Department of Neurology, City Hospital, Birmingham, UK.
Parkinsonism Relat Disord. 2009 Dec;15(10):728-41. doi: 10.1016/j.parkreldis.2009.09.005. Epub 2009 Oct 4.
The effectiveness of oral levodopa in complex Parkinson's disease (PD) is limited by its short half-life, and the resulting pulsatile dopaminergic stimulation leads to complex motor fluctuations and dyskinesia. Several treatments provide more continuous/less pulsatile dopaminergic stimulation by modifying the pharmacokinetics of levodopa or dopamine; however, patients with advanced disease can be refractory to these treatments. In such cases infusion therapies (apomorphine and intraduodenal levodopa) and neurosurgery (deep brain stimulation [DBS]) may be used. The purpose of this systematic review is to assess, as far as possible, the relative effectiveness of these therapies. There were no randomised controlled trials comparing the three treatment modalities or any directly comparable studies, therefore a descriptive analysis of the data was performed. Studies identified for levodopa infusion and DBS supported a significant benefit compared with best medical management in terms of improvements in the proportion of the waking day in a functional "on" state, activities of daily living and motor score. This finding was supported in observational studies for all three therapies. Adverse events were not adequately reported in the majority of included studies and it was therefore not possible to obtain a reliable tolerability profile of the different treatment options. The absence of direct comparative data means that, for the immediate future at least, treatment choices for advanced PD will be determined by clinical judgement and patient preference. There is an urgent need for well-designed clinical trials to generate reliable data to inform the clinical management of this difficult-to-treat subgroup of PD patients.
口服左旋多巴治疗复杂帕金森病（PD）的疗效有限，这是由于其半衰期较短，导致多巴胺能刺激呈脉冲式，从而引发复杂的运动波动和运动障碍。一些治疗方法通过改变左旋多巴或多巴胺的药代动力学来提供更持续/更稳定的多巴胺能刺激；然而，晚期疾病患者可能对这些治疗方法产生抵抗。在这种情况下，可以使用输注治疗（阿扑吗啡和十二指肠内左旋多巴）和神经外科手术（深部脑刺激[DBS]）。本系统评价的目的是尽可能评估这些治疗方法的相对疗效。没有比较三种治疗方式的随机对照试验，也没有任何直接可比的研究，因此对数据进行了描述性分析。左旋多巴输注和 DBS 的研究支持与最佳药物治疗相比，在功能“开”状态下的清醒日比例、日常生活活动和运动评分方面有显著改善。这一发现得到了所有三种治疗方法的观察性研究的支持。大多数纳入的研究没有充分报告不良反应事件，因此无法获得不同治疗选择的可靠耐受性概况。缺乏直接比较数据意味着，至少在近期内，晚期 PD 的治疗选择将取决于临床判断和患者偏好。迫切需要精心设计的临床试验来生成可靠的数据，为这一难以治疗的 PD 患者亚组的临床管理提供信息。
