As many as 30% of schizophrenic patients are resistant to standard antipsychotic medications. Clozapine represents a unique treatment in our armamentarium for schizophrenia as it is helpful in treating 30-50% of the treatment-refractory patients. However, 50-70% of these unfortunate patients do not respond adequately to clozapine, and are left without any viable treatment options. They continue to suffer unrelentingly, and represent a considerable burden to their families and society. This study will investigate electroconvulsive therapy (ECT) as an augmentation strategy for patients who have failed to adequately respond to clozapine. The choice of ECT is based on three converging lines of evidence: in the pre-antipsychotic medication era, ECT was often an effective treatment for schizophrenia; the combination of ECT and antipsychotic medications provides enhanced clinical response; and several case series suggest a benefit when ECT is added to clozapine. Continued clozapine monotherapy and clozapine augmentation with ECT in clozapine refractory schizophrenic patients will be compared in a prospective, random assignment study. We will treat patients who have had at least 12 weeks of an adequate clozapine trial. Sixty-four subjects (32 randomized to clozapine and 32 randomized to clozapine plus ECT) will be treated for up to eight weeks; subjects in the ECT plus clozapine arm will receive up to 16 to 20 bilateral treatments. A naturalistic follow-up will compare subjects who receive continuation ECT with those who do not for an additional 6 months. The results of the study will guide clinicians faced with the problem of how to treat patients who have not been helped by standard antipsychotic medications and do not show an adequate response to clozapine.
