Psycho-pharmacomicrobiomics: a systematic review and meta-analysis

Background: Understanding the interactions between the gut-microbiome and psychotropic medications interact ("psycho-pharmacomicrobiomics") could improve treatment stratification strategies in psychiatry. In this systematic review and meta-analysis, we explored first, whether psychotropics modify the gut-microbiome, and second, if the gut-microbiome affects the efficacy and tolerability of psychotropics. Methods: Following PRISMA guidelines, we searched (November 2022) for longitudinal and cross-sectional studies investigating the effect of psychotropics on the gut-microbiome. The primary outcome was the difference in diversity metrics (alpha and beta) before and after treatment with psychotropics (longitudinal studies), and in medicated compared to unmedicated individuals (cross-sectional studies). Secondary outcomes included the association between gut microbiome and efficacy and tolerability outcomes. Random effect meta-analyses were conducted on alpha diversity metrics, while beta diversity metrics were pooled using distance data extracted from graphs. Summary statistics: SMD and Higgins I2 for alpha diversity metrics, F and R values for beta diversity metrics. Results: Nineteen studies were included in our synthesis; twelve investigated antipsychotics and seven antidepressants. Results showed significant changes in alpha (4 studies; SMD: 0.12; 95% CI: 0.01 to 0.23; P=0.04; I2: 14%) and beta (F=15.59; R2:0.05; P<0.001) diversity metrics following treatment with antipsychotics and antidepressants, respectively. Altered gut microbiome composition at baseline was associated with tolerability and efficacy outcomes across studies, including response to antidepressants (2 studies; alpha diversity; SMD: 2.45; 95%CI: 0.50 - 4.40; P<0.001, I2: 0%). Conclusions: Treatment with psychotropic medications is associated with altered gut microbiome composition, in turn the gut microbiome may influence the efficacy and tolerability of these medications.