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ADHD drugs reduce ME/CFS cognitive dysfunction

satoshikasumi

Senior Member
Messages
113
This is the second study to show benefit of ADHD drugs in ME/CFS patients with concentration difficulties. The first one (done in 2006) examined methylphenidate (Ritalin).
Note that these drugs also reduce fatigue and pain, but to a lesser degree. Fatigue/pain and cognitive problems may not precisely correlate in ME/CFS. See http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049518
Note that antiviral treatments such as Ampligen and Valcyte may also have more effect on cognitive problems than physical fatigue in this disease.
Astonishingly, it has taken almost 30 years since ME/CFS was first described in the 1980s for studies of the older stimulants to appear. There still hasn't really been a study of the effects of caffeine even. Whereas, there were repeated and unsuccessful studies of antidepressants in the first two decades. It certainly would have been much more logical to first try an amphetamine-type drug or caffeine in patients who report tiredness and difficulty concentrating!
Psychiatry Res. 2012 Oct 9. pii: S0165-1781(12)00503-3. doi: 10.1016/j.psychres.2012.09.007. [Epub ahead of print]
Use of Lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: A double blind, placebo-controlled study.

Young JL.
Source

Wayne State University School of Medicine, Detroit, MI, USA; William Beaumont Hospital, Royal Oak, MI, USA; Rochester Center for Behavioral Medicine, Rochester Hills, MI, USA. Electronic address: jyoung@rcbm.net.
Abstract

The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18-60) with chronic fatigue syndrome (CFS). The study's primary outcome measure was the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning. Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70mg/day) of either placebo or LDX for a six-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF-A scores (M(change)=21.38, SD=15.85) than those in the placebo group (M(change)=3.36, SD=7.26), p=0.005, d=1.46. Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed.
 

AFCFS

Senior Member
Messages
312
Location
NC
Its an interesting post and I hope these work for some people. I have been on Adderall, Vyvanse (lisdexamfetamine dimesylate), Intuniv, Concerta, and Strattera, all in varied doses at different times. I know some are not technically stimulants or amphetamine stimulants, but they still seem to act that way.

In any event, with the amphetamine stimulants, including Vyvanse, I would typically get the dopamine drop the first day and feel like I was floating on a high. After that they all steadily progressed to irritability, restlessness, some anxiety, insomnia, and what seemed like a straight jacket for my thoughts.

They seemed to increase my attention to a hyper-focus. At some point, they also seemed to mess with my memory. I recall being in a situation, after on Vyvanse for a while, where someone asked me my telephone number - to write it on a card, and I just drew a blank. Not good. Coming off them was not that hard for me, just a little uncomfortable, but I have heard some people say it is really tough on the mind/body.

Would like to hear if anyone has had better luck with them, particularity over the long haul.
 

Ocean

Senior Member
Messages
1,178
Location
U.S.
Me too AFCFS. I had a very similar experience with ADHD stimulants including the hyperfocus. I also have ADHD in addition to CFS.
 

AFCFS

Senior Member
Messages
312
Location
NC
Me too AFCFS. I had a very similar experience with ADHD stimulants including the hyperfocus. I also have ADHD in addition to CFS.
Yep, it has been suggested to me that I might have some ADHD, but then, when the meds have not helped the pdoc would flip-flop and say that OCD was very similar in some respects and I might have that. In reality I think I have some OC personality traits, but not normally expressed to the point of disorder. After trying meds have decided it is just easier to manage things adaptively, on my own - less side effects, less money on some expensive meds, and I feel more myself.

- Just an aside, but it seems that pdocs want to really have one invest in their DSM labels, which tend to alienate one to a condition that can only be treated under their treatment.
 

AFCFS

Senior Member
Messages
312
Location
NC
Don't they increase concentration for pretty much everyone?
I believe they would. When I see a study like that, aside from the good it may do to help alleviate some people's symptoms, I start to think "looks like they might want to extend marketability."
 

