fluoxetine

SIGNIFICANCE STATEMENT: Fluoxetine, an US Food and Drug Administration-approved selective serotonin reuptake inhibitor reduces solid tumor (breast and melanoma) load through immune mediated tumor cell death and restore antitumor immunity. It remodels tumor microenvironment, activates T cells, reduces cancer stemness and metastasis via regulation of epithelial mesenchymal transition factors, hypoxia Inducible factor 1α, and β-catenin.

SEO exerts antidepressant-like effects in BCRD by modulating hippocampus-centered metabolic and functional networks. Eugenol and 2-phenylethanol were identified as key brain-entry components to function through metabolic pathways. ALOX15 inhibition and CAII improvement were proven to be the main molecular mechanisms. These findings provide mechanistic insights and identify SEO as a promising plant-derived therapeutic candidate for managing cancer-related depression.

P=N/A, N=80, Recruiting, University of Oxford

P=N/A, N=50, Recruiting, Minia University

Wistar rats were randomly assigned to sham, PSD, three XFZY dose (0.216, 0.432, 0.864 g/kg), and fluoxetine (1.80 mg/kg) groups (n = 12 per group)...Furthermore, after depletion of gut microbiota using antibiotic cocktails, these therapeutic effects of XFZY were abolished. In summary, XFZY may alleviate PSD by modulating the gut microbiota and regulating the gut-brain axis, offering a promising direction for future therapeutic research.

P=N/A, N=120, Not yet recruiting, The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

P=N/A, N=83, Not yet recruiting, The Affiliated Zhongda Hospital of Southeast University; The Affiliated Zhongda Hospital of Southeast University

P1/2, N=520, Recruiting, First Affiliated Hospital of Chongqing Medical University | Trial primary completion date: Dec 2025 --> Dec 2026

Acupuncture alleviates depression-like behaviors in CUMS-induced rats by modulating microglial polarization and inhibiting neuroinflammation-mediated pyroptosis. Our findings provide further evidence supporting acupuncture as a viable strategy for depression treatment.

In summary, fluoxetine has highly significant immunoregulatory effects in patients with MDD and not in controls. Unfortunately, these effects only partly attenuate the immune sensitization in MDD.

Fifty male C57BL/6 mice were randomized into control, model, XLP(2.7, 5.4 mg·g~(-1)), and 5-aminosalicylic acid+fluoxetine groups...Furthermore, XLP lowered the levels of TNF-α, IL-1β, IL-6, and IL-23, down-regulated the transcript levels of IL-6 and IL-23α and the protein level of H3K4me3 while up-regulating the protein level of KDM5B in the cerebral cortical area and the colon tissue, and increased the binding of KDM5B to the IL-6 and IL-23α promoters. XLP may affect H3K4me3 demethylation through KDM5B to reduce the production of inflammatory factors and alleviate the inflammatory response, thus ameliorating UC combined with depression.

Attenuating peripheral serotonin using fluoxetine-a selective serotonin reuptake inhibitor (SSRI) antidepressant-ablates TAM-derived EV delivering of inositol metabolic enzymes and sensitizes tumors to cisplatin/PARP inhibitor (PARPi). Our study unveils a systemic serotonin-primed metabolic crosstalk within the tumor microenvironment that potentiates chemoresistance, revealing targetable HR repair regulation beyond cancer-cell-autonomous mechanisms.