Trial lecture - time and place
30.05.2024, 10.15, Auditorium 2, Helga Eng
Antipsychotic treatment in the next ten years: new drugs, new formulations, new ways of prescribing
Conferral summary
Målet med dette arbeidet er å forbedre persontilpasset behandling av schizofreni ved å undersøke farmakogenetikk og metabolisme av antipsykotiske legemidler. Resultatene tyder på at rask legemiddelmetabolisme er en risikofaktor for å få lavere serumkonsentrasjoner enn det som kreves for optimal behandlingsrespons, noe som kan føre til feildiagnostisering av behandlingsresistens. Videre rapporterer vi om genetiske mutasjoner som er assosiert med økt metabolisme av vanlige antipsykotiske legemidler, samt identifiserer kandidatgener som kan være involvert i nevrobiologien ved behandlingsresistent schizofreni.
Main research findings
Schizophrenia is a disabling disorder that often requires long-term antipsychotic treatment. However, antipsychotic treatment is associated with extensive variability in clinical response and side effects. Many patients suffer from treatment resistance and are treated with clozapine which is the most effective but also most toxic among antipsychotics. Therefore, before initiating clozapine treatment, reasons for treatment failure must be investigated. In this project, we investigated the pharmacogenetics and metabolism of antipsychotic drugs in patients with resistant schizophrenia to enhance personalized treatment strategies.
The results suggest that rapid drug metabolism of non-clozapine antipsychotics is an important risk factor for having subtherapeutic serum levels and subsequent treatment failure before initiating clozapine. The NFIB gene plays a role in regulating several genes that encode enzymes central to drug metabolism, particularly CYP2D6. Furthermore, tobacco smoker patients who carry the NFIB and CYP1A genetic variants are at risk of significantly decreased clozapine levels and require higher clozapine doses for optimal clinical response. Finally, genome-wide investigation of treatment-resistant schizophrenia has identified candidate genes that should be investigated in future studies.
The studies are performed using real-world patient data from the therapeutic drug monitoring service at Center for Psychopharmacology in Oslo, Norway.