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

Kinon, Bruce J.; Chen, Lei; Ascher-Svanum, Haya; Stauffer, Virginia L.; Kollack-Walker, Sara; Zhou, Wei; Kapur, Shitij; Kane, John M.; Naber, Dieter

doi:10.1016/j.schres.2009.12.013

« Previous Next »Schizophrenia Research
Volume 118, Issue 1 , Pages 176-182, May 2010

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

Bruce J. Kinon
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
- Corresponding authors. Kinon, is to be contacted at Tel.: +1 317 277 7886; fax: +1 317 433 3410, Kollack-Walker, Tel.: +1 317 433 4654; fax: +1 317 276 7100.
Lei Chen
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
Haya Ascher-Svanum
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
Virginia L. Stauffer
- Lilly, USA, LLC, Indianapolis, IN 46285, USA
Sara Kollack-Walker
- Lilly, USA, LLC, Indianapolis, IN 46285, USA
- Corresponding authors. Kinon, is to be contacted at Tel.: +1 317 277 7886; fax: +1 317 433 3410, Kollack-Walker, Tel.: +1 317 433 4654; fax: +1 317 276 7100.
Wei Zhou
- Lilly, USA, LLC, Indianapolis, IN 46285, USA
Shitij Kapur
- Institute of Psychiatry, King's College of London, London, UK
John M. Kane
- Zucker Hillside Hospital, Glen Oaks, NY 11004, USA
Dieter Naber
- Hamburg, Germany

Received 18 September 2009; received in revised form 11 December 2009; accepted 14 December 2009. published online 18 January 2010.

Abstract

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 (2–6mg/day), and their response status at 2weeks 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.

Abbreviations: ANOVA, analysis of variance, ANCOVA, analysis of covariance, mg, milligram, MADRS, Montgomery–Asberg Depression Rating Scale, MMRM, Mixed Effects Model Repeated Measure, n, number, PANSS, Positive and Negative Syndrome Scale, QLS, Quality of Life Scale, SD, standard deviation, SOFI, Schizophrenia Objective Functioning Instrument, SWN-K, Subjective Well-being on Neuroleptics Scale