Antidepressants, metoprolol and the risk of bradycardia

Case reports and pharmacologic theory suggest that some antidepressants can interfere with the hepatic metabolism of metoprolol by cytochrome P450 2D6 (CYP2D6), potentially increasing the risk of bradycardia. The objective was to characterize the clinical consequences of this potential drug interaction at the population level.

The researchers conducted a population-based, nested case-control study of Ontario residents 66 years of age or older receiving metoprolol. Cases hospitalized for bradycardia were compared with matched controls (4:1) to explore the odds ratio for initiation of antidepressants that inhibit cytochrome p450 2D6 (CYP2D6) (fluoxetine and paroxetine) with that of non-CYP2D6 inhibiting antidepressants (fluvoxamine, citalopram, venlafaxine, and sertraline) within 30 days before hospitalization. From April 1997 to March 2009, the researchers identified 332,254 elderly patients continuously receiving metoprolol, of whom 8,232 (2.5%) were treated in hospital for bradycardia. The adjusted odds ratio for exposure to fluoxetine/paroxetine compared to other antidepressants 30 days prior to hospitalization for bradycardia was 0.76 (95% confidence interval 0.42-1.37). Among older patients receiving metoprolol, the initiation of antidepressants that inhibit CYP2D6 was not associated with a significant increase in the risk of bradycardia as compared to antidepressants that do not inhibit CYP2D6.