Abstract
Clinical interest in the so-called atypical antipsychotics currently focuses on the
possibility of improving the negative symptoms of schizophrenia and the cognitive
dysfunction associated with the disease. While clozapine has been shown to be effective
in this respect, no data are available on zotepine. We report on a double-blind randomized
study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction
in schizophrenia. Cognitive function was operationalized by a maze test in which patients
traversed computer-displayed mazes of increasing complexity. Passage time, route,
and motor errors were evaluated.
25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they
were randomized on zotepine or clozapine and given up to 450 mg of substance each.
Patients were followed for six weeks and evaluated weekly. We report on a subsample
of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons
were recruited as controls. ANOVA with group and course over time as factors was used
for analysis. Both clozapine and zotepine achieved a highly significant decrease in
overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were
equally effective. In the maze tests, motor errors in simple mazes were stable over
time and differentiated schizophrenics from controls as a "trait" marker. In passage
time and maze route, schizophrenics performed worse than controls. An improvement
by medication was evident in both medication groups, but was more pronounced in the
zotepine-treated group. The study confirms previous results on the efficacy of clozapine
and zotepine in treating negative symptoms of schizophrenia. The data presented show
for the first time that zotepine is efficacious in improving cognitive dysfunction,
confirming this substance's value as an atypical antipsychotic.
