Serotonin Reuptake Inhibitors and the Gut Microbiome: Significance of the Gut Microbiome in Relation to Mechanism of Action, Treatment Response, Side Effects, and Tachyphylaxis

Abstract

The monoamine hypothesis of psychopharmacology has been dominating the biological psychiatric research field for decades. Currently psychiatric research has increasingly appreciated psychiatric disorders and suicidal behavior as being highly complex and multi-etiological. In this pathway the gut microbiome and its interrelationship with the brain is gaining traction. The usage of selective serotonin reuptake inhibitors (SSRIs) is increasing in the general population. This is due to their effect on a broad range of psychiatric disorders, and their favorable side effect profile. Still, there are enigmatic aspects about SSRIs, such as the difficulty to predict effect in individual patients, inter-individual differences in side effect, tachyphylaxis (a sudden loss of response to a certain drug), and to date, uncertainties on how they exert their clinical effect. A majority of the serotonin in the human body is produced within the gut, and SSRIs affect enteric neurons. They also exhibit antimicrobial properties that comes with the potential of disrupting microbial hemostasis. We propose that the role of the gut-brain axis and the gut microbiome in relation to psychopharmacology should be more highlighted. With this article, together with similar articles, we would like to provide a hypothetical framework for future studies within this field. We believe that this would have the potential to provide a paradigm shift within the field of psychopharmacology, and result in findings that potentially could contribute to the development of a more personalized and tailored treatment.

Develop a stepwise integrated method to screen biomarkers of Baihe‐Dihuang Tang on the treatment of depression in rats applying with composition screened, untargeted, and targeted metabolomics analysis

“…Therefore, l ‐glutamate, xanthine, and adenine were selected as the target detection compounds. Meanwhile, contents of DA, NE, and 5‐HT in the brain of rats were measured in this study to confirm the classical hypothesis of depression, “monoamine hypothesis” [10,15].…”

Gut microbiome health and dysbiosis: A clinical primer

“…Proton pump inhibitors have been shown to modulate the abundances and densities of commensals throughout the gastrointestinal tract, including increasing Proteobacteria and decreasing Actinobacteria in both the small intestine and colon 34 . Psychiatric and mood disorder medications (e.g., selective serotonin reuptake inhibitors, olanzapine) have also been described as potentially contributing to dysbiosis by exhibiting antimicrobial properties 35 …”

Immune-Mediated Diseases from the Point of View of Psychoneuroimmunoendocrinology

“…The psychiatric link explains why many antidepressants decrease inflammation [ 16 ]. Many of these drugs interfere with the microbiota, which has served to recommend the use of multispecies probiotics [ 78 ]. In turn, inflammation in IMIDs implies a greater metabolic disorder, which increases the risk of suffering from diseases such as obesity or T2D, which in turn increase the incidence of depressive symptoms [ 79 ].…”