SEROQUEL (ICI-204-636), A PUTATIVE ATYPICAL ANTIPSYCHOTIC, IN SCHIZOPHRENIA WITH POSITIVE SYMPTOMATOLOGY - RESULTS OF AN OPEN CLINICAL-TRIAL AND CHANGES OF NEUROENDOCRINOLOGICAL AND EEG PARAMETERS

Preclinical data indicated that seroquel (ICI 204 636) a dibenzothiaze pine with 5-HT2 and D-2-like receptor antagonistic properties, might b e an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients s uffering from schizophrenia or schizophreniform disorder with predomin antly positive symptomatology were treated in an open clinical trial f or 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug w as generally well tolerated, and virtually no adverse extrapyramidal s ide effects such as acute dystonia, parkinsonism or akathisia were obs erved. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a mo derate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36. 1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was a pplied. There were considerable interindividual differences in treatme nt response, with some subjects showing almost full remission of posit ive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing goo d antipsychotic response reported slight initial side effects like mil d sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a m oderate increase of the absolute power in the alpha, theta, and beta f requency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel. Our results sugge st that seroquel may be a well tolerated drug with some antipsychotic properties, exhibiting no extrapyramidal side effects that could be of use in the treatment Of schizophrenic patients with positive symptoma tology. Further double-blind studies with higher doses, in order to te st presumably better efficacy, and with monitoring of plasma levels, a re needed to extend the present results.