The Quantitative Efficacy Model Study Of Four Different Kinds Of Atypical Antipsychotics On Schizophrenia

Background Schizophrenia is a serious psychiatric disorder with a procrastinated course.The long-term effective antipsychotic medication therpy is a big problem in the world.The clinical effect of different kinds of atypical antipsychotic and the long-term outcome of patients in real world is remarkable,so this research compared the long-term follow-up under different atypical drug with treatment discontinuation rate and the effect of long-term function.Objective To analyze the clinical use of four kind of atypical antipsychotics in real world and to investigate the comparative effectiveness,all-cause treatment discontinuation rate and all-cause treatment discontinuation of monotherapy versus polypharmacy in schizophrenia.Methods The study was a there-year prospective,cohort,open and multicenter study.The 706 schizophrenia patients,who were treated with atypical antipsychotic drugs olanzapine,quetiapine,risperidone or aripiprazole were recruited in our study.The following visit time was 13 weeks,26 weeks,52 weeks,78 weeks,104 weeks,130 weeks,and 156 weeks after baseline.We collected patients with atypical antipsychotic medications,such as physiology,pathology,drug combination of clinical data,meanwhile,we measured the blood drug concentration by high performance liquid chromatography mass spectrometry technology.focusing on:(1)Analysis of the condiction of monotherapy and polypharmacy of antipsychotic.The primary outcome measures were all-cause discountinuation rate and time until treatment discountinuation.The secondary outcome included scores on the clinical symptoms,social function,subjective well-being and drug concentration.(2)We chose PSP score as indicators of modeling,and conducted time-effect model with nonlinear mixed effect method(NONMEN),calculating the parameters variation between individuals and individual variation,variation between individuals and individuals within the residual adopts additive model.Results 1.Clinical effect(1)90.2%(637)percent patients discontinued their assigned treatment after 3 years.There was significance about all-cause discontinuation rate among four groups(p = 0.0057),there were differences between quetiapine and risperidone(p=0.033);olanzapine and risperidone(p= 0.003).The all-cause discontinuation rate of risperidone was the highest and the time until treatment discountinuation was shortest.(2)The all-cause discontinuation rate in monotherapy of olanzapine was lower than polypharmacy of olanzapine,the time until treatment discountinuation was longer than polypharmacy.There were no significant difference between monotherapy and polypharmacy of arms in quetiapine risperidone and olanzapine.(3)The blood drug concentration was related with its dosage in olanzapine and risperidone group(p<0.05)and dramatic declined at 24 months after baseline.There was no significant correlation between drug concentration and discontinuation rate.(4)The life quality,social function,and subjective well-being were related with all-cause discontinuation rate(p<0.05).2.Model establishment(1)The change of the PSP in comparison with the baseline value between the four groups have significant difference(P < 0.05);Olanzapine and aripiprazole improved more.(2)The typical value of Emax for olanzapine was 80.3% and 56.7 weeks were needed to achieve 50% of Emax;The typical value of Emax for risperidone was 68.2% and 29.2 weeks were needed to achieve 50% of Emax;The typical value of Emax for aripiprazole was 44.2% and 49.7 weeks were needed to achieve 50% of Emax and The typical value of Emax for quetiapine was 28.4% and 19.8 weeks were needed to achieve 50% of Emax.The typical value of Emax for aripiprazole was obviously increased after adjusting the baseline value.(3)Factors that affect olanzapine efficacy include baseline social function,general symptoms and the oneset frequency;Factors that affect the risperidone efficacy include baseline social function,symptoms,first-episode/relapse,and the course of the disease;Factors that affect aripiprazole efficacy include baseline social function;Factors affecting the quetiapine efficacy function including positive symptoms and the baseline social function.Conclusion 1.90.2%(637)percent patients discontinued their assigned treatment after 3 years.The all-cause discontinuation rate of risperidone was the highest and the time until treatment discountinuation was shortest.The all-cause discontinuation rate in monotherapy of olanzapine was lower than polypharmacy of olanzapine,the time until treatment discountinuation was longer than polypharmacy.The time until treatment discountinuation was longer,the better was the social function and quality of life.2.Long-term medication on the social function of patients with schizophrenia have improved.The factors baseline social function,general symptoms and the oneset frequency,first-episode/relapse,the course of the disease,positive symptoms affect the four kinds of commonly used atypical antipsychotics long-term social function groups pharmacodynamic;which provide some useful suggestions about clinical.