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Neurology and Psychiatry

Cite as: Archiv EuroMedica. 2026. 16; 4. DOI 10.35630/2026/16/Iss.4.19

Received 07 July 2026;
Accepted 06 August 2026;
Published 10 August 2026

EFFECTIVENESS OF THERAPEUTIC INTERVENTIONS FOR CHRONIC FATIGUE SYNDROME: A NARRATIVE REVIEW

Małgorzata Lubowiecka¹ , Zuzanna Lecyk¹ ,
Agata Leszek¹ , Anna Szeszko² ,
Magdalena Cichorzewska² , Weronika Czernek² ,
Michał Stermach³

¹ 4th Military Clinical Hospital with Polyclinic in Wrocław, Poland
² University Clinical Hospital No. 2 of the Medical University of Łódź, Poland
³ Medical University of Warsaw, Poland

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  malgorzatamlubowiecka@gmail.com

ABSTRACT

Background

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a heterogeneous disorder characterized by persistent fatigue, post-exertional malaise, unrefreshing sleep, pain, cognitive symptoms, and impaired daily functioning. Diagnosis is based on clinical criteria and exclusion of other diseases, while reliable biomarkers and standard treatment are lacking.

Aims

This narrative review aimed to summarize the reported effects of cognitive behavioral therapy, exercise-based interventions, nutritional supplementation, rituximab, and rintatolimod in patients with CFS.

Materials and Methods

A structured narrative literature search was performed in PubMed and Google Scholar. ResearchGate was used only to retrieve full-text articles. The search was conducted in June 2026 and covered publications from 2001 to 2025. Of 132 identified publications, 54 were included. Because the studies differed in design, diagnostic criteria, interventions, follow-up duration, and outcome measures, the evidence was synthesized qualitatively.

Results

Cognitive behavioral therapy appeared to show the most consistent beneficial effects, mainly on fatigue and physical functioning, although complete recovery was uncommon. Exercise-based interventions produced mixed results; self-paced aquatic exercise programs were better tolerated, whereas graded exercise did not consistently outperform comparator interventions and was associated with symptom worsening in some patients. Nutritional interventions showed heterogeneous findings, with reported benefits mainly for CoQ10 plus NADH, selenium, creatine, and combined nutraceutical therapy. Rituximab did not show efficacy in a phase III randomized trial. Rintatolimod showed promising effects on exercise tolerance, but further confirmation is required.

Conclusions

Cognitive behavioral therapy may help reduce symptoms and improve functioning in selected patients with CFS, but it should not be presented as curative. Exercise programs should be individualized and adapted to the risk of post-exertional malaise. Nutritional supplementation may have an adjunctive role, but evidence remains heterogeneous. Rituximab cannot be recommended for routine use, while rintatolimod remains investigational. Future studies should clarify which patient subgroups may benefit from specific interventions.

Keywords: chronic fatigue syndrome; myalgic encephalomyelitis; cognitive behavioral therapy; graded exercise therapy; nutritional supplementation; rituximab; rintatolimod; narrative review.

INTRODUCTION

Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a broad term used to describe a condition characterized by persistent, chronic fatigue lasting more than 4–6 months. This fatigue is mainly characterized by an increasing need for sleep that fails to provide rest and cannot be explained by other causes [1–7]. Additionally, patients experience musculoskeletal pain, headaches, mood disturbances, orthostatic intolerance, and cognitive dysfunction, including difficulties with concentration and short-term memory [1–5].

Over the past years, millions of people worldwide have reported daytime fatigue despite proper sleep hygiene [1, 3, 7]. This condition most commonly affects individuals of working age, between 18 and 64 years [7]. The incidence of CFS has significantly increased due to the COVID-19 pandemic, making the disorder a broader clinical problem that requires updated diagnostic criteria and a better understanding of its clinical presentation [1, 3, 8]. Some studies suggest that a considerable proportion of patients with persistent post-COVID symptoms meet the diagnostic criteria for ME/CFS, although the reported prevalence varies between studies [2, 9, 10].

The etiology of this condition remains unclear; however, some sources indicate a significant role of viral infections in its pathogenesis [1, 2]. Numerous studies have concluded that CFS is a complex neuroimmunological disease involving multiple systems [7]. Recent findings have demonstrated elevated cytokine levels, particularly TGF-β, and changes in the gut microbiome in patients with CFS [7].

The main symptom of CFS is profound fatigue, occurring even after minimal exertion and not alleviated by rest [2, 11, 12]. This state is referred to as post-exertional malaise (PEM) [7, 11, 12]. As a result, patients become less productive, and the increasing fatigue throughout the day severely limits their activity and lowers their quality of life [2, 3, 7, 12, 13]. In more severe cases, symptoms may significantly restrict patients' daily social and occupational functioning [7, 10, 12].

Diagnosis is primarily symptomatic and involves the exclusion of other conditions, which prolongs the time to diagnosis and exposes patients to considerable psychological and financial burden [2–4]. Consequently, as many as 91% of patients with symptoms fail to receive a diagnosis [8]. Diagnostic criteria that aid in confirming CFS include the Fukuda criteria, which are the most commonly cited in research studies [4]. Recognition of CFS remains a particularly challenging task due to the lack of reliable diagnostic markers that unequivocally confirm the disease and determine patient status [1, 7]. Although there are certain similarities with fibromyalgia, such as increased pain after exertion, CFS is a distinct disease entity; thus, fibromyalgia should be considered in the differential diagnosis [1, 3, 14].

Treatment focuses mainly on minimizing symptoms, and complete recovery is often impossible [2, 3, 7, 13, 15]. There are no effective pharmacological methods that constitute a gold-standard therapy, and as a result, many diagnosed patients receive suboptimal treatment [3, 7, 16]. Recently, trials using rituximab and rintatolimod have been conducted [7, 17]. Non-pharmacological methods used in therapy can be easily self-administered, such as a healthy diet, cognitive behavioral therapy (CBT), and graded exercise therapy (GET) [2, 3, 6, 7, 12, 13, 16, 17, 18, 19]. However, the effectiveness of these therapeutic approaches has become controversial and remains debated among clinicians [7, 8, 12, 15, 16, 18–22]. Although some studies have shown clinical benefits, the 2021 update of the British National Institute for Health and Care Excellence (NICE) guidelines questioned the quality of some available evidence [16, 21, 23]. As a result, the role of these interventions in CFS treatment remains inconclusive [7, 8, 12, 15, 16, 18–23].

