Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development

  • Arie KaffmanEmail author
  • Jordon D. White
  • Lan Wei
  • Frances K. Johnson
  • John H. Krystal
Part of the Methods in Molecular Biology book series (MIMB, volume 2011)


Most large pharmaceutical companies have downscaled or closed their clinical neuroscience research programs in response to the low clinical success rate for drugs that showed tremendous promise in animal experiments intended to model psychiatric pathophysiology. These failures have raised serious concerns about the role of preclinical research in the identification and evaluation of new pharmacotherapies for psychiatry. In the absence of a comprehensive understanding of the neurobiology of psychiatric disorders, the task of developing “animal models” seems elusive. The purpose of this review is to highlight emerging strategies to enhance the utility of preclinical research in the drug development process. We address this issue by reviewing how advances in neuroscience, coupled with new conceptual approaches, have recently revolutionized the way we can diagnose and treat common psychiatric conditions. We discuss the implications of these new tools for modeling psychiatric conditions in animals and advocate for the use of systematic reviews of preclinical work as a prerequisite for conducting psychiatric clinical trials. We believe that work in animals is essential for elucidating human psychopathology and that improving the predictive validity of animal models is necessary for developing more effective interventions for mental illness.

Key words

Animal models Predictive validity Psychiatry Systematic reviews CRF 



This work was supported by NARSAD Independent Investigator Award 2016, NIMH grant R01 MH-100078, and the Clinical Neuroscience Division of the VA National Center for PTSD.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Arie Kaffman
    • 1
    Email author
  • Jordon D. White
    • 1
  • Lan Wei
    • 1
  • Frances K. Johnson
    • 1
  • John H. Krystal
    • 1
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA

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