Aripiprazole and CYP2D6: A retrospective cohort study evaluating the impact of phenotype on metabolic abnormalities

The aim of this study was to investigate the influence of CYP2D6 functionality on metabolic abnormalities in patients prescribed aripiprazole.

A retrospective cohort review was conducted in patients who had CYP2D6 genotyping and an oral prescription for aripiprazole. Primary outcomes were changes in metabolic parameters from baseline based on CYP2D6 genotype-based phenotype. Patients concurrently taking medications that cause CYP2D6 inhibition were classified as phenoconverters and were categorized as poor metabolizers in subanalyses. Index and post-aripiprazole (after either initiation or dose modification) data were abstracted from the electronic medical record for the following endpoints: body mass index (BMI), blood glucose, glycated hemoglobin, low-density lipoprotein (LDL), triglycerides, and total cholesterol.

In multivariate mixed-effects analysis of 1,562 patients, the genotype-based phenotype cohort had no significant differences. A marginal difference in triglyceride levels was observed between poor metabolizers and normal metabolizers (β = 23.42; range, -4.9 to 51.73; P = 0.11). Findings were similar between poor metabolizers and normal metabolizers when evaluating outcomes encompassing phenoconversion, although poor metabolizers had an increased mean change in LDL levels (β = 10.04; range, 1.46 to 18.61; P < 0.05) and had a decreased mean change in BMI (β = -0.34; range, -0.72 to 0.04; P = 0.08); however, these differences were not statistically significant.

This study suggests that the incidence of metabolic abnormalities beyond LDL may not be higher in CYP2D6 poor metabolizers compared to normal metabolizers. Further research is needed to investigate clinically meaningful outcomes in relation to CYP2D6 and aripiprazole.