Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

“There is uncertainty regarding the cause of ME/ CFS, whether it is a pathologically discrete syndrome (2, 4), whether ME should be considered a subset of CFS or its own distinct disease (6), and whether symptoms are nonspecific and shared by other disease entities.”

“Trials enrolled predominantly middle-aged women from ME/ CFS specialty clinics; used CFS case definitions, primarily the 1994 CDC (3) or Oxford criteria (56), to determine participant eligibility; had small sample sizes (27 trials had <100 participants); and were conducted in the United States and Western Europe (16).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“3% prevalence of ME/CFS in the United States in 1997, corresponding to more than 1 million adults (12).”

“These included GET involving an exercise plan with structured incremental increases in exercise over time (23, 48, 50, 52, 53), qigong exercise (49, 51), and home orthostatic training (54).”

“846 Annals of Internal Medicine • Vol. 162 No. 12 • 16 June 2015 www.annals.org Downloaded From: http://annals.org/ on 07/21/2018 seling and behavior therapies were associated with fewer harms (low strength of evidence) than medications and GET (insufficient evidence).”

“Additional trials enrolling fewer than 30 participants and with durations less than 12 weeks indicated no statistically significant differences compared with placebo for acyclovir (57) and showed improved 36-item ShortForm Survey (SF-36) scores for physical health and function with rituximab (58).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“Nine placebo-controlled trials of medications evaluated the effectiveness of rintatolimod (21, 27), valganciclovir (28), galantamine (26), hydrocortisone (22), hydrocortisone plus fludrocortisone (24), IgG (20), isoprinosine (25), and fluoxetine (23).”

“One of these 2 trials also reported improvement in measures of function (activities of daily living and Karnofsky Performance Scale score) (21), and the other indicated a reduction in use of other medications to relieve CFS symptoms (27).”

“Some propose that an inciting event initiates an immune response that leads to immune and neuroendocrine dysregulation (10, 11).”

“These therapies were compared with usual care, wait-list control, no treatment, relaxation techniques, adaptive pacing (avoiding activities demanding >70% of a participant's perceived energy), anaerobic therapy that promoted gradual return of pleasurable activities (40, 47, 63, 64), graded exercise therapy (GET) (48),…”

“These therapies were compared with usual care, wait-list control, no treatment, relaxation techniques, adaptive pacing (avoiding activities demanding >70% of a participant's perceived energy), anaerobic therapy that promoted gradual return of pleasurable activities (40, 47, 63, 64), graded exercise therapy (GET) (48),…”

“These included GET involving an exercise plan with structured incremental increases in exercise over time (23, 48, 50, 52, 53), qigong exercise (49, 51), and home orthostatic training (54).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“Participants taking rintatolimod reported flu-like symptoms, chills, vasodilatation, and dyspnea (27).”

“In a small, underpowered trial of valganciclovir that enrolled 30 participants with elevated antibody titers who were suspected of having viral-onset ME/CFS, fatigue was improved in the treatment group compared with the placebo group on the basis of 1 scale, but no statistically significant differences were seen for o…”

“The Oxford CFS case definition is the least restrictive, and its use as entry criteria could have resulted in selection of participants with other fatiguing illnesses or illnesses that resolve spontaneously with time (16, 71).”

“These included GET involving an exercise plan with structured incremental increases in exercise over time (23, 48, 50, 52, 53), qigong exercise (49, 51), and home orthostatic training (54).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“One trial met criteria for good quality (31, 33), 5 for fair quality (29, 32, 34, 35), and 1 for poor quality (30).”

“Harms Patients taking formulations of L-carnitine reported sleeplessness and feeling overstimulated (32).”

