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》

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》

Effectiveness of Internet-Based Cognitive Behavior Therapy (Fatigue in Teenagers on the Internet) for Adolescents With Chronic Fatigue Syndrome in Routine Clinical Care: Observational Study.

Internet-based cognitive behavior therapy (I-CBT) for adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been shown to be effective in a randomized controlled trial (RCT; Fatigue in Teenagers on the Internet [FITNET]). FITNET can cause a significant reduction in fatigue and disability. We aimed to investigate whether FITNET treatment implemented in routine clinical care (IMP-FITNET) was as effective, using the outcomes of the FITNET RCT as the benchmark. Outcomes of CFS/ME adolescents who started IMP-FITNET between October 2012 and March 2018 as part of routine clinical care were compared to the outcomes in the FITNET RCT. The primary outcome was fatigue severity assessed posttreatment. The secondary outcomes were self-reported physical functioning, school attendance, and recovery rates. Clinically relevant deterioration was assessed posttreatment, and for this outcome, a face-to-face CBT trial was used as the benchmark. The attitude of therapists toward the usability of IMP-FITNET was assessed through semistructured interviews. The number of face-to-face consultations during IMP-FITNET was registered. Of the 384 referred adolescents with CFS/ME, 244 (63.5%) started IMP-FITNET, 84 (21.9%) started face-to-face CBT, and 56 (14.6%) were not eligible for CBT. Posttreatment scores for fatigue severity (mean 26.0, SD 13.8), physical functioning (mean 88.2, SD 15.0), and full school attendance (mean 84.3, SD 26.5) fell within the 95% CIs of the FITNET RCT. Deterioration of fatigue and physical functioning after IMP-FITNET was observed at rates of 1.2% (n=3) and 4.1% (n=10), respectively, which is comparable to a waiting list condition (fatigue: 1.2% vs 5.7%, χ21=3.5, P=.06; physical functioning: 4.1% vs 11.4%, χ21=3.3, P=.07). Moreover, 41 (16.8%) IMP-FITNET patients made use of face-to-face consultations. IMP-FITNET is an effective and safe treatment for adolescents with CFS/ME in routine clinical care.

Albers E ，Nijhof LN ，Berkelbach van der Sprenkel EE ，van de Putte EM ，Nijhof SL ，Knoop H ... -  《JOURNAL OF MEDICAL INTERNET RESEARCH》

Implementing evidence-based practice for patients with chronic fatigue syndrome.

The aim of our study was to explore whether community-based mental health care centres (MHCs) are able to implement and sustain cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) with the help of an implementation manual. We monitored the implementation process and treatment outcome data of three Dutch MHCs that implemented or sustained CBT for CFS, one in the context of a stepped care programme. We compared these data with findings of other treatment studies conducted in the context of CBT for CFS. All three MHCs included at least 40 patients with dropout rates between 15% and 35% from intention-to-treat to second assessment. Effect sizes ranged between 0.88 and 1.76 for changes in fatigue severity and 0.43 and 1.23 for changes in physical functioning. With one exception, these outcomes were within the range of our benchmark. Contrary to original expectations, we provided additional implementation support to the two MHCs new with CBT for CFS. We concluded that our implementation manual does not seem to substitute external support for team leaders and associated professions during initial implementation of CBT for CFS but may have the potential to make this assistance more efficient. Particular attention should be paid to challenges of implementing stepped care for CFS. Implementation of CBT for CFS in community-based MHCs was monitored. External support was provided in addition to an implementation manual during initial implementation of CBT for CFS. Participating MHCs were generally capable of successfully implementing and delivering CBT for CFS. Implementation of low-intensity interventions for CFS might better be postponed until therapists have sufficient experience with conventional CBT for CFS.

Wiborg JF ，Wensing M ，Tummers M ，Knoop H ，Bleijenberg G ... -  《-》

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 ... -  《-》