Vaccination and clozapine use: a systematic review and an analysis of the VAERS database

In the context of COVID-19 concerns related to the potential interactions between clozapine and vaccination arose. With the ultimate goal of deriving recommendations for clinical practice, we systematically reviewed the current evidence regarding altered vaccine effectiveness in clozapine-treated patients and safety aspects of vaccination, such as haematological changes and the impact of vaccines on clozapine blood levels, in clozapine-treated patients. A systematic PRISMA-conform literature search of four databases (PubMed, PsycINFO, EMBASE and Cochrane Library) complemented by a case-by-case analysis of the Vaccine Adverse Event Reporting System (VAERS) database was performed. We then systematically appraised the joint evidence and tried to derive recommendations for clinical practice. 14 records were included in this analysis. These records consisted of 5 original articles and 9 case reports. Among the original articles, two studies provided data on the association between clozapine use and antibody responses to vaccination, both indicating that clozapine use in schizophrenia may be associated with reduced levels of immunoglobulins. Additionally, three studies examined vaccine safety in clozapine-treated patients, with no clinically significant adverse effects directly attributable to the interplay between vaccinations and clozapine. VAERS Analysis encompassed 137 reports and showed no consistent evidence of an increased risk for clozapine blood level increases or adverse events. We found no evidence indicating that clozapine impairs the effectiveness of vaccines. Moreover, no serious safety concerns seem to apply when patients on clozapine are receiving vaccines. However, it is crucial to acknowledge that data on the interaction between clozapine and vaccines remain limited.