Many different treatment approaches for CFS have been investigated in recent years. However, the available studies have often reported conflicting findings, making it difficult to determine which interventions are truly effective in clinical practice. This has contributed to ongoing debate regarding the management of patients with CFS.

Aims

This narrative review aimed to summarize and critically discuss the available evidence on pharmacological and non-pharmacological interventions used in the treatment of chronic fatigue syndrome, with particular attention to cognitive behavioral therapy, exercise-based interventions, nutritional supplementation, rituximab, and rintatolimod.

Objectives

The specific objectives were to evaluate reported effects of cognitive behavioral therapy and internet-based cognitive behavioral therapy on fatigue, physical functioning, and related clinical outcomes; to summarize the evidence on exercise-based interventions, including graded exercise therapy and self-paced aquatic exercise programs; to assess reported effects of nutritional supplementation on fatigue, sleep, quality of life, and safety; to review available clinical data on rituximab and rintatolimod; and to discuss the limitations of the available evidence and the potential role of individualized treatment strategies.

METHODOLOGY

This study was conducted as a narrative review with a structured literature search to examine the effectiveness of treatment methods for chronic fatigue syndrome. An exhaustive search of electronic databases was conducted to identify prominent studies on treatment strategies for CFS, including PubMed, Google Scholar, and ResearchGate, with the latter source used exclusively to retrieve full texts.

The search was performed in June 2026 and limited to studies published between 2001 and 2025. The search terms used were: ("chronic fatigue syndrome" OR "CFS" OR "myalgic encephalomyelitis") AND ("cognitive behavioral therapy" OR "graded exercise therapy" OR "exercise-based interventions") AND ("nutritional therapy" OR "CoQ10 + NADH" OR "combined nutraceutical therapy" OR "biological therapeutics" OR "rintatolimod" OR "rituximab").

Works were eligible for inclusion if they comprised randomized controlled trials, non-randomized clinical trials, observational studies, cohort studies, case-control analyses, systematic reviews, qualitative research or questionnaire-based studies; involved patients with chronic fatigue syndrome, suffering from unrefreshing sleep, musculoskeletal pain, cognitive difficulties, or post-exertional malaise; evaluated therapeutic interventions such as cognitive-behavioral therapy, exercise-based treatment, nutritional supplementation, or biological therapy; and reported clinically relevant outcomes, including fatigue reduction, increased exercise tolerance, sleep quality, subjective well-being or treatment safety. Only studies published in English and available in full text were considered for inclusion.

Studies were excluded if they focused solely on mechanisms, diagnostic tools or biomarkers without clinical outcomes, as the aim was to assess therapeutic effectiveness rather than pathophysiology alone. Papers centered exclusively on fatigue secondary to other medical conditions, without a CFS diagnosis, were also excluded. In addition, conference abstracts, letters, or editorials were not considered due to lack of adequate methodological background.

Study selection was based on titles and abstracts, followed by full-text evaluation. Of the 132 publications identified, only 54 were included in the review following a stepwise screening process. Interpreting the evidence required caution because the included studies differed substantially in sample size, disease duration, participant characteristics, diagnostic criteria, treatment protocols, dosages, and follow-up periods. Different studies also used varying definitions of treatment response and assessment tools, limiting direct comparability between interventions. For this reason, the findings were synthesized qualitatively rather than quantitatively.

RESULTS

Nutritional Interventions and Dietary Factors

In studies investigating dietary factors relevant to CFS, a total of 327 patients, with a mean age of 43.3 years, were analyzed [24–30]. Sex distribution was reported in six studies, in which women constituted 93.4% of participants [24, 26–30]. At least one dietary supplement was used by 87.5% of patients; multivitamins were the most common (70.8%), and 66.7% simultaneously used 4–10 supplements [24].

In five studies that demonstrated significant improvement in fatigue following nutritional interventions, including two CoQ10 + NADH trials, CoQ10 + selenium, creatine supplementation, and combination nutraceutical therapy, a total of 265 patients were assessed (p < 0.001 to p = 0.038) [25, 26, 28–30]. Notably, three studies involving 192 patients reported significant improvements in sleep following CoQ10 + NADH, antioxidant supplementation, and combination nutraceutical therapy, as measured by the Pittsburgh Sleep Quality Index (PSQI), FibroFatigue Scale (FFS), and Insomnia Severity Index (ISI) questionnaires (p = 0.008–0.018) [25, 27, 28]. However, in one study involving 27 patients receiving CoQ10 + selenium, no effect on sleep was observed (p = 0.480) [26].

Analyses using the 36-Item Short Form Health Survey (SF-36) in two studies on CoQ10 supplementation involving a total of 171 patients indicated significant improvements in quality of life (QoL) in the domains of physical functioning, bodily pain, emotional role functioning, mental health, and overall SF-36 score (p = 0.001–0.048) [25, 26]. Conversely, two studies involving 46 patients, using questionnaires such as the Health-Related Quality of Life (HRQoL) and the 12-Item Short Form Survey (SF-12), found no improvement in QoL (p > 0.05) among those receiving multivitamin-mineral supplementation and combination nutraceutical therapy [27, 28].

A cross-sectional study of patients with CFS demonstrated characteristically higher consumption of nutrients found in fruits and vegetables, yogurts, eggs, poultry, herbal teas, gluten-free products, and water [24]. Higher General Health scores were associated with vitamin C supplementation and higher calcium intake, while herbal supplements were associated with lower Physical Role Limitations scores [24]. In contrast, consumption of evening primrose oil was associated with greater Physical Role Limitations [24]. At the same time, higher intake of omega-3 fatty acids was linked to worse Bodily Pain scores, and alpha-linolenic acid and iodine to poorer General Health outcomes [24].

No adverse events associated with CoQ10 + NADH or antioxidant supplementation were reported in studies involving 255 patients [25, 27, 29]. In studies involving 21 patients receiving creatine and combination nutraceutical therapy, mild side effects included gastritis, headache/migraine, loss of appetite, tachycardia, skin discoloration, weight gain, nausea/vomiting, and sleep disturbances; however, no participant discontinued treatment because of adverse events [28, 30].

