CBT and CFS

Change in grey matter volume cannot be assumed to be due to cognitive
behavioural therapy

Journal: Brain, Advance Access published online on January 29, 2009
Brain, doi:10.1093/brain/awn358

Author: Tom Kindlon

Affiliation: Irish ME/CFS Association, PO Box 3075 Dublin 2, Ireland
E-mail: tomkindlon@oceanfree.net; tkindlon@maths.tcd.ie

Received November 19, 2008. Accepted December 14, 2008.

Sir, In their reply to Dr Bramsen, De Lange et al. (2008Go) use a
type of circular reasoning: cognitive behavioural therapy (CBT), they
say, has previously been shown to be 'effective' for chronic fatigue
syndrome (CFS) so the change they measured must be due to CBT.

First, it needs to be pointed out that CBT is far from a panacea for
CFS. A recent meta-analysis (Malouff et al., 2008Go) of the efficacy
of CBT in treating CFS found an effect size of d = 0.48 (95% CI 0.27–0.69).

In their letter, De Lange et al. (2008Go) refer to a review by
Whiting et al. (2001Go) as part-evidence for their claim that CBT is
effective for CFS. However, this review recommended the use of
objective outcome measures e.g.

     Outcomes such as 'improvement,' in which participants were asked
to rate themselves as better or worse than they were before the
intervention began, were frequently reported. However, the person may
feel better able to cope with daily activities because they have
reduced their expectations of what they should achieve, rather than
because they have made any recovery as a result of the intervention.
A more objective measure of the effect of any intervention would be
whether participants have increased their working hours, returned to
work or school, or increased their physical activities'.

Given one of the aims of CBT (for CFS) has been said to be 'increased
confidence in exercise and physical activity' (O'Dowd et al.), we
cannot have complete confidence that the improvements recorded in CBT
trials thus far represent objective improvements [such as
improvements in grey matter volume (GMV)], rather than simply being
due to altering how patients answer questionnaires. An INAMI report
(2006) on the use of CBT (combined with GET) in over 600 CFS patients
in Belgium found that while patients reported improvements on their
fatigue scores, there was negligible change on the tests of exercise
capacity and there was actually a worsening of their employment
status (as measured by the amount of hours worked per week), both at
the end of the intervention and at follow-up.

CFS is not generally a progressive condition—improvement often occurs
(Nisenbaum et al., 2003Go; Cairns et al., 2005). Indeed, in a recent
uncontrolled study of CBT (Scheeres et al., 2008Go), co-written by
one of the authors (Bleijenberg), a spontaneous recovery rate of 5%
was assumed over a similar period as this study. Thus the authors
have not proven that the 12% improvement in GMV in CFS was due to
CBT. If their logic was applied throughout medicine, control groups
would only be required to test if an intervention was effective as
measured by one or a limited number of outcome measures. After that,
if a positive change in any other outcome measure was recorded in any
uncontrolled study, it would be acceptable for pharmaceutical
companies and others to claim that this must be due to their
'effective' intervention!

References

Cairns R, Hotopf M. A systematic review describing the prognosis of
chronic fatigue syndrome. Occup Med (Lond) (2005) 55:20–31.[CrossRef][Medline]

de Lange FP, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, Meer JW,
et al. Reply to: can CBT substantially change grey matter volume in
chronic fatigue syndrome? Brain (2008) doi: 10.1093/brain/awn208
[Epub ahead of print 30 August 2008].

Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS.
Efficacy of cognitive behavioral therapy for chronic fatigue
syndrome: a meta-analysis. Clin Psychol Rev (2008) 28:736–45.[Medline]

Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC. A
population-based study of the clinical course of chronic fatigue
syndrome. Health Qual Life Outcomes (2003) 1:49.[CrossRef][Medline]

O'D;owd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A.
Cognitive behavioural therapy in chronic fatigue syndrome: a
randomised controlled trial of an outpatient group programme. Health
Technol Assess (2006) 10:1–121. iii-iv, ix-x.[ISI][Medline]

Rapport d'évaluation (2002–2004) portant sur l'exécution des
conventions de rééducation entre le Comité de l'assurance soins de
santé (INAMI) et les Centres de référence pour le Syndrome de fatigue
chronique (SFC) (2006)
http://www.inami.fgov.be/care/fr/doctors/specific-information/sfc-cvs/sfc-cvs04.htm  
(10 September 2008, date last accessed).

