Objective:To study the efficacy and safety of mirtazapine and paroxetine in patients with first-episode climacteric depression. Methods:A 8-week double-blind study was conducted with 90 female patients suffered with climacteric first-episode depression. Subjects were randomly assigned to either mirtazapine (n=45) or paroxetine (n=45). All subjects were evaluated with Hamilton Rating Scale for Depression-17 (HAMD-17), Hamilton Rating Scale for Anxiety,and Treatment Emergent Symptom scale (TESS) at baseline, the end of week 1, 4 and 8 after treatment. The study had lasted for 8 weeks.Results:The response rate between two groups (mirtazapine 88.9% vs paroxetine 82.2%) was similar. There were significant differences on the scores of HAMD between the two groups at the end of 1st and 8th week, and HAMA at the 1st week after treatment(21.3?3.5/25.2?2.9,18.2?3.2/21.5?2.4,t=-2.367、-3.514,P=0.042、0.032;7.2?3.5/9.8?2.3,t=-3.258,P=0.035). Mirtazapine had increased food appetite(15.6%), body weight(13.3%), hydropsia(8.9%), dry mouth(6.7%), sleep disorder and nausea(4.4%). Meanwhile paroxetine had dry mouth(22.2%), sleep disorder(20.0%), nausea(17.8%), tremor(15.6%), restlessness/agitation(13.3%) and sexual disturbance(11.1%).Conclusion:Mirtazapine has rapid response, strongly antidepressive effect in female climacteric first-episode patients and less side-effects.