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CFS: 3 Cases and a Discussion of the Natural History of ADHD

Firestormm

Senior Member
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Cornwall England
I haven't read or tried to access the full paper. A possible sub-category of patients who are unresponsive to whatever 'treatment' this paper has employed for CFS might have ADHD. Only 3 cases. Pretty small to build a model upon. Still, who knows what is in the 'pot' and how many people might benefit from a better examination and more appropriate diagnosis and treatment?

Chronic Fatigue Syndrome:

3 Cases and a Discussion of the Natural History of Attention-Deficit/Hyperactivity Disorder
January 2013.
Abstract:
Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment.
After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication.
After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms.
These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism.
This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain.
These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.
 
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Yeah, let's ignore that symptoms are completely different. If a CFS patient responds to a stimulant instead of a typical anti-depressant, ADHD must be the answer! Just because two disorders have some response to the same drug, does need mean they are the same disorder.

I have never had ADHD symptoms, yet an "ADHD drug" helps me. And not with symptoms related to ADHD, but with orthostatic hypotension. I think the researcher is having trouble realizing that a drug approved for a particular use does not make that drug only useful for that one use.

He also badly misunderstands ME/CFS if he thinks it's all about "chronic fatigue and pain".
 
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15,786
Right. The author runs a behavioral clinic staffed with psychologists and psychiatrists.

Thus anything he observes that isn't solely psychological will still be interpreted as psychiatric.
 
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Nah, have to subscribe/create a logon/whatever. The clinic website just has a list of publications, no links.

And it looks like typical psychobabble, in addition to being on a very small scale, so I'm not really interested enough to look for the full paper. I mean "stimulants make fatigue patients less fatigued" is probably as good as it gets, since there was no reference to specific improvements, etc, in the abstract. Based on that abstract, it sounds like one guy pulling random theories out of various body parts based on his unscientific observations of three undefined patients. Not an actual study or anything.
 

Firestormm

Senior Member
Messages
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Location
Cornwall England
I see from another thread Val, you appear to be taking ADHD medication - Strattera? I know this paper is based on a very small sample, but I wonder if this med was one that they used and if in fact by your own experimentation there is perhaps some link - maybe based solely on symptom relief and some mechanism in the body that produces similar symptoms.

I couldn't see any reference in the FDA information relating to Orthostatic Intolerance (which are the symptoms you appear to suggest have been aided by taking Strattera) - perhaps the attributed symptoms are blurred. Was this a drug you stumbled across yourself - I see you are playing with the doses - or something prescribed for OI?

I'd be interested to learn more about Strattera and OI and if indeed ADHD does have a cross-over with CFS/ME. Will have a search on-line and see if any other papers have suggested a link - even if only as a subset. Might try and read the above paper in full.
 
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I see from another thread Val, you appear to be taking ADHD medication - Strattera? I know this paper is based on a very small sample, but I wonder if this med was one that they used and if in fact by your own experimentation there is perhaps some link - maybe based solely on symptom relief and some mechanism in the body that produces similar symptoms.
The website for the clinic involved lists Strattera as a non-stimulant ADHD drug, so the current paper would not have included it.

I couldn't see any reference in the FDA information relating to Orthostatic Intolerance (which are the symptoms you appear to suggest have been aided by taking Strattera) - perhaps the attributed symptoms are blurred. Was this a drug you stumbled across yourself - I see you are playing with the doses - or something prescribed for OI?
Another forum member with identical OI symptoms had tried it and found it very effective. On that basis I researched it some more, and since it is an NRI, and norepinephrine controls blood pressure, and my norepinephrine levels were quite low, trying it was sensible. Of the NRI's listed, it is also the only one which does not list "hypotension" as a potential side effect - I have enough of that already and hardly want more of it!
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
Thanks Adreno. I will try and get hold of the full paper and do a search for others I think.

I did notice in the FDA Strattera information it in fact warned that Orthostatic Hypotension was a possible side-effect although it appears to only have occurred in very few instances:

Strattera should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure or heart rate such as certain patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease...

Orthostatic hypotension and syncope have been reported in patients taking Strattera. In child and adolescent registration studies, 0.2% (12/5596) of Strattera-treated patients experienced orthostatic hypotension and 0.8% (46/5596) experienced syncope. In short-term child and adolescent registration studies, 1.8% (6/340) of Strattera-treated patients experienced orthostatic hypotension compared with 0.5% (1/207) of placebo-treated patients.

Syncope was not reported during short-term child and adolescent placebo-controlled ADHD registration studies. Strattera should be used with caution in any condition that may predispose patients to hypotension, or conditions associated with abrupt heart rate or blood pressure changes.

