Novel factor-based symptom scores in treatment resistant schizophrenia: implications for clinical trials.

To study the factor structure of symptoms in patients with treatment resistant schizophrenia and whether it is altered by treatment, we analyzed ratings on the Brief Psychiatric Rating Scale (BPRS) from two independent groups of patients with treatment resistant schizophrenia. With confirmatory factor analysis of pre-clozapine BPRS scores in 1074 patients in an administrative data base, the Clozapine Authorization and Monitoring Program (CAMP), we assessed the fit of published factor models and developed a better-fitting model. Model fit was validated in an independent group of 197 research unit participants. Stability of model fit six months post-clozapine was assessed in 834 CAMP patients. A new 4-factor model (negative symptoms, reality distortion, disorganization, and anxiety/depression) had better fit in both data sets than two commonly used factor models, and also fit better post-clozapine. We recommend these four factor scores as clinical trial outcomes in patients with treatment resistant schizophrenia.