Is the effect of cognitive behaviour therapy for chronic fatigue syndrome (ME/CFS) moderated by the presence of comorbid depressive symptoms? A meta-analysis of three treatment delivery formats.

Cognitive behaviour therapy (CBT) for fatigue in chronic fatigue syndrome (ME/CFS) leads to a significant reduction of fatigue and disability and is available in different treatment delivery formats, i.e. internet-based, individual face-to-face and group face-to-face. The aim of this study was to investigate whether moderation of the effects of CBT by clinically relevant depressive symptoms varies between CBT delivery formats. Data from six randomised controlled trials (n = 1084 patients) were pooled. Moderation of clinically relevant depressive symptoms (Brief Depression Inventory for Primary Care) in different treatment formats on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests. Differences in percentages of patients no longer severely fatigued post-CBT were studied by calculating relative risks. The moderator effect of depressive symptoms on fatigue severity varied by delivery format. In internet-based CBT, ME/CFS patients with depressive symptoms showed less reduction in fatigue, and were more often still severely fatigued post-treatment than patients without depressive symptoms. In individual and group face-to-face CBT, no significant difference in treatment effect on fatigue severity was found between patients with and without depressive symptoms. No moderation was found for the other outcomes. In internet-based CBT, ME/CFS patients with comorbid depressive symptoms benefit less, making face-to-face CBT currently the first-choice delivery format for these patients. Internet-based CBT should be further developed to improve its effectiveness for ME/CFS patients with depressive symptoms.

Kuut TA ，Buffart LM ，Braamse AMJ ，Müller F ，Knoop H ... -  《-》

Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis.

Kuut TA ，Buffart LM ，Braamse AMJ ，Csorba I ，Bleijenberg G ，Nieuwkerk P ，Moss-Morris R ，Müller F ，Knoop H ... -  《-》

Internet-Based Cognitive Behavioral Therapy in Stepped Care for Chronic Fatigue Syndrome: Randomized Noninferiority Trial.

Internet-based cognitive behavioral therapy (I-CBT) leads to a reduction of fatigue severity and disability in adults with chronic fatigue syndrome (CFS). However, not all patients profit and it remains unclear how I-CBT is best embedded in the care of CFS patients. This study aimed to compare the efficacy of stepped care, using therapist-assisted I-CBT, followed by face-to-face (f2f) cognitive behavioral therapy (CBT) when needed, with f2f CBT (treatment as usual [TAU]) on fatigue severity. The secondary aim was to investigate treatment efficiency. A total of 363 CFS patients were randomized to 1 of the 3 treatment arms (n=121). There were 2 stepped care conditions that differed in the therapists' feedback during I-CBT: prescheduled or on-demand. When still severely fatigued or disabled after I-CBT, the patients were offered f2f CBT. Noninferiority of both stepped care conditions to TAU was tested using analysis of covariance. The primary outcome was fatigue severity (Checklist Individual Strength). Disabilities (Sickness Impact Profile -8), physical functioning (Medical Outcomes Survey Short Form-36), psychological distress (Symptom Checklist-90), and proportion of patients with clinically significant improvement in fatigue were the secondary outcomes. The amount of invested therapist time was compared between stepped care and TAU. Exploratory comparisons were made between the stepped care conditions of invested therapist time and proportion of patients who continued with f2f CBT. Noninferiority was indicated, as the upper boundary of the one-sided 98.75% CI of the difference in the change in fatigue severity between both forms of stepped care and TAU were below the noninferiority margin of 5.2 (4.25 and 3.81, respectively). The between-group differences on the secondary outcomes were also not significant (P=.11 to P=.79). Both stepped care formats required less therapist time than TAU (median 8 hours, 9 minutes and 7 hours, 25 minutes in stepped care vs 12 hours in TAU; P<.001). The difference in therapist time between both stepped care formats was not significant. Approximately half of the patients meeting step-up criteria for f2f CBT after I-CBT did not continue. Stepped care, including I-CBT followed by f2f CBT when indicated, is noninferior to TAU of f2f CBT and requires less therapist time. I-CBT for CFS can be used as a first step in stepped care. Nederlands Trial Register NTR4809; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4809 (Archived by WebCite at http://www.webcitation.org/74SWkw1V5).