L'engle

moogle
Messages
3,200
Location
Canada
I guess an important distinction would be that we have both cognitive problems and decrease in mental stamina/duration of cognitive focus. The ADHD drugs would I imagine help with cognitive focus, but unless the amount of mental stamina is increased the amount of time we can do work for would still be compromised, I would think.
 

Ocean

Senior Member
Messages
1,178
Location
U.S.
Yep, it has been suggested to me that I might have some ADHD, but then, when the meds have not helped the pdoc would flip-flop and say that OCD was very similar in some respects and I might have that. In reality I think I have some OC personality traits, but not normally expressed to the point of disorder. After trying meds have decided it is just easier to manage things adaptively, on my own - less side effects, less money on some expensive meds, and I feel more myself.

- Just an aside, but it seems that pdocs want to really have one invest in their DSM labels, which tend to alienate one to a condition that can only be treated under their treatment.

Yeah I am doing the same, just managing my symptoms the best I can, no meds. Once I learned I had ADHD it helped a lot in figuring out systems to help manage it. For most of my life I had no idea I had it. I wasn't diagnosed as a kid, which I think partly has to do with being female and the fact that I had good grades. I think it's pretty easy to see if you have ADHD, there are some good questionairres/self tests out there and once you kind of read first person accounts from those who have it, it's pretty easy to identify it in yourself I think. One criteria is that it has to be lifelong since childhood, not a new development.
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
Its an interesting post and I hope these work for some people. I have been on Adderall, Vyvanse (lisdexamfetamine dimesylate), Intuniv, Concerta, and Strattera, all in varied doses at different times. I know some are not technically stimulants or amphetamine stimulants, but they still seem to act that way.

In any event, with the amphetamine stimulants, including Vyvanse, I would typically get the dopamine drop the first day and feel like I was floating on a high. After that they all steadily progressed to irritability, restlessness, some anxiety, insomnia, and what seemed like a straight jacket for my thoughts.

They seemed to increase my attention to a hyper-focus. At some point, they also seemed to mess with my memory. I recall being in a situation, after on Vyvanse for a while, where someone asked me my telephone number - to write it on a card, and I just drew a blank. Not good. Coming off them was not that hard for me, just a little uncomfortable, but I have heard some people say it is really tough on the mind/body.

Would like to hear if anyone has had better luck with them, particularity over the long haul.

Hi,

I don't have ADHD but an autonomic specialist gave me an extremely low dose of adderall to improve circulation to the brain. At a very low dose, I didn't get that hyper-focus, just something that imitated normal attentiveness. But I don't like to take amphetamines so I rarely take any now.

I also took strattera, but because it can treat OI effectively for a percentage of us. For me it nearly took it away. But again, I only took it for a couple of years because my OI got better and I didn't want to take any drugs that weren't essential.

Sushi
 

satoshikasumi

Senior Member
Messages
113
My experience is consistent with the generic advice you hear from ME/CFS docs: We are extremely sensitive to medications, especially those that affect the CNS, and need lower doses. The doses typically used for ADHD might be intolerable for us. The plus side is that we will almost never tolerate doses high enough to cause addiction.

The autonomic nervous system of ME/CFS patients is damaged so that it can't respond flexibly and our brains go through a process of central sensitization. This means that we need to be careful when starting any new medication. It is best to start with a low dose and give the brain time to adapt to it before moving up towards a therapeutic dose.

Even when we are tolerating a medication, we may need to take a drug holiday during periods of relapse or reduced activity. This is a judgment call.
 

searcher

Senior Member
Messages
567
Location
SF Bay Area
Low doses of Adderall help me. I probably take it 4-5 times a week, and usually take 5 mg (whereas my doctor prescribed 30mg a day, but he isn't knowledgeable about CFS.) As long as I am not having a particularly bad day, it really helps. I don't feel close to normal but my concentration improves and I am able to do a little work. When I take regular doses I often get hyperfocused and anxious, and can't get anything done. Sometimes a normal dose will help, but I have found I have to already be feeling relatively decent (clear sinuses, less than average brain inflammation) for them to be helpful. Higher doses can increase my Raynaud's symptoms, which seems to be a relatively common side effect.

