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Management of ME/CFS

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Treatment of chronic fatigue syndrome (CFS) is variable and uncertain, and the condition is primarily managed rather than cured.[1] Beyond two management techniques, no treatments have been accepted as effective. Proposed treatments include medications, medical treatments, and complementary and alternative medicine.

Management techniques

CFS management techniques include behavioral interventions such as cognitive behavioral therapy (CBT, a form of psychological therapy), and graded exercise therapy (GET). Based on multiple randomized clinical trials (RCTs), a systematic review published in the Journal of the Royal Society of Medicine (October 2006)[2] found that these were the only two known treatments that showed some promise. A Dutch group reviewing research findings in the British journal The Lancet also found in 2006 that CBT and GET were the only "interventions found to be beneficial."[3] These findings follow an earlier systematic review in the Journal of the American Medical Association with the same conclusions.[4] Another systematic review published in 2002 found that although CBT was "lending a possible association between improvement in the ability to work and an increase in the number of patients employed", the studies did not have high enough numbers to have strong conclusions. No specific patient characteristics seemed to serve as the best predictors of positive employment outcomes in CFS patients, although depression of greater severity was associated with unemployment.[5] Another systematic review published in 2004 also concluded that depression was the only factor associated with unemployment, and that only "cognitive behavior therapy, rehabilitation, and exercise therapy interventions were associated with restoring the ability to work."[6]

Cognitive behavioral therapy

Since the cause or causes of CFS are not known, CBT tries to help patients understand their individual symptoms and beliefs and develop strategies to improve day-to-day functioning. CBT is not necessarily a cure for CFS, but it can result in improvements.[3]

A systematic review of RCTs has found that cognitive behavioural therapy administered by highly skilled therapists in specialist centres is an effective intervention for people with CFS.[7] A recent (2008) systematic review of CBT concluded, "CBT is more effective than usual care for reducing fatigue symptoms in adults with CFS, with 40% of participants assigned to CBT showing clinical response at post-treatment, in comparison with 26% assigned to usual care control.", however, it also stated that the benefits of CBT in sustaining clinical response at follow up are inconclusive.[8] One uncontrolled study with no follow-up found that CBT could facilitate full recovery in some patients, with 69% of the patient cohort no longer meeting the CDC criteria for CFS and "full recovery" occurring in 23% of CFS patients after CBT using the most comprehensive definition of recovery.[9]

One study involving 22 CFS patients who underwent CBT showed a significant improvement in reported health status, measured physical activity (15%) and tested cognitive performance (6% in 1 of the 3 tests used), and that the CBT resulted in a significant increase in grey matter volume in the prefrontal cortex (regain of 14% towards normal), which was related to the improvement in cognitive speed during the choice reaction time task.[10]

Eleanor Stein states that the most commonly used worldwide model of illness management, the Stanford Model of Chronic Disease Self Management, shows benefits for diabetes and hypertension (conditions in which lifestyle play a strong role), but less benefit for arthritis.[11] Carruthers and Van de Sande in their Overview of the Canadian Consensus Guidelines,[12] note that supportive counselling should not be mis-termed CBT to avoid misleading confusion between the two treatments amongst patients and doctors.

