MN: Writing—original draft. SN: Writing—original draft. VR: Conceptualization, Resources, Supervision, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
Conflicts of interest
As the corresponding author, I declare that this manuscript is original; that the article does not infringe upon any copyright or other proprietary rights of any third party; and that neither the text nor the figures have been reported or published previously. All the authors have no conflict of interest and have read the journal’s authorship statement.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis.Lancet Psychiatry. 2020;7:64–77. [DOI] [PubMed] [PMC]
Mortimer KRH, Katshu MZUH, Chakrabarti L. Second-generation antipsychotics and metabolic syndrome: a role for mitochondria.Front Psychiatry. 2023;14:1257460. [DOI] [PubMed] [PMC]
Sepúlveda-Lizcano L, Arenas-Villamizar VV, Jaimes-Duarte EB, García-Pacheco H, Paredes CS, Bermúdez V, et al. Metabolic Adverse Effects of Psychotropic Drug Therapy: A Systematic Review.Eur J Investig Health Psychol Educ. 2023;13:1505–20. [DOI] [PubMed] [PMC]
Berk M, Köhler-Forsberg O, Turner M, Penninx BWJH, Wrobel A, Firth J, et al. Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.World Psychiatry. 2023;22:366–87. [DOI] [PubMed] [PMC]
Saccaro LF, Aimo A, Panichella G, Sentissi O. Shared and unique characteristics of metabolic syndrome in psychotic disorders: a review.Front Psychiatry. 2024;15:1343427. [DOI] [PubMed] [PMC]
Beverly EA, Gonzalez JS. The Interconnected Complexity of Diabetes and Depression.Diabetes Spectr. 2025;38:23–31. [DOI] [PubMed] [PMC]
Chen H, Cao T, Zhang B, Cai H. The regulatory effects of second-generation antipsychotics on lipid metabolism: Potential mechanisms mediated by the gut microbiota and therapeutic implications.Front Pharmacol. 2023;14:1097284. [DOI] [PubMed] [PMC]
Huang MH, Zeng BS, Tseng PT, Hsu CW, Wu YC, Tu YK, et al. Treatment Efficacy of Pharmacotherapies for Frontotemporal Dementia: A Network Meta-Analysis of Randomized Controlled Trials.Am J Geriatr Psychiatry. 2023;31:1062–73. [DOI] [PubMed]
Goldston K, Baillie AJ. Depression and coronary heart disease: a review of the epidemiological evidence, explanatory mechanisms and management approaches.Clin Psychol Rev. 2008;28:288–306. [DOI] [PubMed]
Wysokiński A, Strzelecki D, Kłoszewska I. Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder.Diabetes Metab Syndr. 2015;9:168–76. [DOI] [PubMed]
Filipčić I, Šimunović Filipčić I, Grošić V, Bakija I, Šago D, Benjak T, et al. Patterns of chronic physical multimorbidity in psychiatric and general population.J Psychosom Res. 2018;114:72–80. [DOI] [PubMed]
Nielsen RE, Banner J, Jensen SE. Cardiovascular disease in patients with severe mental illness.Nat Rev Cardiol. 2021;18:136–45. [DOI] [PubMed]
Austin HA. Chronic physical health conditions and mental illness.Medicine. 2024;52:557–60. [DOI]
Kalia M. Biomarkers for personalized oncology: recent advances and future challenges.Metabolism. 2015;64:S16–21. [DOI] [PubMed]
