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National Collaborating Centre for Primary Care (UK). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy) in Adults and Children [Internet]. London: Royal College of General Practitioners (UK); 2007 Aug. (NICE Clinical Guidelines, No. 53.)

6Management

6.1. Introduction

The GDG was clear that there must be an integrated approach to the management of care for the individual with CFS/ME. There needs to be good communication and regular contact between the healthcare professional and the individual. The healthcare professional should use their clinical judgement to tailor the investigations and interventions required to individual need.

As there are many different symptoms that may concern the patient or the healthcare professional, the healthcare professional needs to have an appropriate level of training in CFS/ME, to avoid over- or underinvestigation of these symptoms.

Complex cases of CFS/ME are common and many patients will be seen by a large number of healthcare professionals. This can lead to unnecessary duplication of investigations and fragmentation of ongoing care. To avoid this, one named clinician should have responsibility for coordinating care for a person with CFS/ME.

There was one key clinical question for this chapter and the evidence and resulting recommendations are presented in four sections: CBT, GET, activity management and other therapeutic interventions (section 6.3); pharmacological interventions (section 6.4); dietary interventions and supplements (section 6.5); and complementary therapies (section 6.6).

6.2. Key clinical question 3 and subquestion 3

Does the evidence show that any particular intervention or combination of interventions is effective in treatment, management or rehabilitation of people with a diagnosis of CFS/ME?

(Subquestion: In people presenting with early suspected CFS/ME what interventions might be effective in preventing progression to CFS/ME?)

6.3. CBT, GET, activity management and other therapeutic interventions

6.3.1. Introduction

It is recognised that patients would access the expertise of the appropriate healthcare professional for advice and support, but the GDG considered that patients should take the lead on any intervention(s) to manage their CFS/ME. The objectives of any programme must be agreed with the patient. They should understand the aims and objectives, and be willing to take part. The suitability, preference, ordering and timing of interventions should be discussed and this may be an iterative process. It was noted that individuals are likely to need staged interventions, where increases in either the severity or complexity of symptoms trigger the use of different interventions or different intensities of intervention (either a reduction – see the section on setbacks/relapses, or an increase – for example the pharmacological treatment of symptoms), as appropriate.

In this guideline, the GDG has used specific definitions of the different therapeutic interventions, and these have been included in the recommendations. Because of the complex nature of these therapies, the GDG considered that some additional information and descriptions would also help the healthcare professionals responsible for delivering these interventions or involved in the care of people accessing them. Such descriptions have been included in the following sections; for a more complete list, please refer to the Glossary.

6.3.1.1. Cognitive behavioural therapy (CBT)

CBT is a specific psychological therapy, based on underlying theoretical principles, with a broad evidence base across a variety of conditions. CBT as recommended for use with people with CFS/ME is described in detail in the recommendations.

CBT is an evidence-based therapy for CFS/ME. It is a collaborative approach that aims to reduce the levels of symptoms, disability and distress associated with CFS/ME. CBT or psychological approaches to CFS/ME do not imply that symptoms are psychological, ‘made up’ or in the patient’s head. CBT is used as part of the overall management for many conditions, including cardiac rehabilitation, diabetes and chronic pain.

6.3.1.2. Graded exercise therapy (GET)

GET is an evidence-based professionally mediated approach to CFS/ME involving appropriate physical assessment, mutually negotiated and meaningful goal-setting and education. An achievable baseline of physical activity is agreed, followed by individually tailored and planned increases in the duration of exercise. This is followed in turn by an increase in intensity when the patient is able, taking into account their preferences and objectives, current activity patterns, sleep, setbacks/relapses and other factors, with the objective of improving symptoms and functioning.

Assessment before beginning a GET programme

An appropriate assessment will include the patient’s history, activity patterns, symptom patterns, functional capacity, sleep patterns, medication and current physical capacity, and other factors as appropriate.

Physical capacity can be determined by a simple, global measure such as a walking test or sit-to-stand test, alongside measures of heart rate and perceived exertion. To avoid triggering post-exertional symptoms, a detailed, strenuous or lengthy physical assessment of range of movement, aerobic fitness or strength should be avoided.

Goals of a GET programme

In clinical trials the ultimate goal of GET that showed benefit was to achieve and maintain 30 minutes of moderate aerobic exercise 5 days out of 7 (for example, a brisk walk). In clinical practice, patient-centred goals should be developed (which may be less or more than those used in the clinical trials). Through discussion, it should be agreed how this could be achieved in everyday life, according to the patient’s individual circumstances and physical ability: for example, a 2 × 15 minutes daily brisk walk to the shop, or a return to some previous active hobby, such as cycling or gardening.

It is important to note that while this is the ultimate (long-term) goal of the GET programme, the patient will not start their programme at this level. The first short-term goal may be gentle stretching or a small, slow walk which (for those that are able) is gradually increased to 30 minutes.

Person centredness

Some patients with CFS/ME report that exercise programmes have been applied inflexibly at times, without consideration of individual circumstances and goals, sometimes with significant adverse responses. Inevitably, patients can feel at a great disadvantage if they are not in control of the programme, their goals and their rate of progression. It is essential that agreement and negotiation are at the very centre of a GET programme, forming a cornerstone at every stage, so that patients feel in control of the activity and their rates of progression.

Healthcare professionals delivering a GET programme should do so with a degree of caution, recognising that for many patients with CFS/ME, GET can cause an increase in symptoms which can be distressing.

Important differences between GET and a general exercise programme

GET is a structured, mutually developed and monitored programme that plans gradual increments of exercise or physical activity, using a specific method shown to be successful for patients with CFS/ME in published research. This is in contrast to a general exercise programme involving simply ‘going to the gym’ or ‘just getting walking a bit more’, or perhaps ‘swimming a few lengths every day’.

What makes GET different from a general exercise programme is the delivery by and liaison with a trained professional (such as a physiotherapist), activity analysis before starting the programme, and mutually agreed starting points and progression.

A GET programme is delivered in partnership with the patient, and after a thorough assessment of current daily activity. It would not be appropriate, for example, for a patient to undertake a GET programme involving swimming if they cannot get up and get dressed every day. The start to their programme is likely to involve a physical functional task involving personal care, for example, or gentle stretches. A GET programme, as described in the guideline recommendations [1.6.2.11–21], is evidence based for ambulant people with mild or moderate symptoms of CFS/ME and has been shown to be of benefit; a general exercise programme is not evidence based for this patient population and can do patients more harm than good.

Unsuccessful general exercise programmes, perhaps undertaken independently by the patient, or under brief advice from professionals not adequately trained in the use of GET, are often begun at a high, unachievable level, with an inappropriately rapid rate of progression, or without adequate professional supervision or support. An unstructured and poorly monitored or progressed exercise programme can cause significant symptom exacerbation, and can arguably make CFS/ME worse.

GET for people with severe CFS/ME

The research trials of GET reviewed in this guideline recruited mainly ambulant participants, with few, if any, people with severe CFS/ME. However, in clinical practice, elements of GET are commonly used successfully in this patient group, such as a gradual increase in gentle walking, or gentle stretches. However, some patients report that they have significant reservations about exercise (aerobic exercise in particular) and that exercise can significantly adversely affect their symptoms and function. It is unlikely that patients with severe CFS/ME will be undertaking aerobic exercise, although they may be able to start the non-aerobic component of the GET programme (such as gentle stretches). If they reach the stage at which aerobic exercise is added to a programme, it is likely that they will now be classified as having moderate or mild CFS/ME.

Activity management strategies (as described in the recommendations) may be an appropriate initial choice of management for people who have severe CFS/ME, or those who do not wish to participate in a GET programme. However, it should be noted that activity management also is not supported by research evidence for people who have severe CFS/ME, but is recommended by expert clinicians. GET may be an appropriate addition to activity management if and when a patient wishes to, or feels ready and able to, further develop their physical capacity and functioning.

6.3.1.3. Activity management

Activity management is a person-centred, collaborative approach to managing symptoms. It is goal directed and promotes the skills of activity grading and analysis to enable patients to improve and/or maintain their function and sense of well-being in self-care, work and leisure roles.

Activity management is the approach that many therapists adopt for those with severe or moderate CFS/ME, and indeed it teaches skills for life to those moving towards a return to work and higher levels of productivity. Patients should have ongoing access to and contact with therapists who use this (and any of the other approaches), such as community rehabilitation teams, occupational therapists, physiotherapists and rehabilitation care assistants. Ideally, patients should be able to refer themselves for ‘top-up’ sessions should life demands make it necessary.

6.3.1.4. Pacing

Pacing is a self-management approach, drawing on some concepts used in activity management, which many patients have reported helpful. However, there is currently no research evidence to support its use, or to determine whether it is beneficial overall. There are several definitions of pacing and the definition as used in this guideline can be found in the Glossary.

6.3.1.5. Sleep management

This includes techniques such as sleep hygiene, which uses behavioural approaches, and changes in environmental conditions which can be introduced to improve the quality of sleep.

6.3.1.6. Relaxation

Relaxation is described as a state characterised by a reduction in physical and mental arousal, leading to feelings of peace, and release from tension and anxiety. Achieving it often requires practice but it can be a helpful strategy for people with CFS/ME.

Relaxation training and memory aids such as organisers and written resource manuals may also be helpful for addressing cognitive problems.

6.3.1.7. Management of setbacks/relapses

People with CFS/ME have variations in the severity of their symptoms and will experience setbacks/relapses or transient increases in fatigue and other symptoms. These setbacks/relapses can vary significantly in their duration and severity, being anything from a slight reduction in function through to severe symptoms resulting in significant disability.

Setbacks/relapses are to be expected as part of the normal course of CFS/ME. With effective management, the frequency, severity and duration of setbacks/relapses should reduce.

Setbacks/relapses appear to be caused by different things; triggers can include, for example, sleep disturbance, overactivity, stress or an active infection (such as a common cold). However, it may not always be possible to identify a cause.

Advice on managing setbacks/relapses may vary according to the cause. For example, it may be advisable to maintain an exercise programme, in agreement with the patient, if stress has been a causative factor, but not if there is an active infection. Difficulty may arise in distinguishing symptoms caused by CFS/ME from those of an active infection, as such symptoms are often similar (for example, increased fatigue, myalgia, headache, sore throat). In this situation, measurable evidence can be helpful (such as taking temperature with a thermometer, evidence of sputum). If an active infection is present, a different approach would then be used.

6.3.1.8. Use of equipment and adaptations

Although many patients with CFS/ME require equipment or adaptations at times for a limited period, others may need to use them in the longer term. Ongoing assessment is needed to ensure that any risks associated with prolonged, inappropriate use of equipment or adaptations are reduced.

6.3.2. Evidence statements

Clinical effectiveness evidence statements

6.3.2.1.

Cognitive behavioural therapy is effective in adults and has been shown to reduce symptoms, improve function and improve quality of life (Evidence level 1+)

6.3.2.2.

Such evidence that is available in children indicates cognitive behavioural therapy is effective in improving physical function, fatigue, school attendance and symptoms (Evidence level 1+)

6.3.2.3.

Five trials investigating incremental physical exercise programmes showed improvements in adults in various health outcomes including mental and physical fatigue, global improvement, disability, sleep, mood and cognition (Evidence level 1+)

6.3.2.4.

Two trials investigating incremental activity programmes showed improvements in adults in various health outcomes including all of the outcomes listed. (Evidence level 2)

6.3.2.5.

Trials used different approaches to incremental physical activity including graded exercise, graded activity and pacing, individually and in combination. It is unclear whether one has a greater beneficial effect than another. (Evidence level 2)

Cost effectiveness evidence statements

6.3.2.6.

The only estimate of cost effectiveness suggests the cost per quality-adjusted life year (QALY) of CBT for people with CFS/ME relative to no-protocol medicine to be £16,036. This estimate includes costs from a NHS perspective.

6.3.2.7.

Evidence suggests that treatment effects of interventions for CFS/ME are incurred over a longer period of time than the follow-up of 14 months, as evaluated in one trial. Although it was decided to not extrapolate on methodological grounds, it can be assumed that if some benefit was maintained to a time horizon of 5 years, the cost per QALY will fall.

6.3.2.8.

There is insufficient evidence to suggest that group CBT is cost effective relative to individual CBT.

6.3.2.9.

No studies were identified dealing with the cost effectiveness of long courses of CBT relative to short courses.

6.3.2.10.

Computerised cognitive behavioural therapy is cost effective in other areas of medicine. There is no evidence regarding the generalisability of this result to CFS/ME.

