IMPROVEMENT OF COGNITIVE FUNCTION IN SCHIZOPHRENIC-PATIENTS RECEIVINGCLOZAPINE OR ZOTEPINE - RESULTS FROM A DOUBLE-BLIND-STUDY

Clinical interest in the so-called atypical antipsychotics currently f ocuses on the possibility of improving the negative symptoms of schizo phrenia and the cognitive dysfunction associated with the disease. Whi le clozapine has been shown to be effective in this respect, no data a re available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitiv e dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes o f increasing complexity. Passage time, route, and motor errors were ev aluated. 25 schizophrenic (DSM-IIIR) patients were included in each gr oup, After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six w eeks and evaluated weekly. We report on a subsample of 26 patients mat ched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as facto rs was used for analysis. Both clozapine and zotepine achieved a highl y significant decrease in overall symptoms (BPRS) and negative symptom s (SANS). Zotepine and clozapine were equally effective. In the maze t ests, motor errors in simple mazes were stable over time and different iated schizophrenics from controls as a ''trait'' marker. In passage t ime and maze route, schizophrenics performed worse than controls. An i mprovement by medication was evident in both medication groups, but wa s more pronounced in the zotepine-treated group. The study confirms pr evious results on the efficacy of clozapine and zotepine in treating n egative symptoms of schizophrenia. The data presented show for the fir st time that zotepine is efficacious in improving cognitive dysfunctio n, confirming this substance's value as an atypical antipsychotic.