Related Experiment Video
Updated: Aug 12, 2026

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
Published on: December 2, 2015
Depression, anxiety, and the cardiovascular system: the psychiatrist's perspective
1College of Physicians and Surgeons, Columbia University, New York, NY 10583, USA. spr2@columbia.edu
Insights
Depression and cardiovascular disease (CVD) are linked, with depression increasing CVD risk. Selective serotonin reuptake inhibitors (SSRIs) show a safer cardiac profile than tricyclic antidepressants (TCAs) for treating comorbid depression and CVD.
Area of Science:
- Cardiology
- Psychiatry
- Pharmacology
Background:
- Comorbidity of depression and cardiovascular disease (CVD) is an inevitable consequence, not coincidental.
- Depression is a significant risk factor for symptomatic, fatal ischemic heart disease and sudden cardiovascular death.
- Treating comorbid depression and CVD requires integrated management, not isolated approaches.
Purpose of the Study:
- To compare the cardiovascular safety of selective serotonin reuptuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in patients with comorbid depression and CVD.
- To evaluate the differential impact of SSRIs versus TCAs on cardiovascular events.
Main Methods:
- A randomized, controlled study comparing the SSRI paroxetine with the TCA nortriptyline at therapeutic levels.
- Assessment of cardiovascular profiles and adverse events in patients receiving either antidepressant.
Main Results:
- The SSRI paroxetine demonstrated a benign cardiovascular profile.
- The TCA nortriptyline induced a significantly higher rate of serious adverse cardiovascular events.
- TCAs possess Type IA antiarrhythmic activity, linked to increased mortality in post-myocardial infarction patients.
Conclusions:
- SSRIs are the preferred choice for treating depression in most patients with comorbid CVD due to their favorable cardiovascular safety.
- Further research into pathophysiologic mechanisms, like platelet activation, may reveal beneficial effects of antidepressants on CVD prognosis.
Abstract:
It is becoming clear that the comorbidity of depression and cardiovascular disease does not occur by chance but rather is an inevitable consequence of the relationship between the conditions. Depression in patients with cardiovascular disease is a significant risk factor for developing symptomatic and fatal ischemic heart disease. Moreover, depressed patients have a higher than expected rate of sudden cardiovascular death. Therefore, appropriate treatment of patients with depression and cardiovascular disease cannot be restricted to considerations of either depression or cardiovascular disease in isolation. The tricyclic antidepressants (TCAs) have various effects on the cardiovascular system, including Type IA antiarrhythmic activity that has been associated with an increased risk of mortality in post-myocardial infarction patients. The selective serotonin reuptake inhibitors (SSRIs) are not associated with adverse cardiac effects. The SSRI paroxetine was compared with a therapeutic level of the TCA nortriptyline in a randomized, controlled study and demonstrated a benign cardiovascular profile, while the TCA induced a significantly higher rate of serious adverse cardiovascular events. On the basis of this favorable cardiovascular profile, the SSRIs should therefore be the preferred choice for the treatment of most patients with comorbid depression and cardiovascular disease. Investigation of putative pathophysiologic mechanisms linking depression and cardiovascular mortality, such as the role of platelet activation, will form the basis for further investigation of antidepressant treatments in order to establish if the antidepressants have a beneficial effect on the prognosis of cardiovascular diseases.
Related Concept Videos
Disorders of the Autonomic Nervous System
Raynaud's disease, also known as Raynaud's phenomenon, is a...
Depression: Overview
Assessment of the Cardiovascular System I: Subjective Data
Initial Enquiry
Ask the patient about their primary concern and thoroughly explore all reported symptoms.
Medical History
Investigate past illnesses affecting the cardiovascular system, such as angina, anemia, rheumatic fever, congenital heart disease, stroke, thrombophlebitis, dysrhythmias, varicosities
Inquire about symptoms...
Stress and Mental Health
Individuals with depression often experience challenges in both their personal and professional...
Psychoneuroimmunology: Cardiovascular Disease
A key area of focus in PNI is the relationship between stress and coronary...
Depressive Disorders: Etiology
Biological Factors in Depression
Biological predispositions significantly influence the risk of developing depressive disorders. Genetic studies highlight the role of variations in the serotonin transporter...

