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Review
. 2022 Dec 1;23(23):15114.
doi: 10.3390/ijms232315114.

Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review

Dmitry Frank  1 , Benjamin F Gruenbaum  2 , Alexander Zlotnik  1 , Michael Semyonov  1 , Amit Frenkel  1 , Matthew Boyko  1
Affiliations
Review

Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review

Dmitry Frank et al. Int J Mol Sci. .

Abstract

Post-stroke depression (PSD) is a biopsychosocial disorder that affects individuals who have suffered a stroke at any point. PSD has a 20 to 60 percent reported prevalence among stroke survivors. Its effects are usually adverse, can lead to disability, and may increase mortality if not managed or treated early. PSD is linked to several other medical conditions, including anxiety, hyper-locomotor activity, and poor functional recovery. Despite significant awareness of its adverse impacts, understanding the pathogenesis of PSD has proved challenging. The exact pathophysiology of PSD is unknown, yet its complexity has been definitively shown, involving mechanisms such as dysfunction of monoamine, the glutamatergic systems, the gut-brain axis, and neuroinflammation. The current effectiveness of PSD treatment is about 30-40 percent of all cases. In this review, we examined different pathophysiological mechanisms and current pharmacological and non-pharmacological approaches for the treatment of PSD.

Keywords: drug therapies; glutamate; monoamines; pathogenesis; post-stroke depression (PSD).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the pathogenesis of PSD. The multimodal pathogenesis of PSD can be best understood by examining the roles of the monoamine system, glutamatergic system, excitotoxicity, gut-brain axis, neuroinflammation, and abnormal neutrophilic response.
Figure 2
Figure 2
The complex pathogenesis of PSD including different molecular, inflammatory, and physiological mechanisms. (HPA—hypothalamic-pituitary-adrenal axis, ANS—autonomic nervous system, GABA—gamma amino-butyric acid, BDNF—brain-derived neurotrophic factor, HLA—human leukocyte antigen complex).
Figure 3
Figure 3
Role of monoamine system in the pathophysiology of post-stroke depression. A schematic mechanism of decreasing concentration of monoamines in the synaptic cleft. (DAT—Dopamine transporter, NET—norepinephrine transporter, SERT—serotonin transporter).
Figure 4
Figure 4
Glutamate excitotoxicity. A schematic of the mechanism of cell death triggered by excessive glutamate release.
Figure 5
Figure 5
Approaches to drug treatment of PSD, categorized by their utilization of monoamine theory, the glutamatergic theory, or others.
See this image and copyright information in PMC

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