Chronic fatigue syndrome
BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7230.292 (Published 29 January 2000) Cite this as: BMJ 2000;320:292All rapid responses
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In Mr. Reid's response to the numerous criticisms levied against him,
he mentions that "Baschetti considers that CFS in the US is misdiagnosed
Addison's disease and in the UK is misdiagnosed depression, and are
therefore different illnesses. The (US) Centers for Disease Control
diagnostic criteria(2) require that the fatigue is unexplained and in
their guidelines stipulate the need to exclude conditions such as
Addison's disease which may explain the fatigue. Depression is not a
reason for exclusion from a diagnosis of CFS and has a similar prevalence
in both US and UK CFS populations."
First, primary disorders are different than secondary disorders. Not
eating because one has cancer is different than not eating because one has
Anorexia Nervosa. So primary Addison's is different than secondary
Addison's, which does not exclude one from a diagnosis of CFS, but rather
is an effect of the disease.
Secondly, should Mr. Reid even be writing papers, and should his
papers be being published if he is either
A) So ignorant of the disease he is writing about that he does not know
that while depression does not exclude one from a diagnosis of CFS, the
CDC does in fact differentiate CFS from major depressive disorders?
or
B) If he is so duplicitous to leave out that rather inconvienent, but
altogether fundamental fact when confronted?
Lastly, and perhaps most importantly, he brings up a rather
controversial finding, namely prevalance rates in US and UK populations.
Contrary to his assertation, prevalance rates of CFS are up to 10x higher
in the UK than in the US, indicating that he and his colleagues are in
fact conducting research on an entirely different illness, combined with
the fact that researchers in the US and Australia have not been able to
duplicate Prof. Wessely's results with CBT and GET studies, the treatment
of choice for "CFS" in Great Britian.(1)
"Toward the late 1990s, Jason, Richman and colleagues (1999) used
more rigorous community-based samples and found that approximately .42% of
the sample was determined to have CFS, or approximately 800,000 people
from the US (Jason, Richman et al., 1999). These overall prevalence
estimates were later corroborated by the CDC in another community-based
sample (Reyes et al., 2003 estimated the CFS prevalence to be .24%).
In Great Britain, community estimates of CFS rates were estimated to
be 2.6% (or 2.6 cases among every 100 people; Wessely et al., 1997)."
http://iacfs.net/p/1,544.html
(1)A Subgroup Analysis of Cognitive Behavioural Treatment Studies.
Fred Friedberg. Journal of CFS 1999:5:3 4:149-159
Competing interests:
CFS patient
Competing interests: No competing interests
According to the Cheif Medical Officer, Chronic Fatigue Syndrome Sufferers are to be considered the Specialists in the Field.
Now I have suffered for the last 16 years, Graded excersise how is this going to help a person that needs help going to the toilet, whom has not been out in months, needs an ambulance to see their consultants at hospital. I would like to add to my learned friends that if you wish to do a research project on CFS / ME then perhaps you should be looking to the whole of a CFS sufferers life, the effects on Family and what they feel. Maybe the researchers in question should actualy have a look at a sufferers web portal, and read some of the articles there the address is Brainfog.org or even SupportME also I would suggest that for a lot of the severe suffers who do not get the help they need, they cannot cope with graded excercise.
CFS sufferers all over the country have been bombarding M.P.'s and Working groups with mail saying that we wish Graded excercise to stop, so the findings from a limited clinical trial cannot be held as evidence when the whole of the CFS community is up in arms!!
D Hazel Chronic Fatigue Sufferer, bed bound, with little Help.
Competing interests: No competing interests
The recent review by Reid et al. (1) ignores one of the nutritional
supplements: l-carnitine. Work by Kuratsune et al. as long ago as 1994 (2)
showed that carnitine metabolism may be disrupted in CFS. Later work has
replicated and extended those results (3,4), and at least one RCT has
shown significant benefits (5). I am aware of at least one other RCT
specifically addressing carnitine. In view of the inclusion of evening
primrose oil and magnesium injections, the absence of carnitine is
puzzling.