Vyvanse made me feel shaky without the positive effects of Adderall, but I am sure the effectiveness of specific medications will differ per person. I haven't tried Ritalin.

I completely understand why a lot of people are hesitant to try stimulants, but I think they are worth consideration for some people. Adderall helps my OI as well, potentially because of improved circulation as Sushi mentioned.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Astonishingly, it has taken almost 30 years since ME/CFS was first described in the 1980s for studies of the older stimulants to appear. There still hasn't really been a study of the effects of caffeine even. Whereas, there were repeated and unsuccessful studies of antidepressants in the first two decades. It certainly would have been much more logical to first try an amphetamine-type drug or caffeine in patients who report tiredness and difficulty concentrating!

I think they might (almost) be on the right track.

Recent research suggests that the (limited) effectiveness of typical ADs may be via the reduction of neuroinflammation and the most potent atypical antidepressants such as Ketamine primarily affect the balance of GABA and glutamate (Ketamine is an NMDA receptor atagonist).

GABA/Glutamate balance may be more important in determining the efficiency of information processing and hence cognitive functions such as attention and executive function.
 
Messages
15,786
It looks like it's thought that the drug they're studying is a dopamine and norepinephrine reuptake inhibitor. An NRI can be extremely helpful for OI symptoms, since norepinephrine is needed to regulate blood pressure. My blood platelet norepinephrine tested very low, which made it a sensible candidate for causing my OI issues.

I'm currently doing 10mg of Strattera (an NRI) twice per day, and my OI seems to be gone for the past 6 weeks or so now. A higher dose did cause the irritable side effects though, and there was a definite rush/high feeling the first few days I started it. But that went away, and I basically mentally/emotionally feel the same way I did before, just able to think clearly now and sit up all day, or even stand up for hours.

But that might only be applicable to NMH type OI, if POTS has a different underlying cause.
 

Wayne

Senior Member
Messages
4,300
Location
Ashland, Oregon
The autonomic nervous system of ME/CFS patients is damaged so that it can't respond flexibly and our brains go through a process of central sensitization. This means that we need to be careful when starting any new medication. It is best to start with a low dose and give the brain time to adapt to it before moving up towards a therapeutic dose. ......... Even when we are tolerating a medication, we may need to take a drug holiday during periods of relapse or reduced activity. This is a judgment call.

I've never tried a prescription stimulant, but do occasionally use Piracetam, known as a nootropic, or "smart drugs". I seem to get the same results that some here are saying they've gotten from pharmaceuticals. I've learned to be very careful not to take it very often (perhaps 1-2x/week), and to only take very small doses (about 5% of the normal recommendation).

Even when I take it this infrequently, I can either get a cognitive boost that can be quite helpful, or I may not react to it well on a given day, and feel a bit of uncomfortable "wiredness", similar to the way I sometimes feel several hours after drinking a bit of coffee (which I don't do very often).
 

HowToEscape?

Senior Member
Messages
626
I've never tried a prescription stimulant, but do occasionally use Piracetam, known as a nootropic, or "smart drugs"......

Piracetam -- First I've ever heard of it. This is a standard prescription, controlled substance or OTC? Does it keep you awake and does it have the lift/crash character of standard stimulants?
 

Wayne

Senior Member
Messages
4,300
Location
Ashland, Oregon
Piracetam -- First I've ever heard of it. This is a standard prescription, controlled substance or OTC? Does it keep you awake and does it have the lift/crash character of standard stimulants?

Hi HTE,

I posted fairly extensively about my Piracetam experiences on the following thread (link below). Feel free to ask me any specific questions you may have.

Piracetam for Cognitive Stuff and Circulation

Best, Wayne
 

vli

Senior Member
Messages
653
Location
CA
I think they might (almost) be on the right track.

