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Analyzing Cardiovascular Effects & Risks of Newer Antidepressants

Depression is a prevalent and serious condition in older adults and those with cardiovascular disease.

Serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression, but when they’re ineffective, alternative antidepressants must be considered.

Key Facts:

  1. Depression in Older Adults and Cardiovascular Patients: Affects 15-20% of patients with coronary heart disease.
  2. Limitations of SSRIs: While generally safe, SSRIs aren’t always effective, necessitating alternative treatments.
  3. Cardiovascular Side Effects: Vital to consider in patients with existing cardiovascular conditions.
  4. Urgent Research Needed: More studies are required to understand the safety and efficacy of non-SSRI antidepressants in these patient groups.

Source: CNS Drugs (2020)

Links Between Depression, Cardiovascular Disease, & Antidepressants

The interplay between depression, cardiovascular disease (CVD), and antidepressants is multifaceted and complex, involving various permutations and relationships.

These interactions significantly impact patient care and treatment outcomes, requiring healthcare providers to navigate a delicate balance in managing these conditions.

Depression and Cardiovascular Disease

  • Depression as a Risk Factor for CVD: Individuals with depression are at a higher risk of developing cardiovascular diseases. The physiological changes associated with depression, such as increased inflammatory markers, changes in the autonomic nervous system, and altered platelet function, contribute to this elevated risk.
  • Impact of CVD on Depression: Experiencing a cardiovascular event or living with a chronic heart condition can lead to psychological distress and trigger depression. The stress and lifestyle changes associated with managing a chronic condition like CVD can also exacerbate depressive symptoms.
  • Worsening CVD Prognosis Due to Depression: Patients with both depression and cardiovascular disease often have a poorer prognosis. Depression can lead to poor adherence to cardiovascular medications, unhealthy lifestyle choices, and reduced motivation to engage in rehabilitative activities, all of which can worsen CVD outcomes.

Antidepressants and Cardiovascular Disease

  • SSRIs and Cardiovascular Safety: SSRIs are generally considered safe for individuals with cardiovascular disease. They are less likely to affect heart rate, blood pressure, or cardiac conduction compared to older antidepressants like tricyclics. However, they are not entirely without risk, and certain SSRIs can prolong the QT interval, especially in susceptible individuals.
  • Non-SSRI Antidepressants and Cardiovascular Risks: Non-SSRI antidepressants, such as SNRIs and atypical antidepressants, may have varying effects on cardiovascular health. Some can increase blood pressure or heart rate, while others might interfere with cardiac conduction. The choice of a non-SSRI antidepressant in a patient with CVD must be made cautiously, considering the individual’s specific cardiovascular risk factors.
  • Tricyclic Antidepressants (TCAs) and Older Agents: TCAs and some older antidepressants are generally less favored in individuals with cardiovascular disease due to their potential to cause orthostatic hypotension, arrhythmias, and other cardiac effects. Their use requires careful monitoring and consideration of the patient’s overall cardiac profile.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)


Venlafaxine is a well-known serotonin-norepinephrine reuptake inhibitor (SNRI) that increases neurotransmitter levels in the brain, potentially improving mood and depressive symptoms.

It’s generally started at a low dose and gradually increased.

However, it’s associated with an increase in blood pressure, particularly at higher doses, which could be a concern for patients with pre-existing hypertension or cardiovascular disease.


Desvenlafaxine, the active metabolite of venlafaxine, shares many of its predecessor’s effects but may offer a slightly different side effect profile due to its unique pharmacokinetics.

Like venlafaxine, it can increase blood pressure and heart rate, necessitating careful monitoring in cardiovascular patients.


Duloxetine is another SNRI, known for its pain-relieving properties in conditions like diabetic neuropathy.

While it’s generally well-tolerated, it can cause a modest increase in heart rate and blood pressure.

Its potential to block cardiac ion channels at high doses could be of concern in patients with existing heart conditions.

Milnacipran & Levomilnacipran

Milnacipran and levomilnacipran are less commonly used SNRIs but have a similar profile to their counterparts.

