Project Goals

Clozapine is generally prescribed if at least two trials of antipsychotic agents have not led to satisfactory clinical improvement. Currently, clozapine is underprescribed worldwide. This study focus on different groups of clozapine users. We make a distinction between new, current and former clozapine users. The overarching goal of the projects is to create a prediction tool for clozapine outcome (response and side effects). This model includes genetic, epigenetic, and clinical data. If we know who will likely respond well and with no severe side-effects to clozapine therapy, doctors might use clozapine more often. We think that this is better for patients that are in an early stage of treatment-resistant schizophrenia, but also for the more chronic patients with treatment-resistant schizophrenia.

The total goals of the study are:
Primary:
1) To predict clozapine efficacy and side effects based on phenotypic and genetic data obtained in this study.

Secondary:
1) To investigate which non-genetic factors, methylation and gene expression levels/patterns predict treatment outcome after initiation of clozapine;
2) As the genetic architecture of schizophrenia has not been fully elucidated, the current project will aid in the further elucidation of the genetic architecture of schizophrenia and any possible differences between ‘regular’ schizophrenia patients (those not considered to be treatment resistant) and those on clozapine (generally considered to be a more homogeneous and severe group).

Patients with a diagnosis of schizophrenia spectrum disorder aged 18 years or older who have taken, will be taking, or are taking clozapine can participate in the study.

The new users will be seen for the study once before initiation of clozapine or in 10 days after initiation, between 4 and 12 weeks after initiation of clozapine and after 6 months, when patients are considered to have reached steady state blood levels of clozapine. Blood will be drawn at each visit and the researcher will conduct a questionnaire which will last approximately 1 hour and 20 minutes. The current and former users will only be seen once. Blood will be drawn during this visit and the researcher will conduct a questionnaire which will last approximately 10 minutes.

Estimated enrollment:
300 new users
4000 current and former users

Study start date pilot: January 2016
Study end date pilot: December 2018
Study start date full study: January 2019
Study end date full study: December 2022 (planned)