“However, no specific virus or other infectious agent has been identified, and not all patients experience a preceding febrile illness (10).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“These included GET involving an exercise plan with structured incremental increases in exercise over time (23, 48, 50, 52, 53), qigong exercise (49, 51), and home orthostatic training (54).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“These therapies were compared with usual care, wait-list control, no treatment, relaxation techniques, adaptive pacing (avoiding activities demanding >70% of a participant's perceived energy), anaerobic therapy that promoted gradual return of pleasurable activities (40, 47, 63, 64), graded exercise therapy (GET) (48),…”

“There is uncertainty regarding the cause of ME/ CFS, whether it is a pathologically discrete syndrome (2, 4), whether ME should be considered a subset of CFS or its own distinct disease (6), and whether symptoms are nonspecific and shared by other disease entities.”

“One trial met criteria for good quality (31, 33), 5 for fair quality (29, 32, 34, 35), and 1 for poor quality (30).”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“The trials were too heterogeneous to allow us to determine whether one type of counseling intervention was more effective than another, and a small trial comparing faceto-face versus telephone CBT indicated no differences between these therapeutic approaches (37).”

“001), but there were no statistically significant differences in serious deterioration measured by a composite score (48, 65).”

“Characteristics of Responders and Nonresponders Four trials suggested that younger patients with less impairment, who are less focused on symptoms, adherent to cognitive therapy programs, and avoid over- and underexertion (that is, they stay within their energy envelope) are more likely to improve in some measures of…”

“In some trials, counseling and behavior therapies improved fatigue (8, 38, 39, 41, 43, 46, 48, 62), physical function (Figure 1) (38, 40, 41, 43, 44, 48), quality of life (42, 45), work impairment (38, 48), and the clinical global impression of change scale (38, 48, 59) (low to moderate strength of evidence).”

“One trial met criteria for good quality (31, 33), 5 for fair quality (29, 32, 34, 35), and 1 for poor quality (30).”

“Some trials were primarily intended to measure intermediate outcomes, such as natural killer cell–mediated cytotoxicity (25), and most were underpowered for the health outcomes relevant to this systematic review.”

“Five trials met criteria for good quality (44–48), 6 for fair quality (36–38, 40, 41, 43), and 3 for poor quality (8, 39, 42).”

“Characteristics of Responders and Nonresponders Four trials suggested that younger patients with less impairment, who are less focused on symptoms, adherent to cognitive therapy programs, and avoid over- and underexertion (that is, they stay within their energy envelope) are more likely to improve in some measures of…”

“One trial met criteria for good quality (31, 33), 5 for fair quality (29, 32, 34, 35), and 1 for poor quality (30).”

“Characteristics of Responders and Nonresponders Four trials suggested that younger patients with less impairment, who are less focused on symptoms, adherent to cognitive therapy programs, and avoid over- and underexertion (that is, they stay within their energy envelope) are more likely to improve in some measures of…”

“One trial met criteria for good quality (31, 33), 5 for fair quality (29, 32, 34, 35), and 1 for poor quality (30).”

“These included GET involving an exercise plan with structured incremental increases in exercise over time (23, 48, 50, 52, 53), qigong exercise (49, 51), and home orthostatic training (54).”

“The Institute of Medicine recently released new diagnostic criteria for CFS that require the presence of postexertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance (7, 72).”

“Galantamine was associated with higher rates of withdrawal and attrition than was placebo, demonstrating a dose-dependent relationship; the highest rates were seen at doses of 15 mg or more per day (26).”

“Abnormal fatigue could correspond to form of chronic fatigue syndrome, in this setting one possible remedy is exercise therapy [30].”

“These studies may be promising; however, no therapeutics that can cure CFS/ME or objective diagnostic methods are available yet [13].”

“Complementary and alternative medicine Nutritional supplements, Acetyl-l-carnitine, Essential fatty acids, Magnesium, Vitamins, Coenzyme Q10 plus Nutritional supplements may improve ME/CFS-related physical and mental fatigue in patients with specific nutritional deficiencies [215].”

“In patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), treatment with the poly-IC12U drug rintatolimod led to an improvement in exercise tolerance and showed dose-sparing effects in a Phase III clinical trial in 2012 [23].”

“Moreover, controlled studies of the antidepressant fluoxetine in people with ME/CFS have demonstrated no benefit [32].”