A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease
A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease
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DOI：
10.1176/ajp.155.11.1512
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发表时间：
1998-11-01
影响因子：
17.7
通讯作者：
Mayeux, R
中科院分区：
文献类型：
--
作者：
Devanand, DP;Marder, K;Mayeux, R
目的：本研究的目的是比较两种剂量的氟哌啶醇和安慰剂在治疗阿尔茨海默病患者的精神病和破坏性行为方面的疗效和副作用。方法：在一项为期 6 周的随机分配、双盲、安慰剂对照试验（A 期）中，对 71 名阿尔茨海默病门诊患者使用氟哌啶醇 2-3 mg/天（标准剂量）和氟哌啶醇 0.50-0.75 mg/天（低剂量）进行了比较。在随后的 6 周双盲交叉阶段（B 期）中，服用标准或低剂量氟哌啶醇的患者转为安慰剂，服用安慰剂的患者被随机分配至标准或低剂量氟哌啶醇。结果：对于完成 A 期的 60 名患者，标准剂量氟哌啶醇是有效的，并且在简明精神病评定量表精神病因子和精神运动性激越方面的得分均优于低剂量氟哌啶醇和安慰剂。根据三组标准，标准剂量（55%-60%）的缓解率高于低剂量（25%-35%）和安慰剂（25%-30%）。标准剂量相对于低剂量的优势在 B 阶段得到了复制。在 A 阶段，标准剂量组的锥体外系症状往往比其他两种情况更严重，主要是因为有一个亚组 (20%) 出现了中度至重度症状。低剂量氟哌啶醇在任何疗效或副作用指标上与安慰剂没有差异。结论：结果表明，氟哌啶醇剂量为 2-3 mg/天时具有良好的治疗效果，尽管有一个亚组出现了中度至重度锥体外系症状。建议起始剂量为 1 mg/天，并逐渐向上剂量滴定。氟哌啶醇观察到的狭窄治疗窗也可能适用于治疗患有精神病和破坏性行为的阿尔茨海默病患者的其他精神安定药。
Objective: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. Method: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. Results: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. Conclusions: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.