Objective To explore the efficacy and safety of venlafaxine combined with quetiapine in the treatment of treatment‐resistant depression (TRD) .Methods A total of 208 TRD patients were randomly divided into two groups ,combination group (n=106) took orally venlafaxine plus quetiapine and control group (n=102) did venlafaxine for 8 weeks .Efficacies were assessed with the Hamilton Depression Scale (HAMD) before and after treatment and adverse reactions with the Treatment Emergent Symptom Scale (TESS) .Results After treatment the HAMD scores of both groups lowered more significantly compared with pretreatment (P<0 .01) ,those at each time‐point were significantly lower in combination than con‐trol group (P<0 .01);at the end of the 8th week obvious and total effective rate were significantly higher in combination than control group (P< 0 .01) .Adverse reactions of both groups were mild and mainly lethargy ,dry mouth and so on .Conclusion Venlafaxine combined with quetiapine has a synergism and an evident effect ,takes effect more rapidly ,and has an evident effect and higher safety compared with single venlafaxine in the treatment of treatment‐resistant depression .%目的：探讨文拉法辛联合喹硫平治疗难治性抑郁症的疗效和安全性。方法将208例难治性抑郁症患者随机分为两组，联合组106例，口服文拉法辛联合喹硫平治疗，对照组102例，口服文拉法辛治疗。观察8周。治疗前后采用汉密顿抑郁量表评定临床疗效，副反应量表评定不良反应。结果治疗后两组汉密顿抑郁量表评分均较治疗前显著下降（P＜0．01），联合组治疗各时点评分均显著低于对照组（P＜0．01）；治疗8周末联合组显效率、总有效率均显著高于对照组（P＜0．01）。两组不良反应均较轻，主要表现为嗜睡、口干等。结论文拉法辛联合喹硫平治疗难治性抑郁症具有增效作用，起效快，疗效显著，安全性高，优于单用文拉法辛治疗。
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