Research progress on the synergistic effect and its mechanisms of antidepressants and antibiotics against resistant pathogens.

Antimicrobial resistance (AMR) poses a critical global health challenge, driving the urgent need for innovative therapeutic strategies. Antidepressants, traditionally used for major depressive disorders (MDD), have recently attracted attention in non-antibiotic research due to their diverse pharmacological properties, including antimicrobial, antifungal, antiviral, anticancer, antiparasitic, and anti-inflammatory activities. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) demonstrated synergistic antimicrobial effects with reduced minimum inhibitory concentrations (MIC) when used in combination with conventional antibiotics, enhancing efficacy against drug-resistant pathogens. Mechanisms underlying this synergy include inhibition of bacterial efflux pumps and disruption of membrane integrity. Despite these promising findings, in vivo studies evaluating antidepressant-antibiotic synergy remain scarce, underscoring the need for further mechanistic and translational research to overcome challenges in clinical application. Overall, antidepressants show significant potential as adjuvants to antibiotics against resistant bacteria, making them promising candidates for combination therapy.