Kinon Bruce J, Kollack-Walker Sara, Jeste Dilip, Gupta Sanjay, Chen Lei, Case Mike, Chen Jian, Stauffer Virginia
Eli Lilly and Company, Indianapolis, IN, USA.
Lilly USA, LLC, Indianapolis IN, USA
J Geriatr Psychiatry Neurol. 2015 Mar;28(1):67-79. doi: 10.1177/0891988714541867. Epub 2014 Jul 9.
The risk of persistent tardive dyskinesia (TD) was compared in patients with acute psychosis or agitation aged 55 years or older who were treated with olanzapine (OLZ) or conventional antipsychotic (CNV) drug therapy.
Patients without TD were randomized to treatment with OLZ (2.5-20 mg/d; n = 150) or CNV (dosed per label; n = 143). Following a 6-week drug tapering/initiation period, patients without TD were treated with OLZ or CNV for up to 1 year. The a priori defined primary outcome end point was persistent TD defined as Abnormal Involuntary Movement Scale (AIMS) scores = 2 on at least 2 items or ≥3 on at least 1 item (items 1-7) lasting at least for 1 month (Criterion A). Post hoc analyses assessed persistent TD meeting the criterion of moderate severity defined as AIMS score ≥3 on at least 1 item persisting for 1 month (Criterion B) and probable TD defined as elevated AIMS scores (Criterion A or B) not persisting for 1 month. Treatment groups were compared using Kaplan-Meier curve with log-rank exact test.
On average, patients were 78 years of age; the predominant diagnosis was dementia (76.7% in the OLZ group and 82.5% in the CNV group). Approximately, 40.6% of patients in the CNV group received haloperidol. No significant difference in time to developing persistent TD was observed during treatment with OLZ or CNV (cumulative incidence: OLZ, 2.5% [95% confidence interval [95% CI]: 0.5-7.0]; CNV, 5.5% [95% CI: 2.1-11.6], P = .193). The exposure-adjusted event rates per 100 person-years were not significantly different between treatment groups: OLZ (2.7) and CNV (6.3; ratio: 0.420; 95% CI: 0.068-1.969). Post hoc analyses revealed a significantly lower risk of at least moderately severe persistent TD persisting for 1 month (P = .012) and probable TD not persisting for 1 month (Criterion A, P = .030; Criterion B, P = .048) in OLZ-treated patients. For those patients without significant extrapyramidal symptoms at baseline, significantly more patients in the CNV treatment group developed treatment-emergent parkinsonism than for patients in the OLZ treatment group (CNV: 70%, 35 of 50 patients; OLZ 44%, 25 of 57 patients; P = .011). No significant difference between the groups was observed for treatment-emergent akathisia (CNV: 6%, 7 of 117 patients; OLZ: 10%, 13 of 130 patients; P = .351).
The cumulative incidence of persistent TD was low and the risk of persistent TD did not differ significantly among predominantly older adult patients having dementia with acute psychosis or agitation treated with OLZ or CNV.
比较了使用奥氮平（OLZ）或传统抗精神病药物（CNV）治疗的55岁及以上急性精神病或躁动患者发生持续性迟发性运动障碍（TD）的风险。
无TD的患者被随机分配接受OLZ（2.5 - 20 mg/d；n = 150）或CNV（按标签给药；n = 143）治疗。在为期6周的药物减量/起始期后，无TD的患者接受OLZ或CNV治疗长达1年。预先定义的主要结局终点是持续性TD，定义为异常不自主运动量表（AIMS）至少2项得分 = 2或至少1项（第1 - 7项）得分≥3，持续至少1个月（标准A）。事后分析评估符合中度严重程度标准的持续性TD，定义为AIMS至少1项得分≥3且持续1个月（标准B），以及可能的TD，定义为AIMS得分升高（标准A或B）但持续时间不足1个月。使用Kaplan - Meier曲线和对数秩精确检验比较治疗组。
患者平均年龄为78岁；主要诊断为痴呆（OLZ组为76.7%，CNV组为82.5%）。CNV组约40.6%的患者接受了氟哌啶醇治疗。在使用OLZ或CNV治疗期间，发生持续性TD的时间无显著差异（累积发生率：OLZ，2.5%[95%置信区间[95%CI]：0.5 - 7.0]；CNV，5.5%[95%CI：2.1 - 11.6]，P = 0.193）。治疗组每100人年的暴露调整事件率无显著差异：OLZ（2.7）和CNV（6.3；比值：0.420；95%CI：0.068 - 1.969）。事后分析显示，接受OLZ治疗的患者中，至少中度严重的持续性TD持续1个月的风险显著较低（P = 0.012），以及可能的TD持续时间不足1个月（标准A，P = 0.030；标准B，P = 0.048）。对于那些基线时无明显锥体外系症状的患者，CNV治疗组出现治疗性帕金森综合征的患者明显多于OLZ治疗组（CNV：70%，共50例患者中的35例；OLZ 44%，共57例患者中的25例；P = 0.011）。治疗性静坐不能在两组之间无显著差异（CNV：6%，共117例患者中的7例；OLZ：10%，共130例患者中的13例；P = 0.351）。
持续性TD的累积发生率较低，在主要为患有痴呆且伴有急性精神病或躁动的老年成年患者中，使用OLZ或CNV治疗时持续性TD的风险无显著差异。
