Grant: Operating Grant

It is estimated that approximately one third of individuals with schizophrenia are 'treatment resistant', meaning that they show a poor response to the drugs (antipsychotics) available. However, there is one antipsychotic, clozapine, that seems to work in this group much better than the other available drugs. Unfortunately, it is associated with a number of side effects that can be serious (e.g. seizures) and even life threatening (changes in white blood cells). One way of monitoring clozapine is to take a blood sample and look at how much is in the blood (levels). There is some work that has also shown these levels might be linked to both response and side effects. To date, though, the work done on levels has been limited and results inconsistent; in addition, little attention has been given to the relationship between levels and certain important side effects. We propose to do a study that will look at a large number of individuals on clozapine, in which we do their levels and link them to different measures of clinical response as well as a number of important side effects. In addition, we will look at genetic markers to see if we can predict who might best respond to clozapine or develop these serious side effects. Schizophrenia is a serious mental illness that is common and profoundly impacts affected individuals and their families. About a third of these individuals are 'treatment resistant', and the only treatment we have with proven efficacy in this group is clozapine. However, this drug also has serious side effects. This project, looking at blood levels and relating them to response and side effects, may allow clinicians to use clozapine more effectively and safely.