There is a trial that is still recruiting in the USA and is in Phase II that looks at OI and will be using Strattera that I have just come across: http://clinicaltrials.gov/ct2/show/NCT00262470

This trial is designed to study the effects of various mechanistically unique medications in controlling excessive increases in heart rate with standing and in improving the symptoms of orthostatic intolerance in patients with this disorder.

Experimental: 2
Atomoxetine
Drug: Atomoxetine

10-40 mg PO x 1 dose
Other Name: Strattera
Drug: Atomoxetine & Propranolol

Atomoxetine 10-40 mg PO x 1 dose AND propranolol 20 mg PO x 1 dose
Other Names:
  • Strattera
  • Inderal

Seems to have been taking a long while to get this Trial going. Began in 2003.
 
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I did notice in the FDA Strattera information it in fact warned that Orthostatic Hypotension was a possible side-effect although it appears to only have occurred in very few instances:

To clarify, this is manufacturer information, and not FDA information or an FDA warning. Also, as you quoted, that information is based solely on studies of children.
 

Firestormm

Senior Member
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5,055
Location
Cornwall England
There is information pertaining to adults throughout that information Val, and all of it has been approved by the FDA - whether it originated with the manufacturer or not.

I came across two sites that are basically reviews from people with CFS who are claiming to have taken Strattera, but nothing thus far from an official source.

The previous link to the Phase II Trial might yield further information - in respect of a treatment for OI - and I'll maybe have a word with Prof. Newton to see if she is aware of this Trial and of these drugs.

It would be interesting to learn how they arrived at all those drugs they are trialling as experimental possible treatments for OI. I will continue looking for any papers published on this one. It would be very good for a drug to be made available to those in our community who experience and are diagnosed with POTS for example.
 

adreno

PR activist
Messages
4,841
I did notice in the FDA Strattera information it in fact warned that Orthostatic Hypotension was a possible side-effect although it appears to only have occurred in very few instances:
Right, and this is hardly surprising. When you take an NRI you're messing with the ANS. This can cause all sorts of changes in blood pressure etc. Be aware that an NRI will improve some forms of OI, but worsen others. Beta-blockers, which has an opposite effect of NRIs, are also used in treating POTS. POTS is very complex, and there is no uniform treatment. Also, POTS and orthostatic hypotension isn't the same thing. In any case, why are we shifting the focus to OI and strattera? It really has got nothing to do with the subject of this thread.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
Right, and this is hardly surprising. When you take an NRI you're messing with the ANS. This can cause all sorts of changes in blood pressure etc. Be aware that an NRI will improve some forms of OI, but worsen others. Beta-blockers, which has an opposite effect of NRIs, are also used in treating POTS. POTS is very complex, and there is no uniform treatment. Also, POTS and orthostatic hypotension isn't the same thing. In any case, why are we shifting the focus to OI and strattera? It really has got nothing to do with the subject of this thread.

Because Strattera is a treatment for ADHD - which is the topic of this thread - and Val was on another thread - as a patient with CFS - finding that Stattera has helped with her OI symptoms.

I'd be interested to learn if any other studies have been found that attempt to link ADHD with CFS (as subsets thereof), and to pursue these kind of treatments in terms of OI.

I'd also like to learn what the treatments were within the paper at the top of this thread.
 

adreno

PR activist
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4,841
I'd be interested to learn if any other studies have been found that attempt to link ADHD with CFS (as subsets thereof), and to pursue these kind of treatments in terms of OI.
Well, for instance methylphenidate has been used as a treatment:

Use of methylphenidate in the treatment of patients suffering from refractory postural tachycardia syndrome.

I do not really see the link with ADHD, however. ADHD is a central disorder (hypoactive PFC), whereas POTS seems to be a peripheral problem. The stimulants and NRIs work for (some types of) POTS because they increase vasoconstriction and pressor response, not because of any central effects on the PFC. The central effects of stimulants would affect fatigue and pain though.

In other words, the article seems to suggest that CFS is a central disorder, similar to ADHD, and as such it is dissimilar to OI. Though OI may cause brainfog, it is not the same disorder as ADHD, not even close. Anyway, none of this is news. We need to see the exact mechanism described in the paper, otherwise it is worthless.
 

adreno

PR activist
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4,841
As I said, this line of thought has been pursued before:
Am J Med. 2006 Feb;119(2):167.e23-30.
Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H.
Source

Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium. daniel.blockmans@uz.kuleuven.ac.be
Abstract

PURPOSE:

Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects ofmethylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.
SUBJECTS AND METHODS:

A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 x 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed bymethylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).
RESULTS:

Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: -0.7, P = .010 for VAS; mean difference: -11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: -1.0, P = .001 for VAS; mean difference: -9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: -1.3, P <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical significant effect (> or =33% improvement or CIS < or =76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.
CONCLUSIONS:

Methylphenidate at a dose of 2 x 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

PMID:16443425
 
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I do not really see the link with ADHD, however. ADHD is a central disorder (hypoactive PFC), whereas POTS seems to be a peripheral problem. The stimulants and NRIs work for (some types of) POTS because they increase vasoconstriction and pressor response, not because of any central effects on the PFC. The central effects of stimulants would affect fatigue and pain though.