Scheeres K, Wensing M, Bleijenberg G, Severens JL. Implementing
cognitive behavior therapy for chronic fatigue syndrome in mental
health care: a costs and outcomes analysis. BMC Health Serv Res
(2008) 8:175.[Medline]

Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramirez G.
Interventions for the treatment and management of chronic fatigue
syndrome: a systematic review. JAMA (2001) 286:1360–8.[Abstract/Free Full Text]

_______________________________________

Reply: Change in grey matter volume cannot be assumed to be due to
cognitive behavioural therapy

Journal: Brain, Advance Access published online on January 29, 2009
Brain, doi:10.1093/brain/awn359

Authors:
Floris P. de Lange1,2, Gijs Bleijenberg3, Jos W. M. van der Meer4,
Peter Hagoort1 and Ivan Toni1

Affiliations:
1 Donders Institute for Brain, Cognition and Behaviour, Radboud
University Nijmegen, The Netherlands 2 Inserm-CEA Cognitive
Neuroimaging Unit, CEA/SAC/DSV/DRM/NeuroSpin, Gif sur Yvette, France
3 Expert Center Chronic Fatigue, Radboud University Nijmegen Medical
Center, The Netherlands 4 Department of General Internal Medicine,
Radboud University Nijmegen Medical Center, The Netherlands

Correspondence to: Dr Floris de Lange, Donders Institute for Brain,
Cognition and Behaviour, PO Box 9101, Nijmegen, NL-6500 HB, The
Netherlands E-mail: florisdelange@gmail.com

Received December 17, 2008. Accepted December 17, 2008.

Sir, We thank Tom Kindlon for his letter, in which he raises several
important issues. We will respond to all the issues in the same order
as they appear in his letter.

First, Tom Kindlon points out that cognitive behavioural therapy
(CBT) is not a panacea for the chronic fatigue syndrome (CFS). It
should be obvious from all previous meta-analyses that CBT does not
lead to a full recovery in all CFS patients (while the exact numbers
on improvement rates depend on a host of experimental factors like
the exact type of therapy given, inclusion criteria of the study, as
well as other factors such as the patient's self efficacy, social
support and physical activity pattern). Nevertheless, it should also
be obvious from these meta-studies that psychotherapeutic
interventions like graded exercise therapy and CBT interventions are
the only interventions that have shown reliable, replicable and
relatively robust improvements in health status in CFS, compared wtih
all other interventions that have been investigated to date.

The second point of Tom Kindlon is that we should have used objective
measures to quantify improvement in health status rather than
questionnaires as the latter may simply reflect changes in response
tendency of the CFS patients. We share the author's preference for
objective measures, which is why all the reported significant
brain–behaviour relations in our manuscript in fact pertain to
objective, quantitative measures [see e.g. Fig. 4 of de Lange et al.
(2008Go)]. The significant relationship between behavioural
improvements and increase in grey matter volume (GMV) was constituted
by the choice reaction time task (Vercoulen et al., 1998Go) and the
digit symbol substitution test of the Wechsler adult intelligence
scale (WAIS-dst) (Wechsler, 1981Go), two objective psychophysical
tasks that are often used as measures of information processing speed
(Chiaravalloti et al., 2003Go). Moreover, improvements in general
physical activity, quantified by objective actigraphic measurements
(Vercoulen et al., 1997Go; van der Werf et al., 2000Go) for a 2-week
period both at baseline and follow-up, showed a trend of significant
relationship with the GMV increase.

Lastly, the author points out that our study, for lack of control
group, has not proven that the increase in GMV is specifically due to
CBT, rather than spontaneous recovery. We agree with the author that
the lack of patient control group limits the scope of our inferences,
as has already been acknowledged both in the manuscript and in the
reply to Dr Bramsen. We would like to point out that the improvement
rate of the sample in our study far exceeded the improvement rate
seen with passive support groups or a waiting list condition (Prins
et al., 2001Go). But crucially, the aim of our study was not to test
whether CBT is an effective intervention for CFS, as has been the
topic of previous studies (Whiting et al., 2001Go; Chambers et al.,
2006Go), but rather to investigate whether there was a relationship
between behavioural improvements following CBT in CFS and changes in
brain morphology. Our data clearly indicate that there are changes in
brain morphology that are contingent upon behavioural improvements
following CBT.

