PURPOSE OF REVIEW: This article reviews the recent evidence for therapeutic strategies for patients with treatment-resistant schizophrenia (TRS) not responding to or only partially responding to clozapine. RECENT FINDINGS: A number of pharmacological and nonpharmacological biological approaches for clozapine-resistant TRS have been evaluated in clinical trials. Among these, the evidence supporting clozapine augmentation by pharmacological approaches is weak and the reported benefits were modest at best. However, the results of a recent randomized trial suggest that electroconvulsive therapy (ECT) may be efficacious for the short-term treatment of patients with clozapine-resistant TRS. SUMMARY: There is currently insufficient evidence for efficacy of pharmacological augmentation strategies to clozapine. ECT may be a promising option, but further research is necessary to confirm its long-term effects. Moreover, further controlled studies are warranted to clarify the potential of other biological and psychosocial approaches to serve as adjuvant treatments in patients with clozapine-resistant TRS.