Figueroa-Hall LK, Xu B, Kuplicki R, Ford BN, Burrows K, Teague TK, et al. Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors.Transl Psychiatry. 2022;12:279. [DOI] [PubMed] [PMC]
Orsolini L, Pompili S, Tempia Valenta S, Salvi V, Volpe U. C-Reactive Protein as a Biomarker for Major Depressive Disorder?Int J Mol Sci. 2022;23:1616. [DOI] [PubMed] [PMC]
Casado ME, Collado-Pérez R, Frago LM, Barrios V. Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies.Int J Mol Sci. 2023;24:1422. [DOI] [PubMed] [PMC]
Tan R, Hu X, Wang X, Sun M, Cai Z, Zhang Z, et al. Leptin Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells through the Cooperative Action of MAPK/ERK1/2, JAK2/STAT3 and PI3K/AKT Signaling Pathways.Int J Mol Sci. 2023;24:15151. [DOI] [PubMed] [PMC]
Wang Y, Fang F, Liu X. Targeting histamine in metabolic syndrome: Insights and therapeutic potential.Life Sci. 2024;358:123172. [DOI] [PubMed]
Halaris A, Prochaska D, Stefanski A, Filip M. C-reactive protein in major depressive disorder: Promise and challenge.J Affective Disord Rep. 2022;10:100427. [DOI]
Hamilton S, Tauseen RA, Wasef N, Wolf A. Early Manifestation of Clozapine-Induced Cardiotoxicity: Detection, Pathophysiology, and Management.Cureus. 2022;14:e27202. [DOI] [PubMed] [PMC]
Sommerfeld-Klatta K, Łukasik-Głębocka M, Krawczak E, Stodolska A, Zielińska-Psuja B. Participation of quetiapine in oxidative stress and inflammation status in the treatment of drug overdose.Acta Pol Pharm. 2023;80:327–33. [DOI]
Fang X, Gao C, Wu W, Hu X, Shao M, Zhou C, et al. The role of the gut microbiome in weight-gain in schizophrenia patients treated with atypical antipsychotics: Evidence based on altered composition and function in a cross-sectional study.Psychiatry Res. 2023;328:115463. [DOI] [PubMed]
Alenazi B, Al Doghaither HA, Al-Ghafari AB, Elmorsy EM. Risperidone-induced bioenergetic disruption in the isolated human peripheral blood monocytes.Toxicol In Vitro. 2024;101:105936. [DOI] [PubMed]
Schneider-Thoma J, Kapfhammer A, Wang D, Bighelli I, Siafis S, Wu H, et al. Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials.Syst Rev. 2021;10:214. [DOI] [PubMed] [PMC]
Burschinski A, Schneider-Thoma J, Chiocchia V, Schestag K, Wang D, Siafis S, et al. Metabolic side effects in persons with schizophrenia during mid- to long-term treatment with antipsychotics: a network meta-analysis of randomized controlled trials.World Psychiatry. 2023;22:116–28. [DOI] [PubMed] [PMC]
Baune BT, Fromme SE, Aberg M, Adli M, Afantitis A, Akkouh I, et al. A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.Eur Arch Psychiatry Clin Neurosci. 2025;275:1453–64. [DOI] [PubMed] [PMC]
Austin-Zimmerman I, Wronska M, Wang B, Irizar H, Thygesen JH, Bhat A, et al. The Influence of CYP2D6 and CYP2C19 Genetic Variation on Diabetes Mellitus Risk in People Taking Antidepressants and Antipsychotics.Genes (Basel). 2021;12:1758. [DOI] [PubMed] [PMC]
Carli M, Kolachalam S, Longoni B, Pintaudi A, Baldini M, Aringhieri S, et al. Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.Pharmaceuticals (Basel). 2021;14:238. [DOI] [PubMed] [PMC]
