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A New Paradigm for Achieving a Rapid Antidepressant Response

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Abstract

The substantive delay (often 4–6 weeks) between the commencement of an antidepressant and any discernible improvement in depressive symptoms is an ongoing concern in the management of depressive disorders. This delay incurs the risk of cessation of medication, self-harm/suicide and ongoing ‘damage’ to the brain caused by the illness. Both historically and now, off-label polypharmacy has been used in clinical practice in an attempt to facilitate both immediate- and long-term relief from symptoms. While somewhat effective, this strategy was unregulated and associated with severe adverse side effects for patients. In this article we proffer an alternative paradigm to achieve a more rapid antidepressant response by conceptualising the gap in terms of windows of response. The Windows of Antidepressant Response Paradigm (WARP) frames treatment response as windows of time in which a clinical response can be expected following initiation of an antidepressant. The paradigm defines three distinct windows—the immediate-response window (1–2 days), fast-response window (up to 1 week) and slow-response window (from 1 week onwards). Newer agents such as rapid-acting antidepressants are considered to act within the immediate-response window, whereas atypical antipsychotic augmentation strategies are captured within the fast-response window. The slow-response window represents the delay experienced with conventional antidepressant monotherapy. Novel agents such as esketamine and brexpiprazole are discussed as examples to better understand the clinical utility of WARP. This framework can be used to guide research in this field and aide the development of newer, more effective antidepressant agents as well as providing a strategy to guide the prescription of multiple agents in clinical practice.

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Authors and Affiliations

  1. Department of Psychiatry, Faculty of Medicine and Health, Northern Clinical School, University of Sydney, Sydney, NSW, Australia

    Gin S. Malhi, Grace Morris, Erica Bell & Amber Hamilton

  2. Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia

    Gin S. Malhi, Grace Morris, Erica Bell & Amber Hamilton

  3. CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia

    Gin S. Malhi, Grace Morris, Erica Bell & Amber Hamilton

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  1. Gin S. Malhi
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Correspondence to Gin S. Malhi.

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Funding

G.S.M. has received grant or research support from National Health and Medical Research Council, Australian Rotary Health, NSW Health, American Foundation for Suicide Prevention, Ramsay Research and Teaching Fund, Elsevier, AstraZeneca, Janssen-Cilag, Lundbeck, Otsuka and Servier; and has been a consultant for AstraZeneca, Janssen-Cilag, Lundbeck, Otsuka and Servier.

Conflict of interest

The authors EB, GM and AH declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received no financial support for the research, authorship, and/or publication of this article.

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Malhi, G.S., Morris, G., Bell, E. et al. A New Paradigm for Achieving a Rapid Antidepressant Response. Drugs 80, 755–764 (2020). https://doi.org/10.1007/s40265-020-01303-1

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