Op naar een gepersonaliseerde clozapinebehandeling

Abstract

BACKGROUND: Clozapine is the most effective treatment for people with treatment-resistant schizophrenia. However, it is prescribed less often than guidelines indicate. AIM: To personalize clozapine treatment, we investigated the efficacy of clozapine as first- or second-line treatment and investigated whether there are factors that were associated with efficacy and side effects. METHOD: We collected a unique cohort of over 800 clozapine users diagnosed with a schizophrenia spectrum disorder. We meta-analyzed factors that were associated with response during clozapine treatment. Additionally, we conducted genetic association analyses to investigate the relations between side effects and symptom severity during clozapinetreatment. RESULTS: From our meta-analyses, we found that clozapine was more effective when used as a first- or second-line treatment. Furthermore, we found that younger age, less negative symptoms and the paranoid subtype of schizophreniawere associated with a better clozapine response. Several specific locations on genes (loci) were associated with clozapine-induced agranulocytosis and neutropenia, while polygenic risk scores were associated with symptom severity. CONCLUSION: We found that clozapine could be effective earlier in treatment and identified factors that could aid the prediction of< response to clozapine treatment in the future. These finding could contribute to the start of a personalized clozapine treatment.