They can increase blood pressure and heart rate, and while studies are limited, they suggest a need for caution and regular monitoring in patients with cardiovascular disease.

Atypical Monoaminergic Antidepressants


Mirtazapine works through a unique mechanism, antagonizing certain serotonin and histamine receptors, which can lead to increased appetite and weight gain — a potential risk factor for worsening cardiovascular health.

However, it doesn’t generally affect heart rate or blood pressure significantly.


Bupropion is notable for its stimulant effects and usefulness in smoking cessation.

It’s generally considered neutral or slightly increasing blood pressure.

However, its tendency to increase heart rate and potential for rare seizures at high doses requires careful consideration in cardiovascular patients.


Vilazodone, a serotonin partial agonist and reuptake inhibitor (SPARI), offers a novel mechanism potentially associated with fewer sexual side effects.

While its cardiovascular profile is relatively benign, the lack of extensive research in patients with heart conditions warrants cautious use.


Vortioxetine is another multimodal antidepressant with a complex action on various serotonin receptors and the reuptake process.

It generally has a minimal impact on blood pressure and heart rate but, like many newer drugs, needs more research in vulnerable populations.


Agomelatine acts on melatonin receptors and serotonin antagonism, offering a unique approach to depression treatment, particularly where sleep disturbances are present.

It doesn’t typically affect heart rate or blood pressure but should be used cautiously due to potential liver toxicity.


Moclobemide is a reversible MAO-A inhibitor with a more favorable side effect profile than traditional MAOIs.

It’s less likely to interact with tyramine-rich foods to cause hypertensive crises but still requires careful monitoring for blood pressure changes and interactions with other medications.

NMDA Receptor Antagonists

Ketamine & Esketamine

Ketamine and its S-enantiomer, esketamine, represent a significant shift in depression treatment, offering rapid relief for some individuals.

However, they can cause a transient increase in blood pressure and heart rate during administration, which may be risky for patients with unstable or poorly managed cardiovascular disease.

How was the study conducted? (Antidepressants & Cardiovascular Effects)

The study on the 12 antidepressants was designed as a qualitative narrative review aimed at comprehensively evaluating the cardiovascular side effects of a range of newer non-SSRI antidepressants.

  • Literature Search: The researchers conducted a thorough search of medical databases like PubMed and Google Scholar. They focused on each of the 12 antidepressants, looking for studies that discussed their cardiovascular effects. The search included terms like the specific antidepressant’s name combined with keywords like “QT,” “QTc,” “heart rate,” “hypertension,” “cardiovascular outcomes,” “arrhythmia,” and more, as well as terms relating to the target populations such as “geriatric,” “older adults,” and “cardiovascular disease.”
  • Selection Criteria: Studies were selected based on their relevance to the cardiovascular effects of the antidepressants, with a focus on geriatric populations and those with cardiovascular conditions. Both clinical trials and observational studies were included to provide a comprehensive overview.
  • Data Extraction: Information was carefully extracted from the selected studies, including details about the antidepressant’s dosing, cardiovascular effects, and any general advantages or disadvantages noted.
  • Qualitative Analysis: The researchers then conducted a qualitative narrative review, synthesizing the data from various studies to provide an in-depth understanding of each antidepressant’s cardiovascular profile.

Recap: Newer Antidepressants & Cardiovascular Risks

In treating depression among older adults and cardiovascular patients, the choice of antidepressant must be weighed carefully against potential cardiovascular side effects.

While SSRIs are often safe and effective, alternative treatments might be necessary.

Each non-SSRI antidepressant has its own risk profile that must be considered in the context of the individual’s overall health and other medications.


  • Individualized Approach: Tailor antidepressant choices to individual cardiovascular risk profiles and closely monitor for side effects.
  • Start Low, Go Slow: Begin with lower doses and titrate slowly, especially in patients with cardiovascular disease.
  • Regular Monitoring: Regularly check blood pressure, heart rate, and other relevant parameters during treatment.
  • Research and Vigilance: Stay informed about the latest research and post-marketing surveillance to understand emerging safety profiles.


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