Peuckmann Vera, Elsner Frank, Krumm Norbert, Trottenberg Peter, Radbruch Lukas
Medical Faculty RWTH, Universitatsklinikum Aachen, Hauptgebäude, Aufzug B 1, Etage 1, Flur 1, Raum-Nr.5, Pauwelsstraße 30, Aachen, Germany, 52074.
Cochrane Database Syst Rev. 2010 Nov 10(11):CD006788. doi: 10.1002/14651858.CD006788.pub2.
In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients fatigue can be severely debilitating, thereby impacting daily activity and quality of life, often with rest not counteracting fatigue. Fatigue frequently occurs in patients with advanced disease and modalities treating cancer often contribute or cause fatigue. Further complicating issues are its multidimensionality, subjective nature, and lack of a consensus definition of fatigue. Pathophysiology is not fully understood and evidence-based treatment approaches are needed.
The objective was to determine efficacy of pharmacological treatments on non-specific fatigue in palliative care. The focus was on patients at an advanced stage of disease, including cancer and other chronic diseases associated with fatigue, aiming to relieve fatigue. Studies aiming at curative treatment (e.g. surgical intervention for early breast cancer) were not included.
We searched EMBASE; Psych Lit, CENTRAL and MEDLINE to June 2009.
We considered randomised controlled trials (RCTs) concerning adult palliative care with focus on pharmacological treatment of fatigue. The primary outcome had to be non-specific fatigue (or related terms such as asthenia).
Results were screened and included if they met the selection criteria. If two or more studies were identified that investigated a specific drug in a population with the same disease, meta-analysis was conducted. In addition, comparison of type of drug investigated in a specific population as well as comparison of frequent adverse effects of fatigue treatment was done by creating overview tables.
More than 2000 publications were screened, and 22 met inclusion criteria. In total, data from 11 drugs and 1632 participants were analysed. Studies investigating amantadine, pemoline, and modafinil in participants with Multiple Sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue could be used for meta-analysis. Amantadine in MS and methylphenidate in cancer patients showed a superior effect. Most studies had low participant numbers and were heterogenous.
AUTHORS' CONCLUSIONS: Based on limited evidence, we cannot recommend a specific drug for treatment of fatigue in palliative care patients. Surprisingly, corticosteroids have not been a research focus for fatigue treatment, although these drugs are frequently used. Recent fatigue research seems to focus on modafinil, which may be beneficial although there is no evidence currently. Amantadine and methylphenidate should be further examined. Consensus regarding fatigue assessment in advanced disease is needed.
在健康个体中，疲劳是对身体或精神压力的一种保护性反应，通常通过休息得以缓解。相比之下，在姑息治疗患者中，疲劳可能会严重削弱身体机能，进而影响日常活动和生活质量，而且休息往往无法消除疲劳。晚期疾病患者经常会出现疲劳，治疗癌症的各种方式也常常会导致或引发疲劳。更复杂的问题在于疲劳具有多维度性、主观性，且缺乏关于疲劳的共识性定义。其病理生理学尚未完全明确，因此需要基于证据的治疗方法。
目的是确定药物治疗对姑息治疗中非特异性疲劳的疗效。重点关注疾病晚期患者，包括癌症患者以及其他与疲劳相关的慢性疾病患者，旨在缓解疲劳。旨在进行根治性治疗的研究（如早期乳腺癌的手术干预）未被纳入。
我们检索了截至2009年6月的EMBASE、Psych Lit、CENTRAL和MEDLINE数据库。
我们纳入了关于成人姑息治疗中以疲劳药物治疗为重点的随机对照试验（RCT）。主要结局必须是非特异性疲劳（或相关术语，如乏力）。
如果结果符合入选标准，则进行筛选并纳入。如果识别出两项或更多研究在患有相同疾病的人群中研究一种特定药物，则进行荟萃分析。此外，通过创建概述表，对特定人群中所研究药物的类型以及疲劳治疗的常见不良反应进行比较。
筛选了2000多篇出版物，22篇符合纳入标准。总共分析了来自11种药物和1632名参与者的数据。对在患有多发性硬化症（MS）相关疲劳的参与者中研究金刚烷胺、匹莫林和莫达非尼，以及在患有晚期癌症和疲劳的患者中研究哌醋甲酯的研究可用于荟萃分析。MS患者使用金刚烷胺以及癌症患者使用哌醋甲酯显示出较好的效果。大多数研究的参与者数量较少且存在异质性。
基于有限的证据，我们无法推荐一种特定药物用于治疗姑息治疗患者的疲劳。令人惊讶的是，尽管皮质类固醇药物经常被使用，但它们尚未成为疲劳治疗的研究重点。近期的疲劳研究似乎集中在莫达非尼上，尽管目前尚无证据表明其有益，但可能有帮助。金刚烷胺和哌醋甲酯应进一步研究。晚期疾病中疲劳评估的共识是必要的。
