Abstract
Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether ‘switching’ early non-responders to another antipsychotic is a better strategy than ‘staying’. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as ⩾20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2–6 mg/day or switch to olanzapine 10–20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching’ strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.
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Acknowledgements
Appreciation is expressed to Heather Fox, Medical Information Specialist with Lilly USA, LLC, for administrative oversight of the editing for this article. We acknowledge Teri Tucker and Caron Modeas for editorial contributions. Ms Tucker and Modeas are medical editors employed full-time by i3 Statprobe, a division of Ingenix, which is a subsidiary of United Health Group. Eli Lilly contracted the editing and formatting of this article with i3 Statprobe.
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Previous Presentation: These data debuted at the annual American Psychiatric Association (APA) congress in Washington, DC, May 3–8, 2008.
Clinical Trials Registration: ClinicalTrials.gov identifier: NCT00337662; http://www.clinicaltrials.gov/
DISCLOSURE
Drs Kinon, Chen, Ascher-Svanum, Stauffer, and Kollack-Walker and Wei Zhou are all employees of Eli Lilly and Company. Dr John Kane serves as a Consultant and/or Advisory Board member for Bristol Meyer Squibb; Otsuka America Pharmaceutical Inc.; Eli Lilly and Company; Janssen; Pfizer; Wyeth; Vanda Pharmaceuticals Inc.; GlaxoSmithKline; Lundbeck; Johnson & Johnson; PGxHealth; and Proteus; is a shareholder of MedAvante; and serves on Speakers Bureaus for Bristol Meyer Squibb, Janssen, AstraZeneca, and Eli Lilly and Company. Dr Shitij Kapur has had affiliations with the following commercial organizations over the last 5 years: AstraZeneca; Bristol Meyers Squibb; Eli Lilly and Company; EMD Pharmaceuticals Inc.; Darmstadt; GlaxoSmithKline; Janssen; Neuromolecular Pharmaceuticals; Otsuka America Pharmaceutical Inc.; Organon Pharmaceuticals USA; Pfizer; Sanofi-Synthelabo; Servier; and Solvay Wyeth. Funding of this study was provided by Eli Lilly and Company.
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Kinon, B., Chen, L., Ascher-Svanum, H. et al. Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia. Neuropsychopharmacol 35, 581–590 (2010). https://doi.org/10.1038/npp.2009.164
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DOI: https://doi.org/10.1038/npp.2009.164
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