Abstract:
This systematic review evaluated the animal and human evidence for pharmacomicrobiomics
(PMx) interactions of antidepressant medications. Studies of gut microbiota effects on
functional and behavioral effects of antidepressants in human and animal models were identified
from PubMed up to December 2022. Risk of bias was assessed, and results are presented as a systematic
review following PRISMA guidelines. A total of 28 (21 animal, 7 human) studies were included
in the review. The reviewed papers converged on three themes: (1) Antidepressants can alter the
composition and metabolites of gut microbiota, (2) gut microbiota can alter the bioavailability of certain
antidepressants, and (3) gut microbiota may modulate the clinical or modeled mood modifying
effects of antidepressants. The majority (n = 22) of studies had at least moderate levels of bias present.
While strong evidence is still lacking to understand the clinical role of antidepressant PMx in human
health, there is evidence for interactions among antidepressants, microbiota changes, microbiota
metabolite changes, and behavior. Well-controlled studies of the mediating and moderating effects
of baseline and treatment-emergent changes in microbiota on therapeutic and adverse responses to
antidepressants are needed to better establish a potential role of PMx in personalizing antidepressant
treatment selection and response prediction.