Summary:
This narrative review examined how psychotropic medications contribute to metabolic disturbances and insulin resistance. These medications are essential for treating severe psychiatric disorders, but they frequently cause metabolic problems such as weight gain, poor lipid and sugar metabolism, and hypertension. Their effects can also involve impaired mitochondrial energy production, increased oxidative stress and chronic low‑grade inflammation, all of which contribute to insulin resistance. The study also explores how psychotropic medications affect appetite‑regulating neurotransmitter pathways and tissues such as the liver, adipose tissue and skeletal muscle. These disruptions reduce fatty‑acid oxidation, promote lipid accumulation and impair glucose metabolism. A main focus of the review is the gut‑brain‑metabolic axis. Psychotropic medications can alter gut microbial composition and weaken intestinal barrier integrity, increasing inflammation and worsening glucose and lipid metabolism. It also notes that antidepressants can modify gut microbial composition. Overall, this study shows that psychotropic medications affect metabolism through effects on mitochondrial function, inflammation, neurotransmitter signalling, tissue metabolism and the gut microbiome. These mechanisms can contribute to insulin resistance and cardiometabolic risk, identifying the need for early monitoring and targeted strategies to protect metabolic health in psychiatric populations.
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Abstract:
Psychotropic medications remain central to psychiatric treatment, yet their use is frequently accompanied by a substantial metabolic burden. Metabolic adverse effects, including weight gain, insulin resistance, dysglycemia, dyslipidemia, and hypertension, complicated clinical management and undermine long-term adherence. Although evidence-based monitoring and mitigation approaches exist, the molecular determinants of individual susceptibility and the drivers of interindividual variability in metabolic outcomes remain insufficiently defined. Emerging evidence identifies the gut-brain-metabolic axis as a key mechanistic interface, with psychotropic medications altering gut microbiota and associated metabolic pathways that contribute to metabolic complications. Multi-omics strategies are beginning to illuminate the complex molecular networks underlying these adverse effects; however, most findings still arise from isolated omics layers, limiting mechanistic resolution and translational utility. Integrative analytical frameworks, including artificial intelligence, now enable the synthesis of molecular, clinical, environmental, lifestyle, and dietary factors to support more precise and individualized intervention. In this narrative review, we synthesize current clinical and mechanistic advances in understanding psychotropic-induced metabolic dysfunction, with a focus on insulin resistance and the gut–brain–metabolic axis and highlight how multi-omics, environmental factors and computational strategies may advance future precision approaches in psychiatric care.
Article Publication Date: 31/03/2026
DOI: 10.3389/fnut.2026.1778794
