The special case of treatment resistant patients
Treatment resistant schizophrenia is one of the most disabling of all psychiatric illnesses, affecting about a third of patients with this illness (~1 million Europeans), a considerable personal, economic and social burden.
To date, the atypical antipsychotic drug clozapine is the only evidence-based treatment for patients with treatment resistant schizophrenia. Because of the side effects associated with clozapine, it is not usually prescribed as a first line therapy in Europe. If two trials of antipsychotics fail, then the patient can be given clozapine but this process might take many years (typically five years but up to a decade). It is at present not possible to predict which patients will require clozapine.
In one study, only half of patients who had schizophrenia that was considered treatment resistant were taking clozapine. Of those not receiving clozapine, half refused and half could not be treated for medical reasons including the failure of previous trials and side effects. Levels of ongoing clinical problems were significantly greater in this group. Thus only just over half of the patients who need clozapine on clinical grounds were actually taking it. While half of these refuse, the rest encounter obstacles to treatment. This illustrates the difficulties of delivering clozapine to treatment-resistant patients.
Improvements in therapeutic drug monitoring and overall safety of clozapine, for example by reducing the risk of ADRs or more effective (e.g. lower) doses, could reduce the number of patients either refusing clozapine therapy, or reduce treatment failure because of lack of efficacy or side effects. The development of treatment resistance should be avoided if possible, and this might also be achieved by giving clozapine to patients much sooner in their illness.
The central aim of CRESTAR is to develop tools which enable patients who need clozapine - because they are not likely to respond to the usual antipsychotics - have access to the drug as early as possible, perhaps within weeks of illness onset, and that clozapine use is as safe as possible in these patients.