Patients’ experiences and effects of non-pharmacological treatment for myalgic encephalomyelitis/chronic fatigue syndrome – a scoping mixed methods review

Figures & data

Table I. The search profile applied in Medline being adapted for the other databases.

Outcome studies: 1 (Fatigue Syndrome, Chronic/or ((CFS adj3 (ME or SEID)) or myalgic encephalo* or chronic fatigue* or fatigue syndrom* or systemic exertion intolerance or PVFS or royal free disease* or akureyri disease or Iceland disease).tw,kf.) and ((randomis* or randomiz* or randomly or trial or intervention? or effect? or impact? or multicenter or multi centre or multicentre or multi centre or controlled or control group? or (before adj5 after) or (pre adj5 post) or ((pre-test or pre test) and (post-test or post test)) or quasiexperiment* or quasi experiment* or evaluat* or time series or time point? or repeated measur*).ti,ab. or ((treatment outcome/and follow up study/) or ((followup or follow up or longitud* or cohort*) and (treatment* or therap* or intervention* or management)).tw,kf. or (treatment* or therap* or intervention* or management).ti.)) 2 Fatigue Syndrome, Chronic/or ((CFS adj3 (ME or SEID)) or myalgic encephalo* or chronic fatigue* or fatigue syndrom* or systemic exertion intolerance or PVFS or royal free disease* or akureyri disease or Iceland disease).tw,kf. 3 limit 2 to (clinical study or clinical trial, all or clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or clinical trial or controlled clinical trial or randomized controlled trial) 4 limit 2 to “therapy (best balance of sensitivity and specificity)” 5 1 or 3 or 4 6 limit 5 to (english language and yr = “2009 -Current”) Qualitative studies about patients’ experiences: (Fatigue Syndrome, Chronic/or ((CFS adj3 (ME or SEID)) or myalgic encephalo* or chronic fatigue* or fatigue syndrom* or systemic exertion intolerance or PVFS or royal free disease* or akureyri disease or Iceland disease).tw,kf.) and ((((“semi-structured” or semistructured or unstructured or informal or “in-depth” or indepth or “face-to-face” or structured or guide) adj3 (interview* or discussion* or questionnaire*)) or (focus group* or qualitative or ethnograph* or ethnological or fieldwork or field work or field stud* or key informant or focus group* or narrat* or phenomenolog* or hermeneutical or ethonurs* or grounded theory)).tw,kf. or interviews as topic/or focus groups/or narration/or qualitative research/) Limited to English language and from January 2009 up till March 2020

Table II. An overview of included papers referring effects of non-pharmacological programmes.

