Rabinak Christina A, Nirenberg Melissa J
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10021, USA.
Arch Neurol. 2010 Jan;67(1):58-63. doi: 10.1001/archneurol.2009.294.
To report and characterize a dopamine agonist (DA) withdrawal syndrome (DAWS) in Parkinson disease.
Retrospective cohort study.
Outpatient tertiary movement disorders clinic. Patients A cohort of 93 nondemented patients with Parkinson disease enrolled in a prospective study of nonmotor and motor disease manifestations. Main Outcome Measure The presence of DAWS, defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with DA withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other Parkinson disease medications, and cannot be accounted for by other clinical factors.
Of 40 subjects treated with a DA, 26 underwent subsequent DA taper. Of these 26 subjects, 5 (19%) developed DAWS and 21 (81%) did not. All subjects with DAWS had baseline DA-related impulse control disorders. Symptoms of DAWS resembled those of other drug withdrawal syndromes and included anxiety, panic attacks, agoraphobia, depression, dysphoria, diaphoresis, fatigue, pain, orthostatic hypotension, and drug cravings. Subjects with DAWS as compared with those without DAWS had higher baseline DA use (mean [SD], 420 [170] vs 230 [180] DA levodopa equivalent daily doses [DA-LEDD], respectively; P = .04) and higher cumulative DA exposure (mean [SD], 1800 [1200] vs 700 [900] DA-LEDD-years, respectively; P = .03). Subjects with DAWS also had considerably lower Unified Parkinson's Disease Rating Scale motor scores than those without DAWS (mean [SD], 21 [5] vs 31 [10], respectively; P = .007), despite comparable disease duration (mean [SD], 7.3 [7] vs 6.3 [4] years, respectively; P = .77) and similar total dopaminergic medication use (mean [SD], 830 [450] vs 640 [610] total LEDD, respectively; P = .52) in the 2 groups.
Dopamine agonists have a stereotyped withdrawal syndrome that can lead to profound disability in a subset of patients. Physicians should monitor patients closely when tapering these medications.
报告帕金森病中多巴胺激动剂(DA)撤药综合征(DAWS)并对其进行特征描述。
回顾性队列研究。
门诊三级运动障碍诊所。
93例非痴呆帕金森病患者组成的队列,参与了一项关于非运动和运动疾病表现的前瞻性研究。
DAWS的存在,定义为一组严重的、刻板的身心症状,与DA撤药呈剂量依赖性相关,导致临床上显著的痛苦或社会/职业功能障碍,对左旋多巴和其他帕金森病药物无效,且不能用其他临床因素解释。
40例接受DA治疗的患者中,26例随后逐渐减少DA用量。在这26例患者中,5例(19%)发生了DAWS,21例(81%)未发生。所有发生DAWS的患者均有基线DA相关的冲动控制障碍。DAWS的症状与其他药物撤药综合征相似,包括焦虑、惊恐发作、广场恐惧症、抑郁、烦躁不安、多汗、疲劳、疼痛、体位性低血压和药物渴求。与未发生DAWS的患者相比,发生DAWS的患者基线DA用量更高(分别为平均[标准差],420[170]与230[180]多巴胺左旋多巴等效日剂量[DA-LEDD];P = 0.04),累积DA暴露量更高(分别为平均[标准差],1800[1200]与700[900]DA-LEDD年;P = 0.03)。尽管两组疾病持续时间相当(分别为平均[标准差],7.3[7]与6.3[4]年;P = 0.77)且总多巴胺能药物用量相似(分别为平均[标准差],830[450]与640[610]总LEDD;P = 0.52),但发生DAWS的患者统一帕金森病评定量表运动评分也显著低于未发生DAWS的患者(分别为平均[标准差],21[5]与31[10];P = 0.007)。
多巴胺激动剂有刻板的撤药综合征,可导致部分患者严重残疾。医生在逐渐减少这些药物用量时应密切监测患者。