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.