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. 2021 Nov 9;16(11):e0259533. doi: 10.1371/journal.pone.0259533

Table 1. Overview of studies selected for review.

Lead author (Year) Title Intervention groups (n) Participants Setting Study design Intervention duration MMAT Quality Score
Age: Mean (SD)
(A-Z)
Sex: Female / Male (%)
Clark (2017) Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial SMC (102) 38.4 (11.9) years Secondary care / Specialist clinic Open-label, pragmatic RCT 8 weeks 5
GET & SMC (97)
79% / 21%
Dailey (2013) Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia No TENS (41) 49.2 (12) years Not stated Randomised, placebo-controlled cross-over 3 weeks 5
Active TENS (41) 98% / 2%
Placebo TENS (41)
Demirbag (2012) The effects of sleep and touch therapy on symptoms of fibromyalgia and depression Control (54) 42.5 (11.8) years Community / Clinic Randomised comparison study with control 6 weeks 3
TMA (54)
SMA (54) 110% / 0%
El Mokadem (2020) Three principles/innate health: The efficacy of psycho-spiritual mental health education for people with chronic fatigue syndrome Waiting list (11) 42.9 (10.5) (range: 19–66) years Not stated Randomised trial with waitlist control 8 weeks 4
Three Principles/Innate Health (11)
86% / 14%
Ericsson (2016) Resistance exercise improves physical fatigue in women with fibromyalgia: a randomized controlled trial Relaxation (63) 51.4 (9.4) years Community / Clinic Multicentre RCT 15 weeks 3
Group-based GET (67) 100% / 0%
Fernie (2016) Treatment Outcome and Metacognitive Change in CBT and GET for Chronic Fatigue Syndrome CBT (116) 40.8 (12.5) (range: 18–75) years Secondary care / outpatient Comparison of CBT & GET in practice 4 months 3
GET (55)
Fitzgibbon (2018) Evidence for the improvement of fatigue in fibromyalgia: a 4-week left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation randomized-controlled trial Sham rTMS (12) 45.6 (12.8) years Secondary care / Lab-based Randomised, double-blind placebo controlled 4 weeks 5
rTMS (14)
92% / 8%
Friedberg (2016) Efficacy of two delivery modes of behavioural self-management in severe chronic fatigue syndrome SMC (46) 48.4 (11.5) years Primary care / home-based Randomised comparison 3 months 4
Self-management & web diaries (39)
88% / 12%
Self-management & paper diaries (39)
Hansen (2013) Heart rate variability and fatigue in patients with chronic fatigue syndrome after a comprehensive cognitive behaviour group therapy program Healthy controls (21) 41.6 (range: 29–67) years Not stated Comparison (healthy controls vs. CFS patients) 4 days 4
CBT / GET / Group therapy (19) 100% / 0%
Heald (2019) Service based comparison of group cognitive behaviour therapy to waiting list control for chronic fatigue syndrome with regard to symptom reduction and positive psychological dimensions Waiting list (28) 43.1 (13.2) years Primary care / specialist clinic Repeated measures–individuals act as own control 8 weeks 4
Group CBT (28)
61% / 39%
Jason (2010) Provision of social support to individuals with chronic fatigue syndrome Waiting list (15) 57.6 (13) years Primary care / home-based Randomised trial with waitlist control 4 months 4
Social support (15) 83% / 17%
Keijmel (2017) Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): a Randomized Controlled Trial Placebo (52) 43.8 (12.1) years Secondary care / Lab-based RCT 24 weeks 4
Doxycycline (52)
CBT (50) 48% / 52%
Kim (2013) Indirect moxibustion (CV4 and CV8) ameliorates chronic fatigue: a randomized, double-blind, controlled study Sham Moxibustion (20) Median: 44 (range: 32–63) years Lab-based Double-blinded RCT 4 weeks 4
