Drug-Drug Interactions: Antidepressants and Beta Blockers

Drug-Drug Interactions: Antidepressants and Beta Blockers
Atuobi Nana Yiadom, Pharm.D., CentraCare Hospital, Paynesville

Background: Beta blockers such as metoprolol, and antidepressants such as fluoxetine, paroxetine, duloxetine and bupropion are commonly prescribed together for the management of cardiovascular disease and depression respectively. These two medication classes also rely on the common CYP2D6 pathway for metabolism. Concurrent administration of antidepressants and beta blockers can result in increased beta blocker exposure, which can lead to drug toxicity and events such as decreased heart rate, hypotension and falls.

Objective: The objective of the study was to investigate whether the interaction between beta blockers and antidepressants with moderate to strong CYP2D6 inhibition resulted in increased morbidity, evidenced by hospitalization or emergency department visits for hemodynamic events.

Study Design: The study was a retrospective cohort study of adults enrolled in the California fee-for-service (FFS) Medicaid Program (Medi-Cal) from January 1, 2004 to December 31, 2011. The study group included Medi-Cal patients who were 18 years or older, enrolled in the FFS program for a minimum of 12 months, and were on an immediate or sustained release beta blocker and antidepressant undergoing CYP2D6 metabolism. The primary outcome was the time to first hospitalization or emergency department visit, suggestive of excessive beta blockade, within 30 days of receiving an antidepressant concurrently with a beta blocker.

Results: A total of 21,292 study participants were identified and met the criteria for the study. The female population represented in the study was 52.1% with 31.2% of the study population receiving a beta blocker and antidepressant concurrently. The discontinuation rate within 30 days of therapy initiation was 61%. Time to hospitalization or emergency department visits showed that 4.3% of the study population experienced adverse outcomes, with dizziness or syncope as a common adverse outcome. A univariate analysis showed that patients on an antidepressant with strong to moderate CYP2D6 inhibition were more likely to experience adverse events than patients on weak CYP2D6 inhibition (1.64 [95% CI 1.14-2.40], P=0.008 vs 1.33 [95% CI 0.91-1.95], P=0.14) and a multivariate analysis adjusted for covariates showed (1.53 [95% CI 1.03-2.81], P= 0.04). Time to hospitalization and emergency department visits for all causes was 37% for patients receiving a beta blocker higher doses of the beta blocker were associated with an increase in hospitalization or emergency department visits.

Limitations: The study hypothesized increased beta blocker concentrations with concurrent use of an antidepressant, but the researchers were not able to quantify plasma concentrations to support their claim. Secondly, the researchers used prescription refills to estimate adherence, which also showed that 61% of patients did not refill the antidepressant after the first 30 days supply. 

Conclusion: The study suggested that concurrent administration of beta blockers and antidepressants with moderate to strong CYP2D6 interaction can lead to serious hemodynamic events requiring hospitalization or an emergency department visit.

Key Point: Beta blockers and antidepressants are commonly prescribed together, and it is important that pharmacists perform a prospective drug use review to decrease adverse events from using these medications together.


  1. Shin, Jaekyu, et al. “Combining Antidepressants with β‐Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction.” Pharmacotherapy, vol. 40, no. 6, 2020, pp. 507–516.