References

Chambers D, Bagnall AM, Hempel S, Forbes C. Interventions for the
treatment, management and rehabilitation of patients with chronic
fatigue syndrome/myalgic encephalomyelitis: an updated systematic
review. J R Soc Med (2006) 99:506–20.[Abstract/Free Full Text]

Chiaravalloti ND, Christodoulou C, Demaree HA, DeLuca J.
Differentiating simple versus complex processing speed: influence on
new learning and memory performance. J Clin Exp Neuropsychol (2003)
25:489–501.[ISI][Medline]

de Lange FP, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der
Meer JW, et al. Increase in prefrontal cortical volume following
cognitive behavioural therapy in patients with chronic fatigue
syndrome. Brain (2008) 131:2172–80.[Abstract/Free Full Text]

Prins JB, Bleijenberg G, Bazelmans E, Elving LD, de Boo TM, Severens
JL, et al. Cognitive behaviour therapy for chronic fatigue syndrome:
a multicentre randomised controlled trial. Lancet (2001)
357:841–7.[CrossRef][ISI][Medline]

van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW, Bleijenberg
G. Identifying physical activity patterns in chronic fatigue syndrome
using actigraphic assessment. J Psychosom Res (2000)
49:373–9.[CrossRef][ISI][Medline]

Vercoulen JH, Bazelmans E, Swanink CM, Fennis JF, Galama JM, Jongen
PJ, et al. Physical activity in chronic fatigue syndrome: assessment
and its role in fatigue. J Psychiatr Res (1997)
31:661–73.[CrossRef][ISI][Medline]

Vercoulen JH, Bazelmans E, Swanink CM, Galama JM, Fennis JF, van der
Meer JW, et al. Evaluating neuropsychological impairment in chronic
fatigue syndrome. J Clin Exp Neuropsychol (1998) 20:144–56.[ISI][Medline]

Wechsler D. WAIS-R, wechsler adult intelligence scale revised. (1981)
New York: The Psychological Corporation.

Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramirez G.
Interventions for the treatment and management of chronic fatigue
syndrome: a systematic review. Jama (2001) 286:1360–8.[Abstract/Free Full Text]

 

 

 

* * *

Tom makes a very good point; when I reduced the amount I was pushing myself to do (i.e., gave myself permission to do less and rest more), I began to feel better.  Not because I had improved by objective measures, but because I was no longer pushing myself to a level that made me sicker.  In fact, by objective measures of how much I was doing each day, you'd have to say I regressed, because I was doing less.

 

Ellen Goudsmit's research on pacing showed that patients felt better, but did not actually accomplish more, when activity was spread out through the day, interspersed with rest periods, rather than "shop till you drop" and then crashing.  Continually "topping off the tank" makes a difference in how we feel, but does not cause an objective improvement.

 

 

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ADVANCE



A Confounding Condition


Treating chronic fatigue syndrome and
fibromyalgia requires addressing the
underlying problems.



Kent Holtorf, MD



Vol. 4 • Issue 4 • Page 37



When it comes to treating patients with chronic
fatigue syndrome (CFS) and fibromyalgia (FM),
doctors are often at a loss. Because they can't figure
out what's wrong, many consider CFS and FM "waste
basket" diagnoses. Others simply dismiss the
symptoms as psychiatric in nature.1-3This certainly
is a disservice to the estimated 4 percent to 7
percent of the population that suffers from these
conditions. These disorders, which strike women four
times as much as men,1-3are consistently
associated with a unique set of physiologic
abnormalities.4-71


Physicians need to employ a multi-­system approach,
instead of resorting to single-drug modalities for
each symptom.12,16,72-87 This comprehensive
approach is largely becoming the standard of care
and is effective in 80 percent of patients with these
conditions.


What is Fibromyalgia?

