Antibiotic Resistance Increased by Common Antidepressants

Bottles of antidepressant pills, (L-R) Wellbutrin, Paxil, Lexapro, Effexor, Zoloft and Fluoxetine, photographed in Miami, Fla., on March 23, 2004. The Food and Drug Administration (FDA) asked makers of popular antidepressants to add or strengthen suicide-related warnings on their labels as well as the possibility of worsening depression. Joe Raedle/Getty Images

Antibiotics are a well-known cause of antibiotic resistance, but they aren’t the only common drug that’s contributing to this global crisis, as demonstrated in a recent University of Queensland (UQ) study.

In a study led by Prof. Jianhua Guo from the UQs Australian Centre for Water and Environmental Biotechnology, researchers found that antidepressants also increased antibiotic resistance.

“As we know, antibiotics are major contributors in inducing the emergence of antibiotic resistance,” said Guo in an email to The Epoch Times.

However, Guo said that little is known about antidepressants’ capacity to also drive the spread of antibiotic resistance, although they have been consumed at an increased rate.

“Thus, this finding to some extent, changed our understanding,” he said.

The study focused on prescription drugs used to treat anxiety and depressive mental health disorders as well as other psychological conditions and investigated the bacterial exposure of five commonly used antidepressants.

“While the overuse of antibiotics is acknowledged as the major driver of bacterial resistance, we wanted to investigate if other common medications were contributing to the problem,” Guo said in a UQ release.

Mental health prescriptions are not uncommon in Australia, with 42.7 million mental health-related medications dispensed in 2020-2021. Mental health prescriptions are also not uncommon in the United States, with 2020 data indicating that 16.5 percent of U.S. adults had taken a prescription medication in the past 12 months for their mental health.

A bottle of Effexor antidepressant pills in Miami, Fla., on March 23, 2004. FDA asked makers of popular antidepressants to add or strengthen suicide-related warnings on their labels as well as the possibility of worsening depression especially at the beginning of treatment or when the doses are increased or decreased. Joe Raedle/Getty Images

Antimicrobial Resistance

The World Health Organisation declared in 2019 that antimicrobial resistance is one of the top 10 threats to global public health. Antimicrobial resistance makes infections increasingly more difficult or sometimes impossible to treat, resulting in the deaths of many people.

In 2019, an estimated 1.27 million people died as a result of antimicrobial resistance, exceeding the death tolls of HIV/AIDS and malaria. A 2016 review estimated that the annual death toll of antimicrobial infections could rise to 10 million by 2050 if global action is not taken.

Testing the Antidepressants

The antidepressants studied were sertraline (Zoloft), escitalopram (Lexapro), bupropion (Welbutrin), duloxetine (Cymbalta), and agomelatine (Valdoxan). Guo said that all of the tested drugs are able to trigger the emergence of antibiotic resistance, but sertraline, duloxetine and fluoxetine had the strongest impact on bacterial resistance to antibiotics.

“Our study showed a marked increase in antibiotic resistance from those three, even at very low doses.”

“Sertraline and duloxetine exhibited the most significant effects, resulting in high numbers of resistant cells (compared to total cells) over a short time period,” he said.

“This is mainly associated with the drug’s oxidative ability and chemical structure.”

Prof. Guo said that a high concentration of sertraline (50 mg/L) induced resistance to the antibiotics: chloramphenicol, tetracycline, and ciprofloxacin. He said that the fold changes of the ratio of resistant cell number to total cell number exhibited an increase that’s almost comparable to the changes observed under antibiotic resistance.

However, Guo said large-scale screening to test which antidepressant types can and cannot trigger antibiotic resistance has not been conducted yet.

Bottles of antibiotics line a shelf at a Publix Supermarket pharmacy in Miami, Fla., on Aug. 7, 2007. Joe Raedle/Getty Images

Why Antidepressants Increase Antibiotic Resistance

Guo noted that the main reason antidepressants could induce antibiotic resistance is directly related to their antimicrobial properties.

“They can trigger bacteria to over-generate ROS, thus damaging and killing bacteria,” he said.

Guo said that the generation of reactive oxygen species (ROS) under exposure to antidepressants was measured, and an over-generation of ROS was found. He also noted that the researchers discovered that gene expressions related to oxidative stress had been upregulated—a process that cells undergo to increase their response to an outside substance or signal.

Guo attributed this overgeneration of ROS to the strong oxidative ability of these drugs, which pose oxidative stress to bacteria and then provoke “an SOS response.” He said that the “SOS response” triggers cellular defence mechanisms that the E. coli bacteria then develop resistance to, causing them to build up resistance against multiple classes of antibiotics.

The research also found that antidepressants can generate enhanced stress signature responses and stimulation of efflux pump expression.

“These responses would be beneficial for bacteria to develop antibiotic resistance,” Guo said.

“For example, stimulation of efflux pump will support bacteria to pump out antibiotics from intracellular to extracellular, thus compromising the efficacy of antibiotics, and making bacteria become multi-drug resistant.”

Bottles of antibiotics line a shelf at a Publix Supermarket pharmacy Aug. 7, 2007, in Miami. Joe Raedle/Getty Images

Potential Side-effects

Guo said that if a patient harbours antibiotic-resistant bacteria caused by antidepressants, there is a risk for them to get a bacterial infection that is difficult to treat.

“Additionally, the antibiotic-like side effects of antidepressants might affect gut microbiota or gut health if some patients regularly take the drugs, which warrants more research,” Guo said.

“This is just our current speculation. It should be noted that more research is needed to fully assess any subsequent impacts on human health.”

He noted that the researchers aim to validate their findings in an animal model first and then perform a cohort study in the future.

Other Common Drugs that Increase Antibiotic Resistance

Antidepressants are not the only common medication outside of antibiotics that can promote the spread of antibiotic resistance. Guo said that in previous studies, the team demonstrated that anti-inflammatories and lipid-lowering drugs could also increase antibiotic resistance via horizontal gene transfer.

“Antibiotic resistance occurs and spreads when bacteria uptake free-living antibiotic resistance genes (ARGs) via bacterial transformation in response to the use of antibiotics,” he said in a prior UQ release.

The study investigated six common non-antibiotic medications and found that nonsteroidal anti-inflammatories, a lipid-lowering drug, and a β-blocker notably supported the bacterial transformation.

UQ Postdoctoral Research Fellow Yue Wang said that given the high use of non-antibiotic medicines, these findings highlight a new concern that non-antibiotics can accelerate the spread of antibiotic resistance.

“They are the iceberg of factors for promoting antibiotic resistance and should not be ignored,” Guo said.