In preceding centuries common thought was that psychiatric disorders originated from the gut. In later years this concept was replaced by the idea of it being a disorder of the brain and that an imbalance of neurotransmitters is the cause of depression and other psychiatric conditions (monoamine hypothesis). This theory has been dominating psychiatric research for the past decades, and selective serotonin reuptake inhibitors (SSRIs) have become a widespread treatment option for psychological disorders. Despite their benefits, their use also presents clinical challenges such as treatment resistance, side effects or loss of effect. Consequently, the monoamine hypothesis has become disputed with other pathophysiological mechanisms having been proposed in recent years. With an appreciation of the pathophysiological complexities, this opinion-based article sought to present alternate views and to suggest areas for future research regarding psychiatric disorders, SSRIs and the gut-brain axis. The gut-brain axis has complex communication and signalling pathways in essence, the gut microbiome can exert significant effects on emotions, behaviours, metabolic risks, and the metabolism of drugs. Nerve cells of the gut also generate substantial amounts of serotonin for use within the gut. Equally, the gut microbiome produces and uses serotonin. It appears that some of the side effects associated with SSRIs, such as weight gain, are mediated via the gut microbiome. Further evidence suggests that SSRIs and several other psychotropic drugs exert antimicrobial action, which can alter the balance and integrity of the gut microbiome. Therefore, it would be valuable to further investigate the impact of long-term SSRI use on the microbial constellation in the gut and whether certain microbiome patterns could help predict treatment responsiveness or side effects, that may be manageable via microbiome manipulation. The authors believe that an advanced understanding of the dynamics of the gut microbiome could provide better and personalized treatment options for mental health conditions. This article provides a brief insight into current thoughts and theories of psychiatric disorders, SSRIs and the gut.