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.
Highlights
Antipsychotics, known for their antagonism of dopamine receptors in the brain, have been widely prescribed for patients with schizophrenia and other mental disorders since the early 1950s (Owen et al, 2016)
The other Randomized controlled trial (RCT) was conducted in children and adolescent patients who had more than 10% increases in body weight after at least 1 year of Second-generation antipsychotic (SGA) treatment
Preclinical and clinical studies have demonstrated that treatment with antipsychotics and metformin had effects on the gut microbiota and the brain
Summary
Antipsychotics, known for their antagonism of dopamine receptors in the brain, have been widely prescribed for patients with schizophrenia and other mental disorders since the early 1950s (Owen et al, 2016). Metformin has been used as an effective pharmaceutical adjuvant for ameliorating antipsychotic-induced metabolic dysfunction (AIMD) (Wu et al, 2007; Samara et al, 2016; Stroup and Gray, 2018). Cumulative evidence has suggested that both antipsychotics and metformin exert their therapeutic effects by influencing gut microbiota metabolism and composition (McCreight et al, 2016; Skonieczna-Zydecka et al, 2018). The gut-brain axis may play a role in the effect of metformin on AIMD. Since there is no direct evidence to support this role, in this perspective, we first review the relationships among the gut-brain axis, metformin, and AIMD and provide a direction for further research. There is increasing evidence suggesting that gut microbiota play a vital role in the regulation of the gut-brain axis. The bidirectional communication of the gut-brain axis is important for maintaining metabolic homeostasis
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