Olanzapine's structural similarities to clozapine and the results of premar
keting clinical trials suggested potential usefulness in treating patients
with treatment-refractory psychoses. Sixteen inpatients from the state hosp
ital with severe, refractory schizophrenic or schizoaffective psychoses rec
eived olanzapine in a prospective, 12-week, open-label trial. The olanzapin
e dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 m
g/day. Mood stabilizers and other antipsychotic agents were discontinued be
fore olanzapine was started. Patients frequently became more agitated withi
n the first several weeks of initiating treatment, requiring the increased
use of benzodiazepines and often leading to the discontinuation of olanzapi
ne. Two patients improved significantly. Overall, significant clinical impr
ovement was noted only for motor side effects. This study concluded that ol
anzapine was not effective in this heterogeneous group with chronic, severe
, treatment-resistant psychosis when used in this manner. Further research
is needed to explain the tendency toward agitation upon transition to olanz
apine, which is reminiscent of reported risperidone complications. Clinicia
ns should be alert for this complication and should minimize concomitant me
dication changes that might add to the risk of emergent agitation.