6.3.3. Clinical evidence summary

6.3.3.1. Summary of evidence presented in Appendix 1

Adults

Ten RCTs met the inclusion criteria for assessment of CBT or modified CBT in people diagnosed with CFS according to one of the recognised case definitions; one also included people with postviral fatigue syndrome. Validity scores (see Appendix 1) for these studies ranged from 1 to 18, with four studies scoring > 13. Comparators differed among studies: CBT was compared to routine medical care in four studies, to relaxation in two studies, to guided support in one study and to leukocyte injections and controls in another study. One study had a sample size of n = 270, the others had sample sizes of < 60.

Eight of the studies reported beneficial effects of CBT on physical functioning, fatigue and global improvement. Two studies with low validity scores (1 and 3 respectively) showed no significant difference.

Six studies of other regimes with either mixed methods or behavioural interventions were reviewed. Only one was a high-quality RCT and this study of multiple symptom-based interventions (including supplements) found significant improvements in favour of the treatment group in symptom scores. However, in such studies it is difficult to determine which interventions are responsible for the observed effects.

Graded exercise therapy

Five RCTs were reviewed which assessed the effects of GET in patients with CFS. Sample sizes ranged from 49 to 148. Validity scores ranged from 9 (two studies) to 17 (three studies). Significant improvements in measures of fatigue and physical function were found in all five RCTs. When exercise was combined with fluoxetine there was no additional effect.

Children

One controlled trial of rehabilitation/CBT in children reported significant improvements in the treatment group in measures of global well-being.

6.3.3.2. Additional clinical evidence

Expert Patient Programme

The Expert Patient Programme (EPP) was introduced into the NHS in 2001. It provides an opportunity for patients with chronic long-term conditions to develop new skills to manage their condition on a day-to-day basis through participation in generic lay-led group workshops. Information is available at http://www.expertpatients.nhs.uk/index.aspx

The CFS/ME Service Investment Programme 2004–2006 received mixed feedback regarding the suitability of the EPP for CFS/ME patients.34 The results of the feedback identified important considerations in using EPP in a CFS/ME context and also noted significant disadvantages of the programme in a CFS/ME setting.{1171] There was general support within the GDG for the use of such programmes, when delivered appropriately, to help people with mild or moderate CFS/ME to manage their symptoms. However, there was less support for the use of peer support programmes for people with severe CFS/ME.

Update of evidence following the systematic review

An update search of evidence on treatments for CFS/ME published following the original review produced five new studies that met the inclusion criteria. A systematic review of interventions for CFS/ME{215}, which searched only PsychInfo and Medline and failed to describe the quality assessment criteria, concluded that CBT generally appeared to be effective. RCTs evaluating GET were also found to have an overall beneficial effect on fatigue and functional work capacity.

Group CBT was compared to education and support and standard medical care in one RCT (n = 153). The authors concluded that ‘group CBT did not achieve the expected change in the primary outcomes (SF-36 physical and mental health) but significant improvements were seen in fatigue, mood, and physical fitness’.35

A small RCT36 (n = 47) evaluated the impact of a community-based programme consisting of an illness management group and one-to-one peer counselling. Significant gains were observed for programme participants across all categories – interpersonal, energy, material, work, well-being and mastery resources. The sample size and subjectivity of the assessment tools limit the generalisability of this study.

6.3.4. Health economics evidence summary

6.3.4.1. Introduction

The clinical benefits of interventions for CFS/ME have been shown in a number of papers (please find detailed descriptions in Appendix 1). The precise nature of the trial design used to evaluate these interventions is of importance but there is little doubt that there are interventions that can improve quality of life. These interventions can be costly, often involving input from more than one member of a multidisciplinary team. A full literature search was undertaken to appraise the volume and quality of the available cost-effectiveness studies.

6.3.4.2. Initial search results

The cost-effectiveness literature search yielded 60 unique records. The abstracts were reviewed, three papers were ordered and their results were extracted. All were cost-effectiveness studies, cost–utility studies or cost–consequence studies, written in English and dealing with interventions regularly used for CFS/ME. Two of the papers primarily considered patients with chronic fatigue rather than CFS/ME. Using the CDC 1994 criteria28, the proportion of the chronic fatigue population with CFS/ME in these studies was 28% and 29%. The extent to which these studies can be extended to a CFS/ME population is discussed at a later point. All three papers were based on published clinical trials. Some information about the interventions is provided in this section and these details should be considered as a summary of the more detailed analysis in the systematic review.

A Dutch study (Severens et al.37) looked at the cost effectiveness of CBT for CFS/ME patients. The analysis was based on a trial where patients were randomly assigned to CBT, guided support groups (SGs) or a no protocol-based intervention in primary care.38 The authors collected cost and quality of life (QoL) data at baseline, after the 8-month treatment period and at follow-up, 6 months after discontinuation of treatment. QoL was measured using a EuroQol questionnaire. It should be noted, however, that there was a difference in the groups at baseline (0.486 for the CBT group and 0.526 for the control, no p value stated). Please refer to Table 2 for details. There does not appear to have been any attempt to correct for this difference between comparison groups, and this may have led to bias in the analysis. Sensitivity analysis was carried out to test the robustness of the result when the incremental health gain is reduced. Please refer to Section 6.3.5.4 for details.

Table 2. The results from the Severens study (costs in 1998 Euros).

Table 2

The results from the Severens study (costs in 1998 Euros).

In the paper, the costs collected were associated with the following: GP care, medical specialist CFS/ME care, physiotherapy, psychology and alternative care provision. The authors noted immediately that the QoL of patients in the SGs was lower than in the no protocol-based intervention group (no p value stated). Since the costs in the former exceeded those in the latter, it was dominated and hence excluded from the rest of the economic evaluation.

Using these data, the authors estimated that the cost per QALY relating to a perspective comprising: (1) a protocol-based treatment costs; (2) treatment costs, other medical costs and patients costs; and (3) these costs plus productivity costs were €60,108, €51,642 and €21,375 respectively. It should be noted that there was a high degree of uncertainty around the ICER (incremental cost-effectiveness ratio) in non-parametric bootstrapping analysis for varying willingness-to-pay thresholds.

Conventional NICE methodology suggests interventions should be viewed from the perspective of the NHS and personal social services. For the reported resource use, NHS specific items were identified and priced to meet the NICE methodology standard. Using the reported QALY differences at 14 months, the baseline result amounts to £16,036 per QALY. The costing of the study to meet NICE standard will be described in detail in Section 6.3.5.

The second paper was a UK study that looked at the cost effectiveness of CBT, graded exercise and usual care for patients with fatigue in primary care.39 Again, this paper was based on a published clinical trial.40 However, the study population was patients with chronic fatigue, of which only a proportion (29%) fulfilled the CDC criteria and thus were CFS/ME patients. It has to be borne in mind that results from this paper are not readily generalisable from chronic fatigue patients to CFS/ME patients, and data on the CFS subgroup were underpowered.40

The paper reported that:

‘consenting patients were randomized to six sessions of CBT or GET. Sessions each lasted 45 min. CBT was delivered by trained cognitive behavioural therapists and included an initial assessment, activity planning, homework and establishing a sleep routine. The aim of the CBT was to enable patients to address negative beliefs regarding symptoms, self-expectations and self-esteem. GET was tailored to each patient’s physical capacity and aimed for a gradual increase in aerobic activities, especially walking, and was delivered by physiotherapists.’

The employed effectiveness data from the clinical trial40 demonstrated a reduction in fatigue in 41 (79%) patients receiving CBT, compared to 35 (71%) patients in the GET arm. For fatigue patients, the cost-effectiveness study estimated that the incremental cost of CBT relative to GET was £519 at baseline (90% CI –£814 to £1904, p = 0.522). However, at follow-up, CBT resulted in a net saving of –£193 (90% CI –£946 to £458, p = 0.62). The authors note that costs and outcomes of CBT and GET were similar, although if values were placed on outcomes, CBT showed improved cost effectiveness.

On the basis of cost-effectiveness acceptability curve analysis, CBT appeared to be more cost effective. For cost-effectiveness studies, the uncertainty reflected in clinical effectiveness papers by statistical significance is replaced with cost-effectiveness acceptability curves. To allow inter-procedural comparison, it is preferable for a cost-effectiveness study to use a generic measurement of outcome with some suggested valuation of an incremental outcome such as a QALY). However, this paper illustrates the probability of the intervention being cost effective based on the valuation of an incremental improvement in the Chalder fatigue scale. For example, the authors estimated that a societal valuation of a four-point improvement of £5000 would mean that there is a 76.6% probability of CBT being cost effective relative to GET for patients with chronic fatigue.

As mentioned above, a CFS/ME subgroup analysis of the trial on which this cost-effectiveness analysis was based could not be carried out due to lack of power, and conclusions from fatigue patients could not be transferred to the CFS/ME population. Despite this, the trial paper reported consistency with other evidence, showing a trend for ‘CBT to have a slight advantage, particularly in the group with CFS’.

Lastly, the literature search identified a UK cost–consequence study which looked at the effect of CBT and counselling in primary care41 and was based on the results of a clinical trial.42 Again, the study population was a chronic fatigue population, of which only a proportion were CFS/ME patients (28%). The clinical paper did not provide adequate subgroup analysis for those in the trial meeting 1994 CDC criteria.28

Therefore, if costs of CBT or counselling in a CFS/ME population are not generalisable from chronic fatigue patients, cost-effectiveness conclusions for CFS/ME patients cannot be reached.

For the general fatigue population, the paper found that a comparison of change scores between baseline and 6-month assessment revealed no statistically significant differences between the groups receiving CBT and counselling in terms of aggregate healthcare costs, patient and family costs or incremental cost effectiveness (cost per unit of improvement on the fatigue score).

6.3.5. Further work after the presentation of results

The GDG considered that the papers dealing primarily with people with chronic fatigue rather than CFS/ME were only of use as background material and results could not be generalised to CFS/ME patients. The group also considered that the timescale employed by the authors in the Dutch paper (Severens et al.37) was insufficient to show the full benefits and extending the timescale was considered.

6.3.5.1. Extending the timescale of the Dutch study

The Dutch economic evaluation37 looked at the costs and benefits of CBT and guided support groups relative to the natural course over 8 months of treatment and 6 months of follow-up. There is evidence suggesting that for some patients, the benefit of CBT can extend beyond that, and up to 5 years. Deale and colleagues reported that 68% of patients receiving CBT rated themselves as ‘much improved’ or ‘very much improved’ at a 5-year follow-up relative to 36% who received relaxation therapy.43

The implicit assumption in Severens and colleagues’37 selection of a 14-month timescale is that the costs and benefits beyond this period return to baseline. The GDG considered that, while both benefits and costs of treatment would be skewed towards the earlier periods, costs would be more so. Assuming that people receiving CBT gain an improvement in utility compared to exercise therapy, and assuming that this can be generalised to the relaxation comparator used by Deale and colleagues,43 maintaining some of the utility gain for a longer period will improve the cost effectiveness of CBT. However, the potential bias posed by the differences in comparison groups for the utility outcome variable at baseline led to the decision that an extrapolations over longer time periods was not sufficiently supported. This is in agreement with Severens and colleagues, who state in their paper that extrapolation over time “was invalid due to [a] lack of understanding between CFS and health state valuation”.37

6.3.5.2. Costing of the Dutch study to meet NICE methodology standards

As stated earlier, the Dutch study37 reported incremental costs per QALY from a treatment protocol, treatment plus patient cost and societal perspective (please see Section 6.3.4.2). In order to meet NICE methodology standards, it was decided to use 2006 NHS prices to match the reported resource use from the trial. This helped to subsequently anticipate the cost effectiveness of CBT in a UK setting.

The paper subdivides costs over the 14 months to those occurring in the treatment period and those occurring during the follow-up period. The costs, together with the effectiveness results of this study, are shown in Table 2. From the original costs presented in this table can be seen that during the intervention period of the first 8 months, there were higher costs in the treatment group than in the ‘no protocol’ comparison group. Meanwhile, the reported resource use in the follow up period in months 8–14 showed that people who had received CBT had lower service use uptake and referrals than the no protocol group. Thus, some of the treatment costs can be expected to be offset by lower follow-up care costs.

For the cost adjustment to a UK NHS perspective, we used 2006 reference costs for Health and Social Care 44, in accordance with NICE methodology. The results of the costing is presented in Table 3.

Table 3. Costing results using resource uses reported that reflect the NHS perspective.

