View Full Version : Safety of long term stimulants:current evidence


Kunga Dorji
07-04-15, 08:24 PM
P { margin-bottom: 0.21cm; }A:link { } While there has been concern about the safety of stimulant medication both for treatment of ADHD and for other indications, current evidence suggests that these concerns may not only be overstated, they may be totally wrong, and , in many situations, long term cause of stimulants may be so beneficial that to deny access to the may be irresponsible.
This document is meant for both patients and clinicians.



For patients the bits you need to read are in bold:
Long-term amphetamine exposure in some animal species is known to produce abnormal dopamine system development or nerve damage,[12][13] but, in humans with ADHD, pharmaceutical amphetamines appear to improve brain development and nerve growth.
Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5 (https://dx.doi.org /10.1007%2Fs00204-012-0815-5). PMID 22392347 (https://www.ncbi.nlm.nih.gov/pubmed/22392347).
Berman S, O'Neill J, Fears S, Bartzokis G, London ED (October 2008). "Abuse of amphetamines and structural abnormalities in the brain" (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC2769923). Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031 (https://dx.doi.org/10.1196%2Fannals.1441.031). PMC 2769923 (https://www.ncbi.nlm.nih.gov /pmc/articles/PMC2769923). PMID 18991959 (https://www.ncbi.nlm.nih.gov/pubmed/18991959).
Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277 (https://dx.doi.org /10.1001%2Fjamapsychiatry.2013.277).
Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies" (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC3801446). J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287 (https://dx.doi.org /10.4088%2FJCP.12r08287). PMC 3801446 (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC3801446). PMID 24107764 (https://www.ncbi.nlm.nih.gov/pubmed/24107764).
Frodl T, Skokauskas N (February 2012). "Meta- analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x (https://dx.doi.org /10.1111%2Fj.1600-0447.2011.01786.x). PMID 22118249 (https://www.ncbi.nlm.nih.gov /pubmed/22118249).



When used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults.
Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry 77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013 (https://dx.doi.org /10.1016%2Fj.biopsych.2014.09.013).
PMID 25499957 (https://www.ncbi.nlm.nih.gov /pubmed/25499957).
Ilieva IP, Hook CJ, Farah MJ (January 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". J. Cogn. Neurosci.:



While Addiction is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical medical use at therapeutic doses.[80][81][41]
Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists" (http://www.accessmedicine.com /content.aspx?aID=16661601). In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill. ISBN 9780071624428.
Kollins SH (May 2008). "A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders". Curr. Med. Res. Opin. 24 (5): 1345–1357. doi:10.1185/030079908X280707 (https://dx.doi.org /10.1185%2F030079908X280707). PMID 18384709 (https://www.ncbi.nlm.nih.gov/pubmed/18384709). "When oral formulations of psychostimulants are used at recommended doses and frequencies, they are unlikely to yield effects consistent with abuse potential in patients with ADHD."
Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin, Germany; London, England: Springer. p. 78. ISBN 9783540686989.
While there had been concern about long term use of stimulants being a risk for Parkinson's disease ( through excitotoxic nerve damage), it would now appear that the reverse is true:
http://www.ncbi.nlm.nih.gov/pubmed/23160937 CNS Drugs. (http://www.ncbi.nlm.nih.gov/pubmed/23160937#) 2013 Jan;27(1):1-14. doi: 10.1007/s40263-012-0017-y.Methylphenidate: a treatment for Parkinson's Disease?Devos D (http://www.ncbi.nlm.nih.gov/pubmed/?term=Devos%20D%5BAuthor%5D&cauthor=true&cauthor_uid=23160937)1, Moreau C (http://www.ncbi.nlm.nih.gov/pubmed/?term=Moreau%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23160937), Delval A (http://www.ncbi.nlm.nih.gov/pubmed/?term=Delval%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23160937), Dujardin K (http://www.ncbi.nlm.nih.gov/pubmed/?term=Dujardin%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23160937), Defebvre L (http://www.ncbi.nlm.nih.gov/pubmed/?term=Defebvre%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23160937), Bordet R (http://www.ncbi.nlm.nih.gov/pubmed/?term=Bordet%20R%5BAuthor%5D&cauthor=true&cauthor_uid=23160937).



