Abstract

Polypharmacy is frequently used to treat mental health conditions.Because the effects of psychotropic medications on a variety of tissue types are currently poorly understood, we investigated the effects of ARI, TRZ, and ARI + TRZ polypharmacy on the post-lanosterol biosynthesis in three cell lines (Neuro2a, HepG2, and human dermal fibroblasts) and seven peripheral tissues of an adult mouse model.The antipsychotic aripiprazole (ARI) and the used in vitro and in vivo models demonstrated effects that were summative or synergistic when ARI and TRZ were administered concurrently. These combinations frequently include medications that inhibit sterol biosynthesis.This was because the 7-dehydrocholesterol reductase enzyme (DHCR7) was significantly disrupted in its function.According to these findings, inhibiting the activity of the DHCR7 enzyme is responsible for at least some of the ARI and TRZ side effects that are not mediated by receptors. All cell lines and somatic tissues showed significant increases in 7-dehydrocholesterol (DHC) and decreases in desmosterol (DES).Because interfering with sterol biosynthesis can potentially hinder the development or functioning of multiple organ systems, particularly when medications with such side effects are used concurrently, we propose that additional research is required.

Keywords: Aripiprazole; Trazodone; Polypharmacy; 7-dehydrocholesterol; 7-dehydrocholesterol reductase; Cholesterol; Desmosterol; Sterols