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Abstract
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BACKGROUND: Beta-blockers and antidepressants are two of the most commonly prescribed drug classes in the United States. Several antidepressants are potent inhibitors of cytochrome P450 2D6 liver enzymes (CYP2D6) and can increase the plasma concentrations of certain beta-blockers when administered concomitantly, potentially leading to serious medical consequences such as hypotension, bradycardia and falls.
OBJECTIVE: The primary objective of this investigation was to determine whether initiating an antidepressant in patients receiving beta-blockers increased the risk of hemodynamic adverse events. Our primary outcome was time to hospital admissions or emergency department (ED) visits for an ICD-9 diagnosis suggestive of excessive beta-blockade.
METHODS: We conducted a survival analysis for adults continuously enrolled in the California Medicaid system (Medi-Cal) between 2004 and 2012. Eligible patients were required to be receiving beta-blocker medications that are primarily CYP2D6 substrates (e.g., metoprolol, propranolol, carvedilol). Univariate and multivariable analysis were performed for patients who concurrently received antidepressants with beta-blockers. An additional multivariable analysis analyzed the association of this combination upon hospitalizations or ED visits for all causes.
RESULTS: A total of 21,292 beneficiaries met inclusion criteria, and 4.3% of patients required hospitalization or ED visits within 30 days of comedication. In multivariable analysis, patients receiving antidepressants with moderate-strong CYP2D6 inhibitory potential (fluoxetine, paroxetine, duloxetine, bupropion) had a greater risk for hospitalization or ED visits for hemodynamic events than those initiated on antidepressants with weak CYP2D6 inhibition for ≤ 30 days, when each was compared to patients receiving no antidepressants (HR=1.53; 95% CI =1.03-2.81; p=0.04 versus HR=1.24; 95% CI=0.82-1.88; p = 0.30). Other demographic variables associated with increased morbidity included advanced age, male sex, higher beta-blocker doses, and African-American race or Hispanic ethnicity.
CONCLUSIONS: Results of this analysis suggest that initiation of certain antidepressants was associated with an increased risk for serious medical sequelae among patients concurrently receiving beta-blockers. Greater risk was observed with antidepressants, which potently inhibit the CYP2D6 enzyme, implying that increased morbidity may be mediated by a metabolic drug interaction.
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Language: en |