	Aim/research question	Setting for intervention, Diagnostic criteria	Interventions and control	Length of follow-up	Sample characteristics	Primary outcome measures	Statistically significant group differences in primary outcome variable, and effect size if reported
Cognitive behavioural therapy (CBT) for adults:
Janse et al., 2018 Netherlands	To test the efficacy of internet-based CBT (iCBT)	Outpatient specialized clinic CDC-94 criteria †	Protocol-driven- feedback iCBT vs. feedback-on-demand iCBT vs. waiting list	At end of therapy at 6 months	80 patients in each three groups, 145 women. Mean age in groups from 37 to 40 yrs	Checklist Individual Strength fatigue severity subscale	No difference between the two iCBT formats, but both groups better fatigue than controls. 43% in iCBT groups reached normal fatigue and 15% in waiting list control group No serious adverse events
Tummers et al., 2012 Netherlands	To test whether a minimal intervention was effective when delivered in a community-based mental health centre	Community-based mental health centre CDC-94 criteria †	Self-instruction booklet based on CBT and email-contacts once every 2 weeks vs. waiting list	At time of completing intervention and waiting list after 6 months	Guided CBT, n=62, 46 women, mean age 36 yrs, illness duration 6 to 464 months Waiting list, n=61, 50 women, mean age 36 years, illness duration 6 to 625 months	Checklist Individual Strength fatigue severity subscale	Decreased fatigue was found in guided CBT group compared with waiting list controls. Controlled effect size was 0.70. 33% showed clinical reduced fatigue compared to 9% in waiting list control group
Tummers et al., 2010 Netherlands	To examine effectiveness of a stepped care guided self-instruction and CBT compared to usual care	Expert centre of ME/CFS CDC-94 criteria †	Stepped care: Minimal self-instruction booklet followed by 6 months individual face to face CBT vs. waiting list followed by CBT	At completion self-instruction/waiting period. After completing additional CBT or regular CBT	Self-instruction and CBT, n=84, 69 women, mean age 37 yrs Waiting list and regular CBT, n=85, characteristics not reported	Checklist Individual Strength fatigue severity subscale	No statistically significant difference between two groups in fatigue, effect size 1.37 Number of patients reaching clinical significant improvement higher in the stepped care group than the other group
CBT for adolescents:
Nijhof et al., 2012 Netherlands	To compare short-term effectiveness of the FITNET programme with usual care in reduction of fatigue, school absence, and physical dysfunction	Outpatient specialist care CDC-94 criteria †	CBT delivered as 21 modules over internet, with interactions between trained CBT therapists and children and their parents separately first once a week and then each other week vs. usual care controls	At 6 months	CBT group, n=68, usual care n= 67, CBT group, 54 girls, mean age 16 yrs and duration of symptoms 16 yrs Usual care group, 57 girls, mean age 16 yrs and duration of disease 19 yrs.	School attendance in % of normal	School attendance in CBT group increased to 84% vs 51% in usual care group, and 75% reached full school attendance at 6 months vs 16% in usual care group.
Rehabilita-tion:
Nunez et al., 2011 Spain	To compare quality of life of those receiving conventional drugs, group CBT and GET with drug and exercise counselling	Outpatient specialist clinic CDC-94 criteria †	Multidisciplinary rehabilitation with CBT, supervised GET and conventional drugs vs. GET counselling and conventional drugs	3 months therapy assessed 1 year after end of the programme	Rehabilitation, n=60, 53 women, mean age 43 yrs and illness duration 32 months Controls, n=60, 48 women mean age 44 years, illness duration 33 months	Medical Outcomes Study-Short Form-36	No group differences in quality of health, worse bodily pain scores in rehabilitation group than control group
Vos-Vromans et al., 2016 Netherlands	To evaluate the difference in treatment effect between CBT and multidisciplinary rehabilitation (MR)	Rehabilitation centres CDC-94 criteria †	CBT alone (tailored to active or passive patients) vs. Rehabilitation (including CBT and a mix of strategies)	26 and 52 weeks after treatment initiation	CBT, n=60, 47 women, mean age 41 yrs and illness duration mostly ≥ 5 yrs MR, n=62, 50 women, mean age 40, illness duration mostly ≥5 yrs	Checklist Individual Strength fatigue severity subscale	Fatigue improved more in MR than in CBT group After one year the improvement in fatigue score was sustained in MR group, but not in the CBT group.
Activity pacing:
Kos et al., 2015 Belgium	To evaluate effectiveness of activity pacing self-management	Outpatient rehabilitation clinic CDC-94 criteria †	Three individual sessions with either activity-pacing self-management (APS) or relaxation therapy (RT)	At end of therapy at 3 weeks	APS, n= 16 women, mean age 39 yrs RT, n= 17 women, mean age 41 yrs	Canadian Occupational Performance Measure (COPM)	COPM performance and COPM satisfaction scores changed significantly in both group with moderate to high effect size in favour of APS group with 33% and 42% in APS group vs. 14% and none in the RT group.
Pinxsterhuis et al., 2017 Norway	To evaluate the effectiveness of a group-based self-management programme	Primary health care setting CDC-94 criteria † CCD criteria ‡	Self-management educational program vs. treatment as usual (controls)	At 6 months and after 1 year	Self-management, n=71, 67 women, mean age 44 yrs, diagnose for 1-21 yrs Controls n=66, 54 women and diagnosis for 0-17 yrs	SF-36 physical functioning subscale	No group difference in physical functioning after 6 or 12 months

† the Centres for Disease Control and Prevention diagnosis criteria

‡ the Canadian Consensus Criteria for diagnosis

Table III. An overview of included papers of patients’ treatment experiences.