Burghardt KJ, Mando W, Seyoum B, Yi Z, Burghardt PR. The effect of antipsychotic treatment on hormonal, inflammatory, and metabolic biomarkers in healthy volunteers: A systematic review and meta-analysis.Pharmacotherapy. 2022;42:504–13. [DOI] [PubMed] [PMC]
Ruiz-Santiago C, Rodríguez-Pinacho CV, Pérez-Sánchez G, Acosta-Cruz E. Effects of selective serotonin reuptake inhibitors on endocrine system (Review).Biomed Rep. 2024;21:128. [DOI] [PubMed] [PMC]
Alruwaili NS, Al-Kuraishy HM, Al-Gareeb AI, Albuhadily AK, Ragab AE, Alenazi AA, et al. Antidepressants and type 2 diabetes: highways to knowns and unknowns.Diabetol Metab Syndr. 2023;15:179. [DOI] [PubMed] [PMC]
Roosterman D, Cottrell GS. The two-cell model of glucose metabolism: a hypothesis of schizophrenia.Mol Psychiatry. 2021;26:1738–47. [DOI] [PubMed] [PMC]
Niculescu AB, Le-Niculescu H. Precision medicine in psychiatry: biomarkers to the forefront.Neuropsychopharmacology. 2022;47:422–3. [DOI] [PubMed] [PMC]
Glannon W. Biomarkers in Psychiatric Disorders.Camb Q Healthc Ethics. 2022;31:444–52. [DOI] [PubMed] [PMC]
Mosiołek A, Pięta A, Jakima S, Zborowska N, Mosiołek J, Szulc A. Effects of Antidepressant Treatment on Peripheral Biomarkers in Patients with Major Depressive Disorder (MDD).J Clin Med. 2021;10:1706. [DOI] [PubMed] [PMC]
Stuchtey FC, Block A, Osei F, Wippert PM. Lipid Biomarkers in Depression: Does Antidepressant Therapy Have an Impact?Healthcare (Basel). 2022;10:333. [DOI] [PubMed] [PMC]
Ferrari M, Godio M, Martini S, Callegari C, Cosentino M, Marino F. Effect of quetiapine on inflammation and immunity: a systematic review.Int J Psychiatry Clin Pract. 2023;27:196–207. [DOI] [PubMed]
Madireddy S, Madireddy S. Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation.Brain Sci. 2023;13:784. [DOI] [PubMed] [PMC]
Afzal M, Siddiqi N, Ahmad B, Afsheen N, Aslam F, Ali A, et al. Prevalence of Overweight and Obesity in People With Severe Mental Illness: Systematic Review and Meta-Analysis.Front Endocrinol (Lausanne). 2021;12:769309. [DOI] [PubMed] [PMC]
Correll CU, Solmi M, Veronese N, Bortolato B, Rosson S, Santonastaso P, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls.World Psychiatry. 2017;16:163–80. [DOI] [PubMed] [PMC]
Grigore I, Ciobotaru OR, Hînganu D, Gurau G, Tutunaru D, Hînganu MV. A Systemic Perspective of the Link Between Microbiota and Cardiac Health: A Literature Review.Life (Basel). 2025;15:1251. [DOI] [PubMed] [PMC]
Yousefsani BS, Salimi A, Imani F, Ramezani M, Shirani K, Seydi E, et al. Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations.Drug Res (Stuttg). 2022;72:343–9. [DOI] [PubMed]
Toczyska K. Direct Effects of Selective Serotonin Reuptake Inhibitors, Fluoxetine, Sertraline and Paroxetine, and Atypical Antipsychotics, Aripiprazole and Clozapine, on Islet Beta Cell Mass and Function [dissertation]. King’s College London; 2022.
Vasileva SS, Yang Y, Baker A, Siskind D, Gratten J, Eyles D. Associations of the Gut Microbiome With Treatment Resistance in Schizophrenia.JAMA Psychiatry. 2024;81:292–302. [DOI] [PubMed] [PMC]
Lambert T. Managing the metabolic adverse effects of antipsychotic drugs in patients with psychosis.Aust Prescr. 2011;34:97–9.