The main characteristics of the nutritional interventions evaluated in the included studies, together with the assessed outcomes, principal findings, and reported adverse effects, are summarized in Table 1.

Clinical Outcomes of Cognitive Behavioral Therapy

Five studies reported overall clinical improvement after CBT, with the proportion of improved patients ranging from 38.7% to 87.0% and an overall estimate of 75.6% [31–35]. In three studies with statistically significant improvement, 85.6% of patients experienced clinical benefit [31–33]. Additional outcomes also supported a positive effect of CBT: 33% of participants reported subjective global improvement, 54.5% met predefined criteria for effective treatment, and 89.3% were satisfied with therapy [33, 37]. However, recovery was uncommon, occurring in only 7 to 8% of patients compared with 3% in the control group, and this difference was not statistically significant [36].

Regarding fatigue improvement, data from five studies indicate that 54.0% (approximately 669/1239) of patients reported improvement, with percentages ranging from 26.0–75.5% across studies [31, 35, 36, 38, 39, 40, 41]. Based on five studies, a significant reduction in fatigue was reported by about 55.4% of patients (659/1188), with a range of 38.7–75.5% [34, 35, 38, 40, 41]. The effect of CBT, as measured by the Chalder Fatigue Questionnaire, resulted in an average change in score from 24.20 to 17.42, with a mean difference of 6.52 points [32]. The overall impact on fatigue improvement was classified as large or very large (d = 0.91–2.28) [32, 35, 38, 40]. Fatigue improvement persisted after 3 months and 1 year of therapy in two different studies [32, 37]. Lack of response to CBT was reported in 23–29.1% of patients, while late response occurred in 22.9% of cases [34, 42]. Approximately 81.1% of patients assessed with the Checklist Individual Strength (CIS-20) still met criteria for clinically significant fatigue after treatment; however, fatigue severity also decreased in this group [34]. Notably, patients participating in CBT achieved fatigue levels within the normal range, and their scores differed by 21–28 percentage points from those of the waiting list group [39]. In the PACE reanalysis, the improvement in energy compared to the control group differed by 13 percentage points (p = 0.004) [36]. Findings from two studies also indicated that factors associated with greater fatigue reduction most commonly included a higher sense of control over the illness, better physical functioning, greater perceived activity, less symptom focus, higher positive affect, and lower levels of depression, anxiety, and stress [34, 42].

In a study of 236 patients assessed with the SF-36 Physical Function questionnaire, physical functioning increased by 14.2 points after CBT, exceeding the threshold for clinically meaningful improvement (MID >10 points), and this effect persisted over one year of observation [37]. In the I-CBT group, the improvement was smaller, at 6.8 points, and did not reach the MID threshold [37]. Similar findings were reported in another study involving 995 patients, in which physical functioning improved by 11.75 points and this improvement was maintained after 3 months [32]. In a randomized controlled trial of web-based CBT, significant improvement in physical functioning compared with the waiting list was observed only in the feedback-on-demand condition [39]. In contrast, protocol-driven internet-based CBT (iCBT) did not produce a significant improvement [39]. The proportion of patients who achieved a normal level of physical functioning (SF-36 ≥75 points) was 50% after CBT and 40% after I-CBT, compared with 20% in the control group, corresponding to differences of 30 and 20 percentage points, respectively [37]. In the PACE reanalysis, physical activity increased by only 4 percentage points compared with the control group, and this difference was not statistically significant (p = 0.34) [36].

In the case of depression associated with CFS, a significant reduction was demonstrated in two studies [31, 34]. At the same time, individuals with higher baseline depressive symptoms achieved worse treatment outcomes and were less likely to experience improvement in fatigue and physical functioning [32].

Anxiety outcomes were inconsistent across studies—one study reported no significant reduction in anxiety following CBT, while another observed group-level improvements in anxiety symptoms [31, 34]. Additionally, higher baseline anxiety was associated with an increased risk of poorer treatment outcomes in a large cohort study [32].

Overall satisfaction with CBT was reported by 89.3–90% of patients in two different studies [31, 32]. In one analysis, 40% of patients reported satisfaction with the treatment [43].

As shown in Table 2, conventional cognitive behavioral therapy demonstrated the most consistent benefits in reducing fatigue and improving physical functioning in patients with Chronic Fatigue Syndrome. Some internet-based CBT interventions also showed beneficial effects; however, their effectiveness was less consistent and varied with treatment format and level of therapist involvement. Overall, CBT-based interventions were associated with high patient satisfaction and could be successfully delivered with varying degrees of therapist support.

Clinical Outcomes of Exercise-Based Interventions

In the PACE reanalysis, graded exercise therapy (GET) resulted in improvement in fatigue in 24% of cases, compared to 13% in the control group [36]. Among patients in the intervention group (INT) who used self-paced aquatic exercises, a significant reduction in fatigue, as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire, was observed (p = 0.005, ES = 0.6) [44]. No increase in fatigue immediately after or 24 h after the 6-minute walk test, and no increase in pain, was observed following the intervention [44]. At the end of the study, fatigue levels were significantly lower in the INT group than in the control group (CON) (p = 0.003) [44]. Based on a study comparing graded exercise self-help (GES) with specialist medical care (SMC), no significant advantage of GES over SMC was found (p = 0.052) [45]. Between short- and long-term follow-up, significant changes in fatigue levels were observed in both the GES and SMC groups (p = 0.001), and SMC participants also showed gradual improvement during later follow-up (p = 0.0247) [45]. The primary endpoint of fatigue improved significantly in 26% of individuals (55/212) in a study comparing the multicomponent intervention FATIGUEWALK (FaW) with treatment as usual (TAU), with a moderate effect size (p < 0.001) [46].