References	Aim/research question	Recruitment methods	Setting	Diagnostic criteria	Research design and analysis	Intervention	Sample characteristics	Findings expressed in the authors’ themes
Broughton et al., 2017 UK	To explore experiences of patients who were completing a treatment at specialist clinics	Convenience sampling	Specialist clinics	Diagnosed- criteria not reported	Semi-structured, individual interviews Thematic analysis	Comprehensive treatment including CBT and GET	14 women. 2 men Age 24 to 62 yrs Illness duration 1 to 17 yrs	Journey to specialist care, Things that hinder treatment Support systems
Cheshire et al., 2020 UK	What are the differences and similarities in treatment perceptions and experiences of guided graded exercise among those reporting improvements compared with those deteriorated?	Strategic sampling according to responses to questionnaires showing much improvements/much deterioration	Specialist clinic	Diagnosed—criteria not reported	Semi-structured, individual interviews Thematic analysis	Guided graded exercise self-help (GES)	17 women, 3 men Age 21 to 66 yrs	Getting started and false starts Indeterminate phase of GES Competing commitments Interfering symptoms and comorbid conditions Maintaining motivation
Chew-Graham et al., 2011 UK	What factors are important for patients to engage in a new intervention?	Purposive sampling from an RCT trial	Primary health care	Diagnosed by Oxford criteria	Semi-structured individual interviews Inductive thematic analysis based on data from those in trial arm	Nurse-led rehabilitation program	13 women, 6 men Age 23 to 61 yrs Illness duration 9 months to 16 yrs	Feeling accepted by therapist Own acceptance of diagnosis Accept of (treatment) model
Dennison et al., 2010 UK	To examine participants’ views and experiences of taking part in family-focused cognitive behavioural therapy	All participants in an RCT around three years earlier were invited	Outpatient clinic at a hospital	Diagnosed—criteria not reported	Semi-structured individual interviews Inductive thematic analysis	Either cognitive behavioural therapy or psycho-education	16 out of 46 invited were interviewed 10 women, 6 men Age 16 to 24 yrs	Pre-therapy ideas and expectations Therapy experiences Perspectives on effectiveness
McDermott et al., 2011 UK	To explore hopes and expectations of patients newly referred to a ME/CFS centre	All referred to the service last five months were invited	Specialist clinic	Diagnosed—criteria not reported	Semi-structured individual interviews Constant comparative analysis	Self-help advice to improve symptoms informed by Lifestyle Management Group Program	20 out of 56 invited were interviewed 17 women, 3 men Age 22 to 60 yrs	Needing a diagnosis In search of guidance and support Engaging with complexity to understand the illness In search of hope for the future
Picariello et al., 2017 UK	To explore the reasons for why some patients engage in treatment more than others, and to assess whether CBT meets patients’ needs	Consecutively recruited if finished or in follow-up after treatment	Specialist clinic	Diagnosed—criteria not reported	Semi-structured individual interviews Inductive thematic analysis	Cognitive behavioural therapy (CBT)	13 out of 32 invited were interviewed 11 women, 2 men Age 18 to 64 yrs	Hopes and expectations Real, not imagined Collaborative therapeutic alliance Motivation and engagement Gain and loss Change
Pinxsterhuis et al., 2015 Norway	To elicit participants’ experiences with a patient education programme and its usefulness	All participants in a patient education, self-management programme were invited	Outpatient clinic at a hospital	Centres for Disease Control and Prevention—1994 criteria and Canadian Consensus Criteria	Focus group interviews immediately and 9 months after the program Thematic analysis	A self-management programme based on envelope and self-efficacy theories	10 out of 33 invited were interviewed 8 women, 2 men Age 32 to 57 yrs Illness duration 2.5 to 20 yrs	Experiences of chaos and insecurity Experiences of understanding, acceptance and coping Mediating factors
Reme et al., 2013 US/UK	To explore the experienes of young people after having undergone Lightening process	Recruited through a website for young people with ME	Members of website forum	Oxford criteria	Semi-structured individual interviews Inductive thematic analysis	Lightening Process	8 females, 1 male Age 14 to 26 yrs Illness duration 2 to 12 yrs	Pretreatment thoughts and expectations Experiences with treatment Perspectives on effectiveness

Figure 1. PRISMA flow chart: the selection of scientific papers for the systematic scoping review.

Janse, A., Worm-Smeitink, M., Bleijenberg, G., Donders, R., & Knoop, H. (2018). Efficacy of web-based cognitive-behavioural therapy for chronic fatigue syndrome: Randomised controlled trial. British Journal of Psychiatry, 212(2), 112–118. https://doi.org/10.1192/bjp.2017.22

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Tummers, M., Knoop, H., van Dam, A., & Bleijenberg, G. (2012). Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: A randomized controlled trial. Psychological Medicine, 42(10), 2205–2215. https://doi.org/10.1017/S0033291712000232

