Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

Abstract

Background: Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date. Methods: RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes. Results: Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C 12 U) and CoQ 10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility. Conclusions: This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.

The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis

“…Thus, one cannot draw conclusions on the effect of applied physiotherapeutic interventions to date for this patient group . The shortage of trials evaluating effectiveness of interventions in ME patients is not specifically related to the physiotherapy field, as it has been seen in pharmacological, psychological and behavioral interventions as well [ 33 , 44 , 84 ].…”

“…Physiotherapists are often involved in the management of ME/CFS patients [ 32 ]. In the last decade, several systematic reviews and meta analyses that included interventions that seem relevant for physiotherapeutic management of adult ME/CFS patients have been published [ 29 , 33 – 46 ]. However, generally, the applied diagnostic criteria were not explicitly accounted for in these reviews.…”

Measures of Fatigue in Patients With Rheumatic Diseases: A Critical Review

“…In RA, the Fatigue VAS very strongly correlated with the MAF at 0.80 and strongly correlated with the SF‐36 VT at 0.71 (n = 7760) . In FMS and in primary SS, the Fatigue VAS correlated strongly with MFI total (general fatigue) at 0.62 and 0.70 but moderately with MFI mental fatigue and reduced motivation (0.32‐0.39), and correlation ranged between moderate and strong for physical fatigue and reduced activity (0.36‐0.67) . In AS (n = 812), the Fatigue VAS correlated with the SF‐36 VT at −0.64 .…”

“…In patients with FMS (n = 78) receiving cognitive‐behavioral therapy (CBT), the subjective fatigue CIS8R improved by a mean (SD) −10.6 (10.7) . In patients with RA who were started on anti–tumor necrosis factor (TNF) therapy (n = 126), the total CIS20R score improved from a median of 85 (IQR ) to a median of 69 (IQR ) over 6 months , whereas in a subset of 59 working‐age patients, CIS20R score improvement was 11.8% at 6 months . In distressed patients with early RA (n = 30), CBT gave a post‐treatment ES of 0.55 for the subjective fatigue CIS8R (0.48 at 6 months) .…”

“…The CIS‐fatigue has been a primary outcome in randomized trials on the effects of CBT in various illness, including CME/CFS .…”