Effect of Metformin on Antipsychotic-Induced Metabolic Dysfunction: The Potential Role of Gut-Brain Axis

Antipsychotics are the first-line medications prescribed for patients with schizophrenia or other mental disorders. Cumulative evidence has revealed that metabolic dysfunctions frequently occur in patients receiving antipsychotics, especially second-generation antipsychotics, and these effects may decrease patient compliance and increase health costs. Metformin is an effective pharmaceutical adjuvant for ameliorating antipsychotic-induced metabolic dysfunction (AIMD) in clinical practice. However, the mechanism of the effects of metformin on AIMD remains unclear. The gut-brain axis is a bidirectional communication system between the gastrointestinal tract and the central nervous system and has been associated with many pathological and physiological conditions, such as those related to metabolism. Antipsychotics interact with and have affinity for dopamine receptors and other receptors in the brain, and treatment with these antipsychotics has been shown to influence gut microbiota metabolism and composition, as observed in both animal and human studies. Metformin exerts an antidiabetic effect that is correlated with activation of AMP-kinase in the hypothalamus, and metformin also influences gut flora. Therefore, the gut-brain axis may play a role in the effect of metformin on AIMD. Since no direct evidence is available, this perspective may provide a direction for further research.