Antidepressants in Alzheimer's Disease: A Focus on the Role of Mirtazapine

Abstract

Mirtazapine belongs to the category of antidepressants clinically used mainly in major depressive disorder but also used in obsessive-compulsive disorders, generalized anxiety, and sleep disturbances. This drug acts mainly by antagonizing the adrenergic α2, and the serotonergic 5-HT2 and 5-HT3 receptors. Neuropsychiatric symptoms, such as depression and agitation, are strongly associated with Alzheimer's disease, reducing the life quality of these patients. Thus, it is crucial to control depression in Alzheimer's patients. For this purpose, drugs such as mirtazapine are important in the control of anxiety, agitation, and other depressive symptoms in these patients. Indeed, despite some contradictory studies, evidence supports the role of mirtazapine in this regard. In this review, we will focus on depression in Alzheimer's disease, highlighting the role of mirtazapine in this context.

Keywords: Alzheimer’s disease; depression; mirtazapine.

Figure 1

The hallmarks of AD are the presence of a Aβ plaques and neurofibrillary tangles. Reprinted from “Alzheimer’s Brain (Disintegrating Microtubule)”, by BioRender.com (2021). Retrieved from [18]. Available online: https://app.biorender.com/biorender-templates (accessed on 16 August 2021).

Figure 2

Findings such as decreased levels of 5-HT, NE, and BDNF, as well as dysregulation of the HPA axis and pro-inflammatory pathways, are associated with depression, contributing to the increase in neurodegeneration phenomena present in AD, such as the presence of Aβ plaques and brain atrophy. Adapted with permission from ref. [48]. Copyright 2019 Frontiers Media S.A. Created with BioRender.com [49]. Available online: https://biorender.com/ (accessed on 16 August 2021).

Figure 3

Summary of the mechanism of action of mirtazapine. This drug is an antagonist of 5-HT2A, 5-HT2C, 5-HT3, H1, and α2 receptors, resulting in antidepressant and sedative effects [107]. Image for illustrative purposes only. Created with BioRender.com [49]. Available online: https://biorender.com/ (accessed on 16 August 2021).