CYP2D6 genotypes and phenotypes, plasma levels and treatment failure with risperidone or aripiprazole: results from a one-year longitudinal study

C. B. Eap; S. Ranjbar; F. Gamma; K. J. von Plessen; A. von Gunten; P. Conus; C. Gras; M. Piras

doi:10.1055/s-0044-1779558

Pharmacopsychiatry, Inhaltsverzeichnis

Pharmacopsychiatry 2024; 57(02): 86-87
DOI: 10.1055/s-0044-1779558

Abstracts │ XVth Symposium of the Task Force Therapeutic Drug Monitoring of the AGNP

Lecture Abstracts

CYP2D6 genotypes and phenotypes, plasma levels and treatment failure with risperidone or aripiprazole: results from a one-year longitudinal study

Authors

C. B. Eap

¹Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland

²School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland

³Center for Research and Innovation in Clinical Pharmaceutical Sciences, University of Lausanne, Lausanne, Switzerland

⁴Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Geneva, Switzerland
S. Ranjbar

⁵Department of Psychiatry, Center for Psychiatric Epidemiology and Psychopathology, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland
F. Gamma

⁶Les Toises Psychiatry and Psychotherapy Center, Lausanne, Switzerland
K. J. von Plessen

⁷Service of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland
A. von Gunten

⁸Service of Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland
P. Conus

⁹Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland
C. Gras

¹Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland
M. Piras

¹Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland

Abstract

Volltext

Risperidone and aripiprazole are metabolized by the cytochrome P450 2D6 (CYP2D6). Individuals can be categorized as ultrarapid, normal, intermediate, or poor metabolizers (UM, NM, IM and PM, respectively). Greater odds of switching from risperidone (but not from aripiprazole) were previously reported among PM and UM. Importantly, the duration of treatment up to switching was unknown.

Treatment duration up to switching was analyzed for risperidone (N=515) and for aripiprazole (N=467). CYP2D6 *3, *4, *5, *6, *9, *10, *41 and *XN alleles were analyzed. Phenoconversion due to co-medication with CYP2D6 strong inhibitors was also considered.

CYP2D6 genotypes and phenotypes significantly influenced plasma levels of aripiprazole plus dehydroaripiprazole, and of risperidone plus 9-OH-risperidone. Considering PM and (IM+NM+UM), 70% and 42% of switching probability from risperidone was found, respectively (p=0.026). The risk of switching increased over time for PM (interaction term:1.01; p=0.011), becoming significant after three months (HR:1.79; p=0.028). Similar results were obtained when considering phenoconversion, although phenoconverted PM risk of switch was constant over time. The incidence of discontinuation from aripiprazole was increased at 3 months (OR:2.57; CI:1.15-5.58) in UM or PM when compared to NM or IM.

Over one year, CYP2D6 PM presented an increasing risk to switch from risperidone over time, the risk becoming significant after three months. PMs or UMs are associated with increased discontinuation rates after 3 months aripiprazole treatment. This supports preemptive genotyping for CYP2D6 prior to using risperidone and aripiprazole with phenoconversion also being taken into account.