(1) Reid, Chalder, Cleare, Hotopf and Wessely "Chronic Fatigue
Syndrome" extract from "Clinical Evidence" BMJ 2000; 320:290-296 (29 Jan).
(2) Kuratsune, Yamaguti, Takahashi, Misaki, Tagawa and Kitani
"Acetylcarnitine Deficiency in Chronic Fatigue Syndrome" Clin. Inf. Dis.
1994; 18(Suppl 1):S62-7.
(3) Kuratsue, Yamaguti, Lindh, Evengarg, Takahashi, Machii,
Matsumura, Takaishi, Kawata, Langstrom, Kanakura, Kitani and Watanabe "Low
Levels of Serum Acetylcarnitine in Chronic Fatigue Syndrome and Chronic
Hepatitis Type C, But Not in Other Diseases" Int. J. Mol. Med. 1998;
2(1):51-6 (July).
(4) Plioplys and Plioplys "Serum Levels of Carnitine in Chronic
Fatigue Syndrome: Clinical Correlates" Neuropsychobiol. 1995; 32:132-8.
(5) Plioplys and Plioplys "Amantadine and l-Carnitine Treatment of
Chronic Fatigue Syndrome" Neuropsychobiol. 1997; 35:16-25.
Gerald R. Campbell, Ph.D.
Competing interests: No competing interests
During my period as a locum I have come across the use vitamin B12
injections as a treatment for chronic fatigue. This is given on occasions
as frequently as 1-2 weeks apart. The patients in question have levels of
B12 greater than 2000 and normal FBP and iron studies. Several of the
patients involved are convinced of the necessity of the treatment and self
refer when feeling particularly tired in order to recieve 'energy
boosting' injections. I would be interested if there is any evidence
supporting this form of treatment.
yours,
A Vance.
Competing interests: No competing interests
Dear Sir,
Chronic Fatigue Syndrome has received considerable attention in
recent years. While the meanings of two of the three words used in naming
this ailment are well understood, viz. ‘chronic’ and ‘syndrome’, little is
really known or understood about the third word, ‘fatigue’, which is
central to Chronic Fatigue Syndrome as well as to other fatigue-related
syndromes. 20 years ago fatigue was described as "the commonest, yet least
understood, and most neglected symptom in clinical medicine".1 This
appraisal has hardly changed since then.
While many attempts are being made to try to define CFS and to
identify its cause(s), and indeed many theories (psychological ,viral or
other infectious agent, immune system or neurologic abnormalities, etc.)
have been advanced to this end, the fact that medical scientists have not
been able to define the nature of fatigue itself in terms of its
fundamental function, and have not even considered what would happen to
life itself if fatigue were to cease to exist, does not augur
particularly well for significant progress being made in the forseeable
future in this field.
Steven Reid et al., in their review article of CFS ( BMJ Jan. 29,
2000, Vol.320: 292-296) present their analysis of various randomised
controlled studies (RCT’s) replete with data, in an attempt to shed some
light on the problem. Their comment on the aetiology of CFS, that ‘the
cause of chronic fatigue syndrome is poorly understood’, says it all. This
despite the plethora of data in the literature. Perhaps the time has come
to heed the comment by Henri Poincaré (1854-1912), the distinguished
French mathematician and philosopher of science (see Encyclopedia
Britannica), who wrote,
"Science is built of facts the way a house is built of bricks; but an
accumulation of facts is no more science than a pile of bricks is a
house."
Data without understanding leads nowhere. Thus far all that appears
to have been achieved in researching fatigue-related syndromes merely
represents a growing pile of bricks. Perhaps we should focus more on
thinking and understanding, and less on data!
Yours sincerely,
David Eidelman.
Eidelman D. Fatigue: Towards an Analysis and a Unified Definition.
Med. Hypoth. 6:517-526, 1980.