Table 3

Costing results using resource uses reported that reflect the NHS perspective.

Table 3 shows the health services used by CFS patients during the treatment period (0–8 months) and during the treatment period and follow up (0–14) in 2006 Pound Sterling from an NHS perspective. The results shown in Table 3 reflect the study finding of cost savings during follow up for CBT patients offsetting some of the initial CBT treatment costs. The cost difference in the treatment period (£640.20) is higher than the cost difference, that is, the increment, over the entire study period (£447.40).

The NHS perspective excluded some of the trial protocol costs, and although unlikely, may not include cost items that would be included in this perspective. Deterministic sensitivity analysis has been carried out to anticipate the level of uncertainty surrounding the incremental cost figure used. Please see Section 6.3.5.3 for details.

With the costs adjusted to a UK perspective, costs were combined with the Dutch study’s effectiveness results to present an ICER. Table 4 summarises the results of the costing and effectiveness data, while Table 5 presents the incremental cost effectiveness ratio based on these figures.

Table 4. Combining UK costing results with Severens paper utility scores.

Table 4

Combining UK costing results with Severens paper utility scores.

Table 5. Incremental analysis using UK costing results and utility scores Severens paper.

Table 5

Incremental analysis using UK costing results and utility scores Severens paper.

The estimate of the incremental cost effectiveness ratio of £16,036 per QALY comparing CBT with no protocol presented in Table 5 lies below the £20–30,000 per QALY willingness to pay threshold and would therefore be considered cost effective.

As stated in section 6.3.4.2, there are some serious concerns regarding the difference at baseline utility, and additional sensitivity analysis was carried out. Please see section 6.3.5.4 for details and results.

6.3.5.3. Sensitivity of the ICER estimate to changes in incremental costs

Table 6Sensitivity analysis for varying incremental cost for CBT compared with no protocol

Incremental costIncremental effectivenessICERs
Varied costs CBT-NC£20.00
Severens utility increment0.02790£716.85
Varied costs CBT-NC£200.00
Severens utility increment0.02790£7,168.46
Varied costs CBT-NC£400.00
Severens utility increment0.02790£14,336.92
Varied costs CBT-NC£600.00
Severens utility increment0.02790£21,505.38
Varied costs CBT-NC£800.00
Severens utility increment0.02790£28,673.84
Varied costs CBT-NC£1,000.00
Severens utility increment0.02790£35,842.29

One-way sensitivity analysis shows that the ICER is not highly sensitive to changes in costs for a care programme containing CBT. If the incremental costs for CBT were increased to almost double (to £800), while keeping all other parameters constant, the cost effectiveness estimate then is £28,674 per QALY.

6.3.5.4. Sensitivity of the result to changes in utility gain

As stated in previous sections, there is a significant difference in baseline QoL between the groups, with the CBT group reporting a lower value than the no-protocol group. This uncontrolled source of bias can result in false treatment effects through regression to the mean effect.

In order to anticipate the magnitude of uncertainty, we conducted some basic sensitivity analysis. It should be noted that although there are methods to adjust for differences in baseline utilities, that is, regression based techniques45, such adjustment was not undertaken in this analysis.

Table 7 presents the results for the sensitivity analysis carried out to anticipate uncertainty surrounding the ICER for CBT compared to no protocol by means of utility gain value changes. It has not been possible to carry out regression based sensitivity analysis using covariates as we did not have access to the trial data. Therefore we resorted to other methods for a deterministic, one way sensitivity analysis.

Table 7. Results from sensitivity analyses (SA) A and B for changes in utility gain.

Table 7

Results from sensitivity analyses (SA) A and B for changes in utility gain.

As it has not been possible to correct for a potential bias, for univariate sensitivity analysis A (SA-A), the reported utility gain was reduced to 75%, 50% and 25% of its original value. For sensitivity analysis B (SA-B) the areas under the curve were calculated using the reported baseline values, as well as an averaged baseline. The area under the curve calculation may not be a valid attempt to correct, however, it resulted in very small differences in QALY gains and therefore shows how sensitive the result to variations in utility gain is. Moreover, graphs illustrated how the difference at baseline affects the areas under the curves, particularly since they become almost identical at 8 and 14 months follow up.

Sensitivity analyses A and B yielded new sets of utility values, which are displayed in Table 7 and were, together with the NHS perspective costs (Section 6.3.5.3) used to calculate new ICERs. In sensitivity analysis A, the ICER is below £25,000 at the lower utility value. If the sensivity analysis is changed to a reduction of utility gain by 50%, CBT is at £32,071 per QALY less likely to be still cost effective. If the increment in utility is reduced to 25% of its present value, CBT does not appear cost effective (£64,143 per QALY).

Sensitivity analysis B shows that the area under the curve calculation leads to CBT being unlikely to be cost effective with £34,548 per QALY. When the baseline difference is equalised, the ICER shoots up to £283,421. This emphasises the importance of correcting for differences at baseline for future guideline updates as regression to mean effect could have a significant impact on the cost effectiveness result.

As stated previously, there is some indication that if any effect of treatment endures in a subset of the population for up to 5 years, the estimates of cost effectiveness in Severens37 are possibly too low, however, it is not possible to quantify these.

6.3.5.5. Is group CBT cost effective relative to education and support and standard medical care?

The GDG felt it would be worthwhile exploring the issue of group CBT. A 12-month follow-up study with 153 participants looked at this area.35 The study was based in the health psychology department of a general hospital and compared group CBT, education and support (EAS), and standard medical care (SMC). The CBT programme was designed to ‘attempt to modify thoughts, beliefs and behavioural responses to symptoms and illness with a view to increasing adaptive coping strategies’. The authors give four key areas of therapy.

The key elements of group CBT highlighted by the authors were,

  • ‘Elucidation of core beliefs about their illness and its management
  • Monitoring of activity levels and introduction of appropriate aerobic, strength and stretching exercises designed to increase fitness, balance and confidence in exercise
  • Behavioural modification of sleep patterns and mood management advice
  • Goal setting’35

The EAS group was included to allow for the effect of receiving a therapy per se and for the cost of the time of the therapist. Both group CBT and EAS were delivered by the same therapists, to cohorts of between 8 and 12 individuals in a series of 8 fortnightly meetings, each lasting 2 hours.

The group CBT intervention branch had statistically significantly higher SF36 scores (p = 0.019) and lower fatigue scores (p = 0.027), and were able to walk faster as measured by shuttle walking (p = 0.0013) relative to the SMC group. Relative to the EAS group, the group CBT patients walked faster and were less fatigued (p = 0.047 and p = 0.011 respectively). The lack of a statistically significant difference in SF36 scores between EAS and group CBT could be due to the effect of CBT being somewhat diluted by the use of larger groups.

There were severe limitations, and reported data relating to cost effectiveness are based on poor quality. Incremental cost-effectiveness ratios (ICERs) were not reported because there was no difference in utility. In addition, the study was underpowered to detect significant differences in costs for performing a cost minimisation analysis. The alternative to cost minimisation analysis would be to use the bootstrapping technique to obtain a cost-effectiveness acceptability curve (CEAC). However, the authors of the study deemed this approach unsuitable since ‘the data quality does not justify the application of sophisticated statistical techniques’.

Therefore conclusions regarding recommendations on group CBT in relation to EAS and SMC cannot be drawn, and conclusive comparisons between group CBT and individual CBT require further research.

6.3.5.6. Cost effectiveness of differing quantities of CBT contact time

As suggested by the GDG, CBT is usually performed over around 12 sessions. However, two trials look at the effect of CBT performed over only 6 sessions.40;46 As described previously, Ridsdale40 did find considerably poorer outcomes from 6 sessions of CBT in people with CFS/ME than in those with general chronic fatigue. However, in people with CFS/ME, fatigue scores still fell by 26% on Chalder’s fatigue scale. The cost-effectiveness issue is whether the additional benefit gained by extending CBT from 6 to 12 or more sessions is a good use of resources.

No papers were identified comparing different lengths of CBT courses. Therefore, comparison between studies was necessary. To compare shorter and longer courses of CBT, studies containing the same outcome measures are needed. If there is a common outcome measure between a paper looking at a short course, and one looking at a relatively long course, incremental cost-effectiveness analysis can be undertaken. However, the measurement of outcomes in CFS/ME is variable and there was no outcome measure common to papers covering short and long regimes. As with any clinical decision, it is important to constantly appraise progress and expectations of the programme. Thus, if clinician and patient feel that a short course has proven adequate, and further CBT is likely to be of little extra value, the cost of extending therapy should be taken into account.

6.3.5.7. Cost effectiveness of computerised cognitive behavioural therapy in CFS/ME

There were no identified papers looking at the cost effectiveness of this approach in CFS/ME. Previous NICE technology appraisal guidance deals with the use of computerised cognitive behavioural therapy (CCBT) for depression and anxiety (see www.nice.org.uk/TA097).47

It should be noted that this appraisal deals with a very different issue. However, in the absence of evidence in a CFS/ME population, the GDG considered the costing and efficacy data from the assessment report as background information.

The Assessment Group for the appraisal developed a decision-analytic model, looking at three specific CCBT products for depression. Since the interventions are not designed for a condition comparable to CFS/ME, the differences between the interventions are not relevant. What is potentially noteworthy is the range of costs of adopting these strategies. The Assessment Group identified costs in the following areas: licence fees, computer hardware, screening of patients for suitability, clinical support, capital overheads and training of staff. The incremental cost of supplying CCBT was £40 (£397 compared to £357 for ‘treatment as usual’). It should be noted that the cost of 1 hour of healthcare provider time is significant. If there is a benefit in providing these computerised services, it might be viable to replace a small section of CBT time with ongoing CCBT support.

The QALY gains through CCBT reported in this appraisal are not of significant interest for this CFS/ME discussion since they refer to a wholly different patient group. However, for information, the assessment report suggests a gain of 0.032 QALYs per individual. If the incremental cost is assumed to generalise to a CFS/ME patient group, and a societal willingness to pay of £20 000 is assumed, the QALY gain required is 40/20,000 = 0.002.

Thus, in so far as the costs and outcomes are generalisable, the evidence suggests that CCBT is cost effective relative to no CCBT.

6.3.6. Clinical scenario questionnaire to GDG and wider group

So that consistent principles were applied in rating the evidence statements, the GDG and the wider survey group assumed the following.