Relationships and performance:
Children with ADHD who use stimulant medications generally have better relationships with peers and family members,[22][33] generally perform better in school, are less distractible and impulsive, and have longer attention spans.[22][33]
Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 111–113. ISBN 9781441913968.


Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. doi:10.2165/11589380-000000000-00000 (https://dx.doi.org

Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect (i.e., dopamine reuptake inhibition) in the brain's reward system.[80] At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system, or the reward pathway in particular, to induce persistent ΔFosB gene expression in the D1-type medium spiny neurons of the nucleus accumbens;[77][80][87] consequently, when used medically and as directed, methylphenidate use has no capacity to cause an addiction.[77][80][87]
77. Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 368. ISBN 9780071481274. "Cocaine, [amphetamine], and methamphetamine are the major psychostimulants of abuse. The related drug methylphenidate is also abused, although it is far less potent. These drugs elicit similar initial subjective effects ; differences generally reflect the route of administration and other pharmacokinetic factors. Such agents also have important therapeutic uses; cocaine, for example, is used as a local anesthetic (Chapter 2), and amphetamines and methylphenidate are used in low doses to treat attention deficit hyperactivity disorder and in higher doses to treat narcolepsy (Chapter 12). Despite their clinical uses, these drugs are strongly reinforcing, and their long-term use at high doses is linked with potential addiction, especially when they are rapidly administered or when high-potency forms are given."



Kim Y, Teylan MA, Baron M, Sands A, Nairn AC, Greengard P (2009). "Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650365). Proc. Natl. Acad. Sci. U.S.A. 106 (8): 2915–20. doi:10.1073/pnas.0813179106 (https://dx.doi.org/10.1073%2Fpnas.0813179106). PMC 2650365 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650365). PMID 19202072 (https://www.ncbi.nlm.nih.gov/pubmed/19202072). "Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use (36, 37). Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood (38). However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction (3, 6–10). Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i.v. administration may lead to addiction (39, 40)."
Nestler EJ (December 2013). "Cellular basis of memory for addiction" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898681). Dialogues Clin. Neurosci. 15 (4): 431–443. PMC 3898681 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898681). PMID 24459410 (https://www.ncbi.nlm.nih.gov/pubmed/24459410). "DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.4"
2013 Jan;27(1):1-14. doi: 10.1007/s40263-012-0017-y.


Legal status:methylphenidate:
Legal status
Clearly given the benefits above and the lack of addictive potential at therapeutic doses this restricted use of psychostulants is not based on any sound evidence at all-- is just nutty. These medications should be able to be prescribed by and any doctor competent to handle them. A permit should be required to prevent doctor shopping and to ensure that the supervising doctor is overseeing the whole tratment. ( IE ensuring that all is being done to minimise the symptoms and consequences of ADHD in all pateints being treated).
Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.[131]
In the United States, methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but present a high potential for abuse. In the United Kingdom, methylphenidate is a controlled 'Class B' substance. Possession without prescription carries with a sentence up to 5 years and/or an unlimited fine, and supplying it is 14 years and/or an unlimited fine.[132] In Canada, methylphenidate is listed in Schedule III of the Controlled Drugs and Substances Act (along with LSD, psychedelic mushrooms, and mescaline, among others), and is illegal to possess without a prescription, pursuant to Part G (section G.01.002) of the Food and Drug Regulations under the Food and Drugs Act. In New Zealand, methylphenidate is a 'class B2 controlled substance'. Unlawful possession is punishable by six-month prison sentence and distribution of it is punishable by a 14-year sentence.
In Australia, methylphenidate is a 'Schedule 8' controlled substance. Such drugs must be kept in a lockable safe before being handed out and possession without prescription carries hefty fines and even imprisonment. In Sweden, methylphenidate is a List II controlled substance with recognized medical value. Possession without a prescription is punishable by up to three years in prison.[133]
In France, methylphenidate is covered by the "narcotics" schedule, prescription and distribution conditions are restricted with hospital-only prescription for the initial treatment and yearly consultations.[134]