Recent research suggests that the (limited) effectiveness of typical ADs may be via the reduction of neuroinflammation and the most potent atypical antidepressants such as Ketamine primarily affect the balance of GABA and glutamate (Ketamine is an NMDA receptor atagonist).

GABA/Glutamate balance may be more important in determining the efficiency of information processing and hence cognitive functions such as attention and executive function.
What I don't understand is, if you look at the stuff Amy Yasko says (which i guess you could ignore), she talks a lot about how glutamate = bad and GABA = good/calming, at least in our illnesses. So why then do we feel MORE RELAXED if/when we take ketamine which stimulates glutamate release, as this yale link verifies?? http://news.yale.edu/2012/10/04/yal...w-ketamine-vanquishes-depression-within-hours
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
What I don't understand is, if you look at the stuff Amy Yasko says (which i guess you could ignore), she talks a lot about how glutamate = bad and GABA = good/calming, at least in our illnesses. So why then do we feel MORE RELAXED if/when we take ketamine which stimulates glutamate release, as this yale link verifies?? http://news.yale.edu/2012/10/04/yal...w-ketamine-vanquishes-depression-within-hours


Well spotted!

This is all mere speculation on my part, but starting from the premise that an optimum balance between excitatory glutamate and inhibitory GABA is essential for efficient neural transmission and cognitive processing than either a hyperarousal (high glut to GABA ratio) or hypoarousal (low glut to GABA ratio) is undersirable and may lead to various behavioural phenotypes - crudely speaking.

Assuming also that a glut/GABA imbalance underlies ADHD, major depressive disorder and ME/CFS then the proposed Ketamine action of raising glutamate strikes me as being counterintuitive (being the wired and tired type which I consider a state of hyperarousal).

I can think of a few scenarios :


(a) MDD does result from a high glut/GABA ratio resulting in neuronal damage due to extracellular glutamate excitotoxicty but that over time glutamate receptors adapt to the high glut levels and are downregulated. This might account for the reduction in neural transmission and the 'vegetative' symptoms associated with MDD. Ketamine further raises glut levels overcoming the downregulated receptors enhancing dendritic growth and neurotransmission transiently.

(b) While classed as an NMDA receptor antagonist, Ketamine acts as an agonist for other types of glutamate receptor and that MDD, like schizophrenia, is a hypoglutamatergic state and Ketamine, as the authors state, transiently raises glutamate levels and restores effcient neurotransmission.

On the other hand another atypical and very effective àntidepressant Stablon appears to clearly work by attenuating excitotoxicity due to high glutamate.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902200/

Perhaps like ADHD (which includes inattentive and hyperactive types) there are different variants of major depressive disorder characterised by hyper of hypo glutamate levels. Perhaps ME/CFS is similar with some with largely 'vegetative' symptoms (high levels of constant fatigue and low activity) and those who tend be hyperactive and crash? I noticed that the Ketamine paper noted therapeutic effects of raised glutamate only in 'responders'.

Which is a long winded way of saying that I don't know.:)

Neurotransmitters are tricky with all sorts of feedback loops and cross-talk. I'll have to look into it further.
 
Messages
76
Location
Australia
I believe they would. When I see a study like that, aside from the good it may do to help alleviate some people's symptoms, I start to think "looks like they might want to extend marketability."

I was on mild dose Ritalin a few years ago, and there was a moderate (but not fantastic) increase in concentration levels. At the time I was working part-time & my ME was manageable (unlike now) but I couldn't say for sure if it was actually a placebo affect. To be honest, I'm glad I'm off the stuff.
 

PhoenixBurger

Senior Member
Messages
202
I would avoid amphetamines at all costs. They play with your dopamine receptors and can burn them out, which can cause a whole other host of major problems. There are direct links between amphetamine use (adderall / ritalin / ecstasy) and eventual development of neurological diseases like parkinsons. Granted it usually happens decades later, but it has been proven. Increased risk by 50 fold or something like that. Not going near the stuff.