Fluoxetine may improve hemodynamic status and organ dysfunction in patients with severe sepsis

1. Adjunctive fluoxetine significantly reduced vasopressor duration and ICU length of stay in patients with severe sepsis.

2. Fluoxetine improved organ dysfunction scores and metabolic recovery but did not significantly reduce short-term mortality.

Evidence Rating Level: 1 (Excellent) 

Sepsis is a leading cause of intensive care unit morbidity and mortality, driven by a dysregulated host inflammatory and metabolic response that results in organ dysfunction and hemodynamic instability. Given emerging evidence that selective serotonin reuptake inhibitors have immunomodulatory and metabolic effects, this randomized controlled trial evaluated fluoxetine as adjunctive therapy in severe sepsis. This single-center, randomized, double-blind, placebo-controlled trial enrolled 46 adults with severe sepsis who were randomized 1:1 to receive fluoxetine 40 mg daily or placebo in addition to standard sepsis care. The primary outcome was duration of vasopressor dependence, with secondary outcomes including organ dysfunction scores, inflammatory biomarkers, lactate levels, ICU length of stay, and 28-day mortality. Patients receiving fluoxetine had a significantly shorter duration of vasopressor use compared with controls (6.2 vs. 7.9 days) and a reduced ICU length of stay. Fluoxetine was also associated with faster improvement in Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores, as well as lower lactate levels by days 7 and 10. Inflammatory markers, including tumor necrosis factor-alpha, interleukin-1, C-reactive protein, and procalcitonin, declined more rapidly in the fluoxetine group. There was no statistically significant difference in 28-day mortality between groups. Overall, fluoxetine appeared to improve hemodynamic recovery and organ dysfunction in severe sepsis without demonstrating a clear mortality benefit, supporting further investigation in larger multicenter trials.

Click here to read this study in PLOS ONE

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