Does Metoprolol Cause Depression?

There is an association, but data is mixed.

Question

Can beta-blockers such as metoprolol cause side effects like depression, anxiety, or feelings of lament? Can this be true during short-term treatment? Also, what other cardiac medications can interact with beta-blockers? Thank you!!

Asked by Fenton On Aug 12, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Aug 14, 2018

DepressionBeta-blockers, such as metoprolol, can cause a variety of side effects including those that impact the Central Nervous System (CNS), cardiovascular, respiratory, and gastrointestinal systems. CNS effects include the possibility of tiredness, dizziness, depression, and short-term memory loss.


Metoprolol And Depression

According to the package insert, depression has been reported in about 5% of all patients on metoprolol. Although it is not clear why this occurs, beta blockers are known to cause fatigue and sexual dysfunction which could be associated with depression. 


Studies evaluating the risk of depression with metoprolol, and beta-blockers in general, show conflicting results.


One large review study, that included over 35,000 patients, produced results indicating that beta-blockers were not associated with an increased risk of depressive symptoms (1). The study concluded:

"The conventional wisdom that beta-blocker therapy is associated with substantial risks of depressive symptoms, fatigue, and sexual dysfunction is not supported by data from clinical trials. There is no significant increased risk of depressive symptoms and only small increased risks of fatigue and sexual dysfunction"

However, many studies that looked at metoprolol alone (not lumped in with other beta blockers), did find an increase in depressive symptoms. A small study that included 154 patients offered the following conclusion (2):

"Metoprolol treatment worsens the depressive and high burnout symptoms, but affords anxiolytic benefits independent of HR reduction in CHF patients with clinical mental disorders."

It does appear that certain beta-blockers are more likely to cause depressive symptoms than others, specifically ones that are 'lipophilic', or 'fat-loving'. Lipophilic drugs are more likely to cross the blood brain barrier and cause CNS side effects than non-lipophilic drugs (3).


A number of studies have reported that lipophilic beta-blockers, which includes metoprolol tartrate (Lopressor), metoprolol succinate (Toprol XL), propranolol and betaxolol are more likely to cause CNS effects that others (4). These CNS effects include:

  • Depression
  • Fatigue
  • Dizziness


Per one study (5):

"Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker."

To sum everything up, metoprolol (both the tartrate and the succinate versions) are associated with causing symptoms of depression. They appear more likely to do so as they are 'lipophilic' beta blockers. More data is needed however to assess the full risk and severity of the side effect.


Be sure to speak with your doctor regarding your concerns if you are experiencing adverse effects with metoprolol.


Read more information regarding metoprolol below.

 

Information About Metoprolol

Metoprolol Succinate is a beta blocker that is considered to be cardioselective (works primarily in the heart). It works in the cardiac muscle to block the sympathetic effect that increases heart rate. It also has effect in the vascular smooth muscle to block vasoconstriction and therefore lower blood pressure. Metoprolol is typically used for heart failure, blood pressure, and heart attack.


It is important to understand that there are two salt forms of metoprolol—tartrate and succinate. Metoprolol tartrate (Lopressor) is the immediate release formulation that is generally taken twice daily. Metoprolol succinate (Toprol XL) is generally taken once daily, but some cardiologists occasionally prefer twice daily dosing. It is important to understand the dose, frequency, and formulation of each prescription.


Common drug interactions with metoprolol include CYP2D6 inhibitors, clonidine, and digoxin. CYP2D6 inhibitors block the enzyme that metabolizes metoprolol. This increases the concentration of metoprolol and can increase the risk for side effects. Examples include quinidine, propafenone, diphenhydramine, and paroxetine.


Clonidine can cause rebound hypertension following withdrawal of clonidine while on metoprolol. Digoxin and other beta blockers slow the atrioventricular conduction and decrease heart rate. This can increase the risk for bradycardia (low heart rate). 

About the Pharmacist

Dr. Kevin Davis Pharm.D

Dr. Kevin Davis is a licensed pharmacist with experience in retail and hospital pharmacy. He graduated from the University of Florida with a Doctor of Pharmacy degree in 2015 and a Master of Healthcare Administration degree from Adventist University in 2017. He is also a Board Certified Pharmacotherapy Specialist since 2016.

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