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Comparison of Treatment Response in Second-Episode Versus First-Episode Schizophrenia

Emsley, Robin MD*; Oosthuizen, Petrus MD*; Koen, Liezl MD*; Niehaus, Dana MD*; Martinez, Lupe MD

Journal of Clinical Psychopharmacology: February 2013 - Volume 33 - Issue 1 - p 80–83
doi: 10.1097/JCP.0b013e31827bfcc1
Brief Reports

This study investigated whether illness progression and treatment refractoriness emerge after relapse in schizophrenia. We compared outcomes in a cohort treated with a standardized protocol for the first and second episodes of illness. The sample comprised 31 participants who (1) had successfully completed a 2-year open-label treatment phase with risperidone long-acting injection (RLAI) for a first episode of schizophrenia; (2) underwent an intermittent treatment extension phase up to 3 years or until recurrence, and (3) entered a further 2-year treatment phase with RLAI for a recurrence episode. For the patients who remained in treatment (n = 14 [45%]), Positive and Negative Syndrome Scale score reductions, response rates, remission rates, time to response, time to remission, functional outcome scores, and modal RLAI doses were similar for the 2 treatment periods. However, 17 (55 %) of the 31 patients discontinued the study in the second episode compared with 14 (28%) of 50 patients in the first episode, suggesting reduced effectiveness of antipsychotics when reintroduced after illness recurrence. Most notably, emergent treatment nonresponsiveness was observed in 5 participants (16%), consistent with the hypothesis that relapse may be biologically harmful in a subset of patients.

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From the *Department of Psychiatry, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, Cape Town, South Africa; and †Janssen Medical Affairs EMEA, Beerse, Belgium.

Received September 21, 2011; accepted after revision May 14, 2012.

Reprints: Robin Emsley, MD, Department of Psychiatry, University of Stellenbosch, PO Box 19063, Tygerberg 7505, Cape Town, South Africa (e-mail:

This study was sponsored by Janssen-Cilag Medical Affairs Europe, Middle East and Africa (EMEA), a division of Janssen Pharmaceutica NV.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

© 2013 Lippincott Williams & Wilkins, Inc.