CHILDHOOD-ONSET SCHIZOPHRENIA - AN OPEN-LABEL STUDY OF OLANZAPINE IN ADOLESCENTS

Objective: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinit y similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For compa rison, data are included from 15 patients who had received g-week open -label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting. Method: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by a ge 12 for whom at least two different typical neuroleptics had been in effective participated in the two separate studies. Some of the patien ts were intolerant of clozapine, although it had been effective (n = 4 ). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement. Results: F or the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in th e Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to ''id eal'' admission status on typical neuroleptics. In contrast, the magni tude of the effect sizes for each of the clinical ratings was larger a t week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS tot al scores were significantly lower at week 6 of clozapine treatment co mpared with week 6 of olanzapine treatment (p = .03). Conclusion: Thes e data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia , but they also suggest the need for a more rigorous double-blind comp arison of these two atypical antipsychotics.