The role of metformin as a treatment for neuropsychiatric illness

Seetal Dodd¹, Luba Sominsky², Dan Siskind³, Chiara C Bortolasci⁴, Andre F Carvalho⁴, Michael Maes⁴, Adam J Walker⁴, Ken Walder⁴, Alison R Yung⁵, Lana J Williams⁴, Hannah Myles⁶, Tayler Watson⁷, Michael Berk⁸

Affiliations

¹ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia. Electronic address: seetald@barwonhealth.org.au.
² Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Barwon Health Laboratory, University Hospital Geelong, Barwon Health, VIC, Australia.
³ Metro South Addiction and Mental Health Service, MIRT, Level 2, 228 Logan Rd, Woolloongabba, Brisbane, Qld 4102, Australia University of Queensland School of Clinical Medicine, Brisbane, Australia Queensland Centre for Mental Health Research, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁴ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
⁵ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia; School of Health Sciences, University of Manchester, Manchester, United Kingdom.
⁶ Discipline of Psychiatry, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia; Northern Adelaide Mental Health Service, Salisbury, SA, Australia.
⁷ Mental Health, Drugs and Alcohol Service, Barwon Health, Geelong VIC, Australia.
⁸ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.

PMID: 36191545
DOI: 10.1016/j.euroneuro.2022.09.002

Review

The role of metformin as a treatment for neuropsychiatric illness

Seetal Dodd et al. Eur Neuropsychopharmacol. 2022 Nov.

. 2022 Nov:64:32-43.

doi: 10.1016/j.euroneuro.2022.09.002. Epub 2022 Sep 30.

Authors

Affiliations

¹ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia. Electronic address: seetald@barwonhealth.org.au.
² Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Barwon Health Laboratory, University Hospital Geelong, Barwon Health, VIC, Australia.
³ Metro South Addiction and Mental Health Service, MIRT, Level 2, 228 Logan Rd, Woolloongabba, Brisbane, Qld 4102, Australia University of Queensland School of Clinical Medicine, Brisbane, Australia Queensland Centre for Mental Health Research, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁴ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
⁵ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia; School of Health Sciences, University of Manchester, Manchester, United Kingdom.
⁶ Discipline of Psychiatry, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia; Northern Adelaide Mental Health Service, Salisbury, SA, Australia.
⁷ Mental Health, Drugs and Alcohol Service, Barwon Health, Geelong VIC, Australia.
⁸ Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.

PMID: 36191545
DOI: 10.1016/j.euroneuro.2022.09.002

Abstract

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.

Keywords: Bipolar disorder; Depression; Diabetes; Mental disorders; Mental illness; Metformin.

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Conflict of interest statement

Declaration of Competing Interest SD has received grant support from the Stanley Medical Research Institute, NHMRC, Beyond Blue, ARHRF, Simons Foundation, Geelong Medical Research Foundation, Harry Windsor Foundation, Fondation FondaMental, Eli Lilly, Glaxo SmithKline, Organon, Mayne Pharma and Servier, speaker's fees from Eli Lilly, advisory board fees from Eli Lilly and Novartis, and conference travel support from Servier. MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier – all unrelated to this work. DS, LJW, KW, AJW, LS, ARY, HM, AFC, CCB, MM, and TW have no conflicts of interest.

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The role of metformin as a treatment for neuropsychiatric illness

Affiliations

The role of metformin as a treatment for neuropsychiatric illness

Authors

Affiliations

Abstract

Conflict of interest statement

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