The role of metformin as a treatment for neuropsychiatric illness

Advances in psychopharmacology have been significantly slower to evolve than in other disciplines of medicine and therefore investigation into novel therapeutic approaches is required. Additionally, concurrent metabolic conditions are prevalent among people with mental disorders. Metformin is a widely used hypoglycaemic agent that is now being studied for use beyond diabetes management. Evidence is emerging that metformin has multiple effects on diverse neurobiological pathways and consequently may be repurposed for treating mental illness. Metformin may have beneficial neuroimmunological, neuroplastic, neuro-oxidative and neuro-nitrosative effects across a range of psychiatric and neurodegenerative illnesses. Mechanisms include glucose lowering effects and effects on AMP-activated protein kinase (AMPK) signalling, however the best evidence for clinical benefit is through the glucose lowering effects, with other mechanisms less supported by the current evidence base. This narrative review aims to draw together the existing evidence for use of metformin as a psychopharmaceutical and present the role of metformin in the context of physical and psychiatric ill health, including metabolic, endocrinological and cancer domains. It not only has therapeutic potential in medical comorbidity but may have potential in core illness domains.