Moxibustion (25) 78% / 22%
Kim (2015) Acupuncture for chronic fatigue syndrome and idiopathic chronic fatigue: a multicenter, nonblinded, randomized controlled trial SMC (50) 42.2 (11.7) years Secondary care RCT 4 weeks 4
Acupuncture & SMC (49)
65% / 35%
Sa-am Acupuncture & SMC (51)
Lee (2015) The effect of oriental medicine music therapy on idiopathic chronic fatigue Waiting list (15) 44.9 (12.4) years Secondary care / outpatient Randomised trial with waitlist control 2 weeks 4
Oriental medicine music therapy (15)
90% / 10%
Maddali (2016) Efficacy of rehabilitation with Tai Ji Quan in an Italian cohort of patients with Fibromyalgia Syndrome Educational course (22) 52.2 (12.2) years Primary care / home-based Randomised comparison 16 weeks 4
Tai Ji Quan (22)
Marques (2015) Effects of a Self-regulation Based Physical Activity Program (The ’4-STEPS’) for Unexplained Chronic Fatigue: a Randomized Controlled Trial SMC (46) 48.1 (11) years Community / home-based Multicentre RCT 12 weeks 3
Self-regulation Based Physical Activity (45) 98% / 2%
Marques (2017) Efficacy of a randomized controlled self-regulation based physical activity intervention for chronic fatigue: mediation effects of physical activity progress and self-regulation skills SMC (46) 48.1 (11) years Primary care / home-based Multicentre RCT 12 weeks 3
Self-regulation Based Physical Activity (45) 98% / 2%
Mist (2018) Randomized Controlled Trial of Acupuncture for Women with Fibromyalgia: group Acupuncture with Traditional Chinese Medicine Diagnosis-Based Point Selection Group Education (14) 54 (12.4) years Community / Specialist clinic Random allocation / repeated measures 10 weeks 4
100% / 0%
Group Acupuncture (16)
Ng (2013) Acupuncture for chronic fatigue syndrome: a randomized, sham-controlled trial with single-blinded design Sham Acupuncture (49) 40.9 (6.6) years Lab-based Single-blinded RCT 4 weeks 3
69% / 31%
Acupuncture (50)
O’Dowd (2006) Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme SMC (51) 41.1 (11.9) years Secondary care / outpatient Double-blind RCT 16 weeks 4
CBT (52)
GET (50) 66% / 33%
Oka (2014) Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial Pharma (15) 38.6 (12.6) years Community / Clinic RCT 2 months 4
Yoga & Pharma (15)
80% / 20%
Perrin (2011) Muscle fatigue in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and its response to a manual therapeutic approach: A pilot study Healthy controls (9) 35.8 (range: 20–55) years Lab-based Comparison–osteopathy vs self-selected treatment vs healthy control 12 months 3
Osteopathic treatment (9)
Any treatment (9) 44% / 56%
Powell (2004) Patient education to encourage graded exercise in chronic fatigue syndrome: 2-year follow-up of randomised controlled trial SMC (34) 33.2 (10.3) years Outpatient / home-based RCT 12 months 3
GET:
Min. intervention (37) 75% / 25%
Telephone intervention (39)
Max. intervention (33)
Racine (2019) Operant Learning Versus Energy Conservation Activity Pacing Treatments in a Sample of Patients With Fibromyalgia Syndrome: a Pilot Randomized Controlled Trial Control (43) No details Community / Clinic RCT 10 weeks 3
Operant learning (17)
Energy conservation activity pacing (24)
Raijmakers (2019) Long-term effect of cognitive behavioural therapy and doxycycline treatment for patients with Q fever fatigue syndrome: One-year follow-up of the Qure study Placebo (52) 43.8 (12.1) years Secondary care / outpatient RCT 24 weeks 4
Doxycycline (52)
CBT (50) 48% / 52%
