Off-Target Effects of Antidepressants on Vascular Function and Structure

Abstract

Depression emerges as a risk factor for cardiovascular disease, and it is thought that successful antidepressant treatment may reduce such a risk. Therefore, antidepressant treatment embodies a potential preventive measure to reduce cardiovascular events in patients with depression. Accumulating evidence indicates that antidepressants have off-target effects on vascular dysfunction and in the early stages of atherosclerosis, which form the basis for cardiovascular disease (CVD) pathogenesis. In this context, we performed a thorough review of the evidence pertaining to the effects of different classes of antidepressant medications on hemodynamic and early atherosclerosis markers. The preclinical and clinical evidence reviewed revealed a preponderance of studies assessing selective serotonin reuptake inhibitors (SSRI), whereas other classes of antidepressants are less well-studied. Sufficient evidence supports a beneficial effect of SSRIs on vascular inflammation, endothelial function, arterial stiffening, and possibly delaying carotid atherosclerosis. In clinical studies, dissecting the hypothesized direct beneficial antidepressant effect of SSRIs on endothelial health from the global improvement upon remission of depression has proven to be difficult. However, preclinical studies armed with appropriate control groups provide evidence of molecular mechanisms linked to endothelial function that are indeed modulated by antidepressants. This suggests at least a partial direct action on vascular integrity. Further research on endothelial markers should focus on the effect of antidepressants on treatment responders versus non-responders in order to better ascertain the possible beneficial vascular effects of antidepressants, irrespective of the underlying course of depression.

Lower vascular conductance responses to handgrip exercise are improved following acute antioxidant supplementation in young individuals with post‐traumatic stress disorder

“…The six participants in the PTSD group who were prescribed medication for their psychological symptoms were not asked to stop their treatment. The most‐used medication ( n = 4) were serotonin reuptake inhibitors (SSRIs), which may be beneficial to vascular function (Dimoula et al., 2022) and do not appear to alter blood pressure in young adults (Romańczyk et al., 2021; Zhong et al., 2017). Though no evaluation of the presence of depression or anxiety was administered, it is well established that these mental disorders are highly comorbid in individuals with PTSD (Ginzburg et al., 2010; Spinhoven et al., 2014).…”

Cardiovascular Considerations in Antidepressant Use

“…Despite the facts regarding mentioned side effects, there are some evidences showing that antidepressants can be beneficial for the cardiovascular system in some manners. SSRIs are manifested to improve endothelial function, vascular inflammation, arterial stiffening and perhaps delaying atherosclerotic events 17 , 18 . Moreover, antidepressant therapy was associated with lower odds of recurrent Myocardial Infarction (MI) in patients with acute coronary syndrome and concomitant depression 19 .…”

Vascular Function in Chronic Non-Communicable Diseases

“…Finally, this Special Issue includes two reviews: the first investigated the importance of evaluating the coexistence of coronary and peripheral disease in erectile dysfunction patients [ 18 ]. The second examined the potential beneficial effects of antidepressant therapies on the reduction of vascular inflammation and of arterial stiffness [ 19 ].…”