To be diagnosed with FM, patients must experience
pain for at least three months. They also must feel
pain upon palpation at 11 out of 18 tender
points.88This criteria, however, is criticized for not
taking into account the essential elements of FM,
such as fatigue, sleep disturbance and cognitive
dysfunction.89-93

For a CFS diagnosis, patients must experience
fatigue that doesn't improve with bed rest. This
fatigue should impair average daily activity levels by
more than 50 percent for at least six months. People
also must experience four or more of the following
symptoms: cognitive dysfunction, sore throat, joint
pain, muscle pain, headaches, nonrefreshing sleep
and post-exertional malaise.94The diagnostic criteria
for FM and CFS are limited. Furthermore, there's no
accepted laboratory marker to define these
conditions. Consequently, physicians have difficulty
properly diagnosing FM and CFS. But despite
different modes of diagnosis (physical exam vs.
history), CFS and FM coexist 50 percent to 70 percent
of the time, depending on the study. Therefore, from
a clinical standpoint, we will consider these illnesses
together. The range of symptoms in these conditions
includes fatigue, sleep disturbances, muscle pain,
cognitive dysfunction, gastrointestinal dysfunction,
headaches and postexertional malaise.

Note that the unique physiologic hallmarks of CFS
and FM don't exist in other fatiguing
illnesses.4-71These syndromes are complicated,
involving pituitary and hypothalamic dysfunction,
immune dysfunction, sleep stage disorder,
mitochondrial dysfunction, hormonal deficiencies,
coagulation defects and chronic infections.

In addition, each physiologic abnormality can
cascade into other problems. For example, chronic
stress can produce hypothalamic, pituitary and
immune dysfunction-signature signs of fibromyalgia.
Immune dysfunction can reactivate viral and
intracellular bacterial infections. This can further
suppress hypothalamic and pituitary function,
causing mitochondrial dysfunction and coagulation
dysregulation.

The hypothalamic and pituitary dysfunction produces
hormonal deficiencies. In a vicious cycle, the chronic
infections can further suppress mitochondrial function
and produce global cellular dysfunction and a
subsequent immune activation that causes a
coagulation defect. This, in turn, worsens cellular
function. This cascade produces multisystem illness
that causes a broad range of often perplexing
symptoms.


The Multisystem Approach

CFS and FM diagnoses often frustrate physicians
because there's no clear cause or treatment. Doctors
typically treat the problem with NSAIDS,
antidepressants and muscle relaxants. But these
drugs are largely ineffective because they fail to
address the underlying roots of the problem.95-109 In
addition, they have a high incidence of significant
side effects, including anxiety and
insomnia.95,69 Muscle relaxants, too, can be
addictive. Serotonin-norepinephrine reuptake
inhibitors (SNRIs) and anticonvulsants may offer
some benefit (Pregabalin is the first medication that
is FDA approved to treat FM), but they're often
ineffective. In addition, the majority of patients
don't tolerate the medication well.108-110Given
these facts, physicians should take the following
multisystem approach to address both diagnoses.


Component One: Stabilize the patient. Physicians
commonly address the pain and sleep disturbances
of CFS and FM with medications. These drugs can
help some patients, but the overwhelming majority
needs further treatment. Sadly, this first stage of
treatment is the only course many doctors prescribe.


Component Two: Mitochondrial enhancement. The
mitochondria are the energy factories for the cells
where sugar is burned and energy is produced in the
form of adenosine-triphosphate (ATP). When the
mitochondria are not working properly, the cells and
tissues of the body are starved for energy. This
abnormality may be the common endpoint for all the
dysfunctions in CFS and FM.

Not only do the reduced amounts of metabolized
glucose produce weight gain, reduced aerobic energy
production requires the body to rely on anaerobic
metabolism. This causes fatigue, muscle pain, poor
concentration, gastrointestinal dysfunction,
headaches and postexertional malaise.

