Larun Lillebeth, Brurberg Kjetil G, Odgaard-Jensen Jan, Price Jonathan R
Norwegian Insitute of Public Health, Postboks 4404 Nydalen, Oslo, Norway, N-0403.
Unit for Primary Care and Clinical Procedures, Norwegian Institute of Public Health, PO Box 4404, Nydalen, Oslo, Norway, 0403.
Cochrane Database Syst Rev. 2016 Dec 20;12(12):CD003200. doi: 10.1002/14651858.CD003200.pub6.
Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004.
The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone).
We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy.
Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome.
We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions.
AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.
慢性疲劳综合征（CFS）的特征是持续存在且医学上无法解释的疲劳，以及肌肉骨骼疼痛、睡眠障碍、头痛、注意力不集中和短期记忆受损等症状。CFS是一个常见、使人衰弱且严重的健康问题。治疗方法可能包括物理干预，如运动疗法，上一次综述是在2004年。
本综述的目的是确定运动疗法（ET）对CFS患者的效果，并与其他任何干预措施或对照进行比较。
• 运动疗法与“被动对照”（如常规治疗、等待名单对照、放松、柔韧性训练）。
• 运动疗法与其他积极治疗（如认知行为疗法（CBT）、认知治疗、支持性治疗、节奏疗法、抗抑郁药等药物治疗）。
• 运动疗法与其他特定治疗策略联合使用与其他特定治疗策略（如运动与药物治疗联合使用与单独药物治疗）。
我们检索了Cochrane协作抑郁、焦虑和神经症对照试验注册库（CCDANCTR）、Cochrane对照试验中心注册库（CENTRAL）和SPORTDiscus，截至2014年5月，使用了一份关于CFS和运动疗法的自由文本术语综合列表。我们通过世界卫生组织（WHO）国际临床试验注册平台（截至2014年5月）查找未发表或正在进行的试验。我们筛选了检索文章的参考文献列表，并联系该领域的专家以获取更多研究。
涉及原发性诊断为CFS且能够参与运动疗法的成年人的随机对照试验。研究必须将运动疗法与被动对照、心理疗法、适应性节奏疗法或药物疗法进行比较。
两位综述作者独立进行研究选择、偏倚风险评估和数据提取。我们使用平均差（MDs）和标准化平均差（SMDs）合并连续的结局测量指标。我们使用风险比（RRs）合并严重不良反应和退出情况。我们为每个结局计算了总体效应大小及95%置信区间（CIs）。
我们纳入了八项随机对照研究，并在本综述中报告了1518名参与者的数据。三项研究使用疾病控制与预防中心（CDC）1994年的标准诊断CFS个体；五项使用牛津标准。运动疗法持续12至26周。七项研究使用有氧运动疗法的变体，如散步、游泳、骑自行车或跳舞，有氧运动强度从非常低到相当严格不等，而一项研究使用无氧运动。对照组包括被动对照（八项研究；如常规治疗、放松、柔韧性训练）或CBT（两项研究）、认知治疗（一项研究）、支持性倾听（一项研究）、节奏疗法（一项研究）、药物治疗（一项研究）和联合治疗（一项研究）。不同研究的偏倚风险各不相同，但在每项研究中，我们的主要和次要结局测量指标的偏倚风险差异不大。
研究人员在八项试验中比较了运动疗法与“被动”对照，这些试验共纳入971名参与者。七项研究一致表明，运动疗法在治疗结束时可减轻疲劳，尽管使用的疲劳量表评分系统不同：一个11项量表，评分系统为0至11分（MD -6.06，95% CI -6.95至-5.17；一项研究；148名参与者；低质量证据）；同一个11项量表，评分系统为0至33分（MD -2.82，95% CI -4.07至-1.57；三项研究；540名参与者；中等质量证据）；以及一个14项量表，评分系统为0至42分（MD -6.80，95% CI -10.31至-3.28；三项研究；152名参与者；中等质量证据）。两组严重不良反应均罕见（RR 0.99，95% CI 0.14至6.97；一项研究；319名参与者；中等质量证据），但数据稀少，综述作者无法得出结论。研究作者报告运动疗法在治疗结束时对睡眠（MD -1.49，95% CI -2.95至-0.02；两项研究；323名参与者）、身体功能（MD 13.10，95% CI 1.98至24.22；五项研究；725名参与者）和自我感知的整体健康变化（RR 1.83，95% CI 1.39至2.40；四项研究；489名参与者）有积极影响。综述作者无法就其余结局得出结论。
研究人员在两项试验（351名参与者）中比较了运动疗法与CBT。一项试验（298名参与者）报告，使用一个评分系统为0至33分的11项量表时，两组在治疗结束时疲劳程度几乎没有差异（MD 0.20，95% CI -1.49至1.89）。两项研究均测量了随访时的疲劳差异，但使用一个评分系统为0至33分的11项疲劳量表（MD 0.30，95% CI -1.45至2.05）和一个评分系统为1至7分的9项疲劳严重程度量表（MD 0.40，95% CI -0.34至1.14）时，两组均未发现差异。两组严重不良反应均罕见（RR 0.67，95% CI 0.11至3.96）。我们观察到身体功能、抑郁、焦虑和睡眠方面几乎没有差异，并且无法就疼痛、自我感知的整体健康变化、卫生服务资源使用和退出率得出任何结论。
关于其他比较，一项研究（320名参与者）表明运动疗法总体上优于适应性节奏疗法，另一项研究（183名参与者）表明运动疗法优于支持性倾听。现有证据过于稀少，无法就药物干预的效果得出结论。
CFS患者通常可能从运动疗法中获益并感到疲劳减轻，且没有证据表明运动疗法会使结局恶化。已观察到运动疗法对睡眠、身体功能和自我感知的总体健康有积极影响，但无法就疼痛、生活质量、焦虑、抑郁、退出率和卫生服务资源等结局得出结论。运动疗法的有效性似乎大于节奏疗法，但与CBT相似。需要进行偏倚风险低且随机的试验，以研究最有益的运动干预的类型、持续时间和强度。
