四种抗精神病药物治疗老年精神分裂症患者1年期停药率的研究

Study of one-year treatment discontinuation rate for the aged patients with schizophrenia treated with 4 antipsychotics

目的:比较4种抗精神病药物治疗老年慢性精神分裂症患者的依从性、疗效和不良反应的差异。方法:系两阶段入组、开放性的随机对照设计,将269例次老年慢性精神分裂症患者随机分成奋乃静组、奥氮平组、利培酮组和奎硫平组,4组患者分别为67例、68例、66例和68例。4组患者分别接受单一可调剂量的奋乃静、奥氮平、利培酮和奎硫平治疗。12个月后,观察4组患者的停药前持续服药时间(TTD)、停药率(TDR)、PANSS量表评分和首要不良反应事件频率。结果:共完成269例次观察,1年期TTD为(8.2±4.3)月,TDR为49.1%,各组患者的全因TDR分别为50.7%、39.7%、62.1%和44.1%,TTD分别为(8.3±4.1)月、(9.4±3.5)月、(6.9±4.6)月和(8.2±4.7)月。4组患者间Kaplan-meier生存分析结果,奥氮平组患者的全因TDR优于利培酮组(x2=9.818,P=0.002),奥氮平组、奎硫平组的因疗效差所致TDR均优于利培酮组(x2=10.831,P=0.001和x2=12.277,P=0.000),因药物不良反应所致TDR的差异无统计学意义(x2=2.871,P=0.412),各组患者间首要停药相关不良反应事件有所差异。PANSS评分疗效比较:以ITT样本分析,只有奥氮平优于利培酮(F=4.438,P=0.005),而基于PPS分析,只有奎硫平优于利培酮(F=8.285,P=0.006)。结论:对老年慢性精神分裂症患者,4种抗精神病药物存在疗效、依从性和不良反应的差异。总体而言,奥氮平优于利培酮,而在持续服药患者中,奎硫平的疗效最佳。

Objective： To evaluate compliance, efficacy and side effects of 4 antipsychotics for treating the aged patients with chronic schizophrenia. Methods： This trail was two-phased enrollment, open-labeled, randomized and controlled. 269 aged patients with chronic schizophrenia were randomly divided into Perphenazine （ n = 67 ）, Olanzapine （ n = 68 ）, Risperidone （ n = 66 ）, and Que-tiapine （n = 68 ） groups. They were treated with a single adjustable dose of the antipsychotic drugs. 12 months later, the time to medi- cation discontinuation （TFD） , treatment discontinuation rate （TDR） , positive and negative syndrome scale （PANSS） score, and the primary side effects of the four groups were observed. Results： 269 cases were completed with the observation with a one-year TFD of （8.2±4.3） months and TDR of 49.1%. The all-cause TTD were （8.3±4.1 ） months, （9.4±3.5） months, （6.9±4.6） months and （8.2±4.7） months, and all-cause TDRs were 50.7% , 39.7% , 62.1% and 44.1% of Perphenazine, Olanzapine, Risperidone, and Quetiapine groups, respectively. The results from Kaplan-meier survival analysis displayed that Olanzapine group was favored over Risperidone group for all-causes TDR （x2 =9. 818, P=0. 002） , that Olanzapine and Quetiapine groups demonstrated the lower TDR due to bad efficacy relative to Risperidone group （x2 = 10. 831, P=0. 001 ; x2 = 12. 277, P=0.000） , and that the difference was not significant in TDR due to intolerable side events （x2 = 2.871, P = 0. 412 ） ; however, these primary events were various among the 4 a- gents. Based on intend-to-treat populations, the analysis on changes of PANSS scores showed that only Olanzapine group was superior to Risperidone group （ F = 4. 438, P = 0. 005 ）, and that only Quetiapine group was superior to Risperidone group （ F = 8. 285, P = 0. 006） based on per-protocol set. Conclusions： For the aged schizophrenia patients, there are different efficacy, compliance and side effects to the 4 agents. Olanzapine is better than Risperidone in general effectiveness, and the patients remaining on Quetiapine may achieve better improvement relative to those on Risperidone.