Objective To explore the clinical efficacy of escitalopram combined with multidisciplinary collaborative management model(MCMM)on adolescents with first-episode major depressive disorder(MDD).Methods Two hundred adolescents with first-episode MDD who admitted to Fuyang Third People's Hospital,Anhui Province,from January 2019 to November 2023,were selected as study participnts.They were randomly divided into a control group and a MCMM group.Both groups of patients received sertraline hydrochloride tablets and routine psychiatric care for 8 weeks.Additionally,the MCMM group received an MCMM intervention on this basis.The clinical efficacy of the interventions,pre-and post-treatment assessments included clinical scale data[Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),and Connor-Davidson Resilience Scale(CD-RISC)],inflammatory factors[interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)],neurotrophin factors[serotonin(5-hydroxytryptamine,5-HT)and glial cell-derived neurotrophic factor(GDNF)]were compared between the two groups.Results Before the intervention,there were no statistical differences in the clinical scale data,inflammatory factors and neurotrophic factors between the two groups(P＞0.05).After 8 weeks of intervention,the HAMD score,HAMA score,serum IL-1β,IL-6,TNF-α,5-HT,and GDNF levels significantly decreased compared with pre-intervention(P＜0.05),while the CD-RISC score significantly increased(P＜0.05).In addition,the MCMM group showed greater reductions in HAMD,HAMA,IL-1β,IL-6,TNF-α,5-HT,and GDNF levels and a greater increase in CD-RISC score compared to the control group(P＜0.05).Conclusion Compared with sertraline combined with routine care,MCMM significantly alleviates anxiety and depression,enhances psychological resilience,and reduces inflammation in MDD patients.