PENGARUH OMEGA-3 TERHADAP PERBAIKAN GEJALA KLINIS DAN KADAR TUMOR NECROSIS FACTOR ALPHA (TNF-α) PADA PASIEN DEPRESI YANG MENDAPATKAN TERAPI FLUOXETINE = The Effect of Omega-3 on Clinical Symptom Improvement and Tumor Necrosis Factor-Alpha (TNF-α) Levels in Depressed Patients Receiving Fluoxetine Therapy

Abstract Background: Depression is a major psychiatric disorder frequently associated with inflammatory dysregulation, including elevated tumor necrosis factor-alpha (TNF-α). Conventional antidepressant therapy such as fluoxetine may not be sufficient to fully address both clinical symptoms and underlying biological mechanisms. Omega-3 fatty acids, known for their anti-inflammatory properties, have been proposed as a promising adjuvant therapy. Objective: To evaluate the effect of omega-3 (EPA + DHA) supplementation on clinical symptoms and TNF-α levels in patients with depression receiving fluoxetine. Methods: A randomized controlled trial was conducted at RSKD Dadi Makassar from January to March 2025. A total of 44 patients with moderate depression, diagnosed according to DSM-5, were randomized into two groups: fluoxetine 20 mg/day plus omega-3 combination EPA 1000 mg + DHA 500 mg/day (n = 22), and fluoxetine 20 mg/day alone (n = 22). Clinical symptoms were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), and serum TNF-α was measured with ELISA at baseline and after six weeks. Data were analyzed using appropriate parametric and non-parametric tests. Results: Both groups showed significant reductions in HAMD-17 scores and TNF-α levels after six weeks (p < 0.05). However, the treatment group demonstrated greater improvements, with mean HAMD-17 reduction of −11.91 compared to −6.27 in controls (p = 0.001), and TNF-α reduction of −344.57 pg/mL compared to −150.03 pg/mL in controls (p = 0.001). A strong positive correlation was observed between post-treatment HAMD-17 scores and TNF-α levels in the treatment group (r = 0.734, p < 0.001), but not in controls. Conclusion: Omega-3 (EPA + DHA) supplementation as an adjuvant to fluoxetine significantly improves depressive symptoms and reduces TNF-α levels, supporting its role as an effective augmentation strategy in depression management.