  1. The person with CFS/ME and healthcare professionals involved in their care will make decisions in partnership. These are directed by the patient’s personal preferences and build on the existing experience and skills of the professional.
  2. All treatments are offered allowing the person with CFS/ME to refuse without compromising the further therapeutic relationship.
  3. There is a good rapport in which the patient and their families/carers feel believed and validated.
  4. Treatment is provided by the NHS in the context of availability of adequate numbers of competent, appropriately trained healthcare professionals.
  5. Minimal waiting times for good-quality services are adhered to.
GDG Round 1GDG Round 2Wider GroupDiscussion
Question and ResultsQuestion and ResultsQuestion and Results
3(a)A programme consisting of a planned increases of aerobic exercise is appropriate....A programme consisting of increases of aerobic exercise (i.e. exercise which increases the pulse rate) is appropriate....Question changed and re-rated
1. for adults with CFS/ME with mild symptomsAgreeAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
2. for adults with CFS/ME with moderate symptomsUncertainAgreeDisagreeRandom selection for wider survey
3. for adults with CFS/ME with severe symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
4. for children with CFS/ME with mild symptomsUncertainAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
5. for children with CFS/ME with moderate symptomsUncertainAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
6. for children with CFS/ME with severe symptomsUncertainUncertainDisagreeGDG was uncertain at round 2, progressed to wider survey
3(b)A programme which allows the person to find a baseline, followed by gradual and sustainable increases in activity/exercise (physical, emotional, cognitive) is appropriate....A programme which allows the person to find a baseline, followed by gradual and sustainable increases in activity/exercise (physical, emotional, cognitive) is appropriate....
1. for adults with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgreeAgreeThe GDG discussed the severely affected following round 1 and due to their uncertainty decided to progress this to Round 2 to be consistent with children.
4. for children with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsUncertainUncertainDisagreeGDG was uncertain at round 2, progressed to wider survey
A programme based upon planned increases in duration of physical activity/exercise followed by increases in intensity leading to aerobic exercise is appropriate....A programme based upon planned increases in duration of physical activity/exercise followed by increases in intensity leading to aerobic exercise (i.e. exercise which increases the pulse rate) is appropriate....
3(c)1. for adults with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
4. for children with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsUncertainUncertainDisagreeGDG was uncertain at round 2, progressed to wider survey
3(d)A programme that encourages self management and builds on the skills of the individual is appropriate
1. for adults with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3(e)A programme involving assessment and management of the emotional impact of CFS/ME is appropriate....
1. for adults with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3(f)Techniques that improve the quality of relaxation and restorative rest are appropriate.......
1. for adults with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3(g)Setting an individually tailored self management strategy (with patient-centred goals) is appropriate....
1. for adults with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3(h)A strategy that always maintains activity levels at substantially less than full capacity in order to have reserve energy for the body to heal itself (can be known as the envelope theory) is appropriate....
1. for adults with CFS/ME with mild symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
2. for adults with CFS/ME with moderate symptomsUncertainDisagreeAgreeRandom selection for wider survey
3. for adults with CFS/ME with severe symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
4. for children with CFS/ME with mild symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
5. for children with CFS/ME with moderate symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
6. for children with CFS/ME with severe symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
3(i)A strategy which involves monitoring thoughts and discusses alternative cognitive or behavioural strategies is appropriate….
1. for adults with CFS/ME with mild symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgree...The GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsUncertainThe GDG decided that this was not consistent with other responses to this statement and could not see any reason why children with mild symptoms should be different from children with moderate or severe and therefore this did not progress.
5. for children with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3(j)A programme that encourages patients to extend their activity capacity is appropriate….
1. for adults with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3(k)Strategies to normalise sleep patterns are appropriate….
1. for adults with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3(l)Complete rest (cognitive, physical and emotional) during significant increases in symptoms (a ‘set-back’) is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
3(m)Equipment and adaptations (e.g. a wheelchair) that aims to allow patients to improve independence and quality of life should be provided as part of a management plan….
1. for adults with CFS/ME with mild symptomsUncertainDisagreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
2. for adults with CFS/ME with moderate symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
3(n)3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
5. for children with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3(p)See BelowIndividual Cognitive Behaviour Therapy (CBT) is appropriate….Reworded substantially see table below for original wording
1. for adults with CFS/MEAgreeUncertainRandom selection for wider survey
2. for children with CFS/MEAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
Group Cognitive Behaviour Therapy (CBT) is appropriate….
1. for adults with CFS/MEAgreeUncertainRandom selection for wider survey
2. for children with CFS/MEAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
See BelowCognitive Behaviour Therapy (CBT) combined with an activity programme is appropriate….
1. for adults with CFS/MEAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
2. for children with CFS/MEAgreeThe GDG reached a consensus in round 2 and the statement did not progress to wider survey
The statements below were included in the first round only. When discussed the GDG decided that they were not required in the second round as they were either unclear, duplicated or too detailed.
1. 3(n)Graded Exercise Therapy (GET) is appropriate….Described in the statements above, GDG decided this was unnecessary.
1. for adults with CFS/ME with mild symptomsAgree
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsUncertain
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
2. 3(o)Graded Activity Therapy (GAT) is appropriate….Described in the statements above, GDG decided this was unnecessary.
1. for adults with CFS/ME with mild symptomsAgree
2. for adults with CFS/ME with moderate symptomsAgree
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsAgree
5. for children with CFS/ME with moderate symptomsAgree
6. for children with CFS/ME with severe symptomsAgree
3. 3(p)Pacing is appropriate….Term is not clearly defined, therefore no useful information would be gained by including this statement.
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsAgree
4. 3(q)Individual (one on one) GET is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsAgree
5. 3(r)Individual (one on one) GAT is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptoms
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsAgree
6. 3(s)Individual (one on one) pacing is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsAgree
2. for adults with CFS/ME with moderate symptomsAgree
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsAgree
7. 3(t)About 6 sessions of group GET is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsUncertain
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
8. 3(u)About 6 sessions of group GAT is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsUncertain
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
9. 3(v)About 6 sessions of group pacing is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsDisagree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptoms
10. 3(w)About 12 sessions of activity management therapy (e.g. GET, GAT or pacing) is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsUncertain
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
11. 3(x)The addition of Cognitive Behaviour Therapy (CBT) techniques to other self- management and/or activity management strategies is appropriate….There were too many factors contributing to the answer to make this statement useful
1. for adults with CFS/ME with mild symptomsAgree
2. for adults with CFS/ME with moderate symptomsAgree
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsAgree
6. for children with CFS/ME with severe symptomsAgree
12. 3(y)Individual Cognitive Behaviour Therapy (CBT) is appropriate….This statement was abridged to adults and children only as above. Severity was not regarded as a factor in whether INDIVIDUAL Group Cognitive Behaviour Therapy was appropriate.
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsAgree
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsAgree
13. 3(z)Group Cognitive Behaviour Therapy (CBT) is appropriate….This statement was abridged to adults and children only above as severity was not regarded as a factor in whether Group Cognitive Behaviour Therapy was appropriate.
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsUncertain
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
14. 3(aa)Cognitive Behaviour Therapy (CBT) combined with an activity programme is appropriate….This statement was abridged to adults and children only above as severity was not regarded as a factor.
1. for adults with CFS/ME with mild symptomsAgree
2. for adults with CFS/ME with moderate symptomsAgree
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
15. 3(ab)About 6 sessions of Cognitive Behaviour Therapy (CBT) is appropriate….Including this statement was not a priority and was discarded for brevity
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsUncertain
3. for adults with CFS/ME with severe symptomsDisagree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain
6. for children with CFS/ME with severe symptomsUncertain
16. 3(ac)About 12 sessions of Cognitive Behaviour Therapy (CBT) is appropriate….Including this statement was not a priority and was discarded for brevity
1. for adults with CFS/ME with mild symptomsUncertain
2. for adults with CFS/ME with moderate symptomsAgree
3. for adults with CFS/ME with severe symptomsAgree
4. for children with CFS/ME with mild symptomsUncertain
5. for children with CFS/ME with moderate symptomsUncertain

6.3.7. Recommendations

Note: numbers in square brackets are as in the NICE guidelines.

Advice on symptom management before diagnosis [1.2.3]

Advice on symptom management should not be delayed until a diagnosis is established. This advice should be tailored to the specific symptoms the person has, and be aimed at minimising their impact on daily life and activities. [1.2.3.1]

Function and quality-of-life management [1.4.2]

Sleep management

Healthcare professionals should provide tailored sleep management advice that includes:

  • Explaining the role and effect of disordered sleep or sleep dysfunction in CFS/ME.
  • Identifying the common changes in sleep patterns seen in CFS/ME that may exacerbate fatigue symptoms (such as insomnia, hypersomnia, sleep reversal, altered sleep–wake cycle and non-refreshing sleep).
  • Providing general advice on good sleep hygiene††.
  • Introducing changes to sleep patterns gradually.
  • Regular review. [1.4.2.1]

If sleep management strategies do not improve the person’s sleep and rest, the possibility of an underlying sleep disorder or dysfunction should be considered, and interventions provided if needed. [1.4.2.2]

Sleep management strategies should not include encouraging daytime sleeping and naps. People with CFS/ME should be advised that excessive sleep does not generally improve physical or mental functioning, and excessive periods of daytime sleep or frequent napping may further disrupt the sleep–wake cycle. [1.4.2.3]

Rest periods

Rest periods are a component of all management strategies for CFS/ME. Healthcare professionals should advise people with CFS/ME on the role of rest, how to introduce rest periods into their daily routine, and the frequency and length appropriate for each person. This may include:

  • Limiting the length of rest periods to 30 minutes at a time.
  • Introducing ‘low level’ physical and cognitive activities (depending on the severity of symptoms).
  • Using relaxation techniques (see recommendation 1.4.2.6). [1.4.2.4]

Healthcare professionals should review the use of rest periods regularly as part of the patient’s management plan. [1.4.2.5]

Relaxation

Relaxation techniques appropriate to the person with CFS/ME should be offered for the management of pain, sleep problems and comorbid stress or anxiety. There are a number of different relaxation techniques (such as guided visualisation or breathing techniques) that can be incorporated into rest periods. [1.4.2.6]

Pacing

People with CFS/ME have reported pacing to be helpful in self-managing CFS/ME. However, healthcare professionals should advise people with CFS/ME that, at present, there is insufficient research evidence on the benefits or harm of pacing. [1.4.2.7]

Diet [1.4.3]

See also recommendations on managing nausea (1.4.1.4) and bowel symptoms (1.4.1.5), and use of supplements (1.4.7.2–4).

Healthcare professionals should emphasise the importance of a well-balanced diet in line with ‘The balance of good health’‡‡. They should work with the person with CFS/ME to develop strategies to minimise complications that may be caused by nausea, swallowing problems, sore throat or difficulties with buying, preparing and eating food. [1.4.3.1]

Healthcare professionals should emphasise the importance of eating regularly, and including slow-release starchy foods in meals and snacks. The physiological consequences of not doing so should be explained to the person with CFS/ME. [1.4.3.2]

Equipment to maintain independence [1.4.4]

For people with moderate or severe CFS/ME, providing or recommending equipment and adaptations (such as a wheelchair, blue badge or stairlift) should be considered as part of an overall management plan, taking into account the risks and benefits for the individual patient. This may help them to maintain their independence and improve their quality of life. [1.4.4.1]

Education and employment [1.4.5]

Having to stop their work or education is generally detrimental to people’s health and well-being. Therefore, the ability of a person with CFS/ME to continue in education or work should be addressed early and reviewed regularly. [1.4.5.1]

Healthcare professionals should proactively advise about fitness for work and education, and recommend flexible adjustments or adaptations to work or studies to help people with CFS/ME to return to them when they are ready and fit enough. This may include, with the informed consent of the person with CFS/ME, liaising with employers, education providers and support services, such as:

  • occupational health services
  • disability services through Jobcentre Plus
  • schools, home education services and local education authorities
  • disability advisers in universities and colleges. [1.4.5.2]

For people with CFS/ME who are able to continue in or return to education or employment, healthcare professionals should ensure, with the person’s informed consent, that employers, occupational health or education institutions have information on the condition and the agreed management plan. [1.4.5.3]

Education

Healthcare professionals should follow the guidance from the Department for Children, Schools and Families§§ on education for children and young people with medical needs, or equivalent statutory guidance. [1.4.5.4]

Healthcare professionals should work closely with social care and education services to ensure a common understanding of the goals of the person with CFS/ME. The use of a flexible approach should be discussed, including home tuition and use of equipment that allows a gradual reintegration into education. [1.4.5.5]

Time in education should not be used as a sole marker of progress of CFS/ME, and education should not be the only activity a person undertakes. There should be a balance between time spent attending school or college and doing homework, and time spent on home and social activities. [1.4.5.6]

Employment

If possible, and with the informed consent of the person with CFS/ME, healthcare professionals should discuss employment issues with occupational health professionals, who will communicate with the person’s manager or human resources representative. If there is no access to occupational health services, the responsible clinician should liaise with the employer directly***. [1.4.5.7]

Strategies that should not be used for CFS/ME [1.4.6]

The following strategies should not be offered to people with CFS/ME:

  • Advice to undertake unsupervised, or unstructured, vigorous exercise (such as simply ‘go to the gym’ or ‘exercise more’) because this may worsen symptoms.
  • Specialist management programmes (see section 1.6) delivered by practitioners with no experience in the condition. [1.4.6.2]

Although there is considerable support from patients (particularly people with severe CFS/ME) for the following strategies, healthcare professionals should be aware that there is no controlled trial evidence of benefit:

  • Encouraging maintenance of activity levels at substantially less than full capacity to reserve energy for the body to heal itself (sometimes known as the envelope theory).
  • Encouraging complete rest (cognitive, physical and emotional) during a setback/relapse. [1.4.6.3]

Strategies for managing CFS/ME should not include:

  • Prolonged or complete rest or extended periods of daytime rest in response to a slight increase in symptoms.
  • An imposed rigid schedule of activity and rest. [1.4.6.4]

Specialist CFS/ME care [1.6]

After a patient is referred to specialist care, an initial assessment should be done to confirm the diagnosis. [1.6.1.1]

If general management strategies (see section 1.4) are helpful for a person with CFS/ME, these should be continued after referral to specialist CFS/ME care. [1.6.1.2]

Cognitive behavioural therapy, graded exercise therapy and activity management programmes [1.6.2]

Choosing and planning treatment

An individualised, person-centred programme should be offered to people with CFS/ME. The objectives of the programme should be to:

  • sustain or gradually extend, if possible, the person’s physical, emotional and cognitive capacity
  • manage the physical and emotional impact of their symptoms. [1.6.2.1]

