Antidepressants Plus Beta Blockers Equals Health Risks

 Individuals who are simultaneously taking certain antidepressants and beta blockers had a decrease in systolic blood pressure (BP) and an increase in their risk for bradycardia, according to new data presented at the American Heart Association’s Hypertension Scientific Sessions (HYP) 2025.

“Patients with both cardiovascular and psychiatric conditions often require beta blockers and antidepressants together, but their interactions can alter drug levels significantly, which is why we aimed to systematically quantify these pharmacokinetic effects,” said lead author Inshal Jawed, MD, of Dow Medical College, Karachi, Pakistan, in an interview.

Some serotonin reuptake inhibitors (SSRIs) inhibit the CYP2D6 enzyme, which plays a key role in metabolizing certain beta blockers, and this inhibition may lead to higher plasma concentrations of the drugs and a greater chance that patients will experience adverse events or exaggerated therapeutic effects, the researchers noted.

In a meta-analysis, Jawed and colleagues identified 65 adults older than 20 years with concurrent depression and hypertension who were taking both beta blockers and antidepressants such as SSRIs/serotonin-norepinephrine reuptake inhibitors (SNRIs), duloxetine, or bupropion.

The researchers examined data on drug plasma concentrations, clearance, and area under the curve (AUC) to assess the effects of the drug interactions. Overall, the patients on antidepressants and beta blockers showed a 15%-20% decrease in systolic BP and a 25% increased risk for bradycardia. 

On a molecular level, for the interaction between SSRIs and CYP2D6-dependent beta blockers, the AUC increased by 2.55-fold, the maximum serum concentration (C_max) increased by 1.94-fold, and the half-life increased by 1.94-fold, but there was no change in the time to reach peak concentration of the drug (T_max).

For the interaction of nebivolol with antidepressants, the AUC increased by 2.76-fold, C_max increased by 1.67-fold, and half-life increased by 1.80-fold. The effects were even greater for the OH-nebivolol metabolite; AUC increased by 2.59-fold, C_max by 1.48-fold, and half-life by 2.15-fold, with no significant difference in T_max. Clinicians should assess drug interactions, dose adjustments, and implement monitoring to ensure optimal outcomes, the researchers concluded.

“We expected interactions, but the magnitude, particularly between the nebivolol and the S enantiomers of beta blockers, was striking,” Jawed told Medscape Medical News. The findings reinforced that these combinations can meaningfully change drug exposure, she added.

However, atenolol and nadolol were not affected by antidepressant medications, the researchers wrote.

In practice, “clinicians should be cautious when prescribing CYP2D6-metabolized beta blockers with SSRIs or other CYP2D6 inhibitors,” Jawed told Medscape Medical News. “Dose adjustment and close monitoring are key, while beta blockers less reliant on hepatic metabolism may be safer alternatives,” she said.

Study limitations included a small population of only 65 participants, which may prevent generalizability, said Jawed. “Larger, prospective clinical studies are needed to confirm these pharmacokinetic changes and assess their impact on real-world patient outcomes.” 

Keep Everyone in the Loop

Hypertension and depression are both common in the population and often coexist, and patients should be closely monitored when co-administering these two categories of medications, particularly when adjusting medication dosages, said Sabrina Islam, MD, MPH, associate professor of medicine in the section of cardiology at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“The key takeaway is that CYP2D6-dependent beta blockers can be upregulated by medications such as SSRIs/SNRIs, which can in turn lead to increased side effects of these medications, including bradycardia and hypotension,” said Islam, who was not involved in the study.

The study findings were not unexpected, but the results can help guide clinical practice by highlighting the two beta blockers (atenolol and nadolol) that have the least interaction with SSRIs/SNRIs, Islam told Medscape Medical News. These drugs can be considered in cases of intolerance to the CYP2D6-dependent beta blockers, she said.

The results were limited by the possible biases inherent in a systematic review, and additional prospective and controlled studies are needed to assess the conclusions, Islam noted. However, studies such as this one are essential not only in educating the healthcare community about the importance of team-based care but also in illustrating the need for discussion among members of the healthcare team, she added.

The study received no outside funding. Jawed and Islam had no financial conflicts to disclose.

https://www.medscape.com/viewarticle/antidepressants-plus-beta-blockers-equals-health-risks-2025a1000oek