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Antibiotic resistance: Antidepressants an ‘overlooked phenomenon’

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GPs are all too familiar with the mounting concerns around antimicrobial resistance.
 
Recent research estimates that 1.27 million people died in 2019 from infections that failed to respond to medication – and, without swift action, that number is expected to significantly climb by 2050.
 
In fact, the World Health Organization has declared antimicrobial resistance as one of the top 10 global public health threats facing humanity.
 
But in the search to better understand and tackle the issue, emerging preliminary research in recent years has started to link non-antibiotic medications as a contributor to the growing problem.
 
Among the latest research is a new study by the University of Queensland (UQ), which points to a range of commonly prescribed antidepressants as potentially compounding the problem.
 
Published in Proceedings of the National Academy of Sciences, the laboratory study focused on bacterial exposure of five of the most common antidepressants prescribed in Australia, including:

• sertraline (Zoloft)
• escitalopram (Lexapro)
• bupropion (Welbutrin)
• duloxetine (Cymbalta)
• and agomelatine (Valdoxan).

Using the E. coli K-12 strain MG1655 – a typical bacterial strain known to be responsive to antibiotics – the team exposed the bacteria to the various antidepressant drugs at varying concentrations over 60 days. This ranged from low level (0.1 mg/L and 1 mg/L) to medium level (10 mg/L), and high level (50 mg/L and 100 mg/L).
 
Over the course of the study period, the bacteria were exposed to various antibiotics, including amoxicillin, ampicillin, cephalexin, chloramphenicol, ciprofloxacin, colistin, erythromycin, kanamycin, levofloxacin, norfloxacin, roxithromycin, tetracycline, and trimethoprim.
 
The research showed that the antidepressants could induce multi-drug resistance, with sertraline and duloxetine exhibiting the most significant effects, even at very low doses, with signs of resistance after just a few days of exposure.
 
Further to that, mathematical modelling predicted that the antidepressants would accelerate the emergence of antibiotic-resistant bacteria and that persister cells would help to maintain the resistance over a longer period of time.
 
Antidepressants are regularly within the top 10 most prescribed medications in Australia, with their use having increased in the wake of the COVID-19 pandemic.  
 
Study lead Professor Jianhua Guo from UQ’s Australian Centre for Water and Environmental Biotechnology described the findings as ‘interesting, but scary’.
 
‘We recognise that antibiotic misuse or overuse causes spread or transmission of antibiotic resistance,’ he told newsGP.
 
‘But now our study has found non-antibiotic pharmaceuticals are playing very similar roles, and this phenomena have been overlooked.’
 
The potential role of antidepressants in antimicrobial resistance first piqued Professor Guo’s interest in 2015, while undertaking a wastewater surveillance study. Seeking to quantify antibiotic resistant genes in the wastewater, Professor Guo’s team found that the concentration was higher in the domestic wastewater samples compared to those from the local hospital.
 
‘This was a little bit strange because you can imagine the hospital has a high concentration for antibiotics, so that should have a high abundance for the antibiotic resistant bacteria or antibiotic resistant genes,’ he said.
 
‘So this phenomenon triggered me – maybe there are other drugs or chemicals that can also play a role. This was the starting point.’
 
As well as identifying the role of the antidepressants, Professor Guo’s latest research also set out to understand the underlying mechanism. His team found that the antidepressants result in a strong oxidative stress response towards bacteria, leading the bacteria to become antibiotic resistant ‘in order to survive or defend against this stress’, the microbiologist explains.
 
The findings raise significant concern, given how commonly antidepressants are prescribed. In Australia alone in 2021, more than 42 million prescriptions were dispensed, while antidepressants comprise 4.8% of the global pharmaceutical market, marginally less than antibiotics (5%).
 
Meanwhile, Professor Guo also has concerns over the potential for antibiotic resistant bacteria to transfer from wastewater to humans and animals.
 
If further research confirms the study findings, Professor Guo anticipates that pharmaceutical companies will need to consider modifying the drugs to avoid such side effects.
 
‘Otherwise, you can treat mental health, but you can trigger secondary or even other problems,’ he said.
 
However, the microbiologist is keen to note that the findings are in no way a signal to doctors to curb prescribing of antidepressants, nor for patients to cease use.
 
He says further studies in animals and humans are needed to evaluate the potential effects antidepressants have on the microbiomes of people and to assess their risk for gastrointestinal disturbances or diseases.
 
‘This is like an early warning,’ Professor Guo said.
 
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antibiotic resistance antibiotics antidepressants antimicrobial resistance microbiome

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