Ridsdale (2012) The effect of counselling, graded exercise and usual care for people with chronic fatigue in primary care: a randomized trial SMC & CBT booklet (75) 39.8 (range: 34–46) years Primary care / home-based RCT 12 months 5
GET (71) 78% / 22%
Counselling (76)
Sharpe (2015) Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial SMC (115) 38 (12) years Primary care / Community Multicentre randomised trial 6 months 3
APT & SMC (120) 77% / 23%
CBT & SMC (119)
GET & SMC (127)
Shu (2016) Acupuncture and Moxibustion have Different Effects on Fatigue by Regulating the Autonomic Nervous System: a Pilot Controlled Clinical Trial Healthy controls (15) 37.1 (14.3) years Lab-based RCT 3 weeks 3
Acupuncture (15) 73% / 27%
Moxibustion (15)
Stubhaug (2008) Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial Placebo (24) 46.32 (8.75) years Not stated RCT 24 weeks 4
Mirtazapine (25)
CBT (23) 82% / 18%
Tummers (2010) Effectiveness of stepped care for chronic fatigue syndrome: a randomized noninferiority trial SMC (85) 38.1 (10.3) years Outpatient / home-based Randomised non-inferiority study 6 months 2
Self-instruction & CBT (84)
79% / 21%
UÄŸurlu (2017) The effects of acupuncture versus sham acupuncture in the treatment of fibromyalgia: a randomized controlled clinical trial Sham Acupuncture (25) 45.4 (8.2) years Community / Specialist clinic RCT 5 weeks 4
100% / 0%
Acupuncture (25)
Van Hoof (2003) Hyperbaric Therapy in Chronic Fatigue Syndrome HBOT: 42 (13) years Lab-based Randomised sampling 1 week 5
Healthy controls (13) 66% / 34%
Infection (13)
Vos-Vromans (2016) Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial CBT (60) 40.3 (11.1) years Community Multicentre RCT 10 weeks 3
Multidisciplinary rehabilitation treatment (62)
80% / 20%
Wearden (2010) Nurse led, home-based self-help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial SMC (100) 44.6 (11.4) years Primary care / home-based Single-blind RCT 18 weeks 4
Pragmatic rehab (95) 78% / 22%
Supportive listening (101)
Weatherley-Jones (2004) A randomized, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome Placebo (50) 38.9 (10.8) years Community / Clinic Triple-blind RCT 6 months 4
Homeopathic medication (53)
59% / 41%
White (2011) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial SMC (160) 38 (12) years Secondary care Multicentre randomised trial 24 weeks 4
APT & SMC (159) 77% / 23%
CBT & SMC (161)
GET & SMC (160)
Wiborg (2015) Randomised controlled trial of cognitive behaviour therapy delivered in groups of patients with chronic fatigue syndrome Waiting list (68) 37.9 (11.3) years Secondary care / outpatient RCT 6 months 5
CBT:
Large group (68)
Small group (68) 77% / 23%
Windhorst (2017) Heart rate variability biofeedback therapy and graded exercise training in management of chronic fatigue syndrome: an exploratory pilot study Biofeedback (13) 50.7 (9.3) years Secondary care / outpatient Randomised study 8 weeks 5
GET (11) 100% / 0%
Wu (2020) Observation on therapeutic efficacy of tuina plus cupping for chronic fatigue syndrome Ginseng lozenges (50) 40.1 (5.1) years Community / Specialist clinic RCT 16 weeks 4
63% / 37%
Tuina & Cupping (50)

Cognitive behavioural therapy (CBT); Chronic Fatigue Syndrome (CFS); Graded Exercise Therapy (GET); Randomised controlled trial (RCT); Adaptive Pacing Therapy (APT); Standard Medical Care (SMC); Transcutaneous electrical nerve stimulation (TENS); Hyperbaric oxygen therapy (HBOT); Touch, Music & Aroma (TMA); Sleep, Music & Aroma (SMA); Repetitive transcranial magnetic stimulation (rTMS); Standard deviation (SD).