Defining treatment refractoriness in schizophrenia

The criteria for treatment refractoriness for the use of clozapine are necessarily set at a high level because of the potential risk of agranulocytosis with this treatment. However, a more liberal definition should be considered to better appreciate the limitations of current therapies and prepare for switching to the next generation of clozapine-like drugs that do not cause agranulocytosis. It is suggested that failure of therapy to bring about the best premorbid level of functioning be considered as a starting point for treatment-resistance.