Competing interests: No competing interests
The problem with most theories about Chronic Fatigue Syndrome is that
they are far too specific- they either focus on a single physical problem
(which not everybody has) or a single type of mental problem (which not
everybody has). The reason why Professor Wessely arouses such controversy
is that he has gone all out for such a theory- it permeates his work and
even seems to influence the editorial policy of the B.M.J.
My current thinking is that Chronic Fatigue Syndrome is a state where
underlying problems are masked by changes in the nervous system (which may
be associated with changes in the immune system, hormonal systems and
behaviour). C.F.S. emerges when masking becomes unsustainable, or
dysfunctional. Masked problems may be neurological, immunological,
muscular, digestive or mental (depression or anxiety).
The first prediction from such a theory is that treatments that
reduce masking will expose problems and this will make some people worse.
Controlled trials of such treatments will inevitably give mixed results.
Treatments which only address masking (such as cognitive behavioural
therapy) will only result in a complete cure if the underlying problems
burn out spontaneously. Does this explain why so many of the treatments
which Prof Wessely has reviewed are mired in controversy?
Competing interests: No competing interests
The review by Reid et al of possible treatment interventions for
chronic fatigue syndrome contains a number of conclusions and
recommendations which appear to reflect the group’s enthusiasm for certain
non-pharmacological approaches to management rather than a truly objective
analysis of the published results (1).
Their summary conclusion that "Two RCTs (randomised controlled
trials) have found that a graded exercise programme can produce
substantial improvements in measures of fatigue and physical
functioning.." is incorrect. The second trial of graded exercise only
produced a small amount of improvement in case level fatigue (ie a 12%
reduction in the number of patients by 26 weeks) and functional work
capacity (ie a 10% improvement at 26 weeks), with no significant changes
in functional status (2). Neither is it correct to claim that there is
"...no evidence that exercise is harmful in people with chronic fatigue
syndrome". Lapp has convincingly demonstrated that over-ambitious exercise
can easily produce a prolonged period of relapse (3) - a finding which is
increasingly being confirmed by reports to the ME Association from people
who have been coerced into participating in badly designed or
inappropriate exercise programmes. Advice from the Medical Defence Union
is that doctors who prescribe exercise programmes risk litigation if a
patient suffers harm as a result - something which should be borne in mind
by those doctors who insist that rest has no place in the management of
chronic fatigue syndrome.
The section on cognitive behaviour therapy exhibited similar bias in
that there was no reference to defects in RCTs which have reported
positive results (eg the second study included a very high percentage of
patients with recognised psychiatric illness; there was no report of
improvement in employment status despite stating the intention to use this
as a subsidiary measure of functioning; outcome improvements began to
decline 17 months after treatment termination (4)). Results from a further
controlled (but non-randomised) trial, which produced no significant
changes in functioning or chronic fatigue syndrome symptoms, were also
omitted (5).
Health service providers who are considering making use of Reid et
al’s clinical evidence to plan future services for chronic fatigue
syndrome patients need to carefully consider whether these outcome results
can justify the enormous cost of introducing two controversial management
approaches which are likely to be met by widespread patient resistance.
Charles Shepherd
Medical Director, ME Association
REFERENCES
1 Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue
syndrome. BMJ, 2000; 320: 292 - 6. (29 January.)
2 Wearden AJ, Morriss RI, Mullis R, Strickland PL, Pearson DJ,
Appleby L, et al. Randomised, double-blind, placebo controlled treatment
trial of fluoxetine and a graded exercise programme for chronic fatigue
syndrome. Br J Psychiatry 1998; 172: 485 - 90.
3 Lapp CW. Exercise limits in chronic fatigue syndrome. Am J of
Medicine 1997; 103: 83 - 4.
4 Sharpe M, Hawton K, Simkin S, Surawy C, Hackmann A, Klimes I, et
al. Cognitive behaviour therapy for chronic fatigue syndrome: a randomised
controlled trial. BMJ 1996;312: 22 - 6.
5 Friedberg F, Krupp LB. A comparison of cognitive behavioural
treatment for chronic fatigue syndrome and primary depression. Clinical
Infectious Diseases 1994; 18 (suppl 1): S105 - 10.