Finally, ADHD is a highly prevalent and highly impairing condition.
Conservative estimates in Australia are about the 4% mark in adults.
A recent paper has shown the incidence in middle aged adults is about 6%
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031500A Population-Based Study of Attention Deficit/Hyperactivity Disorder Symptoms and Associated Impairment in Middle-Aged Adults



A review of the data presented from Prof Alistair Vance of the Royal Children's Hospital yielded the following figures:
Out of every 100 children with ADHD, about 66 will still be diagnosable as ADHD , about 5 will have full resolution of their ADHD and the remaining 29 or so will have symptoms but fall below diagnostic thresholds.
My experience in ADHD suggests that many of that group will fall back into diagnosable ADHD if hit by a crisis.
My overall observations as a GP (about 20 years in the same practice watching many of my middle aged and elderly patients slip into dementia), suggest to me that the ADHD pattern may be a precursor to neurodegenerative disorders – such as Alzheimer's and Caparisons. In this setting symptoms like restless legs may be a prodrome of conditions such as Parkinson's disease.
Given my current awareness of the field of evidence based neuroscience (formerly called functional neurology) and a field that specialises in neurological rehabilitation, there is every reason to believe that this would be a predicted outcome of lifelong ADHD. Given my personal experience of rehabilitation provided by practitioners of functional neurology it is clear that this downhill slide can not only be halted, it can be reversed.




The information on which this summary was based can be found on line by looking at the Wikipedia articles on Dextroamphetamine and Methylphenidate as downloaded Monday 24 May 2015

Kunga Dorji
07-04-15, 08:29 PM
Sorry about the length but the references are important.

SB_UK
07-09-15, 03:15 AM
Though it does feel as though supplying 'reward' in a bottle will serve to prevent us from changing society so life itself supplies 'reward'.

I wonder how much more quickly we'd have arrived at a solution to eg asthma if we didn't have 'rescue' inhalers to keep us going ? A partially overcome problem is kicked down the priority list.

What is the basis to asthma ?
Still working under the assumption that there's an underlying metabolic change perhaps to SCFAs from gut biome digested soluble fibre.

Supplemented by SCFAs from fasting, SCFAs from duration exercise, SCFAs from ketogenic metabolism + SCFAs generated by melanin.

That realisation'd solve the world's obesity + T2D prolems overnight.

Daydreamin22
07-09-15, 10:35 AM
Sounds good. Not saying there's not truth to it, but I think it's bias bc adderall destroyed my life.

Kunga Dorji
07-10-15, 07:09 PM
Though it does feel as though supplying 'reward' in a bottle will serve to prevent us from changing society so life itself supplies 'reward'.

I wonder how much more quickly we'd have arrived at a solution to eg asthma if we didn't have 'rescue' inhalers to keep us going ? A partially overcome problem is kicked down the priority list.

What is the basis to asthma ?
Still working under the assumption that there's an underlying metabolic change perhaps to SCFAs from gut biome digested soluble fibre.

Supplemented by SCFAs from fasting, SCFAs from duration exercise, SCFAs from ketogenic metabolism + SCFAs generated by melanin.

That realisation'd solve the world's obesity + T2D prolems overnight.

SB- it is not "reward in a bottle".
That whole model is totally outdated.

The effect of stimulants on the basal ganglia which are involved in task switching, is much more significant than the effect on the nucleus accumbens ("reward centre").

So it aids directly in more rapid and fluid task switching.
Correctly used it improves blood flow to the frontal lobes and improves the efficiency of the frontostriatal system by raising the resting level of neuronal activity ( Central Integrated State).
It thus improves automatic inhibitory control, especially when combined with a long term program of behaviour modification.

Hathor
07-10-15, 07:21 PM
SB- it is not "reward in a bottle".
That whole model is totally outdated.

.

while I agree with KJ more than SB here, I think stims are often used to force people into a reward/punishment type of existence.

While I am not as anti-stim as SB, I am kind of Glad I never got diagnosed as a youngster, othewise I may have been better at making myself stupid with help from the military industrial complex's babysitting service.

