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

Abstract

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.

Effects of diabetic pharmacotherapy on prolactin hormone in patients with type 2 diabetes mellitus: Bane or Boon

“…Furthermore, diabetic pharmacotherapy may affect prolactin serum levels in patients with T2DM, since metformin is an effective adjuvant therapy in reducing prolactin in antipsychotic induced-hyperprolactinemia,[8] whereas glyburide induces failure in the glucose counter-regulatory response in the secretion of glucagon and anterior pituitary hormones. [9]…”

Metformin Enhances Antidepressant/Antipsychotic Combination Therapy of Schizophrenia With Comorbid Depression in a Murine Model

“…Murine studies suggest that metformin has direct psychotropic effects by metabolic regulation of circulating branched-chain amino acid levels (Zemdegs et al, 2019) and potentiates antidepressants by activating the IGF2 pathway (Poggini et al, 2019). Potential complications of second-generation antipsychotics (SGAs) include obesity and development of the metabolic syndrome (Brooks et al, 2009;Luo et al, 2019). When combined with SGAs, metformin has been shown to reduce weight gain (Correll et al, 2020); this raises the prospect that in addition to its potential psychiatric benefits, the coadministration of metformin with SGAs may benefit overall health.…”

Clinical and pathogenetic rationale for the prevention and treatment of obesity

“…В регуляции оси важную роль играет кишечная микробиота [15] . В толстой кишке здорового человека доминирующий тип микробиоты, Firmicutes и Bacteroidetes, вырабатывают короткоцепочечные жирные кислоты (КЖК), которые влияют на энергетический гомеостаз и регулируют метаболизм глюкозы и липидов в различных тканях .…”