Challenging the assumption that improvement in functional outcomes is delayed relative to improvement in symptoms in the treatment of schizophrenia.

OBJECTIVES: Functional improvement is generally thought to be distal to improvement in psychiatric symptoms in patients with schizophrenia. In this study, we assessed the effects of early response/non-response to an atypical antipsychotic across multiple outcome measures. METHODS: This was a randomized, double-blind, flexible-dose, 12-week study that enrolled chronically-ill patients (n=628) diagnosed with schizophrenia or schizoaffective disorder who were experiencing acute symptom exacerbation. Patients were initially assigned to risperidone drug therapy (2-6 mg/day), and their response status at 2 weeks was determined. Early responders (ERs) continued with risperidone therapy, whereas early non-responders (ENRs) were randomized (1:1) in a double-blind manner to either continue on risperidone or switch to another atypical antipsychotic for 10 additional weeks of therapy. Subsequent treatment outcomes were measured by the Quality of Life Scale (QLS), Schizophrenia Objective Functioning Instrument (SOFI), and Subjective Well-being under Neuroleptics (SWN-K) scale. RESULTS: Compared to ENRs, ERs to risperidone showed significantly more improvement from baseline to endpoint on the QLS total score and all 4 categories (p<.01), the SOFI overall global score and all 4 domains (p<.001), and the SWN-K total score and all 5 subscales (p<.05). Among ERs, the majority of improvement had already been attained by Week 2. There was concordance among clinician- and patient-rated scales across outcomes. CONCLUSION: Improvement across multiple outcome dimensions was not delayed relative to improvement in psychiatric symptoms. Rather, patients who showed an early response to antipsychotic treatment as defined by improvement in psychiatric symptoms also showed early and consistent improvement in functioning, quality of life, and subjective well-being.