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Schizophrenia Bulletin Advance Access originally published online on January 29, 2008
Schizophrenia Bulletin 2008 34(2):275-285; doi:10.1093/schbul/sbm159
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© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Methodological Issues in Current Antipsychotic Drug Trials

Stefan Leucht1,2, Stephan Heres2, Johannes Hamann2 and John M. Kane3
2 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstr. 22, 81675 München, Germany
3 The Zucker Hillside Hospital, Kaufmann Building, 75-59 263rd Street, Glen Oaks, NY 11004

1 To whom correspondence should be addressed; tel: +49-89-4140-4249, fax: +49-89-4140-4888, e-mail: Stefan.Leucht{at}lrz.tum.de.

Every year numerous reports on antipsychotic drug trials are being published in neuropsychiatric journals, adding new information to our knowledge in the field. The information however is often hard for the reader to interpret, sometimes contradictory to comparable available studies and leaves more questions open than it actually answers. Although the overall quality of the studies is rather good, there are manifold options for further improvement in the conception, conduct, and reporting of antipsychotic drug trials. In this survey, we address methodological challenges such as the limited generalizability of outcomes due to patient selection and sample size; the vague or even lacking definition of key outcome parameters such as response, remission or relapse, insufficient blinding techniques, the pitfalls of surrogate outcomes and their assessment tools; the varying complex statistical approaches; and the challenge of balancing various ways of reporting outcomes. The authors present practical examples to highlight the current problems and propose a concrete series of suggestions on how to further optimize antipsychotic drug trials in the future.

Keywords: schizophrenia / drug trials / methodology / antipsychotics


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