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

Abstract

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. 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 moderate 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 applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)