ICI-204,636, AN ATYPICAL ANTIPSYCHOTIC - EFFICACY AND SAFETY IN A MULTICENTER, PLACEBO-CONTROLLED TRIAL IN PATIENTS WITH SCHIZOPHRENIA

ICI 204,636 is a new, potentially atypical antipsychotic. In early pha se II trials, the antipsychotic was well tolerated and results suggest ed efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated o n a larger scale in a 6-week, multicenter, double-blind trial. Hospita lized patients who met DSM-III-R criteria for chronic or subchronic sc hizophrenia with acute exacerbation, as well as other criteria, were r andomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Ra ting Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS ), and Clinical Global Impression Scale (CGI) for efficacy and the Sim pson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p less than or equal to 0 .05) between treatment groups, which favored ICI 204,636, were identif ied throughout the trial. Endpoint differences were significant (by an alysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thoug ht disturbance), BPRS positive-symptom cluster, and CGI Severity of Il lness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild trans ient increases in alanine aminotransferase and a higher incidence of s omnolence and anticholinergic effects compared with placebo. In the do se range studied, treatment with ICI 204,636 did not induce EPS as det ermined by analysis of Simpson Scale total scores and lack of treatmen t-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline a t endpoint (-7.2 mu g/L) was comparable (p = 0.44) to that for placebo (-8.2 mu g/L). These findings distinguish ICI 204,636 from standard a ntipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.