Mitochondria can be poisoned by numerous
substances, including environmental toxins;
pesticides; chronic bacterial, viral and fungal
infections; neurotoxins; and nutritional and hormone
deficiencies. Mitochondria dysfunction has the
greatest impact on the most active tissues, including
the hypothalamus, pituitary, muscle, nerve and
immune cells. These are the major dysfunctions of
these conditions and can significantly explain the
symptoms of CFS/FM. Supplying mitochondrial
intermediates and nutrients, such as magnesium,
carnitine, D-ribose, CoQ10 and glutathione, can
improve mitochondrial function and alleviate
symptoms of CFS and FM.111-116


Component Three: Balance the hormones. An
overwhelming amount of peer-reviewed medical
literature documents pituitary and hypothalamic
dysfunction in CFS and FM patients. As a result,
patients often have multiple hormonal
deficiencies,4-21including thyroid, growth hormone
and cortisol. Physicians often miss these hormonal
deficiencies because standard blood tests lack
sufficient sensitivity to detect such centrally
mediated deficiencies.4-7,17-21However, they need
to pay close attention to the following hormones:

Thyroid. Numerous studies have demonstrated that
central hypothyroidism, as well as cellular resistance
to thyroid hormone, exists in the overwhelming
majority of patients with FM and CFS. This persists,
despite patients having normal thyroid function tests
(TFTs).6,11-16For instance, a study published in the
Journal of Rheumatology looked at the incidence of
central hypothyroidism in patients with FM.6Through
thyrotropin releasing hormone (TRH) testing, all of
the patients with FM had central hypothyroidism,
despite having baseline TFTs in the normal range.
More than 90 percent of the time, standard TSH and
T4 testing misses central medicated
hypothyroidism.117

Emerging evidence, however, shows free T3/reverse
T3 (rT3) ratios can be a useful indicator of tissue
thyroid levels. This may, in fact, help physicians
assess tissue thyroid effect with central
hypothyroidism and chronic physiologic
stress.118-120 nstead of T4 normally converting
intracellularly to the active T3 in peripheral tissue,
T4 is preferentially converted to reverse T3.
Therefore, increasing levels of rT3 and diminishing
levels of T3 are indicators of low tissue thyroid
effect. Free T3 and rT3 tests can be ordered at most
major clinical laboratories. A free T3/rT3 ratio that's
less than 2 pg/ng is consistent with low tissue
thyroid activity.

Because T4 to T3 conversion in these conditions is
diminished, it's not surprising that T4
supplementation has little effect, but that treatment
with T3 is significantly effective.16,121-123In a
double-blinded, placebo-controlled trial by Lowe et
al., T3 therapy was safe and effective for treating
euthyroid (TFTs in the normal range). Patients
reported a highly significant improvement in pain,
fatigue, stiffness, headache, sleep disturbance,
bowel disturbance, depression, cognitive dysfunction,
anxiety, cold intolerance, paresthesias and exercise
endurance. They noted no significant adverse effects,
despite having TFTs that would normally indicate
hyperthyroidism, with a suppressed TSH, low free T4
and high free T3 levels. No adverse effects were
reported on heart, bone, muscle and liver function,
which were monitored every two months for eight
months.121

a small, double-blinded, placebo-controlled
crossover study of four patients, T3 was
administered and withdrawn in two T3 phases and
two placebo phases over nine months.118All patients
had normal baseline TFTs. All significantly improved
in the T3 phases and deteriorated during placebo
phases. No adverse target tissue effects were seen
and all patients chose to continue treatment after
the study's end. This study did not demonstrate any
adverse cardiac or bone effects.123T3 is available as
the brand Cytomel or as a compounded
timed-released preparation, which has the advantage
over Cytomel in minimizing serum fluctuations of T3.
Optimal doses can vary significantly among patients
and should be slowly titrated with careful monitoring
for signs of excess, such as palpitations, rapid heart
rate and anxiety.

Cortisol. Most patients with CFS and FM suffer from
clinically significant adrenocortical dysfunction due to
hypothalamic and pituitary dysfunction. The
hypothalamic and pituitary function in these
conditions (potentially due to mitochondrial function)
results in inadequate cortisol production.4All studies
that have used central acting stimulation testing in
CFS and FM have shown
hypothalamic-pituitary-adrenal (HPA) axis
dysfunction.4However, physicians often believe a
normal serum cortisol level or ACTH stimulation test
generally rules out significant HPA axis dysfunction.
These tests are more useful for primary
hypoadrenalism. They, however, lack sufficient
sensitivity to detect the central HPA axis
dysfunction.4

The current evidence supports using physiologic
doses of cortisol as an appropriate component of a
multisystem treatment protocol for CFS and FM.
Specialists should consider a therapeutic trial of
cortisol in the majority of these patients, especially
those with signs or symptoms consistent with
adrenal dysfunction, low blood pressure and/or serum
levels that are low or in the low-normal range.