Subjective health improvement was reported by 44.1% of study participants (218/494) across three analyses, with rates ranging from 26.6% to 84.2% in individual studies [45, 47, 48]. The lowest rate of subjective health improvement was reported in the GETSET study, at 26.6% [45]. This study also showed that, despite this health improvement, there was no statistically significant difference in this measure between the GES and SMC groups (p = 0.98) [45]. In contrast, the highest percentage of subjective health improvement was observed in the GET vs activity management (AM) study, in which 84.2% of patients rated their condition as "much better" or "very much better" [47]. This study also demonstrated that the percentage of patients reporting substantial or very substantial improvement increased from 29.9% after 6 months to 39.8% after 12 months [47].

Across three studies, deterioration in health status was observed in 27.6% (367/1331) of patients, with results ranging from 7.6% to 32.4% [45, 47, 49]. The lowest rate, at 7.6%, was observed in the GETSET study, which included 158 participants [45]. Additionally, in this study, after a long-term follow-up of 11–36 months, the percentage of patients reporting deterioration in health increased from 1% to 9% in the GES group, a statistically significant change (p = 0.03) [45]. In the GET vs AM study, health deterioration occurred in 22.1% of cases, more frequently in the GET group than in the AM group (27% vs 17%) [47]. However, this difference was not statistically significant (p = 0.069) [47]. The highest rate (32.4%) was observed in a large cross-sectional patient survey (n = 933) [49].

No advantage of GET over comparator groups was found in three different studies [36, 45, 47]. In the GETSET analysis, no significant differences between GET and SMC were observed for fatigue, physical functioning, or subjective health improvement [45]. Similarly, the GET vs AM study found no differences in physical functioning, fatigue, quality of life, or school attendance [47]. Additionally, the long-term follow-up of the PACE trial, which included 641 patients, showed no differences between groups in terms of physical functioning, daily functioning, or overall health status [36]. However, 61% of patients receiving GET significantly improved in physical functioning, compared with 44% in the control group [36].

A self-paced aquatic exercise program and short-term aquatic exercises also did not result in adverse events or worsening of CFS symptoms among the 43 patients [44, 50]. Serious adverse events requiring hospitalization occurred in 1.2% of participants (3/241) in a study comparing GET versus AM; two events occurred in one patient in the GET group, while the remaining two events occurred in two patients in the AM group [47]. However, only one event was considered potentially related to the intervention under study [47]. In the same study, 2.1% of participants discontinued treatment due to worsening health; this occurred more frequently in the GET group than in the AM group (3% vs 1%) [47].

The main characteristics of studies evaluating physical activity interventions in patients with chronic fatigue syndrome, together with the intervention type and principal findings, are summarized in Table 3.

Rituximab therapy

Two studies evaluating rituximab (RTX) for CFS were identified: an uncontrolled, open-label phase II trial and a randomized, placebo-controlled phase III trial (RituxME) [51, 52]. In the open-label trial, a clinically significant response was achieved in 62% (18/29) of participants, of whom 14 were major responders and 4 were moderate responders [51]. The time to achieve major and moderate responses was 23 and 56 weeks, respectively, with the response itself lasting, on average, 97 weeks [51]. Among the major responders, 64.3% (9/14) maintained clinical response at 36 months, while 28.6% (4/14) relapsed before the end of follow-up [51]. In contrast, in the RCT, the overall clinical response was not statistically significant, at 26.0% (20/77) vs 35.1% (26/74) in the placebo group (p = 0.22) [52].

In the open-label trial, improvement in fatigue was reported only among clinically significant responders, while no meaningful improvement was observed among non-responders [51]. In the RituxME trial, RTX did not demonstrate a statistically significant effect on fatigue (p = 0.61–0.80) [52].

Physical function, assessed using the SF-36 questionnaire in the open-label trial, improved from 42.9 to 83.3 points among clinically significant responders; significant improvement was also achieved among responders in self-reported function level [51]. In the RCT, the mean SF-36 Physical Function score improved by 11.5 points over the first 18 months; however, no significant difference between RTX and placebo was observed (p = 0.67) [52]. In the same study, self-reported function level also did not differ significantly between groups (p = 0.48), increasing from 18.8% to 30.9% in the RTX group and from 17.9% to 28.6% in the placebo group [52]. In the open-label trial, among major responders, physical activity averaged 9,829 steps/day (range: 5,794–18,177) during months 15–20, whereas in the RituxME trial, no significant difference in daily steps between rituximab and placebo was observed [51, 52].

Among clinically significant responders, improvements were also observed in several SF-36 quality-of-life domains, including Vitality (+43.6), Social Function (+52.4), Bodily Pain (+41.1), and Mental Health (+16.6) [51].

Among participants in the open-label trial, cases were reported of recurrent sinusitis, repeated upper respiratory tract infections, one urinary tract infection, two allergic reactions, two cases of uncomplicated late-onset neutropenia lasting 5 days, as well as one case each of breast cancer, thrombocytopenia, and choledocholithiasis [51]. In the RCT, adverse events occurred in 81.8% of patients receiving RTX compared with 64.9% of those receiving placebo [52]. Serious adverse events requiring hospitalization occurred in 26.0% of patients receiving RTX (20/77) and 18.9% of patients receiving placebo (14/74) [52]. One case of breast cancer was reported in both the RTX and placebo groups [52].

Rintatolimod therapy

In the Exercise Tolerance Test (ETT), rintatolimod significantly increased exercise duration, with a between-group difference of 67.5 seconds compared with placebo [53]. The proportion of patients achieving a ≥25% improvement in exercise duration was significantly higher with rintatolimod than with placebo (39.0% vs 23.1%, p = 0.013), particularly among patients with a disease duration of 2 to 8 years (51.2% vs 17.6%, p = 0.003) [54]. In this subgroup, a greater increase in vertical rise during the exercise test was also observed (85.2 vs 23.3 feet, p = 0.050) [53]. Among patients achieving a ≥25% improvement in exercise tolerance, significant improvements in Karnofsky Performance Status (KPS) and a 14-point increase in the SF-36 Vitality score were also reported after 40 weeks of treatment; the latter exceeded the minimal clinically important difference (MCID) threshold of 5 points [54].

Table 4 highlights the contrasting outcomes of evaluated pharmacological treatments. While rituximab failed to provide significant clinical benefits over placebo in a large randomized trial, rintatolimod shows promise by significantly improving exercise tolerance, particularly in patients with a shorter disease duration.

DISCUSSION

Main findings

Based on the available evidence, cognitive behavioral therapy (CBT) appears to provide the most consistent beneficial effects among the evaluated interventions. The reported benefits included improvements in fatigue, physical functioning, depression, and overall health status. Evidence for exercise-based interventions was mixed. Some studies showed clinical benefits, whereas others found no significant differences compared with the control groups. Selected nutritional interventions also showed beneficial effects; however, the reported outcomes varied by supplement. In particular, supplementation with CoQ10 + NADH and selenium was associated with improvements in fatigue, sleep quality, and, in some studies, quality of life, suggesting that selected nutritional strategies may serve as a useful adjunct to standard CFS management in some patients. Rituximab cannot currently be recommended due to a lack of demonstrated efficacy in a phase III clinical trial. In contrast, rintatolimod appears to be a promising therapeutic option; however, the limited number of available studies prevents definitive conclusions regarding its clinical effectiveness.

Overall, treatment response in CFS appears to vary considerably between patients. This variability may reflect the complex and heterogeneous nature of the disease, in which immunological, metabolic, and psychological factors are likely involved to different degrees. Consequently, no single treatment is likely to be effective for all patients, making an individualized approach to treatment essential.

Effectiveness of Cognitive Behavioral Therapy

CBT reduced fatigue in a substantial proportion of patients. Although it does not address the underlying pathophysiology of CFS, it appears to reduce symptom severity and improve daily functioning. The large effect sizes reported in several studies further support the clinical usefulness of this intervention [31, 35, 42]. Moreover, these benefits were maintained during long-term follow-up, suggesting that patients can continue to benefit from the coping strategies developed during therapy [31, 37]. However, complete recovery was uncommon, indicating that CBT is more effective at helping patients manage their symptoms than at achieving full remission [36]. This is consistent with the chronic nature of CFS and suggests that the main goals of treatment should be to reduce symptoms, improve functioning, and enhance quality of life rather than to achieve complete recovery [36].

The improvement in physical functioning exceeded the minimally clinically important difference threshold, indicating that the observed benefits were not only statistically significant but also clinically meaningful [37]. However, this evidence was mainly from CBT, while studies on iCBT showed smaller effects [39].

In patients with more pronounced depressive and anxiety symptoms, the effectiveness of CBT may be reduced, highlighting the need for individual adaptation of therapy in each case [34]. Early and effective identification of factors hindering clinical improvement, as well as finding additional methods to address these issues, is also crucial. Patients with less severe depressive and anxiety symptoms achieved better therapeutic outcomes, further emphasizing the need for individualized treatment [34]. This may suggest that baseline mental health status is one of the factors determining the effectiveness of CBT.

Interpretation of Results Regarding Exercise-Based Interventions

The effects of graded exercise therapy (GET) are inconclusive due to the similarity of beneficial changes in fatigue and physical functioning observed in both intervention and control groups. These findings suggest that the observed improvements in health may not be solely attributable to the intervention itself. Still, they may also reflect the effects of specialist medical care, patient education, and the disease's natural course over time. Therefore, the current evidence does not demonstrate a consistent advantage of GET over comparator interventions [47]. The findings of the present review are consistent with the later reanalysis of the PACE trial and current NICE guidelines, both of which question the long-term benefits of GET [36]. However, GET remains controversial because of inconsistent findings across clinical studies [49].

More favorable outcomes were observed among patients participating in self-paced aquatic exercise programs [50]. This suggests that exercise intensity tailored to individual needs is safer and better tolerated in patients with CFS. The lack of increased fatigue and pain after the intervention further supports the effectiveness of appropriately selected physical activity [44, 50].

A significant proportion of patients reporting worsening of health status indicates that exercise interventions are not suitable for all patients. However, there are substantial differences between studies, which may result from different exercise programs and heterogeneous patient populations. Such a large variability in response to physical exercise likely reflects biological differences among patients with CFS. In clinical practice, this means that physical activity should not be implemented according to a uniform protocol, but rather tailored to individual exercise tolerance, symptom severity, and the risk of PEM in different patient groups.

Interpretation of Nutritional Interventions

The beneficial effects of selected supplements on fatigue and sleep may indirectly support the hypothesis that metabolic and mitochondrial disturbances contribute to the pathogenesis of CFS [29]. At the same time, the lack of a clear improvement in quality of life suggests that, based on the available evidence, nutritional supplementation should currently be considered an adjunctive rather than a standalone therapeutic approach [25]. It should also be emphasized that positive effects were observed only for specific preparations, mainly CoQ10 + NADH and selenium, whereas the effectiveness of other nutritional interventions was limited or inconclusive [30].

The variability in treatment response may indicate that only selected patient subgroups benefit from supplementation, possibly due to differences in metabolic status or underlying biological disturbances [24]. However, confirmation of this hypothesis requires further studies. In clinical practice, this means that the decision to introduce supplementation should be made individually, taking into account the patient's clinical status and the available evidence regarding the specific preparation [24].

Rituximab and Rintatolimod

The discrepancy between the results of the open-label study and the large RCT evaluating RTX underscores the importance of controlled trials in evaluating new therapies [51, 52]. In contrast, rintatolimod demonstrated improvements in exercise tolerance and daily functioning, suggesting that it may act through mechanisms underlying reduced physical capacity [53]. The available evidence also suggests that this treatment may be more effective in patients with a disease duration of 2 to 8 years, indicating a greater likelihood of therapeutic response during the earlier stages of the disease [53]. If these findings are confirmed in future studies, earlier diagnosis of CFS may help identify patients who are more likely to benefit from this therapy [53].

Clinical Implications

The variability in treatment response observed across the included studies suggests that CFS is a heterogeneous disorder and that patients may differ in the underlying mechanisms contributing to the disease. As a result, no single treatment is likely to be effective for all patients, and treatment should therefore be individualized.

Based on the available evidence, CBT appears to have the strongest evidence base among the evaluated non-pharmacological interventions. Although supplementation with CoQ10 + NADH and selenium was associated with improvements in selected outcomes, particularly fatigue, sleep, and, in some studies, quality of life, the current evidence is insufficient to recommend these interventions as standalone treatments. Likewise, exercise-based interventions did not consistently show an advantage over control groups. If physical activity is included as part of treatment, exercise programs should be adapted to each patient's individual abilities while taking exercise tolerance and the risk of post-exertional malaise (PEM) into account. At present, there is no evidence to support the routine use of rituximab. Rintatolimod appears to be a promising treatment option, but additional studies are needed before it can be recommended for routine clinical use.

Limitations

The main limitation of this narrative review is the high heterogeneity of the included studies. They differed in sample size, disease duration, participant characteristics, and the diagnostic criteria used for CFS. In addition, the studies used different treatment protocols, intervention doses, treatment durations, and outcome measures, making direct comparisons between interventions difficult. In particular, the use of different diagnostic criteria (Oxford, Fukuda, Canadian Consensus Criteria, and others) may have resulted in the inclusion of clinically heterogeneous patient populations. Another important limitation was the lack of standardized definitions of treatment response and clinically meaningful improvement, as the included studies relied on different endpoints and assessment tools.

Another limitation of this review was the small number of studies on nutritional interventions and pharmacotherapy, which reduces the certainty of conclusions regarding these treatment methods. Furthermore, differences in follow-up duration between studies hindered the assessment of the durability of therapeutic effects. Due to the substantial heterogeneity of the available data, conducting a reliable meta-analysis was not possible; therefore, the conclusions presented are based on a qualitative synthesis of the results.

CONCLUSIONS

Based on the reviewed evidence, cognitive behavioral therapy appears to provide the most consistent benefits among the analyzed interventions for chronic fatigue syndrome. It was associated with reductions in fatigue and improvements in physical functioning and overall health status, although complete recovery was uncommon. Internet-based cognitive behavioral therapy also showed beneficial effects in some studies, but the results were less consistent and appeared to depend on treatment format and therapist involvement.

The effectiveness of exercise-based interventions remains inconclusive. Some studies reported improvements in fatigue or perceived health, particularly with self-paced aquatic exercise programs, but graded exercise approaches did not consistently show superiority over comparator groups. Because symptom worsening was reported in some patients, exercise programs should be individualized and adapted to exercise tolerance and the risk of post-exertional malaise.

Selected nutritional interventions, particularly CoQ10 plus NADH and selenium supplementation, were associated with improvements in fatigue, sleep, and, in some studies, quality of life. However, the evidence remains heterogeneous and does not support the use of nutritional supplementation as a standalone treatment.

Rituximab did not show efficacy in the randomized controlled phase III trial and cannot be recommended for routine use based on current evidence. Rintatolimod showed promising effects on exercise tolerance in selected patients, particularly in those with disease duration of 2 to 8 years, but its clinical role remains investigational and requires confirmation in further high-quality studies.

Overall, the available evidence indicates that treatment response in chronic fatigue syndrome varies substantially between patients, likely reflecting the clinical and pathophysiological heterogeneity of the disorder. Future research should clarify which patient subgroups are most likely to benefit from specific interventions and whether biomarker-based stratification can support more individualized treatment strategies.

DISCLOSURE

Author Contributions

Conceptualization: Małgorzata Lubowiecka, Anna Szeszko, Weronika Czernek.

Methodology: Zuzanna Lecyk, Michał Stermach.

Formal analysis: Agata Leszek, Magdalena Cichorzewska.

Investigation: Zuzanna Lecyk, Agata Leszek, Magdalena Cichorzewska.

Original draft preparation: Małgorzata Lubowiecka, Agata Leszek, Anna Szeszko.

Review and editing: Zuzanna Lecyk, Anna Szeszko, Weronika Czernek.

Supervision: Małgorzata Lubowiecka, Weronika Czernek, Michał Stermach.

All authors contributed to the manuscript and approved the final version for publication.

Funding

This research received no external financial support.

Conflict of Interest

The authors declare that they have no competing interests or conflicts of interest related to this work.

Use of Artificial Intelligence

The authors confirm that no artificial intelligence tools were used to generate, draft, edit, or revise the manuscript. All aspects of the work were completed exclusively by the authors.

REFERENCES

1. De Vera Martín A, Díaz Salazar A, Martín Pérez IM, Martín Pérez SE. Effectiveness of Exercise-Based Rehabilitation in Chronic Fatigue Syndrome: A Systematic Review and Meta-analysis. Int J Exerc Sci. 2025;18(5):495-530. https://doi.org/10.70252/DAYA4589
2. Gotaas ME, Stiles TC, Bjørngaard JH, Borchgrevink PC, Fors EA. Cognitive behavioral therapy improves physical function and fatigue in mild and moderate chronic fatigue syndrome: a consecutive randomized controlled trial of standard and short interventions. Front Psychiatry. 2021;12:580924. https://doi.org/10.3389/fpsyt.2021.580924
3. Liao Z, Zhao S, Fang S, Ren J, Wang S, Kong L, et al. Comparative efficacy of various exercise therapies for chronic fatigue syndrome: A systematic review and network meta-analysis. iScience. 2025;28(12):114178. https://doi.org/10.1016/j.isci.2025.114178
4. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2019;10:CD003200. https://doi.org/10.1002/14651858.CD003200.pub8
5. Ingman T, Smakowski A, Goldsmith K, Chalder T. A systematic literature review of randomized controlled trials evaluating prognosis following treatment for adults with chronic fatigue syndrome. Psychol Med. 2023;53(17):8345-8358. https://doi.org/10.1017/S0033291722002471
6. Sharpe M, Chalder T, White PD. Evidence-based care for people with chronic fatigue syndrome and myalgic encephalomyelitis. J Gen Intern Med. 2022;37(2):449-452. https://doi.org/10.1007/s11606-021-07188-4
7. Kim DY, Lee JS, Park SY, Kim SJ, Son CG. Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med. 2020;18(1):7. https://doi.org/10.1186/s12967-019-02196-9
8. Bateman L, Bested AC, Bonilla HF, Chheda BV, Chu L, Curtin JM, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: Essentials of diagnosis and management. Mayo Clin Proc. 2021;96(11):2861-2878. https://doi.org/10.1016/j.mayocp.2021.07.004
9. Joli J, Buck P, Zipfel S, Stengel A. Post-COVID-19 fatigue: A systematic review. Front Psychiatry. 2022;13:947973. https://doi.org/10.3389/fpsyt.2022.947973
10. Fowler-Davis S, Platts K, Thelwell M, Woodward A, Harrop D. A mixed-methods systematic review of post-viral fatigue interventions: Are there lessons for long COVID? PLoS One. 2021;16(11):e0259533. https://doi.org/10.1371/journal.pone.0259533
11. Vøllestad NK, Mengshoel AM. Post-exertional malaise in daily life and experimental exercise models in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Front Physiol. 2023;14:1257557. https://doi.org/10.3389/fphys.2023.1257557
12. Kuut TA, Buffart LM, Braamse AMJ, Csorba I, Bleijenberg G, Nieuwkerk P, et al. Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis. Psychol Med. 2024;54(10):2513-2524. https://doi.org/10.1017/S0033291723003148
13. Collard SS, Murphy J. Management of chronic fatigue syndrome/myalgic encephalomyelitis in a pediatric population: A scoping review. J Child Health Care. 2020;24(3):411-431. https://doi.org/10.1177/1367493519864747
14. Li X, Pan H, Wang L, Zhou Q, Ma Y, Wang Q, et al. Guidelines on treating fibromyalgia with nonpharmacological therapies in China. J Evid Based Med. 2025. https://doi.org/10.1111/jebm.70044
15. Fan J, Jiao J, Chang HQ, Zhong DL, Liu XB, Li J, et al. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management. J Transl Med. 2025;23:180. https://doi.org/10.1186/s12967-025-07506-y
16. Vink M, Vink-Niese A. The draft report by the Institute for Quality and Efficiency in Healthcare does not provide any evidence that graded exercise therapy and cognitive behavioral therapy are safe and effective treatments for myalgic encephalomyelitis/chronic fatigue syndrome. Diseases. 2023;11(1):11. https://doi.org/10.3390/diseases11010011
17. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(12):841-850. https://doi.org/10.7326/M15-0114
18. Russell C, Kyle SD, Wearden AJ. Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis. Sleep Med Rev. 2017;32:17-28. https://doi.org/10.1016/j.smrv.2016.05.001
19. Vink M, Vink-Niese F. Work rehabilitation and medical retirement for myalgic encephalomyelitis/chronic fatigue syndrome patients: A review and appraisal of diagnostic strategies. Diagnostics (Basel). 2019;9(4):124. https://doi.org/10.3390/diagnostics9040124
20. Vink M, Vink-Niese F. Graded exercise therapy does not restore the ability to work in ME/CFS - Rethinking of a Cochrane review. Work. 2020;66(2):283-308. https://doi.org/10.3233/WOR-203174
21. White P, Abbey S, Angus B, Ball HA, Buchwald DS, Burness C, et al. Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis. J Neurol Neurosurg Psychiatry. 2023;94(12):1056-1063. https://doi.org/10.1136/jnnp-2022-330463
22. Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018;5(2):2055102918805187. https://doi.org/10.1177/2055102918805187
23. Vink M, Vink-Niese A. The updated NICE guidance exposed the serious flaws in CBT and graded exercise therapy trials for ME/CFS. Healthcare (Basel). 2022;10(8):1518. https://doi.org/10.3390/healthcare10081518
24. Weigel B, Eaton-Fitch N, Passmore R, Cabanas H, Staines D, Marshall-Gradisnik S. A preliminary investigation of nutritional intake and supplement use in Australians with myalgic encephalomyelitis/chronic fatigue syndrome and the implications on health-related quality of life. Food Nutr Res. 2021;65. https://doi.org/10.29219/fnr.v65.5730
25. Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sanmartin Sentañes R, Alegre-Martin J. Effect of dietary coenzyme Q10 plus NADH supplementation on fatigue perception and health-related quality of life in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: A prospective, randomized, double-blind, placebo-controlled trial. Nutrients. 2021;13(8):2658. https://doi.org/10.3390/nu13082658
26. Castro-Marrero J, Domingo JC, Cordobilla B, Ferrer R, Giralt M, Sanmartín-Sentañes R, et al. Does coenzyme Q10 plus selenium supplementation ameliorate clinical outcomes by modulating oxidative stress and inflammation in individuals with myalgic encephalomyelitis/chronic fatigue syndrome? Antioxid Redox Signal. 2022;36(10-12):729-739. https://doi.org/10.1089/ars.2022.0018
27. Maric D, Brkic S, Tomic S, Novakov Mikic A, Cebovic T, Turkulov V. Multivitamin mineral supplementation in patients with chronic fatigue syndrome. Med Sci Monit. 2014;20:47-53. https://doi.org/10.12659/MSM.889333
28. Menon R, Cribb L, Murphy J, Ashton MM, Oliver G, Dowling N, et al. Mitochondrial modifying nutrients in treating chronic fatigue syndrome: A 16-week open-label pilot study. Adv Integr Med. 2018;5(1):2-7. https://doi.org/10.1016/j.aimed.2017.11.001
29. Castro-Marrero J, Cordero MD, Segundo MJ, Sáez-Francàs N, Calvo N, Román-Malo L, et al. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015;22(8):679-685. https://doi.org/10.1089/ars.2014.6181