Worm-Smeitink M ，Janse A ，van Dam A ，Evers A ，van der Vaart R ，Wensing M ，Knoop H ... -  《JOURNAL OF MEDICAL INTERNET RESEARCH》

Internet-Based Cognitive Behavioral Therapy for Chronic Fatigue Syndrome Integrated in Routine Clinical Care: Implementation Study.

In a clinical trial, internet-based cognitive behavioral therapy (I-CBT) embedded in stepped care was established as noninferior to face-to-face cognitive behavioral therapy (CBT) for chronic fatigue syndrome (CFS). However, treatment effects observed in clinical trials may not necessarily be retained after implementation. This study aimed to investigate whether stepped care for CFS starting with I-CBT, followed by face-to-face CBT, if needed, was also effective in routine clinical care. Another objective was to explore the role of therapists' attitudes toward electronic health (eHealth) and manualized treatment on treatment outcome. I-CBT was implemented in five mental health care centers (MHCs) with nine treatment sites throughout the Netherlands. All patients with CFS were offered I-CBT, followed by face-to-face CBT if still severely fatigued or disabled after I-CBT. Outcomes were the Checklist Individual Strength, physical and social functioning (Short-Form 36), and limitations in daily functioning according to the Work and Social Adjustment Scale. The change scores (pre to post stepped care) were compared with a benchmark: stepped care from a randomized controlled trial (RCT) testing this treatment format. We calculated correlations of therapists' attitudes toward manualized treatment and eHealth with reduction of fatigue severity. Overall, 100 CFS patients were referred to the centers. Of them, 79 started with I-CBT, 20 commenced directly with face-to-face CBT, and one did not start at all. After I-CBT, 48 patients met step-up criteria; of them, 11 stepped up to face-to-face CBT. Increase in physical functioning (score of 13.4), social functioning (20.4), and reduction of limitations (10.3) after stepped care delivered in routine clinical care fell within the benchmarks of the RCT (95% CIs: 12.8-17.6; 25.2-7.8; and 7.4-9.8, respectively). Reduction of fatigue severity in the MHCs was smaller (12.6) than in the RCT (95% CI 13.2-16.5). After I-CBT only, reduction of fatigue severity (13.2) fell within the benchmark of I-CBT alone (95% CI 11.1-14.2). Twenty therapists treated between one and 18 patients. Therapists were divided into two groups: one with the largest median reduction of fatigue and one with the smallest. Patients treated by the first group had a significantly larger reduction of fatigue severity (15.7 vs 9.0; t=2.42; P=.02). There were no (statistically significant) correlations between therapists' attitudes and reduction in fatigue. This study is one of the first to evaluate stepped care with I-CBT as a first step in routine clinical care. Although fatigue severity and disabilities were reduced, reduction of fatigue severity appeared smaller than in the clinical trial. Further development of the treatment should aim at avoiding dropout and encouraging stepping up after I-CBT with limited results. Median reduction of fatigue severity varied largely between therapists. Further research will help understand the role of therapists' attitudes in treatment outcome.

Worm-Smeitink M ，van Dam A ，van Es S ，van der Vaart R ，Evers A ，Wensing M ，Knoop H ... -  《JOURNAL OF MEDICAL INTERNET RESEARCH》

Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a random

Baos S ，Brigden A ，Anderson E ，Hollingworth W ，Price S ，Mills N ，Beasant L ，Gaunt D ，Garfield K ，Metcalfe C ，Parslow R ，Downing H ，Kessler D ，Macleod J ，Stallard P ，Knoop H ，Van de Putte E ，Nijhof S ，Bleijenberg G ，Crawley E ... -  《Trials》