Competing interests: No competing interests
Sir ,
When they charge others with inflicting psychiatric stigma [1] , the
Reid , Wessely et al. pot is calling the kettle black .
In 1996 Wessely was party to a report [2] confirming that "one-
quarter to one-third of those who fulfil criteria for CFS do not fulfil
any criteria for psychiatric disorder" (p 15 ) . Most patients , and some
research teams , argue that the percentage is higher . Irrespective of
their mental status , Wessely et al. advocate that all CFS patients be
subjected to psychiatric intervention [3] . In the 1996 report , it was
even proposed to administer antidepressants to patients who were not
depressed (p 28) .
Inappropriate psychiatric intervention is not benign . For patients
the inevitable result is psychiatric labelling , with consequent social ,
employment , health care , financial and other penalties . Whatever the
intentions of the CBT school , the effect of their theory and practice is
to brand all CFS patients with psychiatric stigma . It is an evil when
society stigmatises patients who have psychiatric illness . But it is
doubly evil to apply blanket psychiatric stigma to large numbers of
patients who -- by Wessely's own admission -- are not mentally ill .
Psychological distress is a predictable secondary product of CFS ,
and if necessary in such cases the care of a psychiatrist is welcome . By
contrast , the misguided hypotheses of Wessely et al. do great harm , and
augment distress .
With Chronic Fatigue Syndrome , there is a gulf of mutual hostility
and distrust between very many patients and many doctors , a situation
that must be unprecedented in modern medicine . There will be no
substantial progress until this abnormal estrangement is reconciled , to
the satisfaction of both parties . The stigma inseparable from the Wessely
doctrine is not the only source of friction , but it is a potent one .
Horace Reid .
-------------------------------
[1] Reid S et al. , Clinical Evidence - Chronic fatigue syndrome ,
BMJ 2000 ; 320 : 292-296 (14 Feb) .
[2] Chronic Fatigue Syndrome , Report of a joint working group of the
Royal Colleges of Physicians , Psychiatrists , and General Practitioners ,
London , Royal College of Medicine , 1996 .
[3] Sharpe M , & Wessely S , Authors' reply , BMJ 1998 ; 317 :
599 (29 August ) .
Competing interests: No competing interests
Editor
I read with interest the varied opinions on ME/CFS/PVS etc. and,
having a number of years experience successfully treating patients having
received such diagnoses from their GPs and Specialists, thought I would
comment from a Traditional Chinese Medicine (TCM) perspective.
Every patient who attends the Clinic is an individual whatever the
'medical' diagnosis - we have no hang-ups about 'established views'
according to western medical (WM)diagnosis, nor are swayed by trends or
'current wisdom' but use age-old methods of evaluation, differentai
diagnosis, and treatment and find these eminently successful. Although
every new patient is unique and therefore one cannot generalise, our
methods create a high probability of improving their condition. The
shorter the duration of disorder the better the prognosis and quicker the
recovery. The younger and fitter the patient the more probable an early
recovery. The less the patient's environment (home and /or work) is a
causal factor the better the chance of recovery. Certain apparent 'vaccine
induced' ME/CFS states are likely to pattern recovery, perhaps dependent
on antibody state persisting.
Pathogenesis in TCM is very much about lifestyle and environment, and
less about bacteria and viruses - although TCM recognises these factors in
illness as well as parasitic factors. However, environmental factors such
as pulsed magnetic fields, chemicals, employment/relationship stresses and
strains, diet, exercise regimes - in fact all lifestyle factors that can
be accounted for and assessed - are an important consideration when
developing an understanding of why a person developed a disorder.
Thousands of years of anecdote and observation have given TCM
practitioners a great understanding of how particular daily stresses and
strains affect humanity. This knowledge is exceptionally important in
ME/CFS states BECAUSE THEY ARE A CONSEQUENCE OF THESE FACTORS - and I
would include iatrogenic illness as another 'pathogen' to be analysed (eg.