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Tummers, M., Knoop, H., & Bleijenberg, G. (2010). Effectiveness of stepped care for chronic fatigue syndrome: A randomized noninferiority trial. Journal of Consulting and Clinical Psychology, 78(5), 724–731. https://doi.org/10.1037/a0020052

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Nijhof, S. L., Bleijenberg, G., Uiterwaal, C. S., Kimpen, J. L., & van de Putte, E. M. (2012). Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): A randomised controlled trial. The Lancet, 379(9824), 1412–1418. https://doi.org/10.1016/S0140-6736(12)60025-7

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Nunez, M., Fernandez-Sola, J., Nunez, E., Fernandez-Huerta, J. M., Godas-Sieso, T., & Gomez-Gil, E. (2011). Health-related quality of life in patients with chronic fatigue syndrome: Group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clinical Rheumatology, 30(3), 381–389. https://doi.org/10.1007/s10067-010-1677-y

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Vos-Vromans, D. C., Smeets, R. J., Huijnen, I. P., Koke, A. J., Hitters, W. M., Rijnders, L. J., Pont, M., Winkens, B., & Knottnerus, J. A. (2016). Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: A randomized controlled trial. Journal of Internal Medicine, 279(3), 268–282. https://doi.org/10.1111/joim.12402

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Kos, D., van Eupen, I., Meirte, J., Van Cauwenbergh, D., Moorkens, G., Meeus, M., & Nijs, J. (2015). Activity pacing self-management in chronic fatigue syndrome: A randomized controlled trial. American Journal of Occupational Therapy, 69(6905290020), 1–11. https://doi.org/10.5014/ajot.2015.016287

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Pinxsterhuis, I., Sandvik, L., Strand, E. B., Bautz-Holter, E., & Sveen, U. (2017). Effectiveness of a group-based self-management program for people with chronic fatigue syndrome: A randomized controlled trial. Clinical Rehabilitation, 31(1), 93–103. https://doi.org/10.1177/0269215515621362

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Broughton, J., Harris, S., Beasant, L., Crawley, E., & Collin, S. M. (2017). Adult patients’ experiences of NHS specialist services for chronic fatigue syndrome (CFS/ME): A qualitative study in England. BMC Health Services Research, 17(1), 384. https://doi.org/10.1186/s12913-017-2337-6

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Cheshire, A., Ridge, D., Clark, L., & White, P. (2020). Guided graded Exercise Self-help for chronic fatigue syndrome: Patient experiences and perceptions. Disability and Rehabilitation, 42 (3), 368–377.. https://doi.org/10.1080/09638288.2018.1499822

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Chew-Graham, C., Brooks, J., Wearden, A., Dowrick, C., & Peters, S. (2011). Factors influencing engagement of patients in a novel intervention for CFS/ME: A qualitative study. Primary Health Care Research & Development, 12(2), 112–122. https://doi.org/10.1017/S146342361000037X

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Dennison, L., Stanbrook, R., Moss-Morris, R., Yardley, L., & Chalder, T. (2010). Cognitive behavioural therapy and psychoeducation for chronic fatigue syndrome in young people: Reflections from the families’ perspective. British Journal of Health Psychology, 15(1), 167–183. https://doi.org/10.1348/135910709X440034

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McDermott, C., Lynch, J., & Leydon, G. M. (2011). Patients’ hopes and expectations of a specialist chronic fatigue syndrome/ME service: A qualitative study. Family Practice, 28(5), 572–578. https://doi.org/10.1093/fampra/cmr016

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Picariello, F., Ali, S., Foubister, C., & Chalder, T. (2017). ‘It feels sometimes like my house has burnt down, but I can see the sky’: A qualitative study exploring patients’ views of cognitive behavioural therapy for chronic fatigue syndrome. British Journal of Health Psychology, 22(3), 383–413. https://doi.org/10.1111/bjhp.12235

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Pinxsterhuis, I., Strand, E. B., Stormorken, E., & Sveen, U. (2015). From chaos and insecurity to understanding and coping: Experienced benefits of a group-based education programme for people with chronic fatigue syndrome. British Journal of Guidance & Counselling, 43(4), 463–475. https://doi.org/10.1080/03069885.2014.987725

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Reme, S. E., Archer, N., & Chalder, T. (2013). Experiences of young people who have undergone the Lightning Process to treat chronic fatigue syndrome/myalgic encephalomyelitis - a qualitative study. British Journal of Health Psychology, 18(3), 508–525. https://doi.org/10.1111/j.2044-8287.2012.02093.x

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