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The different trajectories of antipsychotic response: antipsychotics versus placebo

Published online by Cambridge University Press:  20 October 2010

T. R. Marques ,
T. Arenovich ,
O. Agid ,
G. Sajeev ,
B. Muthén ,
L. Chen ,
B. J. Kinon  and
S. Kapur
T. R. Marques
Affiliation:
Institute of Psychiatry, King's College London, London, UK
T. Arenovich
Affiliation:
Centre for Addiction and Mental Health, Toronto, Canada
O. Agid
Affiliation:
Centre for Addiction and Mental Health, Toronto, Canada
G. Sajeev
Affiliation:
Centre for Addiction and Mental Health, Toronto, Canada
B. Muthén
Affiliation:
Graduate School of Education and Information, UCLA, Los Angeles, CA, USA
L. Chen
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA
B. J. Kinon
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA
S. Kapur*
Affiliation:
Institute of Psychiatry, King's College London, London, UK
*
*Address for correspondence: S. Kapur, M.B.B.S., Ph.D., F.R.C.P.C., Dean and Professor, PO Box 053, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email: shitij.kapur@kcl.ac.uk)
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Abstract

Background

It is generally accepted that antipsychotics are more effective than placebo. However, it remains unclear whether antipsychotics induce a pattern or trajectory of response that is distinct from placebo. We used a data-driven technique, called growth mixture modelling (GMM), to identify the different patterns of response observed in antipsychotic trials and to determine whether drug-treated and placebo-treated subjects show similar or distinct patterns of response.

Method

We examined data on 420 patients with schizophrenia treated for 6 weeks in two double-blind placebo-controlled trials using haloperidol and olanzapine. We used GMM to identify the optimal number of response trajectories; to compare the trajectories in drug-treated versus placebo-treated patients; and to determine whether the trajectories for the different dimensions (positive versus negative symptoms) were identical or different.

Results

Positive symptoms were found to respond along four distinct trajectories, with the two most common trajectories (‘Partial responder’ and ‘Responder’) accounting for 70% of the patients and seen proportionally in both drug- and placebo-treated. The most striking drug–placebo difference was in the ‘Dramatic responders’, seen only among the drug-treated. The response of negative symptoms was more modest and did not show such distinct trajectories.

Conclusions

Trajectory models of response, rather than the simple responder/non-responder dichotomy, provide a better statistical account of how antipsychotics work. The ‘Dramatic responders’ (those showing >70% response) were seen only among the drug-treated and make a significant contribution to the overall drug–placebo difference. Identifying and studying this subset may provide specific insight into antipsychotic action.

Keywords

Antipsychoticantipsychotic responsegrowth mixture modellingschizophreniatreatment trajectories
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 7 , July 2011 , pp. 1481 - 1488
Copyright
Copyright © Cambridge University Press 2010

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