ME/CFS developing after certain antibiotics, vaccines, and other immune
suppressant 'medication' meted out often against reason, for example broad
spectrum antibiotics for viral infection, vaccination during viral
infection etc.).
Most GPs who refer patients to us are aware that it is best to refer
the case within a few months of onset, such people are usually recovered
within a month or two, rather than after years of unsuccessful medical
intervention; the latter patients are usually made aware that their
treatment regimes may take one to two years for recovery (not a long time
when one has been ill for 12 or 13 years with no hope of change) - the
first year I usually expect about 70% improvement across the board with
much of the remainder following in the next year. Many patients notice
improvements within the first few weeks of treatment when they report a
more 'stable' pattern such that they feel that successive weeks should be
reasonable with no great drop in mood or energy as had been common. The
'long term' ME/CFS sufferers, depending on many factors (age, health at
onset, lifestyle, will to recover, whether recovery can be hampered by
'unreasonable stress' - necessity to return to full time employment too
soon, lack of home and/or medical support, financial and therefore
feeding/living/treatment availability problems etc.) will also recover in
the main but the older the patient the less chance of a full recovery;
many recover to work with general good health but perhaps are left with
'weakness' in a certain muscle or muscle group, perhaps dizziness, lowered
adrenal response to stressful events, greater emotional lability - as Dr.
Choudini states, very much like 'post polio syndrome' or I would say like
a 'post- encephalitis' condition.
Years of obseravtion and much success tempered with analysis of those
who failed to recover leads me to believe that ME/CFS/PVS are similar
despite their varying diagnostic criteria around the world; there are many
paths into the disorder - some described above, and of those too many that
require professional acknowledgement of serious failings in our
environmental, occupational and medical systems resulting in the public
experiencing evermore 'immune deficiency syndromes'. Western medicine does
not have the ability nor expertise to individualise cases, recognise such
'pathogenic' origins, treat consistently and carefully -often for
protracted periods- alongside graduated exercise regimes vary different
people of all ages and lifetsyles with 'immune-enhancing' treatments like
TCM. Patients require much advice on environment change, diet, exercise,
causal relationships that were responsible for the disorder and must play
a part in the recovery process, and many other arpects of our system of
healing that have stood the test of time.
Where are the randomised trials? One requires funding for these to
accur and, as I found 5 or 6 years ago, those interested in funding TCM
research do not have the money and those who have the money are apparently
not interested in our treatments that 'work' but projects which follow
recognised WM focus such as the biochemical and microscopic analysis of
muscle cells, or the trial of a drug that meets the criteria for treating
'a symptom' of the disorder eg. antidepressants for 'alleged' depression.
A last word about ME/CFS - according to TCM one expects to find at
least five different major constitutional patterns in any disorder - so
the same pathogen may affect 5 people differently; one may have a
preponderance of 'heart/small intestine' symptoms (perhaps breathlessness,
unexplainable arrythmias, mild psychosis, insomnia, dopamine
irregularities, irritable bowel, CNS inflammation etc.) another may have
'stomach/spleen' problems (digestive disorders, exceptional muscle
fatigue, myelitis, insulin irregularities etc.), another 'Liver/gall
bladder' symptoms (flank pain, great fatigue, cholecystitis, migrainous
and/or Meniere's-like symptoms, general biliousness, rheumatics, serotonin
irregularities, thyroid problems, general 'hormonal' imbalance, pronounced
emotional lability, PMS, blood flow problems etc. ) then another
'Kidney/Bladder' symptoms (more marked adrenal insufficiency - either
cortisol or noradreanline irregularities, low back pain, libido to
impotence problems, marked anxiety state, fluid metabolism problems,
parasympathetic and parathyroid imbalances etc.) and the fifth -
Lung/large intestine problems (such as breathlessness, bowel upsets, skin
eruptions, sciatic pain, respiratory trouble or sinus problems etc.) .
These aspects of TCM will not be understood by WM until the genetic
propensities of humanity has been revealed through the genome project; yet
TCM, through the benefit of millennia of observation and anecdote, can
already link certain types of people with certain types of pathogenic
response.