In other words, the article seems to suggest that CFS is a central disorder, similar to ADHD, and as such it is dissimilar to OI. Though OI may cause brainfog, it is not the same disorder as ADHD, not even close. Anyway, none of this is news. We need to see the exact mechanism described in the paper, otherwise it is worthless.

I've never really delved into the central versus peripheral aspects of disorders and the effects of drugs, and I think you've provided a very nice and concise explanation here. It could also explain the confusion of the therapist who wrote the paper ... he's primarily focused on psychiatric treatment, so his understanding of some of the more subtle aspects of the human nervous system (especially central versus peripheral) is probably understandably limited.
 

adreno

PR activist
Messages
4,841
Also, for ADHD the D-isomer variant of stimulants (dexamphetamine, dexmethylphendate) is often used, because it has far less peripheral effects than the racemic drugs, but is still very effective for ADHD. In cases of ADHD, you are not interested in peripheral effects, such as vasocontriction. These peripheral effects have even lead to Raynauds in some cases, and are generally unwanted. For OI however, you would of course choose the racemic version.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
To my naive way of thinking, ADHD is about a state of hyperactivity, mental and physical. It is the cognitive aspect of this that interests me the most. If these drugs given as 'stimulants' it would seem contra to any attempt to 'calm' the patient and enable better engagement.

A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years. The symptoms must be persistent, must be more severe than is typically observed in individuals at a comparable level of development, must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and must be present in 2 or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder.

http://www.drugs.com/pro/strattera.html

If the symptoms of ADHD might be said to be similar in some aspects to CFS i.e. the lack of ability to concentrate, process information, constant state of 'arousal' at least mentally and an inability to 'calm' - then treatments for ADHD might have some similar effect on these aspects of CFS.

However, as with all attempts to 'calm' and enable improved concentration etc. there is a risk of further 'fatigue'. This drug Strattera is however a stimulant and this is where I get lost. What is it stimulating? Better concentration etc.? How does that work exactly, as I would have thought you'd want to 'calm' this state of over-arousal.

Many people respond to atomoxetine who don't respond to stimulants (for ADHD). Atomoxetine may be preferred over amphetamine-based stimulants in patients with psychiatric disorders, those who cannot tolerate stimulants, and those with a substance misuse recurring history. Stimulant drugs are not recommended for ADHD patients who suffer from nervous disorders like facial tics, spasms, etc. In such cases Atomoxetine is the better choice.

http://en.wikipedia.org/wiki/Straterra

I will take a closer - layman's - look at this when I get back.

Thanks.
 
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A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and that were present before age 7 years.
So it sounds like an adult-onset ADHD would necessarily be a contradiction in terms. Maybe one of those things people like to use to explain why they aren't paying attention to what other people say ... and useful for therapists that want to broaden their customer base.

Many people respond to atomoxetine who don't respond to stimulants (for ADHD). Atomoxetine may be preferred over amphetamine-based stimulants in patients with psychiatric disorders, those who cannot tolerate stimulants, and those with a substance misuse recurring history.
Bah, you'd think with it being preferred for comorbid psychiatric disorders, the nasty neurologist I saw would've thought it was a great idea for an ME patient :rolleyes:

Stimulant drugs are not recommended for ADHD patients who suffer from nervous disorders like facial tics, spasms, etc. In such cases Atomoxetine is the better choice.
I don't know about tics and spasms, but muscle twitches seem pretty common for ME patients.

I've never tried stimulants (barely even get caffeine), so no idea what effect they'd have on me. I'm also a bit leery of the possibility of a "stimulate you now, PEM you later" effect.
 

adreno

PR activist
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4,841
ADHD is not a state of hyperarousal. It is hypothesized that the dopaminergic connections from the perfrontal cortex to the more primitive sites in the midbrain are hypoactive. This means ADHD patients have less impulse control. You cannot think of the brain as a uniform whole, different regions have different functions, and you can have hypoactivity in some areas and hyperactivity in others. The regions that control wakefulness and pain are also in the midbrain, not the PFC, again this has nothing to do with ADHD. The use of stimulants in ADHD is really not counterintuitive, because they strengthen the dopaminergic connections coming from the PFC, allowing the patients to apply impulse control and concentrate.