{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:27:46Z","timestamp":1786728466296,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for type 2 diabetes mellitus (T2DM) and obesity, show promising potential as a novel treatment for depression, particularly in patients with comorbid metabolic disorders. This narrative review examines the bidirectional relationship between obesity and depression, driven by shared mechanisms such as chronic low-grade inflammation, hypothalamic\u2013pituitary\u2013adrenal axis dysregulation, and impaired neuroplasticity. GLP-1 RAs, including liraglutide and exenatide, demonstrate neuroprotective effects by enhancing brain-derived neurotrophic factor expression and synaptic plasticity, alongside anti-inflammatory properties that reduce proinflammatory cytokines (e.g., tumor necrosis factor-alpha and interleukin-6). They also modulate serotonin turnover in mood-regulating brain regions, mirroring selective serotonin reuptake inhibitors. Preclinical studies in animal models reveal improved behavioral outcomes, while human observational studies and limited clinical trials, such as the LEAD-3 trial, report enhanced mood and quality of life in T2DM and obesity patients. However, challenges, including high treatment costs ($800\u2013$1000\/month), injectable administration, and needle-related anxiety, limit patient adherence, and clinical adoption. The lack of large-scale randomized controlled trials targeting depression as a primary outcome further hinders definitive conclusions. This review highlights GLP-1 RAs\u2019 potential to address both metabolic and depressive symptoms, offering a holistic approach to managing these interconnected conditions. Future research should focus on long-term efficacy, optimal dosing, and overcoming adherence barriers to establish GLP-1 RAs as a viable psychiatric treatment.<\/jats:p>","DOI":"10.4103\/aam.aam_546_25","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:00:19Z","timestamp":1769083219000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Glucagon-like Peptide-1 Receptor Agonists as a Dual-target Strategy for Depression and Metabolic Health: A Narrative Review"],"prefix":"10.4103","author":[{"given":"Visesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Biochemistry, MRAMC, Ambedkar Nagar, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Y. Sree","family":"Sudha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Deoghar, Jharkhand, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debanjan","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Central Coalfields Limited, Bokaro, Jharkhand, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azfar","family":"Mateen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, MRAMC, Ambedkar Nagar, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit Kumar","family":"Mahato","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Deoghar, Jharkhand, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,21]]},"container-title":["Annals of African Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aam.aam_546_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:27:25Z","timestamp":1786724845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aam.aam_546_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":0,"URL":"https:\/\/doi.org\/10.4103\/aam.aam_546_25","relation":{},"ISSN":["1596-3519","0975-5764"],"issn-type":[{"value":"1596-3519","type":"print"},{"value":"0975-5764","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-09-18","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}