Relapse Risk after Discontinuation of Risperidone in Alzheimer's Disease
Relapse Risk after Discontinuation of Risperidone in Alzheimer's Disease
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DOI：
10.1056/nejmoa1114058
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发表时间：
2012-10-18
影响因子：
158.5
通讯作者：
Levin, Bruce
中科院分区：
文献类型：
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作者：
Devanand, D. P.;Mintzer, Jacobo;Levin, Bruce
在阿尔茨海默氏病患者中，对抗精神病药物治疗精神病或激动-攻击有反应的患者，停药后症状复发的风险尚未确定。METHODS阿尔茨海默氏病和精神病或激动-攻击患者接受利培酮开放标签治疗16周。那些对利培酮治疗有反应的人随后以双盲方式随机分配到三种方案之一：继续利培酮治疗32周（第1组），利培酮治疗16周，随后安慰剂治疗16周（第2组），或安慰剂治疗32周（第3组）。主要结果是精神病或激越复发的时间，共有180名患者接受了开放标签的利培酮（平均剂量为0.97 mg/d）。精神病和激越的严重程度降低，尽管锥体外系体征轻度增加; 112例患者符合治疗反应标准，其中110例接受随机化。在随机分组后的前16周，接受安慰剂治疗的组的复发率高于接受利培酮治疗的组（60% [第3组40名患者中的24名]对比33% [第1组和第2组70名患者中的23名]; P = 0.004;安慰剂组的风险比为1.94; 95%置信区间[CI]，1.09至3.45; P = 0.02）。在接下来的16周内，从利培酮转换为安慰剂组的复发率高于继续接受利培酮组（48% [第2组27例患者中的13例] vs 15% [第1组13例患者中的2例]; P = 0.02;风险比，4.88; 95% CI，1.08 - 21.98; P = 0.02）。随机分组后的不良事件和死亡率并没有显着差异，虽然比较是基于少数患者，特别是在最后16 weeks.CONCLUSIONSIn阿尔茨海默氏病患者有精神病或激越反应利培酮治疗4至8个月，停止利培酮与复发的风险增加。（由美国国立卫生研究院和其他机构资助; ClinicalTrials.gov编号，NCT 00417482。
BACKGROUNDAmong patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established.METHODSPatients with Alzheimer's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. Those who had a response to risperidone therapy were then randomly assigned, in a double-blind fashion, to one of three regimens: continued risperidone therapy for 32 weeks (group 1), risperidone therapy for 16 weeks followed by placebo for 16 weeks (group 2), or placebo for 32 weeks (group 3). The primary outcome was the time to relapse of psychosis or agitation.RESULTSA total of 180 patients received open-label risperidone (mean dose, 0.97 mg daily). The severity of psychosis and agitation were reduced, although there was a mild increase in extrapyramidal signs; 112 patients met the criteria for response to treatment, of whom 110 underwent randomization. In the first 16 weeks after randomization, the rate of relapse was higher in the group that received placebo than in the groups that received risperidone (60% [24 of 40 patients in group 3] vs. 33% [23 of 70 in groups 1 and 2]; P = 0.004; hazard ratio with placebo, 1.94; 95% confidence interval [CI], 1.09 to 3.45; P = 0.02). During the next 16 weeks, the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone (48% [13 of 27 patients in group 2] vs. 15% [2 of 13 in group 1]; P = 0.02; hazard ratio, 4.88; 95% CI, 1.08 to 21.98; P = 0.02). The rates of adverse events and death after randomization did not differ significantly among the groups, although comparisons were based on small numbers of patients, especially during the final 16 weeks.CONCLUSIONSIn patients with Alzheimer's disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months, discontinuation of risperidone was associated with an increased risk of relapse. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00417482.)