The rationale and content of the different programmes, including their potential benefits and risks, should be fully explained to the person with CFS/ME. Healthcare professionals should explain that no single strategy will be successful for all patients, or during all stages of the condition. [1.6.2.2]

Healthcare professionals should recognise that the person with CFS/ME is in charge of the aims of the programme. The choice of the programme, its components, and progression throughout the programme should be mutually agreed and based on:

  • the person’s age, preferences and needs
  • the person’s skills and abilities in managing their condition, and their goals (such as improvement or treatment of deterioration of symptoms, prevention of relapse or maintenance)
  • the severity and complexity of symptoms
  • physical and cognitive functioning. [1.6.2.3]

Cognitive behavioural therapy (CBT) and/or graded exercise therapy (GET) should be offered to people with mild or moderate CFS/ME and provided to those who choose these approaches, because currently these are the interventions for which there is the clearest research evidence of benefit. [1.6.2.4

If a full CBT or GET programme is inappropriate or not available, components of CBT or GET should be offered, either individually or more effectively in combination with:

The choice of programme, its components and progression through it should be reviewed regularly, taking into account the goals and abilities of the person with CFS/ME, and other approaches agreed as necessary. [1.6.2.6]

Healthcare professionals should advise people with CFS/ME to contact them if they experience an increase in symptoms that lasts for longer than a few days after starting the specialist programme, or if symptoms are severe or distressing. [1.6.2.7]

Cognitive behavioural therapy (CBT)

A course of CBT should be delivered only by a healthcare professional with appropriate training in CBT and experience in CFS/ME, under clinical supervision. The therapist should adhere closely to empirically grounded therapy protocols. [1.6.2.8]

CBT should be offered on a one-to-one basis if possible. [1.6.2.9]

CBT for a person with CFS/ME should be planned according to the usual principles of CBT, and should include:

  • Acknowledging and validating the person’s symptoms and condition.
  • Explaining the CBT approach in CFS/ME, such as the relationship between thoughts, feelings, behaviours and symptoms, and the distinction between causal and perpetuating factors.
  • Discussing the person’s attitudes and expectations.
  • Developing a supportive and collaborative therapeutic relationship.
  • Developing a shared formulation and understanding of factors that affect CFS/ME symptoms.
  • Agreeing therapeutic goals.
  • Tailoring treatment to the person’s needs and level of functioning.
  • Recording and analysing patterns of activity and rest, and thoughts, feelings and behaviours (self-monitoring).
  • Establishing a stable and maintainable activity level (baseline) followed by a gradual and mutually agreed increase in activity.
  • Challenging thoughts and expectations that may affect symptom improvement and outcomes.
  • Addressing complex adjustment to diagnosis and acceptance of current functional limitations.
  • Developing awareness of thoughts, expectations or beliefs and defining fatigue-related cognitions and behaviour.
  • Identifying perpetuating factors that may maintain or exacerbate CFS/ME symptoms to increase the person’s self-efficacy (sense of control over symptoms).
  • Addressing any over-vigilance to symptoms and related checking or reassurance-seeking behaviours by providing physiological explanations of symptoms and using refocusing/distraction techniques.
  • Problem solving using activity management and homework tasks to test out alternative thoughts or beliefs, such as undertaking pleasure and mastery tasks (tasks that are enjoyable and give a sense of accomplishment).
  • Building on existing assertion and communication skills to set appropriate limits on activity.
  • Managing sleep problems, for example by addressing any unhelpful beliefs about sleep, behavioural approaches to sleep disturbance, stress management, and/or relaxation training (see recommendations 1.4.2.1–6).
  • Treating any associated or comorbid anxiety, depression or mood disorder according to NICE clinical guidelines on these conditions (see section 6).
  • Offering information on managing setbacks/relapses (see section 1.7). [1.6.2.10]
Graded exercise therapy (GET)

GET should be delivered only by a suitably trained GET therapist with experience in CFS/ME, under appropriate clinical supervision. [1.6.2.11]

GET should be offered on a one-to-one basis if possible. [1.6.2.12]

People with mild or moderate CFS/ME should be offered GET that includes planned increases in the duration of physical activity. The intensity should then be increased when appropriate, leading to aerobic exercise (that is, exercise that increases the pulse rate). [1.6.2.13]

GET should be based on the person’s current level of activities (such as physical activity, daily routines, sleep patterns and frequency of setbacks/relapses) and emotional factors, vocational or educational factors and individual goals (details of these may be obtained from an activity diary). The programme should also include sleep and relaxation strategies (see recommendations 1.4.2.1–6). [1.6.2.14]

When planning GET, the healthcare professional should:

  • Undertake an activity analysis to ensure that the person with CFS/ME is not in a ‘boom and bust’ cycle before they increase the time spent in exercise.
  • Discuss with the person the ultimate goals that are important and relevant to them. This might be, for example, a twice-daily short walk to the shops, a return to a previous active hobby such as cycling or gardening, or, for people with severe CFS/ME, sitting up in bed to eat a meal.
  • Recognise that it can take weeks, months or even years to achieve goals, and ensure that this is taken into account in the therapy structure (for example, by setting short- and medium-term goals).
  • Explain symptoms and the benefits of exercise in a physiological context. [1.6.2.15]

When starting GET, the healthcare professional should:

  • Assess the person’s current daily activities to determine their baseline.
  • Agree with them a level of additional low-intensity exercise that is sustainable, independent of daily fluctuations in symptoms, and does not lead to ‘boom and bust’ cycles. This may be sitting up in bed or brushing hair, for example, for people with severe CFS/ME, or gentle stretches or a slow walk.
  • Encourage them to undertake this exercise for at least 5 days out of 7, or build up to this level if and when possible.
  • Advise them that this level of exercise may mildly increase symptoms for a few days (for example, a mild to moderate increase in stiffness and fatigue), explain why this may occur and discuss strategies to mitigate it.
  • Offer information on the management of setbacks/relapses (see section 1.7). [1.6.2.16]
Progressing with GET

When the low-intensity exercise can be sustained for 5 days out of 7 (usually accompanied by a reduction in perceived exertion), the duration should be reviewed and increased, if appropriate, by up to 20%. For example, a 5-minute walk becomes 6 minutes, or a person with severe CFS/ME sits up in bed for a longer period, or walks to another room more often. The aim is to reach 30 minutes of low-intensity exercise. [1.6.2.17]

When the duration of low-intensity exercise has reached 30 minutes, the intensity of the exercise may be increased gradually up to an aerobic heart rate zone, as assessed individually by a healthcare professional. A rate of 50–70% maximum heart rate is recommended. [1.6.2.18]

Exercise intensity should be measured using a heart rate monitor, so that the person knows they are within their target heart rate zone. [1.6.2.19]

If agreed GET goals are met, exercise duration and intensity may be increased further if appropriate, if other daily activities can also be sustained, and in agreement with the person with CFS/ME. [1.6.2.20]

Maintaining exercise

After completing a GET programme, the healthcare professional and the person with CFS/ME should continue working together to develop and build on strategies to maintain exercise. Support should be available, if needed, to enable the person to reinforce the learning and lifestyle changes made and continue GET beyond discharge. [1.6.2.21]

Activity management

Activity management is a goal-oriented and person-centred approach tailored to the needs of the person with CFS/ME. It should include:

  • Understanding that activities have physical, emotional and cognitive components, and identifying these components.
  • Keeping a diary that records cognitive and physical activity, daytime rest and sleep. This will help to set baseline levels of activity (a stable and sustainable range of functioning), identify patterns of over- and underactivity, and develop an activity/exercise strategy.
  • Establishing a baseline; specific activities may need to be increased or decreased while this is happening.
  • Gradually increasing activity above the baseline in agreement with the person.
  • Planning daily activities to allow for a balance and variety of different types of activity, rest and sleep. This may include making a weekly activity schedule.
  • Spreading out difficult or demanding tasks over the day or week.
  • Splitting activities into small achievable tasks according to the person’s level of ability/functioning, followed by gradual increases in the complexity of the tasks.
  • Monitoring, regulating and planning activities to avoid a ‘boom and bust’ cycle.
  • Goal setting, planning and prioritising activities.
  • Explaining the role of rest in CFS/ME and helping the person work out how to build in rest periods and achieve a productive day (see recommendations 1.4.2.1–6).
  • Regularly reviewing activity levels and goals.
  • Offering information on the management of setbacks/relapses (see section 1.7). [1.6.2.22]

Management of setbacks/relapses [1.7]

Preparing for a setback/relapse [1.7.1]

People with CFS/ME should be advised that setbacks/relapses are to be expected as part of CFS/ME. [1.7.1.1]

Healthcare professionals and people with CFS/ME should develop a plan for managing setbacks/relapses, so that skills, strategies, resources and support are readily available and accessible when needed. This plan may be shared with the person’s carers, if they agree. [1.7.1.2]

During a setback/relapse [1.7.2]

Setbacks/relapses may be triggered by factors such as unexpected/unplanned activities, poor sleep, infection or stress. Healthcare professionals, in discussion with the person with CFS/ME, should try to identify the cause(s) of a setback/relapse, but it should be recognised that this may not always be possible. [1.7.2.1]

When managing a setback/relapse, the management plan should be reviewed. Healthcare professionals should discuss and agree an appropriate course of action with the person with CFS/ME, taking into account:

  • the person’s experience
  • possible causes of the setback/relapse, if known
  • the nature of the symptoms
  • the severity and duration of the setback/relapse
  • the current management plan. [1.7.2.2]

When managing setbacks, healthcare professionals should put strategies into place that:

  • Maintain activity and exercise levels if possible, by alternating activities with breaks and pacing activities, as appropriate.
  • Involve talking to families and carers, if appropriate.
  • Recognise distressing thoughts about setbacks/relapses such as ‘this means I’ll never get better’, but encourage optimism.
  • Involve reconsidering and revising the levels and types of symptom control. [1.7.2.3]

In some setbacks/relapses, it may be necessary to reduce, or even stop, some activities and increase the frequency and/or duration of rest periods to stabilise symptoms and re-establish a baseline activity level. This should be discussed and agreed with the person with CFS/ME. [1.7.2.4]

People with CFS/ME should be advised to minimise daytime sleep periods. However, healthcare professionals should recognise that this is not always possible, depending on the severity of a person’s symptoms and the setback. [1.7.2.5]

After a setback/relapse [1.7.3]

After a setback/relapse, healthcare professionals should review the person’s activity levels to re-establish a baseline and review the management plan. A gradual return, when possible, to previous exercise and functional routines should be encouraged. Activity should be increased gradually. [1.7.3.1]

Healthcare professionals should advise on:

  • Slowly decreasing the frequency and duration of rest periods.
  • Continuing the use of relaxation techniques, even when the person with CFS/ME is beginning to feel better. [1.7.3.2]

After a setback, healthcare professionals and people with CFS/ME should review the experience to determine, if possible, whether triggers can be managed in the future, and put strategies in place to do this. [1.7.3.3]

6.3.8. Deriving recommendations

Discussion of the evidence

In reviewing the evidence, the GDG were aware that there was a lack of consistency in terminology and an absence of trial protocols, particularly with respect to graded exercise, graded activity and pacing. This made it difficult to compare like with like across studies.

The GDG regarded the evidence of benefit strongest for CBT, which was clearly defined in the studies. There was a discussion about the construction of a CBT programme. With regard to the number of sessions of CBT, one trial of good methodological quality looked at CBT delivered over 13–16 sessions. The greatest benefit was shown where there was a 6–12-month follow-up. The authors also looked at a 5-year follow-up and these benefits were maintained. The delivery of CBT was also important; it was clear that it needed to be delivered by someone with defined competencies but not necessarily a psychiatrist.

The GDG was clear that CBT was not about unhelpful advice or dictation of illness beliefs, but about changes in lifestyle and learning to achieve improvement within the patient’s abilities. In addition, the objectives of the programme must be agreed with the patient, and they must clearly be willing to take part. The GDG did not regard CBT or other behavioural therapies as curative or directed at the underlying disease process, which remains unknown. Rather, such interventions can help some patients cope with the condition and experience improved functioning, and consequently a improved quality of life.

As CBT is a labour-intensive intervention, it is an expensive option and the GDG considered whether less expensive interventions could be used in certain circumstances (e.g. CCBT). The GDG considered that there was no evidence available for CCBT in this population group and they would be unwilling to recommend it. However, the possibilities of using CCBT as an adjunct for follow-up or relapse prevention were hypothesised.

