Project Goals

Clozapine (CLZ) 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 users, current users and former 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 with an easy test, 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-resistance. The total goals are:

1) To predict CLZ efficacy and ADRs (=treatment outcome) 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 initiating CLZ;
2) As the genetic architecture of SCZ has not been fully elucidated, the current project will aid in the further elucidation of the genetic architecture of SCZ and any possible differences between ‘regular’ SCZ patients (those not considered treatment resistant) and those on CLZ (considered generally to be a more homogeneous and severe group).

 Patients diagnosed with schizophrenia, schizoaffective disorder or schizofreniform disorder, aged 18 years or older and have used, are using or are going to use clozapine, can enter the study.

The new users will be seen for the study once before starting CLZ, between 4 and 12 weeks after initiation on CLZ and after 6 month when patients are considered to have a steady state on CLZ. 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 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:

60 new users

2500 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 2021