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Review
. 2022 Sep;179(17):4181-4200.
doi: 10.1111/bph.15596. Epub 2021 Jul 29.

Perspectives for therapy of treatment-resistant depression

Mariusz Papp  1 , Wiesław Jerzy Cubala  2 , Lukasz Swiecicki  3 , Adrian Newman-Tancredi  4 , Paul Willner  5
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Free article
Review

Perspectives for therapy of treatment-resistant depression

Mariusz Papp et al. Br J Pharmacol. 2022 Sep.
Free article

Abstract

A high proportion of depressed patients fail to respond to antidepressant drug treatment. Treatment-resistant depression (TRD) is a major challenge for the psychopharmacology of mood disorders. Only in the past decade have novel treatments, including deep brain stimulation (DBS) and ketamine, been discovered that provide rapid and sometimes prolonged relief to a high proportion of TRD sufferers. In this review, we consider the current status of TRD from four perspectives: the challenge of developing an appropriate regulatory framework for novel rapidly acting antidepressants; the efficacy of non-pharmacological somatic therapies; the development of an animal model of TRD and its use to understand the neural basis of antidepressant non-response; and the potential for rapid antidepressant action from targets (such as 5-HT1A receptors) beyond the glutamate receptor. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.

Keywords: 5-HT1A receptors; animal models; deep brain stimulation; ketamine; regulatory challenges; somatic therapies; treatment-resistant depression.

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References

REFERENCES

    1. Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2018). The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation? Pharmacology & Therapeutics, 190, 148-158. https://doi.org/10.1016/j.pharmthera.2018.05.010
    1. Aguiar, R. P., Soares, L. M., Meyer, E., da Silveira, F. C., Milani, H., Newman-Tancredi, A., Varney, M., Prickaerts, J., & Oliveira, R. M. W. (2019). Activation of 5-HT1A postsynaptic receptors by NLX-101 results in functional recovery and an increase in neuroplasticity in mice with brain ischemia. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 99, 109832.
    1. Aleksandrova, L. R., Phillips, A. G., & Wang, Y. T. (2017). Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism. Journal of Psychiatry & Neuroscience, 42, 222-229.
    1. Aleksandrova, L. R., Wang, Y. T., Anthony, G., & Phillips, A. G. (2019). Evaluation of the Wistar-Kyoto rat model of depression and the role of synaptic plasticity in depression and antidepressant response. Neuroscience and Biobehavioral Reviews, 105, 1-23.
    1. Alexander, S. P. H., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators. (2019). The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. British Journal of Pharmacology, 176, S21-S141. https://doi.org/10.1111/bph.14748

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