Previous investigations on the relationship between global rating measures and symptoms have not considered the additional role of functioning. In this naturalistic study, we examined the relationship between symptom domains and functioning on Clinical Global Impression scales for severity (CGI-S) and improvement (CGI-I) in a sample of patients with schizophrenia assessed to be treatment resistant. Participants were patients with a diagnosis of schizophrenia or schizoaffective disorder who failed 2 prior antipsychotic trials and were considered candidates for clozapine. Theywere assessed on the 18-item Brief Psychiatric rating Scale (BPRS), Social Occupational Functioning Assessment Scale (SOFAS), and CGI-S at baseline. A subset of patients was followed up at 6 weeks after initiation of clozapine and assessed on the CGI-I. The independent effects of symptom domains and functioning on the CGI scales were examined viamultivariate regressionmodels. Brief Psychiatric rating Scale positive factor (P < 0.001) and SOFAS (P < 0.001) scores were significant determinants of CGI-S at baseline. Multivariate models suggested that relative change measures had a better fit for the CGI-I compared to absolute change measures (R2 = 0.72 vs R2 = 0.61, respectively). Improvements in BPRS positive (P < 0.001) and affect (P = 0.002) factors and SOFAS (P = 0.030) scores were significant determinants of CGI-I. Ratings of 1 and 2 on the CGI-I corresponded to a mean relative change in the BPRS total of 65% and 41%, respectively. Positive symptoms were a key determinant of clinicians' impression of severity and improvement in this study. Although psychosocial functioning played a large part in determining severity, it was not as significant in the assessment of improvement.
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