Traditionally, for those patients who are unable to obtain adequate positive symptom control or sustain a response with at least 2 dopamine receptor-2 (D2)-blocking agents at therapeutic doses for at least 6 weeks, clozapine is the recommended drug of choice. An estimated 30–60% of these patients will respond to clozapine and have what can be described as a clozapine-responsive psychosis (10, 15, 16). Patients who do not have an optimal response to clozapine and continue to experience prominent positive symptoms have clozapine-resistant psychosis or an ultra-resistant psychotic disease (11). Currently, there are no therapies that address this most severe form of neural-dysconnectivity in schizophrenia.