The Effects Of 12 Antipsychotics Used For The Treatment Of Schizophrenia On Glucose And Lipid Metabolism:a Network Meta-analysis

Objective:We aimed to evaluate and compare the effects of 12 antipsychotic drugs(ziprasidone,lurasidone,aripiprazole,risperidone,amisulpride,quetiapine,paliperidone,asenapine,haloperidol,sertindole,clozapine and olanzapine)on blood glucose and blood lipid levels in schizophrenic patients by using network meta-analysis.Methods:We searched the PubMed,Cochrane Library and EMBASE database to obtain randomized controlled trials(RCT)about the effects of 12 antipsychotic drugs on blood glucose and lipid levels in schizophrenias.Retrieval time for the three databases was up to December 31,2017.We screened literature according to pre-established inclusion and exclusion criteria,and assessed the risk of the included studies.Stata 13.0 software was used for statistical analysis.The 12 antipsychotics compared with each other and ranked according to the effects on blood glucose and lipid by network meta-analysis.Results:(1)65 studies were finally included in the meta-analysis,of which 20 were clearly stated as open-label,39 were stated as blinding and 6 as RCT only.There were 12892 schizophrenia patients included in our study.The age range of the patients was 15-65 years old.(2)52 studies reported the change of fasting blood glucose levels before and after treatment.When compared to placebo,only olanzapine was associated with significantly increased glucose levels(MD: 3.77,95%CI:0.12~7.42).Moreover,olanzapine was associated with a significantly greater change in the glucose levels than ziprasidone(MD: 5.48,95% CI: 1.81~9.16),lurasidone(MD: 5.48,95%CI:1.81~9.16)or risperidone(MD: 2.80,95%CI:0.73~4.86).Based on the results of probabilistic ranking,the effect on blood glucose from small to big was ziprasidone,lurasidone,aripiprazole,risperidone,amisulpride,quetiapine,paliperidone,asenapine,haloperidol,sertindole,clozapine and olanzapine.(3)48 studies reported the change of total cholesterol levels before and after treatment.When compared to placebo,quetiapine(MD:9.67,95%CI:3.83~15.50),asenapine(MD: 12.16,95%CI : 1.50~23.16),clozapine(MD : 20.19,95%CI :12.80~27.58)and olanzapine(MD: MD:15.96,95%CI:11.57~20.34)was associated with significantly increased total cholesterol levels.Moreover,olanzapine and clozapine were associated with a significantly greater change in the total cholesterol levels than some of other antipsychotic drugs.The results based on the probability ranking showed that the effect on total cholesterol levels from small to large was: ziprasidone,lurasidone,paliperidone,amisulpride,aripiprazole,risperidone,haloperidol,quetiapine,asenapine,sertindole,olanzapine and clozapine.(4)37 studies including 10 antipsychotics reported the change of plasma high-density lipoprotein levels before and after treatment.The results of comparisons between the 12 drugs showed that olanzapine was associated with significantly decreased in the high-density lipoprotein levels compared to ziprasidone(MD:-1.70,95%CI :-3.38~-0.02),lurasidone(MD:-2.72,95% CI:-4.86~-0.58),risperidone(MD:-1.70,95% CI:-3.07~-0.34)and sertindole(MD:-5.18,95% CI:-10.26~-0.11).Based on the results of probabilistic ranking,the effect on high-density lipoprotein levels from small to big was sertindole,lurasidone,risperidone,ziprasidone,aripiprazole,quetiapine,haloperidol,paliperidone,olanzapine and amisulpride.(5)29 studies including 10 antipsychotics reported the change of plasma low-density lipoprotein levels before and after treatment.When compared to placebo,quetiapine(MD: 5.23,95%CI : 0.60~9.86)and olanzapine(MD: 8.77,95%CI :5.39~12.16)were associated with significantly increased low-density lipoprotein levels.At the same time,quetiapine was associated with a significantly greater change in the low-density lipoprotein than ziprasidone(MD: 5.81,95% CI: 0.16~11.47).Olanzapine was associated with a significantly greater change in the low-density lipoprotein levels than many other antipsychotics.Based on the results of probabilistic ranking,the effect on low-density lipoprotein levels from small to big was ziprasidone,paliperidone,aripiprazole,lurasidone,amisulpride,risperidone,haloperidol,sertindole,quetiapine and olanzapine.(6)49 studies reported the change of triglyceride levels before and after treatment.The results showed that amisulpride(MD:33.56,95%CI:8.04~59.08),quetiapine(MD:21.06,95%CI:7.95~34.17),clozapine(MD: 43.29,95%CI:27.13~53.45)and olanzapine(MD: 31.35,95%CI : 20.92~41.78)were significantly increased triglyceride levels compared to placebo.Moreover,the four kinds of drugs significantly increased triglyceride levels compared with other types of antipsychotics.Based on the results of probabilistic ranking,the effect on triglyceride levels from small to big was lurasidone,aripiprazole,asenapine,ziprasidone,paliperidone,risperidone,haloperidol,sertindole,risperidone,olanzapine,amisulpride and clozapine.Conclusion:Olanzapine was associated with significantly increased glucose levels;quetiapine,asenapine,clozapine and olanzapine were associated with significantly increased total cholesterol levels.The effects on total cholesterol levels ranged from large to small,followed by clozapine,olanzapine,acenapine and quetiapine;olanzapine was associated with significantly decreased in the high-density lipoprotein levels compared to ziprasidone,risperidone and sertindole;olanzapine had the greatest effect on the low-density lipoprotein levels,followed by quetiapine;clozapine,amisulpride,olanzapine and quetiapine were associated with significantly increased triglyceride levels.