Dexmedetomidine in the Treatment of Depression: An Up-to-date Narrative Review

Tamadhir Al-Mahrouqi1, 2, Mohammed Al Alawi1, Rafael C. Freire3, 4, *
1 Department of Behavioural Medicine, Sultan Qaboos University Hospital, Muscat, Oman
2 Psychiatry Residency Training Program, Oman Medical Speciality Board, Muscat, Oman
3 Department of Psychiatry and Centre for Neuroscience Studies, Queens University, Kingston, Canada
4 Laboratory of Panic and Respiration, Institute of Psychiatry, Federal University of Rio de, Janeiro, Rio de Janeiro, Brazil

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© 2023 Al-Mahrouqi et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Psychiatry and Centre for Neuroscience Studies, Queens University, Kingston General Hospital, 76 Stuart St, Kingston, ON, Canada. K7L 2V7; Tel: +1 613-548-7839; Fax: +1 613-548-6030; E-mails:;


Depressive disorders (DD) are common, and their prevalence is expected to rise over the next decade. Depressive disorders are linked to significant morbidity and mortality. The clinical conundrum of depressive disorders lies in the heterogeneity of their phenomenology and etiology. Further, the currently available antidepressants have several limitations, including a delayed onset of action, limited efficacy, and an unfavorable side effect profile. In this review, Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor (α2-AR) agonist, is proposed as a potentially novel antidepressant with multiple mechanisms of action targeting various depression pathophysiological processes. These mechanisms include modulation of the noradrenergic system, regulation of neuroinflammation and oxidative stress, influence on the Brain-Derived Neurotrophic Factor (BDNF) levels, and modulation of neurotransmitter systems, such as glutamate. The review begins with an introduction before moving on to a discussion of DEX's pharmacological features. The pathophysiological and phenomenological targets of DD are also explored, along with the review of the existing preclinical and clinical evidence for DEX's putative anti-depressant effects. Finally, the review ends by presenting the pertinent conclusions and future directions.

Keywords: Dexmedetomidine, Adrenergic alpha-agonists, Antidepressant, Depression, Major depressive disorder, Treatment resistant-depression.