Université Laval, Québec, Canada.
Clin Ther. 2010;32 Suppl 1:S21-31. doi: 10.1016/j.clinthera.2010.01.003.
Patterns of discontinuation of atypical antipsychotic drugs, including the return to therapy after an interruption, have not been examined longitudinally.
This study was conducted to describe discontinuation patterns of atypical antipsychotic drugs across a spectrum of outpatients in the province of Québec.
This retrospective, inception cohort study employed data from the Québec health insurance board databases and the Québec hospitalization registry on Québec Drug Plan beneficiaries between the ages of 20 and 64 years who first filled a prescription for any antipsychotic drug between January 1, 2000, and December 31, 2007. Five subcohorts were constructed according to the initial antipsychotic received: either 1 of the 4 atypical antipsychotics covered by the Québec drug plan at the time of the study-olanzapine, quetiapine, risperidone, and clozapine-or polytherapy (>1 atypical antipsychotic, or 1 atypical and 1 typical antipsychotic). Discontinuation was defined as a failure to refill the initial prescription within 2 times the days' supply of the preceding claim. In individuals who discontinued initial drug treatment, a new course of treatment was defined as initiation of treatment with any antipsychotic drug after a first treatment discontinuation. Discontinuation of a second course of treatment was defined as failure to refill a prescription for the second drug within 2 times the days' supply of the preceding claim. Patients were followed from initiation to December 31, 2004, ineligibility for the drug plan, or death, whichever came first. Kaplan-Meier curves and Cox regression models were used to compare discontinuations and new courses of treatment by initial atypical antipsychotic.
The overall cohort consisted of 46,074 drug plan beneficiaries who had initiated antipsychotic treatment during the specified period. The majority of individuals were female (54.6%) and lived in urban areas (79.2%); the median age ranged from 40 to 44 years. The mean (SD) duration of follow-up was 2.67 (1.91) years. Compared with individuals whose initial therapy was olanzapine, those whose initial therapy was quetiapine had a significantly higher likelihood of discontinuing initial treatment (adjusted hazard ratio [AHR] = 1.06; 95% CI, 1.04-1.09; P < 0.001). The likelihood of discontinuing initial treatment was significantly lower among those whose initial therapy was risperidone (AHR = 0.93; 95% CI, 0.90-0.95; P < 0.001), clozapine (AHR = 0.56; 95% CI, 0.46-0.68; P < 0.001), or polytherapy (AHR = 0.69; 95% CI, 0.64-0.74; P < 0.001). Those whose initial therapy was quetiapine were significantly less likely than those whose initial therapy was olanzapine to begin a second course of treatment (AHR = 0.95; 95% CI, 0.90-0.99; P = 0.02). Compared with individuals who initiated a second course of treatment with olanzapine, those who initiated a second course with quetiapine were more likely to discontinue again (AHR = 1.09; 95% CI, 1.04-1.14; P < 0.001), whereas those who initiated a second course with risperidone were less likely to discontinue again (AHR = 0.95; 95% CI, 0.90-1.00; P = 0.04).
This study population had a high risk of discontinuing initial atypical antipsychotic therapy within 1 year. Those who discontinued had a low likelihood of returning to treatment, and those who did return to treatment had a high likelihood of discontinuing again. These patterns of use may have serious consequences for patients' health and for the utilization of health services.
包括中断后重新开始治疗在内的非典型抗精神病药物的停药模式尚未进行纵向研究。
本研究旨在描述安大略省一系列门诊患者中使用非典型抗精神病药物的停药模式。
这项回顾性的、初始队列研究使用了魁北克省健康保险委员会数据库和魁北克省住院登记处的数据,这些数据来自于 2000 年 1 月 1 日至 2007 年 12 月 31 日期间年龄在 20 至 64 岁之间的魁北克药物计划受益人,他们首次开了任何一种抗精神病药物的处方。根据最初接受的抗精神病药物,将患者分为五个亚组:4 种非典型抗精神病药物中的 1 种,这 4 种药物在研究时都包含在魁北克药物计划中——奥氮平、喹硫平、利培酮和氯氮平,或者是联合治疗(> 1 种非典型抗精神病药物,或 1 种非典型和 1 种典型抗精神病药物)。停药定义为在 2 倍于前一次用药的天数内未重新配药。对于那些停止初始药物治疗的患者,新的治疗过程定义为在第一次停药后开始使用任何抗精神病药物的治疗。第二次药物治疗的停药定义为在 2 倍于前一次用药的天数内未重新配药。从开始治疗到 2004 年 12 月 31 日、药物计划丧失资格或死亡,以先发生的为准,对患者进行随访。Kaplan-Meier 曲线和 Cox 回归模型用于比较初始非典型抗精神病药物的停药和新的治疗过程。
总的队列包括在指定期间开始抗精神病药物治疗的 46074 名药物计划受益人。大多数患者为女性(54.6%),居住在城市地区(79.2%);中位年龄在 40 至 44 岁之间。平均(标准差)随访时间为 2.67(1.91)年。与初始治疗为奥氮平的患者相比,初始治疗为喹硫平的患者停药的可能性显著更高(调整后的危险比 [AHR] = 1.06;95%CI,1.04-1.09;P < 0.001)。与初始治疗为利培酮(AHR = 0.93;95%CI,0.90-0.95;P < 0.001)、氯氮平(AHR = 0.56;95%CI,0.46-0.68;P < 0.001)或联合治疗(AHR = 0.69;95%CI,0.64-0.74;P < 0.001)的患者相比,开始初始治疗的可能性显著降低。初始治疗为喹硫平的患者开始第二次治疗的可能性显著低于初始治疗为奥氮平的患者(AHR = 0.95;95%CI,0.90-0.99;P = 0.02)。与开始第二次奥氮平治疗的患者相比,开始第二次喹硫平治疗的患者再次停药的可能性更高(AHR = 1.09;95%CI,1.04-1.14;P < 0.001),而开始第二次利培酮治疗的患者再次停药的可能性较低(AHR = 0.95;95%CI,0.90-1.00;P = 0.04)。
本研究人群在 1 年内停止初始非典型抗精神病药物治疗的风险很高。那些停药的患者再次开始治疗的可能性较低,而那些再次开始治疗的患者再次停药的可能性较高。这些使用模式可能对患者的健康和卫生服务的利用产生严重后果。