Methylphenidate for the treatment of apathy in Alzheimer disease: Prediction of Response Using Dextroamphetamine Challenge
Methylphenidate for the treatment of apathy in Alzheimer disease: Prediction of Response Using Dextroamphetamine Challenge
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DOI：
10.1097/jcp.0b013e318172b479
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发表时间：
2008-06-01
影响因子：
2.9
通讯作者：
Lanctot, Krista L.
中科院分区：
文献类型：
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作者：
Herrmann, Nathan;Rothenburg, Lana S.;Lanctot, Krista L.
冷漠是阿尔茨海默病(AD)的一种常见行为症状，高达70%的患者存在这种症状。AD和非AD人群中的冷漠与多巴胺能脑奖励系统的功能障碍有关，这表明针对该系统的药物治疗靶向可能是治疗AD冷漠的有效方法。因此，我们对13名麻木不仁的AD患者(6名男性，7名女性；平均年龄77.9岁[SD，7.8岁]；迷你精神状态检查评分，19.9[SD，4.7])进行了一项随机、双盲、安慰剂对照的交叉试验。患者接受哌醋甲酯(10 mg PO，每天两次)或相同的安慰剂治疗，分两个2周阶段进行，间隔1周的安慰剂冲洗。所有患者在使用哌醋甲酯治疗前都参加了右旋苯丙胺激发试验(10毫克口服剂量)，以衡量多巴胺大脑奖励系统的功能完整性。总体而言，根据冷漠评估量表的总变化分数，服用哌醋甲酯的患者比服用安慰剂的患者有更大的改善(治疗结束-基线：Wilcoxon Z=-2.00；P=0.047)。然而，与安慰剂相比，服用哌醋甲酯的患者发生至少I次不良事件的比例明显更高(3vs1；chi(2)=4.33P=0.038)。2例患者服用哌醋甲酯后出现严重不良反应，包括妄想、烦躁、愤怒、易怒和失眠，停药后症状消失。对哌醋甲酯的反应与右旋苯丙胺激发后在连续操作任务中注意力不集中的增加有关。精神刺激剂可能对治疗AD患者的冷漠特征有效，而多巴胺能变化可能预测反应。
Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years [SD, 7.8 years]; Mini Mental Status Examination score, 19.9 [SD, 4.7]). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a I-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline: Wilcoxon Z = -2.00; P = 0.047). However, a significantly greater proportion of patients experienced at least I adverse event with methylphenidate compared with placebo (3 vs 1; chi(2) = 4.33, P = 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.