After consultation on the draft guideline was complete, the GDG continued discussions on the recommendations, based on the comments from the stakeholders. For details of changes and responses to stakeholder comments, please see the comments table which can be found on the NICE website at www.nice.org.uk

Areas where little evidence was found

Little or no evidence was found for the effectiveness of sleep management, rest, relaxation or pacing for people with CFS/ME. The GDG’s view was that advice on these self-help techniques would be helpful as patients generally find them useful.

The GDG found it difficult to find a precise definition for activity management and therefore to find evidence for its effectiveness. As it is based on similar principles and goals to graded exercise therapy the GDG made consensus recommendations regarding activity management.

No evidence was found on the management of setbacks and therefore the GDG devised consensus recommendations. Stakeholders commented that the term ‘relapse’ was preferred by patients. However, the view of the GDG was that relapse was defined differently clinically and to use the term in isolation would cause confusion.

Questionnaire

The GDG agreed that evidence-based CBT as discussed above was appropriate, but was uncertain about the benefits of individual versus group CBT. In the wider survey healthcare professionals agreed that both were appropriate, whereas patients were uncertain about, and disagreed with, individual and group CBT respectively. Because of the high-quality evidence showing the benefits of CBT, the GDG recommended it as best practice, but did not make a recommendation regarding individual versus group CBT as there was neither evidence nor consensus. The GDG noted that it was always the patient’s choice whether or not to participate. They acknowledged that CBT has not always been applied appropriately or consistently. Therefore they have made detailed recommendations on how it should be delivered.

With regard to GET, because of the confusion of terminology and protocols in the studies, the GDG developed clinical scenario statements that detailed the approach rather than naming the intervention.

Both the evidence and the GDG consensus support gradual increases in aerobic exercise in people with mild to moderate CFS/ME. The patients in the wider survey did not support this view, as indicated by the response to 3a2 (see section 6.3.6). Healthcare professionals rated this as ‘uncertain’ but did not disagree with the statement. The view of the GDG was that all interventions have the potential to cause harm as well as provide benefit. GET is no different, but the overall research evidence is that the benefits outweigh any harmful effects.

Some patient surveys have described poor experiences with exercise therapies, though these experiences were usually from unstructured or inflexible exercise programmes, often delivered by untrained personnel. Such poor experiences should be avoidable by using a programme based on patient participation and in which the patient retains control over goal-setting and the pace of progress. This is a core feature of GET. The GDG has therefore developed detailed recommendations describing the intervention as well as recommendations about what is appropriate.

There was both a lack of evidence and no consensus about whether GET is appropriate for people, in particular children, with severe CFS/ME. Therefore the GDG did not recommend GET for people with severe CFS/ME but elements of it may be appropriate.

There is no evidence to support the ‘envelope theory’ of maintaining levels at substantially less than capacity in order to have a reserve. The results from the wider group indicated that patients generally support this approach while healthcare professionals do not. The GDG supported the view that people with CFS/ME need to learn to ‘listen to’ body energy levels in order to manage their daily life and that sudden large increases in activity were not advisable. There was however, concern that consistently maintaining activity levels at lower than capacity would not lead to an improvement in symptoms and/or level of functioning.

6.4. Pharmacological interventions

6.4.1. Evidence statements

6.4.1.1.

At present, there is equivocal and limited evidence on the overall benefits of pharmacological treatments for CFS/ME. (Evidence level 1+)

6.4.1.2.

The evidence shows that immunoglobulin therapy in adults with CFS/ME is not of benefit (Evidence level 1+)

6.4.1.3.

Little evidence exists on interventions for those severely affected with CFS/ME.

6.4.1.4.

The evidence shows that immunoglobulin therapy in children with CFS/ME is not of overall benefit (Evidence level 1+)

6.4.1.5.

There is insufficient evidence of benefit of other immunological therapies. (Evidence level 1−)

6.4.2. Clinical evidence summary

6.4.2.1. Summary of evidence presented in Appendix 1

The view of the GDG was that symptomatic treatment should be provided on the basis of general principles of symptom management, except where it was inappropriate for people with CFS/ME. As discussed in the introduction (section 1.5), the GDG did not address the general management of individual symptoms as each symptom would have needed a guideline in itself. The evidence review presented was based on searches of the evidence for the management of CFS/ME (see key clinical questions above), not for the management of individual symptoms. (For example, a trial looking at the management of neuropathic pain in patients with CFS/ME would have been identified.)

The pharmacological studies reviewed included treatment with anticholinergic agents, antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs)), NADH (nicotinamide adenine dinucleotide), dexamphetamine, antihypertensive agents and steroids. Study quality was variable, with validity scores ranging from 2 to 19. Sample sizes were generally small with half of the 21 studies retrieved having fewer than 50 participants. Very few of the RCTs evaluating pharmacological interventions suggested a beneficial effect.

No benefit was found in patients with CFS/ME from treatment with anticholinergic agents, antidepressants, antihypertensives or growth hormone. Results were mixed in trials of oral NADH and melatonin as well as in the studies of steroid therapy and MAOIs. A trial of dexamphetamine found significant improvements in fatigue in the treated patients but reduced food consumption was a side effect. Adverse events serious enough to cause people to withdraw from the study were also noted with galanthamine hydrobromide, phenelzine, fludrocortisone and fluoxetine.

Immunological/antiviral treatment

Several immunological and antiviral treatments were evaluated in 11 retrieved studies. There were mixed results in three RCTs of the effects of immunoglobulin in adults: one found improvements in symptom scores and functional capacity; a second found improvements in immune measurements but not functional or symptom measures; and a third found no improvement in any outcomes. The methodological quality of these studies was between 13 and 16 out of 20 on the validity assessment. One study of interferon showed an increase in physical activity (p value not provided) and another showed improvements only in immune measurements but not in QoL measures. Use of Ampligen showed an improvement in functional ability and cognitive function but not in depression scores. The combination of leukocyte extract and CBT appeared to improve general health in one study of 49 patients, but not physical or functional capacity. In one RCT of acyclovir, a significant negative effect was reported for anxiety, depression and confusion. No differences in trials of gancyclovir, inosine pranobex, the antihistamine terfenadine or vaccination with staphylococcus toxoid were found.

People with severe CFS/ME

Very limited numbers of studies indicated the degree of severity of CFS/ME in participants. Two RCTs compared people who had been ill for shorter or longer times. There was no significant difference in response to fludrocortisone in one study or to a broad-based management programme in the other.

Children

Only two RCTs of children with CFS/ME were retrieved. One RCT of immunoglobulin G showed a significant improvement in functional score of 25% or more in the intervention group.

6.4.2.2. Additional clinical evidence

No new evidence was found in the update searches.

6.4.3. Health economics evidence summary

The management of symptoms is an important consideration in cost effectiveness as both costs and benefits are likely to stretch recurrently into the future. The table shows the potential costs of the types of pharmacological intervention..

Type of interventionDetail (NP, non-proprietary)DoseAnnual cost (£)*
SSRIFluoxetine (Prozac)20 mg/day201
ThyroxineLevothyroxine (NP)25 μg/day12
TricyclicAmitriptyline (NP)25 mg/day13
Skeletal muscle relaxant/antispasmodicDiazepam (NP)2 mg/day12
Baclofen (NP)10 mg/day10
Clonazepam (Rivotril)500 μg/day14
*

Data sourced from the BNF (2006)

Apart from SSRIs, the cost implications of the pharmacological interventions referred to in the table above not ruled out in GDG ratings are small. Therefore, cost is unlikely to be a valid reason for deeming these interventions to be inappropriate.

Although there is some evidence regarding infectious triggers for CFS/ME, there is no research evidence on how such triggers might influence clinical management (including pharmacological treatment). While this must be acknowledged, the application of health economics to this evidence poses significant methodological problems. Good cost-effectiveness work is necessarily predicated on good-quality clinical studies, and for the results to be most useful, the outcome of an intervention should be given in a quantified QoL format (such as through an SF-36 or EQ5D questionnaire). While evidence of this kind may be available in the future, the literature search did not retrieve anything substantial at the present time. Therefore, health economics has little to say on this school of interventions other than that they should be judged using the standard core components of health economics.

6.4.4. Clinical scenario questionnaire to GDG and wider group

So that consistent principles were applied in rating the evidence statements, the GDG and the wider group assumed the following.

  1. The person with CFS/ME and healthcare professionals involved in their care will make decisions in partnership. These are directed by the patient’s personal preferences and build on the existing experience and skills of the professional.
  2. All treatments are offered allowing the person with CFS/ME to refuse without compromising the further therapeutic relationship.
  3. There is a good rapport in which the patient and their families/carers feel believed and validated.
  4. Treatment is provided by the NHS in the context of availability of adequate numbers of competent, appropriately trained healthcare professionals.
  5. Minimal waiting times for good-quality services are adhered to.

For the GDG’s first rating round, the wording of the evidence statements was consistent with those in other sections, that is ‘The use of …… is appropriate.’ However, in discussion following the round 1 ratings, it became clear that the GDG believed that while many of these therapies should not be routinely prescribed, they may be appropriate in certain circumstances for certain individuals. The objective of these statements was to determine which drugs the GDG agreed should not be used to manage particular symptoms for patients with CFS/ME. Therefore many of the statements were clarified to detail the circumstances, and the GDG changed the statement wording from ‘appropriate’ to ‘inappropriate’. All questions that were changed were re-rated in round 2 regardless of their rating in round 1.

