GLEXJ activates CaMKIV-CREB signaling by upregulating TRPC6 in the hippocampus of PTSD rats, leading to improved dendritic spine dynamics and synaptic remodeling. This mechanism contributes to the attenuation of fear memory generalization. Given the limitations of current PTSD treatments, these findings offer potential avenues for developing more effective therapeutic strategies.

P2, N=20, Recruiting, University of Nebraska | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

These results identify sertraline and indatraline as immunostimulatory agents for cancer treatment. More generally, this research shed light on novel therapeutic avenues harnessing lysosomal cholesterol transport to regulate immunogenic cell death.

P2, N=161, Completed, Charite University, Berlin, Germany | Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> Jun 2024 | Trial primary completion date: Feb 2025 --> Jun 2024

P4, N=300, Recruiting, University of Pennsylvania | Trial completion date: Feb 2026 --> Jul 2026 | Trial primary completion date: Feb 2026 --> Jul 2026

P=N/A, N=50, Not yet recruiting, University of Oxford | Initiation date: Jul 2024 --> Feb 2025

P=N/A, N=200, Recruiting, Severance Hospital | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P2, N=186, Not yet recruiting, National Institute of Allergy and Infectious Diseases (NIAID)

P4, N=288, Not yet recruiting, Johns Hopkins University

P3, N=145, Recruiting, Ain Shams University

P1/2, N=50, Not yet recruiting, University of Oxford

Interestingly, we show that PSPH amplifications in glioblastoma facilitate the expression of immune suppressor galectin-1, which can be inhibited by sertraline treatment. Collectively, we revealed that ser/glyhigh glioblastomas are characterized by enhanced clonogenicity, migration, and suppression of the immune system, which could be tackled using combined sertraline/chloroquine treatment, revealing novel therapeutic opportunities for this subgroup of GBM patients.

P=N/A, N=220, Completed, Zunyi Medical University Zhuhai Campus; The Fifth Affiliated (Zhuhai) Hospital of Zunyi Medical University

P=N/A, N=44, Not yet recruiting, The First Affiliated Hospital of the People's Liberation Army Air Force Military Medical University; The First Affiliated Hospital of the People's Lib

P4, N=400, Completed, The Second Xiangya Hospital, Central South University; The Second Xiangya Hospital, Central South University

P2/3, N=191, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=300 --> 191

P4, N=150, Recruiting, University of Cincinnati | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2025 --> Sep 2026

P=N/A, N=40, Not yet recruiting, Flinders University

We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.

P3, N=316, Active, not recruiting, Children's Hospital Los Angeles | Trial completion date: Dec 2025 --> Jul 2026

P2, N=150, Active, not recruiting, University of Florida | Trial completion date: Sep 2024 --> Jan 2025 | Trial primary completion date: Sep 2024 --> Jan 2025

Depression degree in patients with malignant bone tumors correlates with serum inflammatory factors and thyroxine levels. Measurement of serum inflammatory factors and thyroxine levels can assess the progression and prognosis of depressed patients.

Additional candidates like pinocembrin, which reduces NSCLC cell invasion by modulating epithelial-mesenchymal transition, and citalopram, an SSRI with anti-carcinogenic properties, were also identified. These findings provide valuable insights into the molecular underpinnings of NSCLC and suggest new directions for therapeutic strategies through drug repurposing.

P2, N=59, Completed, Imperial College London | Unknown status --> Completed

Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability.

One hour before CUMS, rats were given a treatment with acupuncture, electroacupuncture, sham-acupuncture, or fluoxetine (2.1 mg/kg)...Additionally, our findings indicate that acupuncture also modulates the ERK and Caspase-3 apoptotic pathways in the hippocampus of CUMS rats. This study suggests that acupuncture may play a potential preventive role by regulating hippocampal neuroinflammatory response, levels of oxidative stress, apoptotic processes, and enhancing synaptic plasticity.

Fluoxetine and CUR-N373 can inhibit CVB4 replication in macrophage cultures...The cytolytic activity of activated GM-CSF macrophages was higher towards CVB4-persistently infected 1.1B4 cells than mock-infected 1.1B4 cells. In conclusion, macrophages may play a role in CVB4 infection of pancreatic cells, and are capable of inducing lysis of infected pancreatic cells.

P1/2, N=49, Completed, University of California, Irvine | N=96 --> 49

Retrospective analysis reveals that SSRI use correlates with a lower risk of metastasis among patients with HCC. Our study describes a role for SSRIs in cancer metabolism, establishing a rationale for their repurposing as potential anti-cancer drugs for HCC.

P4, N=132, Not yet recruiting, China Medical University Hospital | Phase classification: P1 --> P4 | N=66 --> 132

P1, N=30, Recruiting, Duke University | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P1/2, N=100, Recruiting, Yale University | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jun 2025

P2, N=105, Not yet recruiting, University of Texas Southwestern Medical Center | Initiation date: Sep 2024 --> Apr 2025

The rats were randomly divided into normal group, model group, CD300f blocker(CLM1, 2 μg·kg~(-1)) group, CD300f agonist(Fcγ, 5 μg·kg~(-1)) group, positive drug(0.18 g·kg~(-1) metformin+1.8 mg·kg~(-1) fluoxetine) group, and high-dose and low-dose(20.52 and 10.26 g·kg~(-1)) Zuogui Jiangtang Jieyu Formula groups. They could up-regulate the protein expression of presyna-ptic membrane SYN and postsynaptic membrane PSD-95 in hippocampal neurons and finally improve the damage to the hippocampal synaptic microenvironment. In conclusion, this research confirmed that Zuogui Jiangtang Jieyu Formula effectively alleviated the depression-like behavior and inhibited inflammatory activation of microglial cells in the hippocampus of rats with DD, and the mechanism might be related to the regulation of CD300f/TLR4 signal to alleviate the damage to hippocampal synaptic microenvironment.

Results suggest that R- and S-ketamine have pro-neurogenic and anti-inflammatory properties, however, this is mediated by inhibition of the kynurenine pathway only in the context of IL-1b. Overall, this study enhances our understanding of the mechanisms underlying ketamine's antidepressant effects in the context of different inflammatory phenotypes, ultimately leading to the development of more effective, personalised therapeutic approaches for patients suffering from depression.

P1, N=60, Recruiting, University of Maryland, Baltimore | Trial primary completion date: Feb 2025 --> Sep 2025

P2, N=100, Recruiting, Johns Hopkins University | Trial primary completion date: Mar 2027 --> Jul 2027

P4, N=0, Withdrawn, Nova Scotia Health Authority | Completed --> Withdrawn

Age, antidepressant type, duration of antidepressant use, and comorbidities could be risk factors for NAFLD in patients with depression. Furthermore, mirtazapine can cause steatosis in both AML-12 and MIHA cell lines and may promote the development of NAFLD through the TLR4/MyD88/NF-κB signaling pathway. This study lays a solid foundation for further research on depression and NAFLD and can contribute to the prevention and treatment of these two diseases.

P1, N=64, Recruiting, University of Maryland, Baltimore | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Sep 2025

Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.

P4, N=150, Recruiting, University of Cincinnati | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025