Can Selective Serotonin Reuptake Inhibitors (SSRIs) cause bradycardia?

SSRIs and Bradycardia: Clinical Considerations

SSRIs can cause bradycardia in rare cases, though this is not among their common cardiovascular effects. While SSRIs are generally considered safer from a cardiovascular perspective than tricyclic antidepressants, case reports have documented instances of bradycardia and syncope associated with SSRI use 1.

Mechanism and Risk Factors

The mechanism of SSRI-induced bradycardia likely involves:

• Direct central nervous system effects of increased serotonin on medullary cardiovascular regulation 1
• Inhibition of cardiac Na+ and Ca2+ channels, similar to class I + IV antiarrhythmic effects 2

Risk factors that may increase the likelihood of bradycardia with SSRIs include:

• Concurrent use of other medications that affect heart rate (particularly cyclosporine, as documented in case reports) 3
• Pre-existing cardiovascular conditions
• Elderly patients (who are generally more susceptible to cardiovascular side effects)

Evidence from Guidelines

According to the European Heart Journal, SSRIs have been classified as medications with "a propensity of inducing QT prolongation" 4. This has led regulatory agencies to take action:

• Both FDA and EMA have limited the recommended maximum doses of certain SSRIs (particularly citalopram and escitalopram) due to QT-prolonging effects 5
• For patients older than 60 years of age, the maximum recommended dose is further reduced 4

A Danish nationwide registry study found that treatment with SSRIs was significantly associated with cardiac arrest (OR = 1.21), though this study didn't specifically focus on bradycardia 4.

Clinical Presentation

When bradycardia occurs with SSRI use, it may present as:

• Decreased heart rate (typically below 60 bpm)
• Possible accompanying symptoms including faintness or syncope 1
• Symptoms may appear shortly after initiation or dose increase

Management Considerations

If SSRI-induced bradycardia is suspected:

1. Evaluate the clinical significance of the bradycardia (symptomatic vs. asymptomatic)
2. Consider dose reduction if bradycardia is mild and the patient is benefiting from the SSRI
3. Consider discontinuation if bradycardia is severe or symptomatic
4. Monitor ECG in high-risk patients, particularly those with:
   • Pre-existing cardiovascular disease
   • Concomitant use of other medications that affect heart rate
   • Elderly patients

Comparative Cardiac Safety

• SSRIs are generally considered to have better cardiac safety profiles than tricyclic antidepressants 2
• Among SSRIs, citalopram has been reported to have an increased risk of electrocardiographic abnormalities 6
• In a study of SSRI poisoning in animals, there were no deaths in 313 SSRI-poisoned dogs, suggesting relative safety even in overdose 6

Important Caveats

• Bradycardia is not listed among the common adverse effects of SSRIs in major guidelines 4
• The risk appears to be relatively low compared to other cardiovascular effects like QT prolongation
• Individual susceptibility varies, and some patients may be more prone to this effect than others

When prescribing SSRIs, particularly in patients with cardiovascular risk factors or in elderly patients, clinicians should maintain awareness of the potential for bradycardia as a rare but documented adverse effect.