GDG Round 1
Question and Results
GDG Round 2
Question and Results
Wider Group
Question and Results
Discussion
2(a)The use of thyroxine where the individual has LOW thyroxine levels is appropriate….
1. for adults with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(b)The use of thyroxine where the individual has NORMAL thyroxine levels is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2.
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(c)The use of SSRIs where the individual is depressed is appropriate….The use of selective serotonin re-uptake inhibitors (SSRIs) (for example fluoxetine/Prozac or paroxetine/Seroxat) where the individual is moderately or severely depressed is INAPPROPRIATE….In the first round the GDG was unclear about the severity of symptoms of depression, the statement was clarified and went to round 2. See discussion about appropriate and inappropriate above.
1. for adults with CFS/ME with mild symptomsUncertainDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsUncertainDisagreeUncertainRandom selection for wider survey
3. for adults with CFS/ME with severe symptomsAgreeDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
1. for children with CFS/ME with mild symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2. for children with CFS/ME with moderate symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
3. for children with CFS/ME with severe symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2(c)The use of venlafaxine where the individual has pain difficulties AND is moderately or severely depressed is INAPPROPRIATEThis statement was added following the 1st round discussion
1. for adults with CFS/ME with mild symptomsNot includedDisagree….The GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsNot includedDisagree….The GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
3. for adults with CFS/ME with severe symptomsNot includedDisagree….The GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2(c)The use of venlafaxine where the individual has sleep and pain difficulties AND is NOT moderately or severely depressed is INAPPROPRIATEThis statement was added following the 1st round discussion
1. for adults with CFS/ME with mild symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
3. for adults with CFS/ME with severe symptomsNot includedAgreeAgreeRandom selection for wider survey
2(d)The use of Tricyclics where the individual is depressed is appropriate….The use of tricyclics (for example amitriptyline) where the individual has sleep and pain difficulties AND is moderately or severely depressed is INAPPROPRIATEIn the first round the GDG was unclear about the severity of symptoms of depression, the statement was clarified to indicate and progressed to round 2. See discussion about appropriate and inappropriate above.
1. for adults with CFS/ME with mild symptomsUncertainDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsUncertainDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
3. for adults with CFS/ME with severe symptomsUncertainDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
4. for children with CFS/ME with mild symptomsUncertainDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
5. for children with CFS/ME with moderate symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
6. for children with CFS/ME with severe symptomsUncertainUncertainDisagreeGDG was uncertain at round 2, progressed to wider survey
2(e)The use of tricyclics (for example amitriptyline) where the individual has sleep and pain difficulties AND is NOT moderately or severely depressed is INAPPROPRIATEThis statement was added following the 1st round discussion to test use without depression
1. for adults with CFS/ME with mild symptomsNot includedDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsNot includedDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
3. for adults with CFS/ME with severe symptomsNot includedDisagreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
4. for children with CFS/ME with mild symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
5. for children with CFS/ME with moderate symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
6. for children with CFS/ME with severe symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2(f)The use of gabapentin where the individual is depressed is appropriate….The use of gabapentin where the individual has pain difficulties is INAPPROPRIATE.........This statement was clarified following the 1st round discussion. See discussion about appropriate and inappropriate above.
1. for adults with CFS/ME with mild symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2. for adults with CFS/ME with moderate symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
3. for adults with CFS/ME with severe symptomsDisagreeUncertainDisagreeGDG was uncertain at round 2, progressed to wider survey
4. for children with CFS/ME with mild symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
5. for children with CFS/ME with moderate symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
6. for children with CFS/ME with severe symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2(g)The use of Monoamine oxidase inhibitors where the individual is depressed is appropriate….The use of monoamine oxidase inhibitors (for example phenelzine or isocarboxazid) where the individual has pain difficulties AND the individual is moderately or severely depressed is INAPPROPRIATE….This statement was clarified following the 1st round discussion. See discussion about appropriate and inappropriate above.
1. for adults with CFS/ME with mild symptomsDisagreeAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsDisagreeAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
3. for adults with CFS/ME with severe symptomsDisagreeAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
4. for children with CFS/ME with mild symptomsDisagreeUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
5. for children with CFS/ME with moderate symptomsDisagreeUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
6. for children with CFS/ME with severe symptomsDisagreeUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
2(g)The use of monoamine oxidase inhibitors (for example phenelzine or isocarboxazid) where the individual has pain difficulties AND the individual is NOT moderately or severely depressed is INAPPROPRIATE….
T
This statement was added following the 1st round discussion to clarify the above.
1. for adults with CFS/ME with mild symptomsNot includedUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
2. for adults with CFS/ME with moderate symptomsNot includedUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
3. for adults with CFS/ME with severe symptomsNot includedAgreeAgreeRandom selection for wider survey
4. for children with CFS/ME with mild symptomsNot includedAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsNot includedAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsNot includedAgreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(h)The use of glucocorticoids (such as hydrocortisone) where the individual’s primary symptom is pain is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(i)The use of mineralocorticoids (such as fludrocortisone) where the individual’s primary symptom is pain is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(i)The use of Dexamphetamine where the individual’s primary symptom is fatigue is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(j)The use of methylphenidate where the individual’s primary symptom is fatigue is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(k)The use of Melatonin is appropriate….The use of melatonin where the individual has sleep difficulties is INAPPROPRIATE….See discussion about appropriate and inappropriate above.
1. for children with CFS/ME with mild symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2. for children with CFS/ME with moderate symptomsUncertainUncertainDisagreeGDG was uncertain at round 2
3. for children with CFS/ME with severe symptomsUncertainDisagreeDisagreeGDG was uncertain at round 2
2(l)The use of anti-herpes agents (such as acyclovir) where the individual has had herpes viral infection is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(m)The use of anti-herpes agents (such as acyclovir) where the individual has NOT had herpes viral infection is appropriate….
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(n)The use of gut anti-spasmodics (such as mebeverine, alverine and peppermint oil) where the individual has bowel symptoms is appropriate….The use of gut anti-spasmodics (such as mebeverine, alverine and peppermint oil) where the individual has bowel symptoms is INAPPROPRIATE.See discussion about appropriate and inappropriate above.
1. for adults with CFS/ME with mild symptomsUncertainDisagreeDisagreeRandom selection for wider survey
2. for adults with CFS/ME with moderate symptomsUncertainDisagreeDisagreeRandom selection for wider survey
3. for adults with CFS/ME with severe symptomsUncertainDisagreeThe GDG reached a consensus in the first round and the statement did not progress to wider survey.
4. for children with CFS/ME with mild symptomsUncertainDisagreeDisagreeRandom selection for wider survey
5. for children with CFS/ME with moderate symptomsUncertainDisagreeThe GDG reached a consensus in the first round and the statement did not progress to wider survey.
6. for children with CFS/ME with severe symptomsUncertainDisagreeThe GDG reached a consensus in the first round and the statement did not progress to wider survey.
2(o)The use of gut anti-spasmodics (such as mebeverine, alverine and peppermint oil) where the individual has NO bowel symptoms is appropriate….The GDG reached a consensus in the first round and the statement did not progress to Round 2
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2(p)The use of skeletal anti- spasmodics (such as diazepam, baclofen, and clonazepam) where the individual has muscle pain, cramps or twitching is appropriate….The use of skeletal anti-spasmodics (such as diazepam, baclofen, and clonazepam) where the individual has MODERATE OR SEVERE muscle pain, cramps or twitching is INAPPROPRIATE….This statement was clarified following the 1st round discussion. See discussion about appropriate and inappropriate above.
1. for adults with CFS/ME with mild symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2. for adults with CFS/ME with moderate symptomsUncertainUncertainDisagreeGDG was uncertain at round 2, progressed to wider survey
3. for adults with CFS/ME with severe symptomsDisagreeDisagreeThe GDG reached a consensus in the first round and the statement did not progress to wider survey.
4. for children with CFS/ME with mild symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
5. for children with CFS/ME with moderate symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
6. for children with CFS/ME with severe symptomsDisagreeUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2(p)The use of skeletal anti-spasmodics (such as diazepam, baclofen, and clonazepam) where the individual has NO muscle pain is INAPPROPRIATE….This statement was clarified following the 1st round discussion to separate from above.
1. for adults with CFS/ME with mild symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
2. for adults with CFS/ME with moderate symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
3. for adults with CFS/ME with severe symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
4. for children with CFS/ME with mild symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
5. for children with CFS/ME with moderate symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.
6. for children with CFS/ME with severe symptomsNot includedAgreeThe GDG reached a consensus in the round 2 and the statement did not progress to wider survey.

6.4.5. Recommendations

Note: numbers in square brackets are as in the NICE guidelines.

General management strategies after diagnosis [1.4]

Symptom management [1.4.1]

There is no known pharmacological treatment or cure for CFS/ME. However, symptoms of CFS/ME should be managed as in usual clinical practice. [1.4.1.1]

No research evidence was found to support the experience of some people with CFS/ME that they are more intolerant of drug treatment and have more severe adverse/side effects. However, if people with CFS/ME have concerns, healthcare professionals may consider starting drug treatment for CFS/ME symptoms at a lower dose than in usual clinical practice. The dose may be increased gradually, in agreement with the patient. [1.4.1.2]

Drug treatment for children and young people with CFS/ME should be started by a paediatrician. However, prescribing may be continued in primary care, depending on the preferences of the patient and their carers, and local circumstances. [1.4.1.3]

See also recommendations in section 6.5.5.

Strategies that should not be used for CFS/ME [1.4.6]

The following drugs should not be used for the treatment of CFS/ME:

Pharmacological interventions for symptom control [1.6.3 – note after referral for specialist CFS/ME care]

If chronic pain is a predominant feature, healthcare professionals should consider referral to a pain management clinic. [1.6.3.1]

Prescribing of low-dose tricyclic antidepressants, specifically amitriptyline, should be considered for people with CFS/ME who have poor sleep or pain. Tricyclic antidepressants should not be offered to people who are already taking selective serotonin reuptake inhibitors (SSRIs) because of the potential for serious adverse interactions. [1.6.3.2]

Melatonin may be considered for children and young people with CFS/ME who have sleep difficulties, but only under specialist supervision because it is not licensed in the UK. [1.6.3.3]

6.4.6. Deriving recommendations

Discussion of the evidence

Before beginning their review of the evidence, the GDG agreed that they would be sceptical of any intervention that was supported by one small trial only and would not make an evidence statement on this basis. The GDG did not find strong evidence for any pharmacological or immunological therapies. The number of patients in each trial was generally small and many diverse outcomes were measured, making it difficult to reach conclusions or to compare trials.

In addition, particularly with immunoglobin studies, there were large dosage variations across the studies which made any comparison difficult; there is not necessarily a dose–response effect and different doses may elicit very different effects. It was agreed that the Staphylococcus toxoid papers should be rejected as the patients studied were women with muscle pain/fibromyalgia and thus not representative of a CFS/ME population. The complication and side-effect rates were also very high in the immunoglobin studies. The GDG agreed that they did not want to make any evidence statements on immunotherapy.

The GDG was also mindful of the side effects or adverse effects of many of the treatments reviewed. The GDG felt unable to exclude the use of pharmacological interventions for which evidence is lacking to support or reject their use and included these in the questionnaire. It is felt that much research is needed to evaluate appropriate pharmacological interventions, with an emphasis on adverse effects and safety.

After consultation on the draft guideline was complete, the GDG continued discussions on the recommendations, based on the comments from the stakeholders. For details of changes and responses to stakeholder comments, please see the comments table which can be found on the NICE website at www.nice.org.uk

Expert co-optees

The GDG invited co-optees with expertise in the management of CFS/ME in children to a meeting to discuss difficult areas. The co-optees’ view was that the drugs primarily used for the management of the condition in children were:

The GDG discussed with them the use of SSRIs as this is an area of uncertainty. The co-optees’ view was that SSRIs, in particular fluoxetine, are used for adolescents but not for younger children. Their view was that opinion varied on using them for low mood as opposed to comorbid clinical depression. They were sometimes used in patients who have low mood and have tried other treatments. As opinion varied the GDG decided to include SSRIs in the questionnaire.

After consultation on the draft guideline was complete, the GDG continued discussions on the recommendations, based on the comments from the stakeholders. For details of changes and responses to stakeholder comments, please see the comments table which can be found on the NICE website at www.nice.org.uk

Questionnaire

As is demonstrated by the results of the questionnaire, there is a great deal of uncertainty within both the GDG and the wider group regarding the appropriateness of many of the drug treatments for the symptoms of CFS/ME. There was some consensus that some drugs may be helpful in particular circumstances, and recommendations were made for these. The GDG agreed that the general principles of care when prescribing drugs to a person with CFS/ME in order to manage symptoms were to:

  • use any drug with caution
  • start with low doses
  • discuss prescription with the patient, who must give informed consent.

The GDG’s discussion of the questionnaire results concluded as follows.

SSRIs: It appears from the questionnaire that there was reasonable consensus that SSRIs are no less useful for people with CFS/ME than for those with other conditions. There was consensus that SSRIs were the preferred first-line treatment for mood disorders in line with the NICE depression guideline (www.nice.org.uk/CG023). Caution should be exercised due to the sensitivity of many CFS/ME patients to drugs.

Venlafaxine: There was a strong consensus from the GDG and both patients and healthcare professionals that venlafaxine was generally inappropriate but further research is needed. The GDG decided not to make a negative recommendation as venlafaxine may be appropriate in some situations.

Tricyclics: The wider group consensus was that tricyclics were inappropriate for children with severe pain and sleep problems and depression. The GDG decided that tricyclics at low dose should be considered as a treatment option for adults and children to relieve pain and sleep symptoms. If depression was present, the use of low-dose tricyclics was not considered an appropriate option as they are only effective at higher doses. However, the prescribing of tricyclics should only be undertaken after referral to specialist CFS/ME care.

Gabapentin: The GDG noted that the wider survey was supportive of gabapentin in people with severe CFS/ME. The GDG was uncertain why this was the case. Because of its side effects, the GDG did not think that gabapentin should be used for mild pain, but there will be certain individual cases where it might be considered despite its relatively high side-effect profile. The GDG decided not to make a positive or negative recommendation.

Monoamine oxidase inhibitors: There was agreement on the questionnaires that these should not be used and the GDG made a negative recommendation.

Melatonin: The wider survey group was strongly in favour of its use. The view of the GDG was that the use of melatonin might be considered for sleep disorders, although it is not licensed.

Gut antispasmodics: NICE is currently developing a clinical guideline on the management of irritable bowel syndrome. Gut antispasmodics should be used as normal.

Antivirals and immunoglobins: The consensus was that they do not have benefit in the treatment of CFS/ME.

6.5. Dietary interventions and supplements

6.5.1. Evidence statements

6.5.1.1At present, evidence is insufficient to support a beneficial effect of dietary supplements, including essential fatty acids in CFS/ME. (Evidence level 1++)

6.5.2. Clinical evidence summary

6.5.2.1. Summary of evidence presented in Appendix 1

Eleven studies were reviewed that addressed the treatment of CFS/ME patients with supplements. Only three of these studies had validity ratings > 10 and all sample sizes were < 90. No significant effects were noted in RCTs of general supplements, pollen extract and medicinal mushrooms. There was no effect on symptoms nor any general improvement with use of acclydine and amino acids. Studies that examined essential fatty acid supplements were conflicting, with one good-quality RCT reporting no improvements and one slightly larger controlled trial conducted in patients with postviral syndrome reporting an overall beneficial effect. This trial showed greater shifts towards normal levels of fatty acid concentration in treatment groups, most of which were statistically significant, as well as improvements in symptom measures. One small good-quality RCT showed that magnesium supplements had an overall positive effect of improvements in measures of energy and pain, emotional reactions, general health and laboratory measures, but not in sleep, physical mobility or social isolation. However, two of 34 participants in this study developed a rash and dropped out.

