Despite being one of the most common and debilitating mood disorders, bipolar disorder is often misdiagnosed and undertreated. Its pathogenesis is complex, with significant patient variability and inconsistent treatment effectiveness. The brain gut microbiota axis plays a critical role in bipolar disorder by modulating neurotransmitter secretion, gut peptides, and systemic inflammation. However, the mechanisms by which psychotropic treatments influence gut microbiota composition and their implications for clinical outcomes remain poorly understood. This systematic review evaluated the impact of psychotropic drugs on gut microbiota and their potential role in bipolar disorder treatment outcomes. A comprehensive search across Ovid MEDLINE, Embase, APA PsycINFO, Scopus, and PubMed yielded 314 articles, of which 12 met the inclusion criteria. Key findings indicate that psychotropic treatments increase the abundance of both beneficial bacteria associated with maintaining gut health and pathogenic bacteria linked to metabolic dysfunctions. Notably, females demonstrated more pronounced changes in microbial diversity following psychotropic treatment. Patients treated with psychotropics also exhibited an increased abundance of gut bacteria associated with multidrug antibiotic resistance. Among bipolar disorder patients treated with quetiapine, responders, those showing improved depressive symptom scores, had distinct gut microbiome profiles more similar to healthy individuals compared to nonresponders. These responders also displayed neural connectivity patterns comparable to those of healthy subjects. These findings highlight the dual impact of psychotropic medications on gut microbiota, with potential implications for both gut and mental health. While beneficial bacteria may support gut health, the increased prevalence of antibiotic resistant and metabolically disruptive bacteria raises concerns. Further research is needed to unravel the functional consequences of these microbial shifts and their role in treatment efficacy. This review underscores the promise of leveraging gut microbiota profiles for personalized treatment strategies, aiming to optimize therapeutic outcomes while mitigating side effects in bipolar disorder.
