Clozapine and Treatment Resistance - CRESTAR
The CRESTAR collaboration - Pharmacogenomic biomarkers as clinical decision making tools for treatment of schizophrenia
Why are we doing this research?
About one third of patients with schizophrenia do not respond adequately to treatment with antipsychotic medication. To date the only medicine with proven benefit in such “treatment refractory” patients is clozapine. However, at present clinicians are not able to predict in advance who will require treatment with clozapine. As a result, many people spend years taking treatments that are ineffective, before finally being offered clozapine, which adds to their distress and may even lead to worse long-term outcomes than if clozapine had been started earlier.
So why not recommend clozapine from the outset? A further problem is that clozapine has severe side effects, including a very rare but potentially fatal reduction in white blood. At present, we are unable to predict which patients are at risk from these rare side effects, meaning that all patients taking clozapine are required to take regular blood tests to monitor their blood counts. This approach has been very successful in improving the safety profile of clozapine. However, regular blood tests are inconvenient, and some patients are put off taking clozapine for this reason. In many cases, patients are denied a treatment that could help them live full and productive lives.
The primary aim of CRESTAR is to develop clinical prediction tools that will help clinicians to determine in advance (a) which patients are likely to require clozapine, and (b) which patients are at risk of side effects. Treatment would then be tailored to the individual patient, so that effective treatment could be started sooner, and treatment with clozapine would be safer, and require less monitoring, since blood monitoring would be focussed on those patients who were truly at risk.
What are we doing?
CRESTAR is hosted at the Department of Social, Genetic and Developmental Psychiatry at King’s College London but is an international effort, involving 10 centres in the UK, Iceland, Germany, Denmark, Sweden and the Netherlands. We will use clinical, epidemiological and genetic data in very large numbers of individuals to develop algorithms to predict treatment resistance and propensity to the adverse effects of clozapine. The ultimate aim is to produce evidence-based, decision-making tools for clozapine prescription. In parallel, we will assess ethical and regulatory issues related to this approach, and examine the health economics of predisting treatment response and adverse events.
Who is involved?
Dr James MacCabe
Dr Sophia Frangou
We are collaborating with colleagues from the department of Social, Genetic and Developmental Psychiatry, including the Principal Investigator of the project, David Collier.
Who funds the study?
The project is funded by a grant from the European Union via the Seventh Framework Programme for Research and Technological Development.
Dr James MacCabe