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Efficacy of web-based cognitive–behavioural therapy for chronic fatigue syndrome: randomised controlled trial

  • A. Janse (a1), M. Worm-Smeitink (a1), G. Bleijenberg (a2), R. Donders (a3) and H. Knoop (a1)...

Face-to-face cognitive–behavioural therapy (CBT) leads to a reduction of fatigue in chronic fatigue syndrome (CFS).


To test the efficacy of internet-based CBT (iCBT) for adults with CFS.


A total of 240 patients with CFS were randomised to either iCBT with protocol-driven therapist feedback or with therapist feedback on demand, or a waiting list. Primary outcome was fatigue severity assessed with the Checklist Individual Strength (Netherlands Trial Register: NTR4013).


Compared with a waiting list, intention-to-treat (ITT) analysis showed a significant reduction of fatigue for both iCBT conditions (protocol-driven feedback: B = −8.3, 97.5% CI −12.7 to −3.9, P < 0.0001; feedback on demand: B = −7.2, 97.5% CI −11.3 to –3.1, P < 0.0001). No significant differences were found between both iCBT conditions on all outcome measures (P = 0.3–0.9). An exploratory analysis revealed that feedback-on-demand iCBT required less therapist time (mean 4 h 37 min) than iCBT with protocol-driven feedback (mean 6 h 9 min, P < 0.001) and also less than face-to-face CBT as reported in the literature.


Both iCBT conditions are efficacious and time efficient.

Declaration of interest


Corresponding author
Correspondence: H. Knoop, Academic Medical Center (AMC), University of Amsterdam, Department of Medical Psychology, Amsterdam Public Health Research Institute, P.O. Box 22660, 1100DD Amsterdam, the Netherlands. Email:
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Efficacy of web-based cognitive–behavioural therapy for chronic fatigue syndrome: randomised controlled trial

  • A. Janse (a1), M. Worm-Smeitink (a1), G. Bleijenberg (a2), R. Donders (a3) and H. Knoop (a1)...
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Cognitive Behavorial Therapy for Chronic Fatigue Syndrome: neither efficacious nor save

Frank Twisk, Researcher, ME-de-patiënten Foundation
Lou Corsius, Researcher
08 March 2018

Janse et al. (1) investigated the effect of two variants of cognitive-behavioural therapy through the internet (iCBT) in Chronic Fatigue Syndrome (CFS): iCBT with protocol-driven feedback (iCBT FP) and iCBT with feedback on demand (iCBT FD).

Beforehand it should be acknowledged that CBT trials into CFS suffer from a high preselection bias, i.e. self-selection, since, according to two of the authors in another study (2), patients seem to be sceptical about psychological interventions.

According to the study (1) large subgroups (iCBT FP: 31%, iCBT FD: 29%) reported “clinically relevant depressive symptoms”, while depression and other psychological conditions which could explain “chronic fatigue” exclude the diagnosis CFS (2). It is feasible that many patients who improved suffered from depression, not from CFS.

Comparing the number of patients working full-time in this study (1) and other studies, e.g. (3), the CFS (2) (?) patients can be qualified as ‘mild cases’. Since CFS is a heterogeneous condition, the results of this study (1) cannot be generalized to CFS.

Dropout-rates are not reported, while the authors assume a dropout-rate of 15% (1) and other studies by the same group reported even higher drop-out rates (2).

“A substantial number of patients did not fully adhere to the interventions.” Besides one could question whether accessing treatment modules and email contact are ‘strict criteria’ to guarantee adherence to the graded activity protocol. While the authors state that “The treatment is tailored to a patient’s current activity pattern as assessed with actigraphy”, (increased) activity levels were not included in the adherence criteria.

According to the authors, both iCBT conditions are efficacious, since 29/80 (36%) in the iCBT FP and 34/80 (43%) in the iCBT FD achieved the ‘normal range’ for CIS F fatigue, compared to 12/80 (15%) in the waiting list (WL) group (1). However, the treatment effects of iCBT FP and iCBT FD in the study are by far insufficient to achieve ‘normal levels of fatigue’ (CIS F ≤27) as defined in another study of two of the authors (2). Looking at the SIP 8 and SF-36 physical functioning scores after intervention at the group level (scores at the individual level are not reported), both iCBT groups would still be qualified as “severely disabled”.

The effect of iCBT FP and iCBT FD on objective measures are not reported, but other studies by the research group showed that the CBT protocol has no effect on the (low) physical activity levels, number of hours worked or cognitive test scores (2).

The authors label their intervention CBT (1). However looking at the protocol, the intervention investigated not only incorporated CBT, aimed at “behaviours and beliefs” perpetuating “fatigue and impairment”, but also implied a graded activity program, often qualified as Graded Exercise Therapy (GET). Several large-scale patient surveys and studies, e.g. (4), implicate that CBT, especially when combined with GET, can cause iatrogenic harm and is not safe (5).

In conclusion, the study does not substantiate the claim that iCBT/GET for CFS is efficacious, while there are several indications CBT/GET is not a safe therapy.

1. Janse A, Worm-Smeitink M, Bleijenberg G, et al. Efficacy of web-based cognitive -behavioural therapy for chronic fatigue syndrome: randomised controlled trial. Br J Psychiatry 2018; 213: 112-118. doi: 10.1192/bjp.2017.22.

2. Twisk FNM, Corsius LAMM. An analysis of Dutch hallmark studies confirms the outcome of the PACE trial: cognitive behaviour therapy with a graded activity protocol is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis. Gen Med Open 2017; 1: 1-13 doi: 10.15761/GMO.1000117.

3. Sunnquist M, Jason LA, Nehrke P, et al. A comparison of case definitions for Myalgic Encephalomyelitis and chronic fatigue syndrome. J Chronic Dis Manag 2017; 2: 1013. PMID: 29104961.

4. Cheshire A, Ridge D, Clark L, et al. Why patients with chronic fatigue syndrome/Myalgic Encephalomyelitis improve or deteriorate with graded exercise therapy. J Psychosom Res 2016; 85: 59. doi: 10.1016/j.jpsychores.2016.03.146.

5. Twisk F. Studies and surveys implicate potential iatrogenic harm of cognitive behavioral therapy and graded exercise therapy for myalgic encephalomyelitis and chronic fatigue syndrome patients. Res Chronic Dis 2017; 1: 13-14.

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Conflict of interest: None declared

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