fluoxetine (EDG005)

Infectious, inflammatory, and clinical outcomes among patients prescribed trifluoperazine or amoxapine: a retrospective cohort study using real-world data.

Malik Omar O, Rodriguez-Fernandez Jorge J, Yakubu Aliu Opeyemi AO, Farrag Wedad W et al.

The rise of antimicrobial resistance and limited development of new antibiotics have increased interest in drug repurposing. Preclinical evidence suggests that certain psychotropic drugs, including trifluoperazine (TFP) and amoxapine (AXPN), possess antimicrobial or immunomodulatory properties. However, their effects on infection risk in clinical populations are largely unknown. This study evaluated whether TFP or AXPN use is associated with altered risks of infectious illnesses, systemic inflammation, and mortality compared to patients not taking antidepressants. This retrospective cohort study utilized TriNetX, a federated network of de-identified electronic health records from over 75 million patients. Patients prescribed TFP, AXPN, fluoxetine, or no antidepressants/antipsychotics (general control) were assigned to mutually exclusive cohorts. Age- and sex-matched comparisons were conducted for four groups. Assessed outcomes included bacterial and viral infections (e.g., Clostridioides difficile), severe acute respiratory syndrome coronavirus 2, an etiological agent of COVID-19, as well as for pneumonia and sepsis, inflammatory markers (C-Reactive Protein, Erythrocyte Sedimentation Rate, ferritin, and procalcitonin), Intensive Care Unit admission, and mortality. Risk ratios (RR), odds ratios (OR), 95% confidence intervals, and Kaplan-Meier survival analyses were performed for significant findings. Overall, 2,177 TFP and 834 AXPN patients met the inclusion criteria. TFP was associated with significantly lower rates of ENT/dental infections across all three age groups compared with general controls (RR 0.316-0.405, all p ≤ 0.002). It was also consistently associated with increased leukocytosis across all age strata. Reduced COVID-19 incidence was observed primarily in older adults (70-90 years) versus general controls. AXPN showed fewer associations overall, with a significant reduction in C. difficile infection (RR 0.458, p = 0.025) and lower leukocytosis (RR 0.685, p = 0.012) in the 70-90 age group compared with fluoxetine. Most other outcomes, including pneumonia, sepsis, and other inflammatory markers, did not differ significantly when compared to general control or fluoxetine groups. These exploratory findings identify potential signals linking TFP and AXPN to infection susceptibility. Given the study design, these observations are hypothesis-generating and require confirmation in future prospective studies.

Fluoxetine activates melanocyte stem cells indirectly through the epithelial 5-hydroxytryptamine (5-HT) receptor 1A/Wnt signaling to regenerate melanocytes.

Zhang Xiaofeng X, Song Xinhao X, Zhu Min M, Yu Meng M et al.

Melanocyte stem cells (McSCs) serve as the major origin of epidermal melanocytes in adults and fulfill a critical function in skin homeostasis, repair, and regeneration. Preclinical and clinical studies confirm McSCs have therapeutic potential for diseases including vitiligo. This study shows fluoxetine treatment is associated with McSC activation. Using narrow-band UVB (NB-UVB) irradiation as a positive control, we found 14-day fluoxetine treatment was associated with an increased number of epidermal melanocytes in the McSC-depletion mouse model, an effect correlated with upregulated hair follicle McSC activation 1-3 days post-treatment. Consistently, in McSC-specific Tg(-1.1tfap2b:eGFP)cpu108 zebrafish, we observed increased epidermal melanocyte numbers and McSC activation after 2-day fluoxetine treatment. Notably, at the study timepoint, unlike NB-UVB irradiation, fluoxetine treatment was associated with no oxidative stress, DNA damage, apoptosis, or inflammation in mouse skin. Furthermore, 5-hydroxytryptamine receptor 1A (HTR1A) and Wnt7a colocalized in hair germ epithelial cells on day 3, with both molecules upregulated in fluoxetine-treated group. Conditioned medium from fluoxetine-treated HaCaT cells (24 h) applied to SK-MEL-2 cells (48 h) indicated that fluoxetine indirectly activated Wnt signaling through epithelial HTR1A, regulating melanocyte differentiation. Collectively, this study provides a foundation for investigating the dynamic behavior of early melanocytes and developing skin repair strategies.

Acute Urinary Retention Developing After Fluoxetine Treatment.

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Effectiveness of fluoxetine and mindfulness therapy in improving depression in people with Type 2 Diabetes Mellitus in Primary Care Settings (DIAMAND)-A single-blind, parallel-group, randomized controlled trial from Bengaluru.

Raveendranathan Dhanya D, Ruben Johnson-Pradeep JP, Goud B Ramakrishna BR, Nataraj Anupama A et al.

Depression and type 2 diabetes mellitus (T2DM) share a bidirectional relationship. This comorbidity is associated with poor glycemic control, reduced medication adherence, and impaired quality of life. Evidence comparing pharmacological and psychological interventions for mild depression in T2DM within primary care settings remains limited. To compare the effectiveness of Fluoxetine, Mindfulness therapy, combination Fluoxetine + Mindfulness, and treatment as usual (TAU) in reducing depressive symptoms among individuals with T2DM and mild depression. This single-blind randomized controlled trial (RCT) was conducted among individuals (n = 200) with T2DM and mild depression recruited from the Bengaluru site of the multi-center diabetes mellitus and depression (DIAMAND) study. Participants were randomized to Fluoxetine, Mindfulness therapy, combination treatment, or TAU. Depression severity, medication adherence, diabetes self-management, quality of life, HbA1c, and random blood sugar (RBS) were tested over 4 months. Repeated Measures ANOVA (RMANOVA) and effect size estimates were used for analysis. Depressive symptoms improved significantly over time across all study arms; and no significant between-group differences were observed in depression outcomes. No significant differences were found between groups for glycemic control, medication adherence, diabetes self-management, or quality of life. Effect sizes for reduction in depressive symptoms compared with TAU were 0.48 for Mindfulness, 0.45 for fluoxetine, and 0.31 for combination treatment. In this RCT, depressive symptoms and medication adherence improved across all study arms; however, none demonstrated superiority over TAU. Mindfulness-based interventions may represent feasible, scalable, low-intensity approaches for mild depression in primary care settings. Future adequately powered studies with longer follow-up are needed to evaluate long-term effectiveness of psychological and pharmacological interventions.