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Towards personalized treatment with clozapine

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.

Comments：

This study aimed to investigate the efficacy and side effects of clozapine treatment in people with treatment-resistant schizophrenia and identify factors associated with response to treatment. The study collected data from over 800 clozapine users diagnosed with schizophrenia spectrum disorder and conducted meta-analyses and genetic association analyses.

The study found that clozapine was more effective when used as a first- or second-line treatment, and younger age, less negative symptoms, and the paranoid subtype of schizophrenia were associated with a better clozapine response. Specific locations on genes (loci) were associated with clozapine-induced agranulocytosis and neutropenia, while polygenic risk scores were associated with symptom severity.

These findings suggest that clozapine could be used earlier in treatment and that certain factors could aid in predicting response to clozapine treatment. Personalized clozapine treatment based on these factors could potentially improve outcomes for people with treatment-resistant schizophrenia.

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S2711 DBZ (Dibenzazepine) DBZ (Dibenzazepine) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

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