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A precision medicine approach to pharmacological adjuncts to extinction: a call to broaden research

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Abstract

There is a pressing need to improve treatments for anxiety. Although exposure-based therapy is currently the gold-standard treatment, many people either do not respond to this therapy or experience a relapse of symptoms after treatment has ceased. In recent years, there have been many novel pharmacological agents identified in preclinical research that have potential as adjuncts for exposure therapy, yet very few of these are regularly integrated into clinical practice. Unfortunately, the robust effects observed in the laboratory animal often do not translate to a clinical population. In this review, we discuss how age, sex, genetics, stress, medications, diet, alcohol, and the microbiome can vary across a clinical population and yet are rarely considered in drug development. While not an exhaustive list, we have focused on these factors because they have been shown to influence an individual’s vulnerability to anxiety and alter the neurotransmitter systems often targeted by pharmacological adjuncts to therapy. We argue that for potential adjuncts to be successfully translated from the lab to the clinic empirical research must be broadened to consider how individual difference factors will influence drug efficacy.

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Notes

  1. Indeed, there is some evidence that DCS can lead to enhanced fear if given after poor within-session extinction, potentially because it enhances the reconsolidation of the original fear memory (e.g., Litz et al. 2012). The extent to which any adjunct might affect extinction versus reconsolidation and how this is influenced by various factors associated with a clinical population should be examined when considering the development of novel pharmacological adjuncts to therapy.

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Acknowledgements

We thank the funding bodies that supported our work: Australian Government Research Training Program Scholarships to GK, MAB, DC, and AAS; a Project Grant from the National Health and Medical Research Council to RR and KB (NHMRC; APP1086855), an Australian Research Council Discovery Early Career Researcher Award to KB (DE170100392), and an Australian Research Council Discovery grant to RR (DP150104835).

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Authors and Affiliations

  1. School of Psychology, The University of New South Wales, Sydney, Australia

    Gabrielle King, Kathryn D. Baker, Madelyne A. Bisby, Diana Chan, Anthea A. Stylianakis, Kelsey S. Zimmermann & Rick Richardson

  2. APC Microbiome Institute, University College Cork, Cork, Ireland

    Caitlin S. M. Cowan

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  1. Gabrielle King
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  2. Kathryn D. Baker
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  3. Madelyne A. Bisby
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  4. Diana Chan
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  5. Caitlin S. M. Cowan
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  6. Anthea A. Stylianakis
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  7. Kelsey S. Zimmermann
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  8. Rick Richardson
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Correspondence to Gabrielle King.

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This article belongs to a Special Issue on Psychopharmacology of Extinction.

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King, G., Baker, K.D., Bisby, M.A. et al. A precision medicine approach to pharmacological adjuncts to extinction: a call to broaden research. Psychopharmacology 236, 143–161 (2019). https://doi.org/10.1007/s00213-018-4999-0

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