How to identify and manage non-response to clozapine?

Clozapine is the only approved treatment for Treatment-Refractory Schizophrenia. Here we describe a case series of three hospitalized patients with clozapine nonresponse. One of them responded to clozapine after dose adjustments were made for an interaction between clozapine and ciprofloxacin. The other two cases remained clozapine nonresponders despite optimizing clozapine treatment. However, both these patients responded to other antipsychotic medications (APMs) with better tolerability than observed with clozapine treatment. This case series focuses on diagnosing a genuine from a pseudo-nonresponse to clozapine and to consider other APMs in genuine nonresponse before switching to invasive interventions, such as ECT.