COVID-19 mRNA Therapeutics Meet Psychotropic Drugs

Abstract

In 2021, the Centers for Disease Control and Prevention prioritized vaccination for mentally ill individuals as psychiatric illness was added to the list of COVID-19 risk factors. Currently, there are very few studies on mRNA vaccine efficacy in patients with SPI in treatment with psychotropic drugs. The messenger RNA (mRNA) vaccines for COVID-19, Pfizer-BioNTech and Moderna, were authorized in the US on an emergency basis in December of 2020. The rapid distribution of these therapeutics around the country and the world led to millions of people being vaccinated in a short time span, an action that decreased hospitalization and death but also heightened the concerns about adverse effects and drug-vaccine interactions.

Both psychotropic drugs, especially phenothiazines, and the COVID-19 mRNA vaccine enter cells via the endocytic pathway and may compete for this ingress pathway.  In this chapter, the modified mRNA therapeutics through the endocytic labyrinth and beyond, showing the events that must occur at each step to lead to the formation of neutralizing antibodies against the S(pike) protein, were followed.

The Vaccine Adverse Event Reporting System (VAERS) has gained additional attention during the COVID-19 pandemic, specifically regarding the rollout of mRNA therapeutics. However, for VAERS, the absence of a reporting platform for drug-vaccine interactions left these events poorly defined. For example, chemotherapy, anticonvulsants, and antimalarials were documented to interfere with the mRNA vaccines, but much less is known about the other drugs that could interact with these therapeutics, causing adverse events or decreased efficacy. In addition, SARS-CoV-2 exploitation of host cytochrome P450 enzymes, reported in COVID-19 critical illness, highlights viral interference with drug metabolism. For example, patients with severe psychiatric illness (SPI) in treatment with clozapine often displayed elevated drug levels, emphasizing drug-vaccine interaction. More studies are needed to assess the interaction between the major classes of psychotropic drugs, including antipsychotics, antidepressants, and mood stabilizers, with the mRNA therapeutics.