The Studying About The Effects Of Topiramate In Preventing Lanzapine-Induced Weight Gain And Glucose And Lipid Metabolic Dysfuction

OBJECTIVE:To explore the effect of topiramate in preventing olanzapine-induced weight gain and glucose, lipid, insulin, leptin metabolic dysfuction and in therapeutic effect . The purpose of the studying is to search new and safe drug to prevent and treat metabolism syndrome to be resulted in by atypical antipsychotics and to provide some evidence for the use of topiramate in clinic.METHODS: In the 12 week placebo-controlled study, Sixty Chinese Han first-episode schizophrenic patients were randomly divided into two treatment groups, one with olanzapine(10-20mg/d) plus topiramate(100-200mg/d)(n=30), and one with olanzapine (10-20mg/d) plus placebo (n=30).In the baseline and the 2, 4, 8, 12 week after treatment ,body mass, body mass index (BMI), waist circumference, hip circumference, waist-hip ratio (WHR) was measured. In the baseline and the 4, 12 week after treatment, fasting blood glucose(FBG), triglycerides(TG), cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin (INS), leptin (Leptin) was measured. The symptom and efficacy was assessed with the Positive and Negative Symptoms Scale (PANSS) and Clinical Global Impression (CGI) in the baseline and the 2, 4, 8, 12 week after treatment. The side effect was assessed with Treatment Emergent Symptom Scale (TESS) in the baseline and the 2, 4, 8, 12 week after treatment. RESULTS: (1) There was a significant increase in body weight , BMI ,WC and hip circumference within each group from baseline to week 12 (p<0.01).There was an increase of WHR in placebo group in the end of week 12 (p<0.05).The increase of weight gain, BMI, WC , hip circumference in topiramate group was less than that in placebo group in the 4, 8, 12 week after treatment (p<0.05). The increase of WHR in topiramate group was less than that in placebo group in the end of week 12 after treatment (p<0.05).The lower rate of weight increase of more than 7% from baseline to week 12 was in topiramate group than in the placebo group (15% vs 64%; p<0.001). (2) There was a significant increase of TG, TC, LDL, INS and leptin and a decline of HDL in each group from baseline to week 12(p<0.05).There was no significant change of FBS in each group from baseline to week 12(P>0.05). The increase of TG, LDL, INS and female leptin in topiramate group was less than that in placebo group in the end of week 12 after treatment (p<0.05).(3) There was a significant difference of PANSS and CGI score in each group before and after treatment(p<0.01). There was no significant difference of the rate of reduction of the PANSS total score, the positive symptom score , the negative symptom score between two groups(P>0.05). There was a higher rate of reduction of the general mental pathological symptom score in topiramate group than in placebo group in the end of week 2 and 4 after treatment (p<0.05). There was no significant difference of CGI and TESS score between two groups.CONCLUSIONS: Topiramate addition therapy is effective and safe in attenuating olanzapine-induced weight gain and glucose and lipid metabolic dysfuction in the first-episode schizophrenic patients.Topiramate addition therapy can improve the general mental pathological symptoms more rapidly in the early treatment.