Physiologic replacement of cortisol at doses of 5 mg
to 15 mg a day are safe, with little or no associated
risk. Such physiologic doses don't carry the risk of
adrenal and immune suppression or bone loss, which
are well known risks of pharmacological doses of
corticosteroids. Cortisol treatment carries
significantly less risk and a greater potential for
benefit than standard treatments, such as
antidepressants, muscle relaxants, anticonvulsants
and narcotics.4

Growth hormone. Studies also show CFS and FM
patients have diminished secretion of growth
hormone, a single-chain polypeptide produced in the
pituitary gland with a wide range of metabolic and
cellular effects. Growth hormone stimulates the
production of insulin-like growth factor-1 (IGF-1) in
the liver. Both play an important role in regulating
body composition, lipid profiles, tissue repair, cardiac
and neuronal functioning and bone mineral density. A
great deal of peer-reviewed research, including
long-term randomized control trial data, has
demonstrated that growth hormone replacement can
improve energy, strength, cardiac function, cognitive
function, immunity and psychological well-being. It
also decreases body fat, increases lean muscle and
improves quality of life. In addition, it significantly
improves symptoms in these conditions with little or
no side effects.7-21,124

Because of the pulsatile nature of growth hormone
production and short half-life (20 to 50 minutes),
routine serum growth hormone levels cannot be used
to determine overall production. However, IGF-1
levels correlate with overall growth hormone
production and are relatively stable in the serum.
While a normal IGF-1 level doesn't rule out a
significant growth hormone deficiency, the IGF-1
level is the best estimate of growth hormone
production and effect. Low-normal IGF-1 levels are
consistent with a relative growth hormone deficiency.

Titrating the dose of growth hormone to achieve
IGF-1 levels in the upper limit of normal is safe, well
tolerated and offers significant clinical benefits.
Typical doses are 0.5-2 iu injected subcutaneously
daily. Patients can start with a three-month
therapeutic trial. We must monitor for water
retention, which can produce joint pain and carpal
tunnel syndrome. Insulin sensitivity may temporarily
decline as well. Such treatment is generally well
tolerated and if such side effects do occur, they
usually resolve with a reduction in dose.

Because of the synergistic nature of hormones, small
doses of multiple hormones are generally superior to
large doses of any one hormone. Each hormone,
however, should be started one at a time so we can
best monitor for potential side effects.


Component Four: Treat the infectious ­components.
A great deal of medical literature documents the
multiple infections that may either cause or
contribute to CFS and FM.39-48,125-128Likely, this is
due to the immune dysfunction seen with these
conditions, which allows opportunistic organisms and
other infections to flourish. This includes a variety of
viruses such as Epstein Barr (EBV), cytomegalovirus
(CMV), human herpes virus 6 (HHV6) and intracellular
bacterial infections, such as mycoplasma, Chlamydia
pneumonia and Borrelia burgdorferi (Lyme disease).
Various antimicrobial treatments directed at such
infections are significantly beneficial.


Component Five: Address unique etiologies. Several
cycles of dysfunction occur in these conditions that
can produce unique pathological etiologies. For
instance, chronic infections can cause an abnormal
immune activation of coagulation. This produces a
fibrin coating on the lumen of the vessel, causing
impaired oxygen and nutrient transfer.2,57-62

If suspected, the diagnosis can be made by testing a
coagulation panel of soluble fibrin monomer,
thrombin-antithrombin complex, D-dimer and
plasminogen activator-inhibitor-1.57-62Heparin can
help such patients.12,58

Evidence also suggests that neurotoxins are a
potential cause or contributing factor to CFS and FM
symptoms.129-131Visual contrast sensitivity testing
and serum C3(a) and C4(a) can help us assess the
potential for such exposure.


