When Clozapine Is Insufficient for Schizophrenia, Then What?

Although clozapine is typically considered to be the gold-standard treatment for difficult cases of schizophrenia, as many as 70% of clozapine-treated patients respond inadequately. Based on promising results in open studies, investigators conducted a randomized, controlled trial enrolling 39 inpatients with schizophrenia who showed persistent psychotic symptoms at moderate or more-severe levels after at least 12 weeks of clozapine with plasma levels ≥350 ng/ml.

Patients continued clozapine and either were treated or were not treated with bilateral electroconvulsive therapy (ECT) for 8 weeks (72% men; 54% white; mean age: clozapine-only group, 43; combination-treatment group, 36). Raters blinded to group assignment performed weekly assessments. At the end of treatment (mean, 16 treatments), 50% of patients treated with ECT met responder criteria (≥40% reduction in psychotic symptoms) versus 0% of those without ECT treatment. All nonresponders in the clozapine-only arm eventually received ECT; 47% met response criteria. No impact was seen on negative symptoms. Adverse reactions were few and minor.