Objective To analyze the treatment trajectory and revelant factors of serotonin reuptake inhibitors (SSRIs) in patients with first-episode major depression after single-drug treatment. And to provide ideas for early optimal treatment. Methods This study was a real-world study in which 82 untreated outpa-tients with first-episode depression were enrolled for SSRIs monotherapy. The Eysenck Personality Test (EPQ),the Liebowitz Social Anxiety Scale (LSAS),Yale -Brown Forced Scale (Y-BOCS),Social Function Deficit Scale (SDSS) were used to assess all patients at baseline. Then the patients were treated with SSRIs monotherapy. Patients who did not achieve a HAMD-17 20% reduction rate in the second week switched to receive another SSRIs monotherapy application. Follow-up to the 12th week to analyze treatment trajectory and identify factors associated with treatment trajectory. Results The psychotism personality trait ( B=-0. 287,95%CI=-0. 701~-0. 071,P=0. 009) and age ( B=0. 099,95%CI=0. 014~0. 244,P=0. 017) were related to treatment trajectories. The psychotism personality trait did not directly influence the treatment trajectory but influenced the treatment indirectly through agitation and the effect value was 0. 016,which ac-counted for 10. 76% of the total effect. Social anxiety and avoidance,depression,anxiety,obsessive-compul-sive symptoms and social dysfunction at baseline were not associated with antidepressant efficacy. Conclusion Psychoticism can predict the efficacy of antidepressants treatment as a mediator at the second week of treat-ment.