6.5.2.2. Additional clinical evidence

No new evidence was found.

6.5.3. Health economics evidence summary

No evidence was found.

6.5.4. Clinical scenario questionnaire to GDG and wider group

So that consistent principles were applied in rating the evidence statements, the GDG and the wider group assumed the following.

  1. The person with CFS/ME and healthcare professionals involved in their care will make decisions in partnership. These are directed by the patient’s personal preferences and build on the existing experience and skills of the professional.
  2. All treatments are offered allowing the person with CFS/ME to refuse without compromising the further therapeutic relationship.
  3. There is a good rapport in which the patient and their families/carers feel believed and validated.
  4. Treatment is provided by the NHS in the context of availability of adequate numbers of competent, appropriately trained healthcare professionals.
  5. Minimal waiting times for good-quality services are adhered to.
  6. Doses were in line with the recommended daily allowance where available.

In reviewing the results of the first round, the GDG had assumed in general that any food supplement was considered as a treatment for CFS/ME, not as a contribution to general health. This needed to be made explicit, and therefore statements progressing to Round 2 were clarified.

GDG Round 1
Question and Results
GDG Round 2
Question and Results
Wider Group
Question and Results
Discussion
Dietary Supplements
4(a)Vitamin B12 injections should be used in….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(b)Vitamin C should be used in…..The GDG reached a consensus in the first round and the statement did not progress to Round 2
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(c)Co-enzyme Q10 should be used in….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(d)Magnesium should be used in….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(e)Echinacea should be used in….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(f)Nicotinamide adenine dinucleotide (NADH) should be used in….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(g)Essential Fatty acids should be used in….Essential fatty acids are appropriate for the treatment of….Question reworded to make clear that it was about treatment of CFS/ME not general health.
1. adults with CFS/ME with mild symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2. adults with CFS/ME with moderate symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
3. adults with CFS/ME with severe symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
4. children with CFS/ME with mild symptomsDisagreeDisagreeThe GDG reached a consensus in Round 2 and the statement did not progress to Wider survey
5. children with CFS/ME with moderate symptomsDisagreeDisagreeThe GDG reached a consensus in Round 2 and the statement did not progress to Wider survey
6. children with CFS/ME with severe symptomsDisagreeDisagreeUncertainRandom inclusion
4(h)Multivitamin and mineral supplements are appropriate for the treatment of
1. for adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. for adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. for adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. for children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. for children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. for children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
Diets
4(i)An anti-candida (low yeast, low sugar) diet is appropriate for….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(j)An exclusion diet followed by food challenges where the individual has bowel symptoms should be used in...An clinically supervised exclusion diet followed by food challenges where the individual has moderate or severe bowel symptoms is appropriate for….Statement was modified to make clear the severity of the symptoms and clinical supervision.
1. adults with CFS/ME with mild symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
2. adults with CFS/ME with moderate symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
3. adults with CFS/ME with severe symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
4. children with CFS/ME with mild symptomsDisagreeUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
5. children with CFS/ME with moderate symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
6. children with CFS/ME with severe symptomsUncertainUncertainAgreeGDG was uncertain at round 2, progressed to wider survey
4(k)An exclusion diet followed by food challenges where the individual is has no bowel symptoms should be used in….
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2

6.5.5. Recommendations

Note: numbers in square brackets are as in the NICE guidelines.

Symptom management [1.4.1]

If a person experiences nausea as part of CFS/ME, this should be managed conventionally, including giving advice on eating little and often, snacking on dry starchy foods and sipping fluids. The use of anti-emetic drugs should be considered only if the nausea is severe. [1.4.1.4]

Although exclusion diets are not generally recommended for managing CFS/ME, many people find them helpful in managing symptoms, including bowel symptoms. If a person with CFS/ME undertakes an exclusion diet or dietary manipulation, healthcare professionals should seek advice from a dietitian because of the risk of malnutrition. [1.4.1.5]

Complementary and supplementary therapies [1.4.7]

See also section 6.6.5.

There is insufficient evidence for the use of supplements – such as vitamin B12, vitamin C, co-enzyme Q10, magnesium, NADH (nicotinamide adenine dinucleotide) or multivitamins and minerals – for people with CFS/ME, and therefore they should not be prescribed for treating the symptoms of the condition. However, some people with CFS/ME have reported finding these helpful as a part of a self-management strategy for their symptoms. [1.4.7.2]

People with CFS/ME who are using supplements should be advised not to exceed the safe levels recommended by the Food Standards Agency†††. [1.4.7.3]

Some people with CFS/ME need supplements because of a restricted dietary intake or nutritional deficiencies. Healthcare professionals should seek advice from a dietitian about any concerns. [1.4.7.4]

6.5.6. Deriving recommendations

Discussion of the evidence

When the GDG reviewed the evidence for nutritional supplements, it was regarded as weak and inconclusive. The studies were small and the outcome measures diverse and in many cases not clearly defined. Therefore no conclusions could be reached.

This view was supported by the questionnaire responses. While supplements may be useful for general health, the GDG agreed that they could not be recommended for the management of CFS/ME.

Although weight loss may occur in people with CFS/ME, it was not considered to be a defining symptom of the condition. The GDG noted that profound weight loss is often a symptom of a serious underlying disorder so should not be attributed to CFS/ME without appropriate assessment and investigation. The GDG also noted the need for expert dietetic input where there is concern about nutritional intake.

After consultation on the draft guideline was complete, the GDG continued discussions on the recommendations, based on the comments from the stakeholders. For details of changes and responses to stakeholder comments, please see the comments table which can be found on the NICE website at www.nice.org.uk

6.6. Complementary therapies

6.6.1. Evidence statement

6.6.1.1The evidence found on the effects of complementary therapies for CFS/ME is inadequate in terms of quantity and/or quality.

6.6.2. Clinical evidence summary

6.6.2.1. Summary of evidence presented in Appendix 1

Trials of complementary therapies included studies on the effectiveness of homeopathy, massage therapy and osteopathy in treating CFS symptoms. One high-quality study of homeopathic treatments showed a significant improvement in fatigue and on some physical dimensions of the functional limitations profile. Massage therapy and osteopathy appeared to improve measures of fatigue, back pain and sleep, but the quality of these studies was very poor.

6.6.2.2. Additional clinical evidence

No new evidence was found.

6.6.3. Health economics evidence summary

No evidence was found.

6.6.4. Clinical scenario questionnaire to GDG and wider group

So that consistent principles were applied in rating the evidence statements, the GDG and the wider group assumed the following.

  1. The person with CFS/ME and healthcare professionals involved in their care will make decisions in partnership. These are directed by the patient’s personal preferences and build on the existing experience and skills of the professional.
  2. All treatments are offered allowing the person with CFS/ME to refuse without compromising the further therapeutic relationship.
  3. There is a good rapport in which the patient and their families/carers feel believed and validated.
  4. Treatment is provided by the NHS in the context of availability of adequate numbers of competent, appropriately trained healthcare professionals.
  5. Minimal waiting times for good-quality services are adhered to.

Following the first round the GDG decided to use a global statement in the wider questionnaire about complementary therapies in general rather than asking about specific techniques.

Complementary TherapiesGDG Round 1
Question and Results
GDG Round 2
Question and Results
Wider Survey
Question and Results
Discussion
4(l)Acupuncture should be used in….Acupuncture by a registered therapist is appropriate for symptom control in…….Question refined for second round
1. adults with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
2. adults with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
3. adults with CFS/ME with severe symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
4(m)Homeopathy by a registered therapist is appropriate for symptom control in…Homeopathy should be used in….Homeopathy by a registered therapist is appropriate for symptom control in…
1. adults with CFS/ME with mild symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
2. adults with CFS/ME with moderate symptomsUncertainUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
3. adults with CFS/ME with severe symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2 The GDG reached a consensus in the first round and the statement did not progress to Round 2
4. children with CFS/ME with mild symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
5. children with CFS/ME with moderate symptomsDisagreeThe GDG reached a consensus in the first round and the statement did not progress to Round 2
6. children with CFS/ME with severe symptomsDisagree
4(m)Other complementary therapies by a registered therapist are appropriate for symptom control in…This statement was developed by the GDG to abridge statements above and represent complementary therapies.
1. adults with CFS/ME with mild symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey progressed to wider survey progressed to wider survey
2. adults with CFS/ME with moderate symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
3. adults with CFS/ME with severe symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
4. children with CFS/ME with mild symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
5. children with CFS/ME with moderate symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey
6. children with CFS/ME with severe symptomsNot includedUncertainUncertainGDG was uncertain at round 2, progressed to wider survey

6.6.5. Recommendations

Note: numbers in square brackets are as in the NICE guidelines.

Complementary and supplementary therapies [1.4.7]

See also section 6.5.5.

There is insufficient evidence that complementary therapies are effective treatments for CFS/ME and therefore their use is not recommended. However, some people with CFS/ME choose to use some of these therapies for symptom control, and find them helpful. [1.4.7.1]

6.6.6. Deriving recommendations

Discussion of the evidence

As with drug therapy, the GDG agreed that they would view with scepticism evidence supported by only one small trial and would not make an evidence statement in these circumstances. It was therefore decided not to make an evidence statement on homeopathy.

After consultation on the draft guideline was complete, the GDG continued discussions on the recommendations, based on the comments from the stakeholders. For details of changes and responses to stakeholder comments, please see the comments table which can be found on the NICE website at www.nice.org.uk

Questionnaire

The questionnaire confirmed a high level of uncertainty about the benefit of complementary therapies in the management of CFS/ME. The GDG decided that whilst such therapies may be helpful for individuals as part of their own management, they could not be recommended as part of treatment for CFS/ME.

6.7. Review and ongoing management

No evidence was found regarding review and ongoing management. The GDG agreed the following recommendations.

6.7.1. Recommendations

Note: numbers in square brackets are as in the NICE guidelines.

Review and ongoing management [1.8]

Regular, structured review should be undertaken for all people with CFS/ME. The review should include, if appropriate:

  • Assessing improvement or deterioration in symptoms.
  • Assessing any adverse or unwanted effects of therapy.
  • Ongoing investigations.
  • Considering the need to repeat investigations (for children and young people, repeating investigations should be considered if there is no improvement after 1 year).
  • Reviewing the diagnosis, especially if signs and symptoms change (see recommendation 1.2.1.4).
  • Considering referral to specialist CFS/ME care.
  • Reviewing equipment needs.
  • Assessing any additional support needs (see sections 1.1 and 1.4). [1.8.1.1]

The timing of the reviews should depend on the severity and complexity of symptoms, the effectiveness of any interventions, and the needs of the person with CFS/ME. [1.8.1.2]

For general advice on sleep hygiene, see the NHS Direct website (www​.nhsdirect.nhs.uk).

Food Standards Agency (2006) ‘The balance of good health’. London: Foods Standards Agency. Available from www​.food.gov.uk/multimedia​/pdfs/bghbooklet.pdf

NHS Plus has produced guidance on the occupational aspects of the management of CFS/ME, available from www​.nhsplus.nhs.uk (search for ‘chronic fatigue syndrome’).

Data sourced from the BNF (2006)

Footnotes

††

For general advice on sleep hygiene, see the NHS Direct website (www​.nhsdirect.nhs.uk).

‡‡

Food Standards Agency (2006) ‘The balance of good health’. London: Foods Standards Agency. Available from www​.food.gov.uk/multimedia​/pdfs/bghbooklet.pdf

§§

See www​.dcsf.gov.uk

***

NHS Plus has produced guidance on the occupational aspects of the management of CFS/ME, available from www​.nhsplus.nhs.uk (search for ‘chronic fatigue syndrome’).

†††

See www​.food.gov.uk

NICE is developing guidance on the management of long-term sickness and incapacity; publication is expected in December 2008 (details available from www​.nice.org.uk).

Copyright © 2007, Royal College of General Practitioners.
Cover of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy)
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy) in Adults and Children [Internet].
NICE Clinical Guidelines, No. 53.
National Collaborating Centre for Primary Care (UK).

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