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Schizophrenia is a severe psychiatric illness with a lifetime morbidity risk of around 1 %. Symptoms include hallucinations, delusions, poverty of thought and emotion and social withdrawal and cognitive deficits. Although newer antipsychotics affecting multiple neurotransmitter receptors facilitate therapy, many patients still do not achieve full response. Despite intensive study, the molecular etiology of schizophrenia remains enigmatic in many ways. The dopamine hypothesis of schizophrenia still plays an important role, although pharmacological studies, brain imaging analyses and genetic research indicate additional dysfunctions of glutamate, GABA and serotonin transmission. This article reviews the pathophysiological background of the disorder, its implications for pharmacological treatment and possible directions for future research.

Clozapine has advantages over standard antipsychotics in refractory schizophrenia. Studies on the efficacy of clozapine in the maintenance treatment are sparse and suffer from methodological limitations. Despite this fact clozapine ranked second in a survey dealing with the preference of this antipsychotic in the long-term treatment of schizophrenia. Doctors report on using a mean of 130 mg/d in this indication which is considerably less than the doses used in most of the published long-term trials. The discrepancy between the popularity of clozapine and the lack of sound empirical data on its long-term efficacy is discussed.

The efficacy and tolerance of zotepine and haloperidol were examined in 40 patients suffering from paranoid schizophrenia (DSM III). The study period was 6 weeks. Psychopathology was assessed with BPRS and CGI. Documentation of side effects was done with DOTES. The safety parameters were pulse, blood pressure, leucocyte count, liver enzymes, ECG and EEG, determined at different times. Both treatment groups improved significantly without any differences in respect to efficacy. The patients who had been treated with zotepine had significantly fewer extrapyramidal side effects. However, transient increases in liver enzyme levels were seen more frequently in the zotepine group. There were no differences between the groups in respect to other side effects.

Zotepine, a neuroleptic exercising a 5-HT2-antagonistic effect, was employed in a double-blind study in the treatment of schizophrenic patients with predominantly negative symptoms and was compared to haloperidol. In contrast to the patients treated with haloperidol, significant improvements were seen in the zotepine group during the observation period, according to all assessment scales that were employed. The patients of the zotepine group also developed fewer clinical side effects. The results of the study confirm previous positive impressions gained in earlier open studies with zotepine.