Dubath C, Gholam-Rezaee M, Sjaarda J, Levier A, Saigi-Morgui N, Delacrétaz A, et al. Socio-economic position as a moderator of cardiometabolic outcomes in patients receiving psychotropic treatment associated with weight gain: results from a prospective 12-month inception cohort study and a large population-based cohort.Transl Psychiatry. 2021;11:360. [DOI] [PubMed] [PMC]
Radha Krishnan RP, Dzidowska M, Zheng D, Wong ZS, Buckley NA, Raubenheimer JE. Cardiometabolic adverse effects of long-term antipsychotic treatment in children and adolescents with non-psychotic disorders: a systematic review of available evidence.Eur Child Adolesc Psychiatry. 2025;[Epub ahead of print]. [DOI] [PubMed]
Fornaro M, Miola A, De Berardis D, Squassina A, Manchia M, Solmi M. Perspectives on Precision Psychiatry Using Antipsychotics in the Management of Bipolar Disorder.Brain Sci. 2025;15:430. [DOI] [PubMed] [PMC]
Foster A, Wang Z, Usman M, Stirewalt E, Buckley P. Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians.Neuropsychiatr Dis Treat. 2007;3:965–73. [DOI] [PubMed] [PMC]
Arranz MJ, Gonzalez-Rodriguez A, Perez-Blanco J, Penadés R, Gutierrez B, Ibañez L, et al. A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments.Transl Psychiatry. 2019;9:177. [DOI] [PubMed] [PMC]
O’Brien SM, Scott LV, Dinan TG. Antidepressant therapy and C-reactive protein levels.Br J Psychiatry. 2006;188:449–52. [DOI] [PubMed]
Vázquez-Bourgon J, Gómez-Revuelta M, Mayoral-van Son J, Labad J, Ortiz-García de la Foz V, Setién-Suero E, et al. Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort.Eur Psychiatry. 2022;65:e48. [DOI] [PubMed] [PMC]
Abo Alrob O, Alazzam S, Alzoubi K, Nusair MB, Amawi H, Karasneh R, et al. The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population.Medicina (Kaunas). 2019;55:320. [DOI] [PubMed] [PMC]
Owen RR, Drummond KL, Viverito KM, Marchant K, Pope SK, Smith JL, et al. Monitoring and managing metabolic effects of antipsychotics: a cluster randomized trial of an intervention combining evidence-based quality improvement and external facilitation.Implement Sci. 2013;8:120. [DOI] [PubMed] [PMC]
Bertossi F. A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain.Cureus. 2024;16:e55733. [DOI] [PubMed] [PMC]
Kamath S, Sokolenko E, Collins K, Chan NSL, Mills N, Clark SR, et al. IUPHAR themed review: The gut microbiome in schizophrenia.Pharmacol Res. 2025;211:107561. [DOI] [PubMed]
Huang J, Liu C, Yang Y, Kang D, Xiao J, Long Y, et al. The effects of probiotics plus dietary fiber on antipsychotic-induced weight gain: a randomized clinical trial.Transl Psychiatry. 2022;12:185. [DOI] [PubMed] [PMC]
Mötteli S, Vetter S, Colla M, Hotzy F. Are probiotics effective in reducing the metabolic side effects of psychiatric medication? A scoping review of evidence from clinical studies.Transl Psychiatry. 2024;14:26. [DOI] [PubMed] [PMC]
Singh P, Meenatchi R, Ahmed ZHT, Thacharodi A, M R, Kumar RRS, et al. Implications of the gut microbiome in cardiovascular diseases: Association of gut microbiome with cardiovascular diseases, therapeutic interventions and multi-omics approach for precision medicine.Med Microecol. 2024;19:100096. [DOI]
Chang SC, Goh KK, Lu ML. Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives.World J Psychiatry. 2021;11:696–710. [DOI] [PubMed] [PMC]
Bernardo M, Rico-Villademoros F, García-Rizo C, Rojo R, Gómez-Huelgas R. Real-World Data on the Adverse Metabolic Effects of Second-Generation Antipsychotics and Their Potential Determinants in Adult Patients: A Systematic Review of Population-Based Studies.Adv Ther. 2021;38:2491–512. [DOI] [PubMed] [PMC]
