Psycho-pharmacomicrobiomics: a systematic review and meta-analysis

Abstract

Understanding the bi-directional interplay between the gut microbiome and the effects of psychotropics medications (“psycho-pharmacomicrobiomics”) could lead to improved treatment stratification and personalised interventions strategies in psychiatry. In this systematic review and meta-analysis, we explored first, whether psychotropic medications modify the gut microbiome, and second, if the gut microbiome affects the efficacy and tolerability of psychotropic drugs. Following PRISMA guidelines, we searched from inception to November 2022 for longitudinal and cross-sectional studies investigating the effect of psychotropic medications (namely antipsychotic, antidepressants, and mood stabilisers) 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 features (at baseline and changes after treatment) with 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 included SMD, 95% CI, and Higgins I2 for alpha diversity metrics, F and R values for beta diversity metrics. Nineteen studies were included in our synthesis; twelve investigated antipsychotics and seven antidepressants. Results showed significant changes in alpha (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 (alpha diversity; SMD: 2.45; 95%CI: 0.50 – 4.40; P<0.001, I2: 0%). Females, but not males, patients treated with antipsychotics showed reduced alpha diversity compared to untreated controls (SMD: -0.68; 95% CI: -1.31 to -0.04; P=0.04; I2: 37.61%). These findings suggest that: 1. Treatment with psychotropic medications are associated with altered gut microbiome composition; 2. The gut microbiome may influence the efficacy and tolerability of these medications. Further studies using translational approaches to clarify mechanisms and direction of causality are indicated.