To the Editor: We report significant sinus bradycardia in a patient presenting with an acute coronary syndrome shortly after beginning bupropion therapy to assist with smoking cessation.

A 53-year-old man was attended by paramedics for typical ischaemic chest pain. He had sinus bradycardia (45 beats/min) and hypotension (blood pressure, 85/60 mmHg), and was found to have a serum troponin I concentration of 1.2 μg/L, but no diagnostic electrocardiographic changes. He was admitted to our hospital with an acute coronary syndrome. He reported his medications at the time of admission as including metoprolol 50 mg twice daily (for hypertension) and paroxetine 20 mg daily (for depression).

The patient was given multiple doses of intravenous atropine (total, 1.2 mg) and adrenalin (total, 2 mg). After an adrenalin infusion was begun, he developed ventricular tachycardia (170 beats/min), but his cardiac rhythm spontaneously returned to sinus bradycardia. Two days after admission, two coronary stents were successfully deployed in a critically stenosed right coronary artery. Bradycardia (45–50 beats/min) persisted.

The following day, it was discovered that 3 weeks previously, the patient’s general practitioner had prescribed bupropion 150 mg twice daily to assist with smoking cessation, which he had been taking up until the day of admission.

Bradycardia continued until hospital discharge. One month after discharge, he was in sinus rhythm (60 beats/min) and was clinically well.

Bupropion is a selective noradrenalin, dopamine and serotonin reuptake inhibitor. The mechanism by which it enhances the ability of patients to abstain from smoking is unknown.1 Bupropion inhibits the activity of the cytochrome P450 2D6 isoenzyme, which metabolises metoprolol.2 Concurrent use of bupropion and metoprolol can increase serum metoprolol levels, and clinically significant bradycardia has been reported.3 Further, paroxetine, a selective serotonin reuptake inhibitor (SSRI), is a potent cytochrome P450 2D6 inhibitor, which would have further increased serum metoprolol levels. Bradycardia associated with metoprolol and paroxetine dual therapy has been described.5 Additionally, there is the potential for serotonin syndrome to develop in a patient administered multiple SSRIs. In our patient, the administration of bupropion and paroxetine could have potentially led to serotonin syndrome.6

Our patient’s pharmacological profile was complex, with potential adverse pharmacodynamic effects. The most likely precipitant of the patient’s bradycardia was his acute coronary syndrome, although bupropion may have contributed. The case highlights the potential for significant drug interactions when new drug therapies are initiated. Bupropion and metoprolol (and other drugs metabolised by the cytochrome P450 2D6 isoenzyme pathway) should be co-administered with caution. The importance of common pathways of drug metabolism should be recognised to avoid potential adverse events, particularly when multiple medications are used.