Component Six: Maintenance. We need to adjust
therapies and wean patients to minimal core
treatments. With improvement, medications can be
discontinued, generally one at a time. During this
phase, patients can be seen less often. We generally
wean patients off medications before supplements.
We also can successfully take patients off narcotic
pain relievers. Symptomatic improvement usually
correlates with improved cortisol, growth hormone
and thyroid levels. So we can adjust hormones as
well. However, most patients feel better with the
optimal supplemented thyroid levels. Continued
thyroid supplementation also appears to prevent
relapses.


Multisystem Efficacy

A multisystem approach is becoming the standard of
care for patients with CFS and FM. And studies are
backing this approach. For example, Teitelbaum et
al. performed a randomized, double-blinded,
placebo-controlled, intent-to-treat study on 72
FM/CFS patients. The goal was to assess the
effectiveness of an integrative treatment approach
that simultaneously treated the nutritional
deficiencies, chronic infections and hormonal
dysfunctions that exist with these
conditions.72Overall, 90 percent of patients had
significant improvements vs. placebo in visual analog
scores (p < 0.0002), the Fibromyalgia Impact
Questionnaire (p < 0.0005) the tender point index (p
< 0.0001) and ovezrall response (p < 0.0001) with
no significant reported side effects.

The Journal of Chronic Fatigue Syndrome recently
reported our center's novel use of a computerized
symptom assessment that evaluated the
multisystem treatment protocol for more than 500
consecutive patients with CFS and FM.4Ninety-four
percent of patients had overall improvement by the
fourth visit, with 75 percent noting significant overall
improvement and 62 percent reporting substantial
overall improvement. In subsequent visits, the
majority of patients continued to improve. The
average energy level more than doubled by the
fourth visit, going from an average of 2.98 at
baseline to 6.39, and then to 6.77 and 7.67 at the
seventh and ninth visits, respectively.

The average sense of well-being more than doubled
by the fourth visit, increasing from a baseline
average of 3.03 then to 6.29, 7.45 and 6.83 on the
fourth, seventh and ninth visit, respectively.


Subsequently, more than 40 physicians were trained
to use a simplified treatment algorithm at 17 centers
across the country. This multicenter study included
more than 4,000 consecutive CFS and FM patients
who were treated with this simplified algorithm and
tracked via the same computerized patient
assessment system. Eighty-five percent of patients
improved by the fourth visit. By the seventh visit, 62
percent of patients reported significant improvement,
and 46 percent indicated substantial improvement.87
By addressing the multiple physiologic abnormalities
that occur with CFS and FM, we can give our patients
hope for dealing with these debilitating disorders.





References:


1. Ehrlich GE. Pain Is Real; Fibromyalgia Isn't. J
Rheumatol. 2003 Aug;30(8):1666-7.

2. Wolfe F. Stop Using the American College of
Rheumatology Criteria in the Clinic. J Rheumatol
200;30:8:1671-2.

3. Smythe H. Fibromyalgia Among Friends. J
Rheumatol. 2004 Apr;31(4):627-30.

4. Holtorf K. Diagnosis and Treatment of
Hypothalamic-Pituitary-Adrenal (HPA) Axis
Dysfunctionin Patients with Chronic Fatigue
Syndrome (CFS) and Fibromyalgia (FM). J Chronic
Fatigue Syndrome 2008;14(3):59-88.

5. Riedel W, Layka H, Neeck. Secretory pattern of
GH, TSH, thryoid hormones, ACTH, cortil, FSH, and
LH in patients with fibromyalgia syndrome following
systemic injection of the relevant
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``````````````


Kent Holtorf, MD, is an expert in treating chronic
fatigue syndrome, fibromyalgia, complex endocrine
dysfunction and chronic infections (including EBV,
HHV6 and Lyme disease). Dr. Holtorf received his
doctorate of medicine from St. Louis University with
residency training at UCLA. He has personally trained
numerous physicians across the country to effectively
treat chronic fatigue syndrome, fibromyalgia and
chronic infectious diseases. Additionally, Dr. Holtorf
was the founding medical director and developed the
protocols for Fibromyalgia and Fatigue Centers and
other facilities across the country.




Disclosure: Dr. Holtorf indicates that he has no
affiliations with any commercial entities, directly or
indirectly referenced in this article.





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