Psychological Medicine

  • Psychological Medicine / Volume 41 / Issue 06 / June 2011, pp 1291-1300
  • Copyright © Cambridge University Press 2010. The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <>. The written permission of Cambridge University Press must be obtained for commercial re-use.
  • DOI: (About DOI), Published online: 07 October 2010

Original Articles

The heterogeneity of antipsychotic response in the treatment of schizophrenia

M. Casea1, V. L. Stauffera1, H. Ascher-Svanuma2, R. Conleya1, S. Kapura3, J. M. Kanea4, S. Kollack-Walkera1, J. Jacoba1 c1 and B. J. Kinona2

a1 Lilly USA, LLC, Indianapolis, IN, USA

a2 Eli Lilly and Company, Indianapolis, IN, USA

a3 Institute of Psychiatry, King's College London, UK

a4 Zucker Hillside Hospital, Glen Oaks, NY, USA


Background Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response.

Method Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine.

Results Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified.

Conclusions This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.

(Received March 22 2010)

(Revised August 02 2010)

(Accepted August 21 2010)

(Online publication October 07 2010)


c1 Address for correspondence: J. Jacob, Ph.D., Lilly Corporate Center, DC 4133, Indianapolis, IN 46285, USA. (Email: