Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background and Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with post-exertional malaise, as well as changes to sleep, autonomic functioning, and cognition. Mind-body interventions (MBIs) utilize the ongoing interaction between the mind and body to improve health and wellbeing. Purpose: To systematically review studies using MBIs for the treatment of ME/CFS symptoms. Materials and Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL were searched (inception to September 2020). Interventional studies on adults diagnosed with ME/CFS, using one of the MBIs in comparison with any placebo, standard of care treatment or waitlist control, and measuring outcomes relevant to the signs and symptoms of ME/CFS and quality of life were assessed for inclusion. Characteristics and findings of the included studies were summarized using a descriptive approach. Results: 12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga. The outcomes measured most often were fatigue severity, anxiety/depression, and quality of life. Fatigue severity and symptoms of anxiety/depression were improved in nine and eight studies respectively, and three studies found that MBIs improved quality of life. Conclusions: Fatigue severity, anxiety/depression and physical and mental functioning were shown to be improved in patients receiving MBIs. However, small sample sizes, heterogeneous diagnostic criteria, and a high risk of bias may challenge this result. Further research using standardized outcomes would help advance the field.


Introduction
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with multiple symptoms including postexertional malaise, orthostatic intolerance, pain, sleep problems, and impaired cognitive more, by enhancing self-knowledge and patients' abilities to work through their problems and reduce stress, MBIs may improve their quality of life and wellbeing [27].
Several MBIs such as mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), yoga, and Qigong have been studied in ME/CFS patients, but to our knowledge, have not yet been included in any systematic review or meta-analysis. There are some promising results to improve anxiety, fatigue, depression, quality of life, and physical functioning [28][29][30][31][32] in ME/CFS. In this systematic review, we evaluated the effectiveness and safety of MBIs that were studied in individuals diagnosed with ME/CFS. The results of this review will inform the design and methodology of future randomized controlled trials.

Objectives
The objectives of this study were to systematically review studies of MBIs for the treatment of ME/CFS symptoms and to report any adverse events reported for these approaches in ME/CFS patients.

Materials and Methods
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [33]. The protocol of this systematic review was registered at PROS-PERO (CRD42018085981).

Population, Intervention, Control, Outcome-Study Design (PICO-S)
The population of interest was adults (≥18 years old) diagnosed or symptom-matched with one of the ME/CFS case definitions (Appendix A, Table A1). Patients with any other conditions were included in this review, as long as they were diagnosed with ME/CFS. Interventions of interest included any of the MBIs listed in Table 1 and any placebo, the standard of care treatment or waiting list as a control group. To be eligible for inclusion, multiple-arm interventional studies were also required to have at least one of the control groups mentioned above.
All outcomes relevant to the signs and symptoms of ME/CFS and quality of life were considered. The outcomes included fatigue, sleep refreshment, pain, anxiety (stress, nervousness, etc.), depression (mood, hopefulness, and helplessness), quality of life, performance (physical, mental, emotional), work-related outcomes (employment, income, etc.), and physical health symptoms such as sore throat, tender lymph nodes, and muscle weakness (Table 1).
Study designs eligible for inclusion were parallel/cross-over/N-of-1 randomized controlled trials (RCTs), controlled clinical trials (CCTs), single-arm experimental (within subject control group), controlled before and after studies, or cohort studies.

Search Methods
Five electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Register of Controlled Trials (CENTRAL)) were searched from inception to September 2020. Search terms were based on those presented in Table 1; an example is found in Appendix B. No limitation was implemented in terms of publication dates. English language restriction was applied. The reference lists of included studies, and systematic reviews, were reviewed to identify additional studies.

Selection of Studies
Two review authors (MK, DJ) independently screened all the titles and abstracts retrieved from the search in order to identify those that may meet the inclusion criteria. They classified studies as being relevant, possibly relevant and irrelevant. Three reviewers (MK, DJ, SKA) independently assessed the full texts of all relevant and possibly relevant studies to assess inclusion. Discrepancies were resolved by referring to a senior review author (ES, SV).

Data Collection
Standardized data extraction forms were used to extract data from full-text articles. Extracted data included general characteristics of the study (first author, publication year, country, settings, design), sample size, age and sex distribution in groups, diagnosis methods, type of MBI and other relevant data including frequency and duration, control (active or passive), primary outcome, secondary outcomes, primary and secondary measurement tools, length of study, follow up period, statistically significant outcomes, and adverse events reported. Data extraction was completed by one reviewer (DJ) and independently verified by a second reviewer (SKA). Disagreements between the authors were resolved by discussion until consensus was reached; if consensus could not be reached, a senior reviewer's opinion was sought.

Data Analysis
This systematic review was conducted to determine which outcomes and outcome measures were used in the studies of MBIs for the treatment of ME/CFS patients and whether the interventions were effective. General information of the included studies along with the statistically significant and insignificant outcomes were described. We present the findings of studies using different diagnostic criteria (e.g., Oxford criteria, CDC criteria) separately. We also report whether studies assessed adverse events, their absence or presence, and frequencies. A meta-analysis was not performed due to heterogeneous interventions and outcomes used in the included studies. Cochrane risk of bias assessment tool was used by two independent review authors (SKA, SP) to assess sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias [34] in RCTs. Other study designs including single-arm experimental studies were also appraised by two independent reviewers (SKA, SP) for risk of bias using Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies of Intervention (ACROBAT_NRSI) which was recently renamed ROBINS-I [35]. Domains for assessing the risk of bias in these studies include bias due to confounding, selection of participants, measurement of interventions, a departure from the intended intervention, missing data, measurement of outcomes, and selection of the reported result.

Patient Involvement
Patient engagement in health research can improve the quality, relevance and impact of the research [36,37]. To recruit patient research partners in this study, a "call for patient representative" letter was developed and distributed among patients, caregivers and advocates. Three patient partners were selected based on their educational background, personal experience, and health status to participate in the study team. They did not receive any financial compensation. They participated regularly in teleconference calls and skype meetings. They also provided feedback and participated in team discussions via email. They contributed to the protocol design, development of the literature search strategy, the condition/diagnosis definitions, and outcome selection.

Design
Six studies were prospective RCTs with at least one eligible control group [28,30,[39][40][41]45]. One manuscript presented a brief report of three studies in which one was a prospective RCT and the other two were single-arm experimental studies [29]. Five additional publications were also single-arm experimental studies [10,38,[42][43][44].

Population
Participants were all adults diagnosed with ME/CFS (n = 564 total; sample size range n = 9-150). Six studies used the Center for Disease Control and Prevention (CDC) criteria for the diagnosis of their patients [28,[39][40][41]45,51]. One study used the 2003 Canadian criteria [43]. One study used Oxford criteria [29], one study used both CDC and Oxford criteria [30] and three studies used a combination of CDC criteria with 2003 or 2005 versions of Canadian criteria and 2011 international consensus criteria [10,42,44].

Comparison
Participants assigned to the control group were either placed on the waiting list [28][29][30]40,41] or received standard medical care [39]. They were advised to keep their usual lifestyle activities including seeking general medical care but not to participate in any activities similar to the intervention of interest.

Effects of Interventions
Due to heterogeneous interventions and outcome measures used in the included studies, a meta-analysis was not performed. The statistically significant outcomes reported by these studies are presented in Tables 3 and 4. Tables A3 and A4 show the statistically insignificant outcomes.              In comparison to the control group, both mental and physical fatigue scores improved significantly in four included studies using MBCT [30], isometric yoga [28], Qigong exercise [41] and Baduanjin Qigong [40]. Two studies showed within-group fatigue improvement in participants receiving an 8-week mindfulness therapy [29] and in participants receiving a 10-week relaxation program [39] (Tables 3 and 4) Anxiety and depression were improved in participants receiving Baduanjin Qigong compared to the controls after 16 sessions (9 weeks) of therapy [40]. Depression was improved in participants after 4 months of Qigong exercise [41] and 8 weeks of MBCT [30] compared to the control groups. Surawy et al. [29] also showed improvement of anxiety after 8 weeks of MBSR/MBCT intervention compared to the control group.
In comparison to the control group, quality of life improved in participants receiving Qigong exercise [41,70,71] and cognitive-behavioral stress management [45]. Tables 3 and 4 show the details of all the significant outcomes of the included studies according to the diagnosis of ME/CFS (Oxford or CDC criteria).

Risk of Bias in the Included Studies
All the included RCT studies were assessed at a high risk of bias in relation to the lack of blinding of participants and personnel. We were not able to assess the risk of bias in many areas as most of the studies were poorly reported ( Figure 2). The risk of bias assessment for the single-arm experimental studies using the ROBINS-I assessment tool is shown in Table A5.

Discussion
This is the first systematic review of studies using MBIs in patients with ME/CFS. The MBIs used in these studies were mindfulness-based stress reduction and mindfulness-based cognitive therapy, relaxation, Qigong, and yoga.
It was also suggested that ME/CFS may be a neurophysiological disorder in the brain caused by repeated incidental or unnecessary stimuli in the limbic system, which is known as the threat response/protection center. These stimuli can be emotional, psychological, chemical, and/or physiological and they can keep the threat response center on a continuous high alert [105]. Connections between the amygdala and sympathetic, hypothalamic and other limbic brain systems can initiate a series of stimulations and uncontrolled reactions throughout the whole body, which could be considered as the root cause of CFS symptoms [105].
With increasing knowledge based on neuroplasticity and the impact of limbic function on somatic symptoms, the potential mechanisms of MBIs might be explained. There is growing interest in using MBIs and many programs are being offered directly to the public to assist with mental and physical health. One of these programs developed specifically for ME/CFS (25) has shown modest success in functional ability in a clinical audit. Because patients are accessing MBI programs, there is an urgent need for evidence as to whether these programs are having an impact on the core symptoms of ME/CFS or mainly address the secondary dissatisfaction that comes with having a chronic, poorly understood disease for which there is no cure. In this review, the MBIs used in the included studies were quite heterogenous. Two studies used relaxation techniques, five studies used movement-based therapies including different forms of yoga and Qigong and the remaining ones used various forms of mindfulness and cognitive-based approaches. Table A6 describes these interventions briefly.
In this systematic review, we found the most commonly measured outcomes were fatigue severity, anxiety and depression, and quality of life or its components (e.g., physical and mental functioning). When compared to the control group, fatigue severity, mental functioning and anxiety/depression mostly improved in patients receiving MBIs. However, poor reporting, small sample sizes, different diagnostic criteria, and a high risk of bias may challenge this result. It is also worth noting that these symptoms are not specific and can be found not only in some individuals with ME/CFS but also in individuals with many other physical and mental health conditions.
According to the 2015 Institute of Medicine report [1], impaired function, postexertional malaise and unrefreshing sleep are the core symptoms in ME/CFS patients. None of our included studies, however, measured post-exertional malaise. One study measured sleep using a self-reporting scale which improved after 9 weeks of Qigong exercise [40]. Physical or mental functioning and functional performance were mostly measured using self-report scales and only one study measured performance using objective measures [51].
In contrast, anxiety and depression and some cognitive constructs were commonly measured in the included studies. While these symptoms are important, they are secondary and not the key features of ME/CFS. Reporting secondary outcomes while omitting measurement of the core symptoms of a disease may lead to inaccurate conclusions about treatment effectiveness.
Previous studies have used a variety of definitions for the diagnosis of ME/CFS. Lack of consensus and competing definitions act as a barrier for research in this field. Most of the studies in this systematic review used the 1994 CDC criteria for the diagnosis of ME/CFS and two studies used Oxford criteria.
The Oxford criteria were developed at a consensus meeting [46]. They do not require the presence of any symptom other than disabling fatigue. The presence of other symp-toms such as immune, autonomic and mood symptoms differentiate ME/CFS from other common medical and psychiatric conditions including major depression. It has long been suspected that the Oxford criteria may therefore fail to exclude individuals with other fatiguing conditions [14,19].
To address this concern, the Agency for Healthy Research and Quality (AHRQ) in the United States conducted a sensitivity analysis in which the outcomes of treatment studies using the Oxford criteria were compared with studies using other criteria (mostly the 1994 CDC Criteria) [14]. They found that whereas most studies using the Oxford criteria showed some benefits for CBT, studies using the CDC criteria were mixed with no overall benefit. With regards to graded exercise therapy, exclusion of the trials using the Oxford case definition left insufficient evidence about the effectiveness of graded exercise therapy on any outcome. Studies of other therapies were not affected as primary studies had small sample sizes and a high risk of bias. These findings confirm that the choice of inclusion criteria impacts study outcomes. The AHRQ concluded that future research should retire the use of the Oxford case definition. The National Institutes of Health held a consensus workshop to guide the future of ME/CFS research [19]. For similar reasons as the AHRQ, they also recommended that the Oxford Criteria should be retired.
The 1994 CDC criteria also have significant drawbacks. They require four out of eight criteria but none are mandatory. This means two subjects identified with these criteria may have no symptoms in common with each other-one might have four and the other, another four. Moreover, minor symptoms may overlap with the symptoms of psychiatric disorders including major depression [14].
The Institute of Medicine [1] has proposed diagnostic criteria which are very similar to the Canadian Consensus Criteria [88]. They require patients to have moderate, substantial or severe disabling fatigue, post-exertional malaise and unrefreshing sleep for at least half of the time and one of the cognitive impairments or orthostatic intolerance symptoms. Conclusions about the effectiveness of interventions will be possible once studies use the same diagnostic criteria and measure core outcomes using standardized measures.

Strengths and Limitations
Assessment of a broad range of mind-body approaches and outcomes in a systematic fashion was one of the main strengths of this systematic review. Engaging patients in the process of designing the review protocol and in reviewing the findings increase the applicability and relevance of the findings of this study.
As we found a diverse range of interventions and outcomes across the included studies; we were not able to perform a meta-analysis. We also may have missed some relevant information by including only studies published in the English language.

1.
As recommended by the Institute of Medicine report, using objective measures is a priority in studies of ME/CFS. There are several symptoms such as post-exertional malaise, cognitive dysfunction, orthostatic intolerance, and changes including impaired immune function and abnormal brain functions that could be measured objectively.

2.
Future RCTs will benefit from larger sample sizes. Investigators must use an appropriate randomization method and ensure outcome assessors are blinded to the group identity of the participants. They should measure and report the outcomes specified in their protocol in order to avoid selective reporting.

Conclusions
In this systematic review, we described the current literature on MBIs for the treatment of ME/CFS. Future clinical trials will benefit from the findings of this study in terms of what outcomes and outcome measures are mostly used in previous studies. We showed that the included studies did not report measuring post-exertional malaise as a core outcome of ME/CFS. On the other hand, fatigue severity, anxiety/depression and mental functioning were shown to be improved in the patients receiving MBIs. However, poor reporting, small sample sizes, different diagnostic criteria, and a high risk of bias may challenge this result. We highlight the need for further research to use objective and standardized outcomes and outcome measures for making definitive conclusions.

Conflicts of Interest:
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Advisor Group, Year Identifier Case Definition and Required Symptom(s)
London criteria-V2, (Dowsett et al., 1994) [106] These three criteria must all be present for a diagnosis of M.E./PVFS Exercise-induced fatigue precipitated by trivially small exertion -physical or mental -relative to the patient's previous exercise tolerance Impairment of short-term memory and loss of powers of concentration, usually coupled with other neurological and psychological disturbances such as emotional lability, nominal dysphasia, disturbed sleep patterns, disequilibrium or tinnitus Fluctuation of symptoms, usually precipitated by either physical or mental exercise Canadian Consensus Criteria, (Carruthers et al., 2003) [88]

ME/PVFS
For a diagnosis of CFS/ME, a patient must meet the following criteria 1-6 and adhere to item 7: Fatigue Post-exertional malaise and/or fatigue Sleep dysfunction Pain Two or more of the following neurological/cognitive manifestations: Confusion Impairment of concentration and short-term memory consolidation Disorientation difficulty with information processing categorizing and word retrieval perceptual and sensory disturbances One or more symptoms from two of the following categories: Autonomic manifestation (e.g., orthostatic intolerance, postural orthostatic tachycardia syndrome, . . . ) Neuroendocrine manifestation (e.g., loss of thermostatic stability, sweating episode, . . . ) Immune manifestation (e.g., tender lymph nodes, recurrent sore throat, . . . ) Illness lasting ≥6 months

ME/CFS
Definition of Research CFS/ME criteria: Over the past 6 months, persistent or recurring chronic fatigue that is not lifelong and results in substantial reductions in previous levels of occupational, educational, social and personal activities Post-exertional malaise and/or fatigue Unrefreshing sleep or disturbance of sleep quantity or rhythm disturbance Pain (or discomfort) that is often widespread and migratory in nature. At least one symptom from any of the following: Myofascial and/or joint pain (e.g., deep pain, abdomen/stomach pain, or achy and sore muscles. Pain, stiffness, or tenderness may occur in any joint but must be present in more than one joint and lacking edema or other signs of inflammation) Abdominal and/or head pain (e.g., stomach pain or chest pain). Headaches often described as localized behind the eyes or in the back of the head (includes headaches localized elsewhere, including migraines; headaches would need to be more frequent than they were before, which would indicate a new pattern of a new type as compared to headaches previously experienced (i.e., location of pain has changed, nature of pain has changed), or different in severity type as compared to headaches previously experienced by the patient) Two or more of the following neurological/cognitive manifestations: Impaired memory (self-reported or observable disturbance in the ability to recall information or events on a short-term basis) Difficulty focusing vision and attention (disturbed concentration may impair the ability to remain on task, to screen out extraneous/excessive stimuli) Loss of depth perception Difficulty finding the right word Frequently forget what wanted to say Absent-mindedness Slowness of thought Difficulty recalling information Need to focus on one thing at a time Trouble expressing thought Difficulty comprehending information Frequently lose train of thought Sensitivity to bright lights or noise Muscle weakness/muscle twitches At least one symptoms from two of the following categories: Autonomic manifestation: Neurally mediated hypotension, postural orthostatic tachycardia, delayed postural hypotension, palpitations with or without cardiac arrhythmias, dizziness or fainting, feeling unsteady on the feet-disturbed balance, shortness of breath, nausea, bladder dysfunction, or irritable bowel syndrome Neuroendocrine manifestation: Recurrent feelings of feverishness and cold extremities, subnormal body temperature and marked diurnal fluctuations, sweating episodes, intolerance of extremes of heat and cold, marked weight change-loss of appetite or abnormal appetite Immune manifestation: Recurrent flu-like symptoms, non-exudative sore or scratchy throat, repeated fevers and sweats, lymph nodes tender to palpitation-generally minimal swelling observed, new sensitivities to food, odors, or chemicals ME Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport, are prominent features. Although signs and symptoms are dynamically interactive and causally connected, the criteria are grouped by regions of pathophysiology to provide general focus. A patient will meet the following criteria A. Post-exertional neuro-immune exhaustion (PENEpen'-e): Compulsory This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuro-immune regions. Characteristics are as follows: 1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse 2.
Post-exertional symptom exacerbation: e.g., acute flu-like symptoms, pain and worsening of other symptoms.

3.
Post-exertional exhaustion may occur immediately after activity or be delayed by hours or days.

4.
Recovery period is prolonged, usually taking 24-h or longer. A relapse can last days, weeks or longer.

5.
Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
B. Neurological impairments: At least one symptom from three of the following four symptom categories 1.
Short-term memory loss: e.g., difficulty remembering what one wanted to say, what one was saying, retrieving words, recalling information, poor working memory 2. Pain a.
Headaches: e.g., chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; migraine; tension headaches b.
Significant pain can be experienced in muscles, muscle-tendon junctions, joints, abdomen or chest. It is non-inflammatory in nature and often migrates, e.g., generalized hyperalgesia, widespread pain (may meet fibromyalgia criteria), myofascial or radiating pain 3. Sleep disturbance a. Disturbed sleep patterns: e.g., insomnia, prolonged sleep including naps, sleeping most of the day and being awake most of the night, frequent awakenings, awaking much earlier than before illness onset, vivid dreams/nightmares b.
Unrefreshed sleep: e.g., awaken feeling exhausted regardless of the duration of sleep, day-time sleepiness 4. Neuro-sensory, perceptual and motor disturbances a. Neurosensory and perceptual: e.g., inability to focus vision, sensitivity to light, noise, vibration, odor, taste and touch; impaired depth perception b.
Immune, gastro-intestinal and genitourinary Impairments: At least one symptom from three of the following five symptom categories 1. Flu-like symptoms may be recurrent or chronic and typically activate or worsen with exertion. e.g., sore throat, sinusitis, cervical and ⁄or axillary lymph nodes may enlarge or be tender on palpitation 2.
Susceptibility to viral infections with prolonged recovery periods 3.
Sensitivities to food, medications, odors or chemicals d. Energy production⁄ transportation impairments: At least one symptom 1. Cardiovascular: e.g., inability to tolerate an upright position-orthostatic intolerance, neurally mediated hypotension, postural orthostatic tachycardia syndrome, palpitations with or without cardiac arrhythmias, light-headedness/dizziness 2.
Loss of thermostatic stability: e.g., subnormal body temperature, marked diurnal fluctuations; sweating episodes, recurrent feelings of feverishness with or without low-grade fever, cold extremities 4.
Intolerance of extremes of temperature           Low risk of bias (the study is comparable to a well-performed randomized trial with regard to this domain), Moderate risk of bias (the study is sound for a nonrandomized study with regard to this domain but cannot be considered comparable to a well-performed randomized trial), Serious risk of bias (the study has some important problems). Table A6. Brief descriptions of mind-body interventions used in the included studies.

MBIs Definition
Relaxation therapies https://www.nccih.nih.gov/health/relaxation-techniques-for-health (accessed on 13 June 2021). "Relaxation techniques include a number of practices such as progressive relaxation, guided imagery, biofeedback, self-hypnosis, and deep breathing exercises. The goal is similar in all: to produce the body's natural relaxation response, characterized by slower breathing, lower blood pressure, and a feeling of increased well-being".
Movement-based interventions https://www.nccih.nih.gov/health/yoga-what-you-need-to-know (accessed on 13 June 2021). "Although classical yoga also includes other elements, yoga as practiced in the United States typically emphasizes physical postures (asanas), breathing techniques (pranayama), and meditation (dyana). There are many different yoga styles, ranging from gentle practices to physically demanding ones. Differences in the types of yoga used in research studies may affect study results. This makes it challenging to evaluate research on the health effects of yoga. Yoga and two practices of Chinese origin-tai chi and qi gong-are sometimes called "meditative movement" practices. All three practices include both meditative elements and physical ones".
https://www.nccih.nih.gov/health/tai-chi-and-qi-gong-in-depth (accessed on 13 June 2021). "Tai chi and qi gong are centuries-old practices that involve certain postures and gentle movements with mental focus, breathing, and relaxation. The movements can be adapted or practiced while walking, standing, or sitting. In contrast to qi gong, tai chi movements, if practiced quickly, can be a form of combat or self-defense".

MBIs Definition
Mindfulness and cognitive-based Mindfulness-based stress reduction (MBSR): "The program is conducted as an 8-to 10-week course for groups of up to 30 participants who meet weekly for 2-2.5 hr for instruction and practice in mindfulness meditation skills, together with a discussion of stress, coping, and homework assignments". 1 Mindfulness-based cognitive therapy (MBCT): "MBCT incorporates elements of cognitive therapy that facilitate a detached or de-centered view of one's thoughts, including statements such as "thoughts are not facts" and "I am not my thoughts." This decentered approach also is applied to emotions and bodily sensations". 1 Cognitive-behavioral stress management (CBSM) is based on cognitive restructuring: "CBSM interventions reduce distress by teaching relaxation techniques; modifying patients' outlook, cognitive appraisals, and coping strategies; and when performed in a group format may also improve their perceptions of social support". 2 Acceptance commitment therapy (ACT) is based on psychological flexibility. "This is defined as the ability to act in line with important long-term goals or values in life, even in the presence of negative experiences (e.g., non-acute somatic symptoms or psychological distress). Psychological flexibility is a complex overarching behavioral construct that includes several behavioral processes such as acceptance/non-acceptance and cognitive fusion/diffusion". 3 25. guided meditation.mp. 26