Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial
Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s1474-4422(10)70106-x
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发表时间：
2010-06-01
期刊：
影响因子：
48
通讯作者：
Weintraub, Daniel
中科院分区：
文献类型：
--
作者：
Barone, Paolo;Poewe, Werner;Weintraub, Daniel
背景抑郁症在帕金森氏病患者中很常见，但缺乏证据表明抗抑郁药物在这一人群中的疗效。由于帕金森病患者的抑郁可能与多巴胺能功能障碍有关，我们旨在评估多巴胺激动剂普拉克索治疗帕金森病患者抑郁症状的疗效。方法我们在轻中度帕金森病患者中进行了为期12周的随机、双盲、安慰剂对照(1：1比)的普拉克索(0.125-1 mg，每天3次)与安慰剂的比较试验。来自12个欧洲国家和南非的76个中心的患者被纳入其中，如果他们正在接受没有运动波动的稳定的抗帕金森病治疗，并且有抑郁症状(15项老年抑郁量表评分=5，统一帕金森病评定量表[UPDRS]第一部分抑郁条目评分为2)。通过使用随机数字生成系统，患者按中心随机分配，每组四人。临床监测员、主要研究人员和患者被蒙蔽到治疗分配中。主要终点是Beck抑郁量表(BDI)评分的变化，所有至少有一次基线后疗效评估的接受治疗的患者都包括在主要分析中。我们还用回归模型进行了预先指定的路径分析，以评估BDI和UPDRS第三部分(运动评分)变化之间的关系。这项试验注册在ClinicalTrials.gov，编号NCT00297778和EudraCT，编号2005-003788-22。在随机分为普拉克索组和安慰剂组的296名患者中，有287名患者进入了初步分析：普拉克索组139人，安慰剂组148人。调整后，普拉克索组和安慰剂组的BDI评分分别下降了5.9分(SE 0.5)和4.0分(0.5)(差异1.9，95%CI 0.5-3.4；p=0.01，ANCOVA)。调整后，普拉克索组和安慰剂组的UPDRS运动评分分别下降了4.4(0.6)分和2.2(0.5)分(差异2.2，95%可信区间0-7-3-7；p=0.003，ANCOVA)。通径分析显示，普拉克索对抑郁症状的直接疗效占总疗效的80%(p=0.04)。普拉克索组144名患者中有105名患者报告了不良事件，安慰剂组152名患者中有101名患者报告了不良事件。普拉克索组的不良反应与该药物的已知安全性相符。解释普拉克索主要通过直接的抗抑郁作用改善帕金森病患者的抑郁症状。在帕金森病患者的临床治疗中应考虑这种影响。
Background Depression is common in patients with Parkinson's disease, but evidence on the efficacy of antidepressants in this population is lacking. Because depression in patients with Parkinson's disease might be related to dopaminergic dysfunction, we aimed to assess the efficacy of the dopamine agonist pramipexole for treatment of depressive symptoms in patients with Parkinson's disease.Methods We did a 12-week randomised, double-blind, placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg three times per day) compared with placebo in patients with mild-to-moderate Parkinson's disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms (15-item geriatric depression scale score >= 5 and unified Parkinson's disease rating scale [UPDRS] part 1 depression item score a 2). Patients were randomly assigned by centre in blocks of four by use of a randomisation number generating system. Clinical monitors, the principal investigator, and patients were masked to treatment allocation. The primary endpoint was change in Beck depression inventory (BDI) score and all treated patients who had at least one post-baseline efficacy assessment were included in the primary analysis. We also did a pre-specified path analysis with regression models to assess the relation between BDI and UPDRS part 3 (motor score) changes. This trial is registered with ClinicalTrials.gov, number NCT00297778, and EudraCT, number 2005-003788-22.Findings Between March, 2006, and February, 2008, we enrolled 323 patients. Of 296 patients randomly assigned to pramipexole or placebo, 287 were induded in the primary analysis: 139 in the pramipexole group and 148 in the placebo group. BDI scores decreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexole group and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI 0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjusted mean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points in the placebo group (difference 2.2, 95% CI 0-7-3-7; p=0.003, ANCOVA). Path analysis showed the direct effect of pramipexole on depressive symptoms accounted for 80% of total treatment effect (p=0.04). Adverse events were reported in 105 of 144 patients in the pramipexole group and 101 of 152 in the placebo group. Adverse events in the pramipexole group were consistent with the known safety profile of the drug.Interpretation Pramipexole improved depressive symptoms in patients with Parkinson's disease, mainly through a direct antidepressant effect. This effect should be considered in the clinical management of patients with Parkinson's disease.