

“…Data suggested that TRS patients on clozapine treatment are at no greater risk of developing neutropenia or agranulocytosis if contracting COVID-19 than the noninfected population and that only a mild, transient drop in ANC is to be expected. 9,83 Ever since vaccines for SARS-CoV-2 became available, their short-term and long-term safety profile has been a major concern. Early reports suggested an increased risk of hematological abnormalities, such as thrombocytopenia, after the administration of Moderna and Pfizer-Bi-oNTech.…”

Magnesium Citrate Powders from Waste Bitterns via Crystallization and Spray Drying

“…3130 and 2280 tonnes in 2016, respectively. Consumption is forecast to rise to 7830 tonnes in total by 2023 …”

“…After liquid/solid separation, the hydrate is then thermally treated at 150–190 °C to yield the anhydrous form. , This process is considered to be the conventional technology and has been applied by manufacturers worldwide (Jungbunzlauer, Global Calcium, Ningxiang Xinyang Chemical, etc.) to produce magnesium citrate products. ,,, Lab-scale studies designed to prepare magnesium citrate from magnesium-bearing ores such as magnesite (MgCO 3 ) and dolomite (CaCO 3 ·MgCO 3 ) have been described as an alternative. , The process involves acid-citric leaching to yield magnesium citrate solutions, followed by precipitation/crystallization to form magnesium citrate hydrates with subsequent conventional drying. Magnesium citrates have also been synthesized via spray drying of leach solutions .…”