Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting

Author:

Tomizawa Yoshihiro1ORCID,Kurokawa Shunya2,Ishii Daiki13,Miyaho Katsuma4,Ishii Chiharu1,Sanada Kenji4,Fukuda Shinji356,Mimura Masaru2,Kishimoto Taishiro2

Affiliation:

1. Division of Pharmacotherapeutics, Faculty of Pharmacy, Keio University, Tokyo, Japan

2. Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan

3. Institute for Advanced Biosciences, Keio University, Yamagata, Japan

4. Department of Psychiatry, Showa University School of Medicine, Tokyo, Japan

5. Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kanagawa, Japan

6. Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan

Abstract

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

Funder

KAKENHI

Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology

Japan Agency for Medical Research and Development Core Research for Evolutional Science and Technology

Japan Science and Technology Agency Exploratory Research for Advanced Technology

Takeda Science Foundation

Food Science Institute Foundation

Program for the Advancement of Research in Core Projects under Keio University’s Longevity Initiative

Japan Dairy Association J-milk

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Psychiatry and Mental health,Pharmacology

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