Another systematic review on CBT[2] finds that "CBT was associated with a significant positive effect on fatigue, symptoms, physical functioning and school attendance." The reviewers state that the quality of many recent trials on CBT are lower quality randomized controlled trials or trials that did not involve random allocation. The reviewers also state that one recent, good quality trial of CBT in children and adolescence supports the effectiveness of CBT. The reviewers state that reasons for withdrawals typically remain unreported, and that a degree of publication bias seems to be present in CFS/ME literature as a whole. In one study, the effect of CBT has been demonstrated up to five years after therapy.[13] A large evaluation study in Belgium, however, lead to the conclusion that while on average CBT may cause patients to feel somewhat better, objective measurement shows no reduction in their disability. The report mentions that the results of the Belgian study are not as good as the results reported in published evidence based studies. The report considers that patient selection was different, and furthermore that most evidence-based studies used individual therapy, whereas the Belgian reference centres performed the therapy mostly in groups of 3-11 patients.[14][15] Another recent study found that CBT improved self-reported cognitive impairment but not actual neuropsychological test performance[16]. A previous study by some of the same authors found no relationship between neuropsychological impairment on standardized tests and self-reported memory and concentration problems, that neuropsychological functioning was not related to fatigue or depression, and that slowed speed of information processing and motor speed were related to low levels of physical activity[17]). According to researchers of one study, CBT usually aims at reducing fatigue but can also reduce pain, although higher pain at baseline was associated with a negative treatment outcome.[18] The place of CBT for children, young people and the severely affected is uncertain.[citation needed] There is also little research into the efficacy of CBT for severely affected patients.

Related treatments

Many CFS patients face the stress of economic and legal problems. CFS sufferers may lose jobs, marriages, and the ability to work at all, causing severe financial loss and distress. A study which included 45 CFS patients found that psychodynamic counselling has comparable effectiveness to cognitive behavioral therapy (CBT) in the treatment of chronic fatigue syndrome.[19]

Some CFS patients have comorbid depression and/or anxiety.[20] Dr. David Smith, a former medical advisor to the ME Association in the UK who reports to have successfully treated many children using antidepressants and therapy,[21] offers a possible explanation on his website.[22]

Graded exercise therapy

Several rehabilitation programs have been proposed which involve supervised or self-monitored graded exercise or activity. [citation needed] Such programs are designed to overcome deconditioning, increase strength and cardiovascular health [citation needed], despite that there is no evidence that deconditioning is a significant factor in activity limitation, or that patients do not make the most of their restricted ability. Programs are said to incorporate considerable education wherein the sufferer learns to start at an appropriate level of activity (based upon intensity and duration) which is incrementally increased, at a rate which supposedly does not substantially increase symptoms. [citation needed]

A New Zealand study suggests that GET may result in self-reported improvement by reducing the degree to which patients focus on their symptoms[23] although there is no evidence that CFS patients disproportionately focus on symptoms, rather that common CFS definitions fail to describe patients' symptomology adequately.

Other proposed management techniques

Pacing

Pacing involves the patient limiting their activity and energy expenditure so that they live within the confines of the illness, rather than trying to do too much and then suffering from a "crash" later. The theory is that by limiting activity to what is sustainable, the patient will be able to gradually increase it over time.

At the present time there is little evidence showing how effective pacing is.[24]

Breathing therapy

A pilot study published in the journal Physiother Theory Pract. in Mar 2008 indicates a subgroup of CFS patients may benefit from breathing retraining, to increase lung tidal volume and lower respiratory rates. [25]

Energy envelope theory

Similar to pacing, the basic principle of the envelope theory is to increase activity while avoiding "overexertion." Supporters of this theory argue that "by collecting time series data on fluctuations in energy levels, important clinical observations can be made in respect to a client's unique condition and experience with CFS."[26]

The results of a study into the effectiveness of the envelope theory in CFS were published in 2008. According to the authors, the findings of the study confirmed the validity of the Energy Envelope Theory use in CFS as they indicate that those participants who expended energy beyond their level of perceived daily energy suffered from more fatigue, pain, anxiety and depression, had a poorer quality of life and were more disabled.[27]

Proposed pharmacological treatments

Although some drugs are used to treat symptoms of CFS, no pharmacological treatments have been established as effective against CFS itself.

Antidepressants

Antidepressants are often prescribed to CFS patients. Their purpose can be to treat secondary depression or mood swings, but low dosage tricyclic antidepressants are sometimes prescribed to improve sleep quality and reduce pain.[28] However, antidepressants often have side effects, some of which can increase CFS symptoms,[citation needed] and baseline metabolism differs between patients.

