The Center for Hospice & Palliative Care, Buffalo, New York, USA.
J Pain Symptom Manage. 2012 Jan;43(1):68-77. doi: 10.1016/j.jpainsymman.2011.03.026.
Fatigue is highly prevalent in populations with advanced illness and is often associated with depressed mood. The role of psychostimulant therapy in the treatment of these conditions remains ill defined.
To evaluate the response of fatigue and depression in patients with advanced illness to titrated doses of methylphenidate (MP) as compared with placebo.
In a randomized, double-blind, placebo-controlled trial, 30 hospice patients, both inpatients and outpatients, who had fatigue scores of at least four on a scale of zero to 10 (0=no fatigue and 10=worst fatigue), were randomly assigned to receive either 5mg of MP at 8 am and 1 pm or placebo. Doses of MP were titrated every three days according to response and adverse effects. Home care patients were monitored daily by telephone and visited by a research nurse on Study Days 0 (baseline), 3, 7, and 14. Fatigue was assessed using the Piper Fatigue Scale as the primary outcome measure and validated by the Visual Analogue Scale for Fatigue and the Edmonton Symptom Assessment Scale (ESAS) fatigue score. Subjects in inpatient facilities were interviewed or assessed by staff on an identical schedule. Depressive symptoms were assessed by the Beck Depression Inventory-II, Center for Epidemiologic Studies Depression Scale, and the ESAS depression score. Primary statistical analysis was conducted using repeated-measures multivariate analysis of the variance.
Both MP- and placebo-treated groups had similar measures of fatigue at baseline. Patients taking MP were found to have significantly lower fatigue scores (Piper Fatigue Scale, Visual Analogue Scale for Fatigue, and ESAS) at Day 14 compared with baseline. The improvement in fatigue with MP treatment was dose-dependent; the mean average effective dose was 10mg on Day 3 and 20mg on Day 14 (dose range of 10-40 mg). Placebo-treated individuals showed no significant improvement in fatigue. For patients with clinically significant depression on Day 0, treatment with MP was associated with a significant reduction in all test indices for depressed mood. For the placebo group, the changes in measures of depression were less than observed in the treatment group but were inconsistent between assessment tools. No significant toxicities were observed.
MP reduced symptoms of fatigue and depression when compared with placebo. The effect of MP on fatigue was dose-dependent and sustained over the duration of the study.
疲劳在患有晚期疾病的人群中非常普遍，并且常常与情绪低落有关。在治疗这些病症方面，精神兴奋剂治疗的作用仍然没有明确界定。
评估经滴定剂量哌醋甲酯（MP）治疗与安慰剂治疗后，晚期疾病患者的疲劳和抑郁症状的反应。
在一项随机、双盲、安慰剂对照试验中，将 30 名住院和门诊的姑息治疗患者随机分为两组，这些患者的疲劳评分均至少为 0 到 10 分制的 4 分（0 分表示没有疲劳，10 分表示最严重的疲劳），分别接受 5mg MP 每日上午 8 点和下午 1 点或安慰剂治疗。根据反应和不良反应，每隔三天调整一次 MP 剂量。家庭护理患者每天通过电话接受监测，并在研究第 0 天（基线）、第 3 天、第 7 天和第 14 天由研究护士进行访问。疲劳采用派珀疲劳量表作为主要结局测量指标，并通过疲劳视觉模拟量表和埃德蒙顿症状评估量表（ESAS）疲劳评分进行验证。住院患者按照相同的时间表由工作人员进行访谈或评估。抑郁症状采用贝克抑郁量表第二版、流行病学研究中心抑郁量表和 ESAS 抑郁评分进行评估。主要的统计分析采用重复测量多元方差分析进行。
MP 治疗组和安慰剂治疗组在基线时的疲劳测量值相似。与基线相比，接受 MP 治疗的患者在第 14 天的疲劳评分（派珀疲劳量表、疲劳视觉模拟量表和 ESAS）显著降低。MP 治疗的疲劳改善与剂量有关；第 3 天的平均有效剂量为 10mg，第 14 天为 20mg（剂量范围为 10-40mg）。接受安慰剂治疗的个体在疲劳方面没有明显改善。对于第 0 天有临床显著抑郁症状的患者，MP 治疗与所有抑郁测试指标的显著降低相关。对于安慰剂组，抑郁测量值的变化小于治疗组，但在评估工具之间不一致。未观察到明显的毒性。
与安慰剂相比，MP 可减轻疲劳和抑郁症状。MP 对疲劳的作用与剂量有关，并且在研究期间持续存在。
