The spreading of antibiotic resistance is responsible annually for over 700,000 deaths worldwide, and the prevision is that this number will increase exponentially. The identification of new antimicrobial treatments is a challenge that requires scientists all over the world to collaborate. Developing new drugs is an extremely long and costly process, but it could be paralleled by drug repositioning. The latter aims at identifying new clinical targets of an “old” drug that has already been tested, approved, and even marketed. This approach is very intriguing as it could reduce costs and speed up approval timelines, since data from preclinical studies and on pharmacokinetics, pharmacodynamics, and toxicity are already available. Antidepressants and antipsychotics have been described to inhibit planktonic and sessile growth of different yeasts and bacteria. The main findings in the field are discussed in this critical review, along with the description of the possible microbial targets of these molecules. Considering their antimicrobial activity, the manuscript highlights important implications that the administration of antidepressants and antipsychotics may have on the gut microbiome.
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