Overall, studies into the use of antidepressants in CFS have had mixed results. Some studies have shown a reduction in symptoms with antidepressant use, while others have shown no benefit.[29][30][31][32]

Autonomic nervous system stimulants

Drugs such as atomoxetine (Strattera), which stimulate the autonomic nervous system, appear to have positive effects in some people with CFS symptoms. Amphetamines and amphetamine analogs may help some patients. For example, methylphenidate (Ritalin) has been found to be significantly better than placebo in relieving fatigue and concentration disturbances in a minority of CFS patients but more research is needed into the long term effects.[33] Modafinil (Provigil), a medication designed to aid in maintaining wakefulness, has had some positive effect on individuals with CFS, but has not been properly studied. A small study suggested that long-term treatment with modafinil may not be beneficial for CFS patients.[34]

Hormones

Treatment with steroids such as cortisol and thyroid hormones has been studied. Trials of hydrocortisone have had mixed results leading to the conclusion that treatment with the drug is not recommended.[35] A combination of hydrocortisone and fludrocortisone was not effective.[36]

NADH

A study of reduced nicotinamide adenine dinucleotide NADH reported positive results in 1999. 26 patients were given NADH or placebo for four weeks. After an additional four weeks, patients were treated for a final month with the treatment they had not received in the first month. The authors reported that eight patients had a ten percent improvement with NADH and two patients improved with placebo.[37] In 2000, several errors in the methodology and statistical analysis of the study were reported by two researchers who claimed the authors refused to provide their data for analysis. They were concerned that the paper was being used inappropriately for "vigorous marketing of NADH as a treatment."[38] A subsequent study with 12 patients receiving NADH found only transient improvements and no long-term differences compared with patients receiving nutritional supplements and psychological therapy.[39]

Immune modulation

Multiple trials of immunoglobulin, based on the theory that immunomodulation could help treat CFS, have had inconclusive results.[3]

In experiments with staphylococcal toxoid vaccine administered to fibromyalgia/chronic fatigue syndrome (FM/CFS) patients, increased serological responses to toxins paralleled clinical improvements as measured by a fibromyalgia questionnaire and a psychopathological rating survey.[40] A group of 14 vaccine treated FM/CFS patients had significant improvement over placebo in seven of 15 symptoms after three months of injections. A follow-up with 23 patients included regular toxoid injections for several years. Half of the patients recovered to find part- or full-time jobs.[41] In 2002, a similar study treated 50 FM/CFS patients each with placebo or toxoid. A third of the toxoid group and a tenth of the placebo group had improvement after weekly injections followed by monthly boosters. The effects ended when injections were stopped.[42]

Complementary and alternative medicine

Complementary and alternative medicine usage

People with CFS may use more alternative medicine treatments than people without CFS.[43] In a twin study, 91% of twins with CFS and 71% without CFS used at least one alternative treatment. Many twins thought alternative treatments were helpful.[44]

Dietary supplements

Carnitine

Two randomized controlled trials found some benefit from dietary supplementation with L-carnitine or its esters. L-carnitine, but not amantadine, showed improvement in several parameters.[45] Two kinds of L-carnitine alone and together were tested in a second trial, where the different carnitines had slightly different effects.[46]

Magnesium

Positive results from a trial of magnesium delivered by injection to magnesium deficient CFS patients were published in 1991,[47] but three subsequent studies did not find magnesium deficiency as a general problem in CFS patients. Magnesium treatments and dietary supplements are classified as having unknown effectiveness against CFS.[48] However, one review recommends magnesium dietary supplementation because magnesium deficiencies are difficult to rule out and serious side effects are rare.[49]

Essential fatty acid treatments

Companies that sell dietary supplements known as essential fatty acids (EFA) have proposed that they could be used as a CFS treatment.[50] A review of CFS treatments compared two studies of essential fatty acids, concluding that they showed mixed results. Dietary supplements are classified as having unknown effectiveness.[48]

References

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