Treatment-resistant schizophrenic patients respond to clozapine after olanzapine non-response

Background: Treatment-resistance in schizophrenia remains a public health problem. Clozapine has been shown to be effective in about one third of this population, but carries with it medical risks and weekly blood draws. As olanzapine is a drug with a very similar biochemical profile to clozapine, it is important to evaluate whether non-response to olanzapine predicts clozapine non-response. Methods: Forty-four treatment-resistant patients received eight weeks of olanzapine, either in a double-blind trial or subsequent open treatment at a mean daily dose of 25 mg/day. Two of 44 patients (5%) responded to olanzapine treatment. Patients who did not respond could then receive clozapine. Twenty-seven subsequently received an 8-week open trial of clozapine. Results: Patients who did and did not receive clozapine did not differ demographically or in psychopathology. Eleven of 27 (41%) met a priori response criteria during clozapine treatment (mean dose 693 mg/day) after failing to respond to olanzapine. Conclusions: This study demonstrates that failure to respond to olanzapine treatment does not predict failure to clozapine. Treatment-resistant patients who fail on olanzapine may benefit from a subsequent trial of clozapine.