Why switch from a selective serotonin reuptake inhibitor (SSRI) to bupropion in a patient with heart failure?

Why Switch from SSRI to Bupropion in Heart Failure

Bupropion should be strongly considered over SSRIs in heart failure patients because it has a superior cardiovascular safety profile, does not cause orthostatic hypotension, does not adversely affect cardiac conduction or left ventricular function, and avoids the potential risks of SSRIs including QT prolongation and hyponatremia. 1, 2

Cardiovascular Safety Advantages of Bupropion

Absence of Orthostatic Hypotension

• Bupropion does not cause orthostatic hypotension, a critical advantage in heart failure patients who are already at risk for hypotensive episodes due to their cardiac medications (ACE inhibitors, beta-blockers, diuretics). 1, 3, 2
• In direct comparison studies, imipramine caused severe orthostatic hypotension requiring drug discontinuation in 50% of heart failure patients, while bupropion caused no such problems. 2
• Patients who previously experienced tricyclic-induced orthostatic hypotension did not show orthostasis when switched to bupropion. 3

Preserved Cardiac Function

• Bupropion has no deleterious effect on left ventricular ejection fraction in patients with impaired left ventricular function, as demonstrated by radionuclide angiography studies. 1, 2
• In 36 depressed inpatients with preexisting left ventricular impairment, ventricular arrhythmias, and/or conduction disease, bupropion did not exacerbate ventricular arrhythmias or cause significant conduction complications. 1
• The drug had no effect on pulse rate and maintained stable cardiovascular parameters throughout treatment. 1, 3

Lack of Conduction Abnormalities

• Unlike tricyclic antidepressants which cause subclinical delays in cardiac conduction, bupropion does not adversely affect cardiac conduction. 3
• High-speed ECG and 24-hour portable ECG monitoring in cardiac patients showed no conduction complications with bupropion therapy. 1

SSRI-Related Cardiovascular Concerns in Heart Failure

QT Prolongation Risk

• SSRIs, particularly citalopram, can cause QT interval prolongation predisposing to ventricular tachycardia, a potentially fatal arrhythmia in heart failure patients with already compromised cardiac function. 4
• This risk is particularly concerning given that heart failure patients often have baseline electrolyte abnormalities and are on multiple QT-prolonging medications.

Hyponatremia Risk

• SSRIs carry a risk of hyponatremia, which can be particularly problematic in heart failure patients who are already at risk due to diuretic therapy and neurohormonal activation. 5
• Bupropion may have a lower risk profile for hyponatremia compared to SSRIs. 5

Drug Interaction Concerns

• SSRIs have theoretical interactions with other serotonergic drugs, which can lead to serotonin syndrome. 4
• This becomes relevant in heart failure patients on complex medication regimens.

Clinical Implementation Algorithm

When to Switch

1. Any heart failure patient currently on an SSRI for depression should be evaluated for switch to bupropion, particularly if they have:

   • Left ventricular systolic dysfunction 1, 2
   • Ventricular arrhythmias 1
   • Conduction disease 1
   • Orthostatic symptoms 3, 2
   • Hyponatremia 5

2. For new depression diagnoses in heart failure patients, bupropion should be first-line rather than SSRIs. 1, 2

Dosing Considerations

• Bupropion was safely used at mean doses of 442 mg/day in cardiac patients, though starting low and titrating is prudent. 1
• Patients should continue their cardiac drug regimens (beta-blockers, ACE inhibitors, diuretics) without interruption during the switch. 1

Monitoring Requirements

• Monitor supine blood pressure, as bupropion can cause a rise in supine blood pressure (though not orthostatic hypotension). 1
• Watch for exacerbation of baseline hypertension, which occurred in 2 patients (approximately 6%) in cardiac studies. 1
• Continue standard heart failure monitoring including pulse, blood pressure, and clinical status. 4

Critical Caveats and Pitfalls

Hypertension Monitoring

• While bupropion does not cause orthostatic hypotension, it can increase supine blood pressure and may exacerbate baseline hypertension. 1
• This occurred in approximately 6% of cardiac patients and required drug discontinuation in some cases. 1
• Blood pressure should be monitored closely, especially during dose titration.

Not for All Cardiac Patients

• The evidence base for bupropion's safety is specifically in patients with left ventricular impairment, ventricular arrhythmias, and conduction disease. 1, 2
• In overdose situations, bupropion can cause severe cardiotoxicity including cardiogenic shock, though this is not relevant to therapeutic dosing. 6, 7

Discontinuation Rate

• Approximately 14% of cardiac patients discontinued bupropion due to adverse effects in clinical studies, including hypertension exacerbation. 1
• This is still favorable compared to the 50% discontinuation rate with tricyclics due to orthostatic hypotension. 2

Contraindications to Consider

• Patients with uncontrolled hypertension should have blood pressure optimized before starting bupropion. 4
• Seizure history remains a contraindication to bupropion regardless of cardiac status.