Abstract: Objective To explore the effect of topiramate on olanzapine-induced weight gain and glucose,lipid,insulin,leptin metabolic dysfuction. Methods In the 8 week placebo-controlled study,sixty schizophrenic patients with weight gain(≥7%) induced by olanzapine were randomly divided into two treatment groups,one with olanzapine plus topiramate (n=30),and one with olanzapine plus placebo(n=30),During the period the two groups use the treatment of olanzapine,treatment groups combined the topiramate,the beginning dose is 50 mg/day,the fifth day with 100 mg/day,not more than 200 mg/day.The control group used the placebo,without any other antipsychotic.Before treatment and the 8 week after treatment body mass,body mass index(BMI),waist-hip ratio(WHR),fasting blood glucose(FBG),triglycerides(TG),cholesterol (TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL).Insulin(INS),leptin(Lep) was measured with radio-immunity method. Results ①The weight gain,BMI,WHR in group were less than those in placebo group in the 8 weekdend(P<0.05).②there was a significant decrease in TG,TC,LDL,INS and leptin in topiramate group in the 8 weekend(P<0.05).there was no significant change of FBS，blood fat，INS,LEP in 8 weekend in control group(P＞0.05).③the serum level of leptin was significantly correlated with weight gain,BMI,WHR,INS in both two groups before treatment and in the 8 weekend(r＝0.372-0.489，P<0.05). Conclusion Topiramate addition therapy is effective in attenuating olanzapine-induced weight gain and TG,LDL,INS,LEP metabolic dysfunction in schizophrenic patients.Topiramate addition therapy can provide a new drug treatment way to weight gain and glucose lipid metabolic dysfunction of antipsychotics.