Medical Journal of Mashhad university of Medical Sciences

Medical Journal of Mashhad university of Medical Sciences

Antimicrobial Synergy Between Antidepressants and Antibiotics: Mechanisms and Safety Implications

Document Type : Review article

Authors
Milad Kashi 1
Yasaman Hariri 1
Mohammad Arjomandzadegan 2
Hossein Haghighi 1
Aref Shariati 2
1 Student research committee, Arak University of Medical Sciences, Arak, Iran
2 Infectious Diseases Research Center (IDRC), Arak University of Medical Sciences, Arak, Iran
10.22038/mjms.2025.88620.5035
Abstract
Resistance to antimicrobial agents poses a significant threat to global public health, necessitating urgent development of novel therapeutic strategies to combat drug-resistant pathogens. Antidepressants, which have been traditionally used to treat depressive disorders, have recently attracted considerable attention in the field of non-antibiotic drug research due to their multiple pharmacological properties, including antimicrobial, anticancer, and anti-inflammatory activities. In addition to their direct antimicrobial activities, recent studies have shown that these drugs can act as adjuvants to enhance the efficacy of conventional antibiotics against resistant bacteria. This synergistic effect has been demonstrated, especially in combination with antibiotics such as quinolones, aminoglycosides, carbapenems, tetracyclines, polymyxin B and sulfonamides, against bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Helicobacter pylori, Staphylococcus aureus and Enterococcus spp. The mechanisms of these effects appear to be related to inhibition of bacterial efflux pumps, suppression of microbial growth and proliferation, anti-biofilm activity and compromise of cell membrane integrity. Nonetheless, the utilization of antidepressants represents potential risks. These compounds may disturb the intestinal microbiota, leading to dysbiosis and possibly contributing to the development of antibiotic resistance. Also, their persistence in the environment and entry into the food chain has raised concerns about human health and the ecosystem. This review discusses both the antibacterial synergistic effects and underlying mechanisms of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) in combination with antibiotics, as well as the associated safety and environmental considerations.
Keywords
antidepressants
antibiotics
drug-resistant pathogens
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Medical Journal of Mashhad university of Medical Sciences
Volume 69, Issue 4
May 2026
Pages 575-587