We all have 'similar' immune systems, musculoskeletal structure and
functions, general physiological mechanisms, emotional and mental
faculties. Yet if we are struck by a virus, say Epstein Barr, our
'similarities' ensure a small range of similar signs and symptoms will be
revealed, but our constitutional differences will ensure that any
developing chronic disorder sparked by that initial pathogenic insult will
see us exhibit unique complex patterns of 'disorder' as our genetics,
lifestyle, social, cultural and environmental idiosyncracies take over;
TCM is used to recognising and restoring balance to such complexities of
life.
Regards
John H.
No compelling interests other than a great desire to heal the sick
and to help point out the erroneous arguments Western medicine is locked
in over a complex condition for which it has neither the expertise nor
methodlogy with which to deal with. So many patients tell me their GP
still does not recognise the existence of M.E.
Competing interests: No competing interests
A meta-analysis of the efficacy of CBT for CFS calculated the Cohen's d value to be 0.48
As should be obvious to most people who look at results of
intervention studies, treatments can show "statistically significant"
improvements but one intervention can be much more "effective" than
another. For this purpose, effect measures such as Cohen's d are
calcuated.
For a meta-analysis of the efficacy of CBT for CFS patients, Malouff
et al[1] calculated d, using the following method: "Separate mean effect
sizes were calculated for each category of outcome variable (e.g., fatigue
self-rating) and for each type of outcome variable (mental, physical, and
mixed mental and physical). Studies generally included multiple outcome
measures. For all analyses except those that compared different categories
or types of outcome variables, we used the mean effect size of all the
relevant outcome variables of the study."
Table 1 in this paper lists the effect sizes found in various papers
in an easily accessible form.
The mean effect size Malouff et al[1] found across the studies was
d=0.48, which they said was "nearly a medium effect size by the standards
suggested by Cohen (1988)". The 95% Confidence Interval was 0.27 to 0.69
(see Table 2). For anyone unfamiliar with Cohen's d values, they are not
bounded by 1; also, the higher the score, the bigger the "effect size"
i.e. the more "effective" a treatment was found to be. Cohen's d values
are considered to be a small effect size at 0.2, a moderate effect size at
0.5, and a large effect size at 0.8[2].
The overall Cohen's d value that Malouff et al[1] would most likely
have been lower than 0.48 if Lloyd et al[3] had been included; as the
current review points out: "there was no significant difference in
outcomes between cognitive behavioural therapy and standard care when the
Karnofsky scale and symptom report on a visual analogue scale were used."
Malouff et al said this "study was excluded because we were unable to
obtain the information necessary to determine an effect size."
With regard to the diagnositic criteria issue, Malouff et al[1] did a
moderator analysis: "there was a nonsignificant trend towards studies that
used the Oxford diagnostic criteria having a larger effect size than
studies that used the CDC 1994 diagnostic criteria. If this difference
continues to be found in future studies, one might wonder whether clients
with the medical-problem
criteria required only for the CDC standards are harder to treat and
perhaps different in other important ways as well." They later pointed
out: "Conclusions that can be drawn from the moderator analyses are
limited because the analyses included a relatively low number of studies,
which created low power for identifying significant differences. Hence,
the finding of no significant differences between two levels of a possible
moderator might be due to low power rather than the absence of
a difference."
Tom Kindlon
[1] Malouff, J. M., et al., Efficacy of cognitive behavioral therapy
for chronic fatigue syndrome: A meta-analysis. Clinical Psychology Review
(2007), doi:10.1016/j.cpr.2007.10.004
[2] Cohen J: Statistical power analysis for the behavioural sciences.
Edited by: 2. New Jersey: Lawrence Erlbaum; 1988.
[3] Lloyd A, Hickie I, Brockman A, Hickie C, Wilson A, Dwyer J, et
al. Immunologic and psychological therapy for patients with chronic
fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med 1993;
94: 197-203
Competing interests:
Assistant Chairperson, Irish ME/CFS Association - for Information, Support & Research (voluntary position)
Competing interests: No competing interests