30. Godlewska BR, Sylvester AL, Emir UE, Sharpley AL, Clarke WT, Martens MAG, et al. Six-week supplementation with creatine in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A magnetic resonance spectroscopy feasibility study at 3 Tesla. Nutrients. 2024;16(19):3308. https://doi.org/10.3390/nu16193308
31. Heald A, Barber L, Lyon Jones H, Farman S, Walther A. Service based comparison of group cognitive behavior therapy to waiting list control for chronic fatigue syndrome with regard to symptom reduction and positive psychological dimensions. Medicine (Baltimore). 2019;98(39):e16720. https://doi.org/10.1097/MD.0000000000016720
32. Adamson J, Ali S, Santhouse A, Wessely S, Chalder T. Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: Outcomes from a specialist clinic in the UK. J R Soc Med. 2020;113(10):394-402. https://doi.org/10.1177/0141076820951545
33. van der Schaaf ME, Geerligs L, Toni I, Knoop H, Oosterman JM. Disentangling pain and fatigue in chronic fatigue syndrome: A resting state connectivity study before and after cognitive behavioral therapy. Psychol Med. 2024;54(13):3128-3137. https://doi.org/10.1017/S0033291723003690
34. Van Oudenhove L, Debyser S, Vergaelen E, Claes S, Van Den Houte M. Predictors of treatment response trajectories to cognitive behavioral therapy for chronic fatigue syndrome: A cohort study. J Psychosom Res. 2024;186:111954. https://doi.org/10.1016/j.jpsychores.2024.111954
35. Albers E, Nijhof LN, Berkelbach van der Sprenkel EE, van de Putte EM, Nijhof SL, Knoop H. Effectiveness of Internet-based cognitive behavior therapy (Fatigue in Teenagers on the Internet) for adolescents with chronic fatigue syndrome in routine clinical care: Observational study. J Med Internet Res. 2021;23(8):e24839. https://doi.org/10.2196/24839
36. Wilshire CE, Kindlon T, Courtney R, Matthees A, Tuller D, Geraghty K, et al. Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol. 2018;6(1):6. https://doi.org/10.1186/s40359-018-0218-3
37. Gotaas ME, Stiles TC, Bjørngaard JH, Borchgrevink PC, Fors EA. Cognitive behavioral therapy improves physical function and fatigue in mild and moderate chronic fatigue syndrome: A consecutive randomized controlled trial of standard and short interventions. Front Psychiatry. 2021;12:580924. https://doi.org/10.3389/fpsyt.2021.580924
38. Worm-Smeitink M, Monden R, Groen RN, van Gils A, Bekhuis E, Rosmalen J, et al. Towards personalized assessment of fatigue perpetuating factors in patients with chronic fatigue syndrome using ecological momentary assessment: A pilot study. J Psychosom Res. 2021;140:110296. https://doi.org/10.1016/j.jpsychores.2020.110296
39. Janse A, Worm-Smeitink M, Bleijenberg G, Donders R, Knoop H. Efficacy of web-based cognitive-behavioural therapy for chronic fatigue syndrome: Randomised controlled trial. Br J Psychiatry. 2018;212(2):112-118. https://doi.org/10.1192/bjp.2017.22
40. Rauwerda NL, Kuut TA, Braamse AMJ, Nieuwkerk P, Boss HM, Knoop H, et al. Co-occurrence of severe fatigue and insomnia: Implications for the outcome of cognitive behavioural therapies. Behav Cogn Psychother. 2025. https://doi.org/10.1017/S1352465825100945
41. Worm-Smeitink M, Janse A, van Dam A, Evers A, van der Vaart R, Wensing M, et al. Internet-based cognitive behavioral therapy in stepped care for chronic fatigue syndrome: Randomized noninferiority trial. J Med Internet Res. 2019;21(3):e11276. https://doi.org/10.2196/11276
42. Heins MJ, Knoop H, Burk WJ, Bleijenberg G. The process of cognitive behaviour therapy for chronic fatigue syndrome: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue? J Psychosom Res. 2013;75(3):235-241. https://doi.org/10.1016/j.jpsychores.2013.06.034
43. Vos-Vromans DCWM, Smeets RJEM, Huijnen IPJ, Köke AJA, Hitters WMGC, Rijnders LJM, et al. Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: A randomized controlled trial. J Intern Med. 2016;279(3):268-282. https://doi.org/10.1111/joim.12402
44. Broadbent S, Coetzee S, Calder A, Beavers R. Physical function and psychosocial outcomes after a 6-month self-paced aquatic exercise program for individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Eur J Appl Physiol. 2025;125(6):159. https://doi.org/10.1007/s00421-025-05759-5
45. Clark LV, McCrone P, Pesola F, Vergara-Williamson M, White PD. Guided graded exercise self-help for chronic fatigue syndrome: Long term follow up and cost-effectiveness following the GETSET trial. J Psychosom Res. 2021;145:110484. https://doi.org/10.1016/j.jpsychores.2021.110484
46. Serrat M, Navarrete J, Ferrés S, Auer W, Sanmartín-Sentañes R, Nieto R, et al. Effectiveness of an online multicomponent program (FATIGUEWALK) for chronic fatigue syndrome: A randomized controlled trial. Health Psychol. 2024;43(4):260-271. https://doi.org/10.1037/hea0001346
47. Gaunt DM, Brigden A, Harris SRS, Hollingworth W, Jago R, Solomon-Moore E, et al. Graded exercise therapy compared to activity management for paediatric chronic fatigue syndrome/myalgic encephalomyelitis: Pragmatic randomized controlled trial. Eur J Pediatr. 2024;183(5):2201-2212. https://doi.org/10.1007/s00431-024-05458-x
48. Powell P, Bentall RP, Nye FJ, Edwards RH. Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. BMJ. 2001;322(7283):387-390. https://doi.org/10.1136/bmj.322.7283.387
49. Geraghty K, Hann M, Kurtev S. Myalgic encephalomyelitis/chronic fatigue syndrome patients' reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. J Health Psychol. 2019;24(10):1318-1333. https://doi.org/10.1177/1359105317726152
50. Broadbent S, Coetzee S, Beavers R. Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: A pilot study. Eur J Appl Physiol. 2018;118(8):1741-1750. https://doi.org/10.1007/s00421-018-3913-0
51. Fluge Ø, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, et al. B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome: An open-label phase II study with rituximab maintenance treatment. PLoS One. 2015;10(7):e0129898. https://doi.org/10.1371/journal.pone.0129898
52. Fluge Ø, Rekeland IG, Lien K, Thürmer H, Borchgrevink PC, Schäfer C, et al. B-lymphocyte depletion in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2019;170(9):585-593. https://doi.org/10.7326/M18-1451
53. Strayer DR, Young D, Mitchell WM. Effect of disease duration in a randomized phase III trial of rintatolimod, an immune modulator for myalgic encephalomyelitis/chronic fatigue syndrome. PLoS One. 2020;15(10):e0240403. https://doi.org/10.1371/journal.pone.0240403
54. Strayer DR, Carter WA, Stouch BC, Stevens SR, Bateman L, Cimoch PJ, et al. A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLoS One. 2012;7(3):e31334. https://doi.org/10.1371/journal.pone.0031334

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