While stims may be demonized unfairly, a large and possibly;e main way they are used is to help people make themselves credulous herded animals without much knowledge.

http://www.homeschooloasis.com/pic-JohnTaylorGatto-withquote.jpg

Kunga Dorji
07-10-15, 10:12 PM
while I agree with KJ more than SB here, I think stims are often used to force people into a reward/punishment type of existence.

While I am not as anti-stim as SB, I am kind of Glad I never got diagnosed as a youngster, othewise I may have been better at making myself stupid with help from the military industrial complex's babysitting service.

While stims may be demonized unfairly, a large and possibly;e main way they are used is to help people make themselves credulous herded animals without much knowledge.

http://www.homeschooloasis.com/pic-JohnTaylorGatto-withquote.jpg

There is much to agree with here, but I use the stimulants to make me calmer, happier, and more effective. I am already well versed in the issue of the "consensus trance" and now I find I can activate myself as a far more effective and articulate advocate for the ideas I support ( and we clearly have huge overlap here Eeyore).
I see the worst results when the stimulants are used to make children conform and obey in emotionally toxic environments.

mildadhd
07-10-15, 11:00 PM
I agree with SB_UK in that the rewards and punishments are found in the environment/world.

The dopaminergic system seeks the reward.

When I receive a reward/medication my SEEKING system calms down.

Promoting a non threatening environment is more important than taking medication for me.

It is for me anyway.

But medication really helps to.

Age of development is also a giant factor in what treatment approach to try first.

I agree with Daydream22 in that medication is not for everyone.

I agree with Kunga Dorji and Eeyore that medication can be a valuable tool, especially past the early critical period of development.

It is for me anyway.

But if I was younger, I would experiement with a free playful compassionate, non threatening environments to promote development before ever trying medication.

Not medicated right now, I am sure there is parts I am missing, looking forward to reading this thread tommorrow after I take medication.

Great thread/discussion.

P

someothertime
07-11-15, 12:51 AM
infants two months old, are capable of interactional and affective symmetry... assuming cognition plays a lesser role, intersubjectivity facilitated via improved task metacognition short circuits the primal emotive symmetry.......

thus, we must re-order thought before the thoughts themselves.

SB_UK
07-11-15, 04:17 AM
a reward/punishment type of existence.


That's it - meds provide reward and de-activate punishment.
2 modes.

But if reward relates to the individual and punishment to behaviours inconsistent with species wellbeing - then we're given 2 sets of instructions - to do what's best for the individual AND what's best for the species.

At least what's not damaging to the species.

2 programs through having 2 DA mechanisms; that's sweet.

meadd823
07-11-15, 05:44 PM
SB- it is not "reward in a bottle".
That whole model is totally outdated.

The effect of stimulants on the basal ganglia which are involved in task switching, is much more significant than the effect on the nucleus accumbens ("reward centre").

So it aids directly in more rapid and fluid task switching.
Correctly used it improves blood flow to the frontal lobes and improves the efficiency of the frontostriatal system by raising the resting level of neuronal activity ( Central Integrated State).
It thus improves automatic inhibitory control, especially when combined with a long term program of behaviour modification.


Some times it is hard to remember what we are talking about here, so I posted a quote to remind myself .....The topic here is the scientific evidence that long term use of ADD medication at therapeutic dosages does not cause brain damage ...... some of the stupid crap I did before treating my ADD may have.......

Seeing as I came here over a decade ago already on adderall for 7 or 8 years and I remain of the same dosage of adderall as I type this today my anecdotal experience seems to line up with science ......... Some times I do feel brain damaged as I can not seem to remember like I did a few short years ago. I allowed this to really bother me until I looked back and saw the tremendous changes I have undergone in the last two years ..... My memory is not any worse I simply have more to remember. I have undergone a complete career change, two job changes, home health to clinical, my home life has changed, I not only work 40+ hours a week I still manage multiple colonies of cats, keep tabs on my aging mother, this bring me to my next point

Pilgrim
07-11-15, 06:49 PM
Watching the aborant behaviour of my family leaves a certain mark on your psyche. Then struggling through school and the massive blows to ones self esteem, that settle ones outlook when one becomes an adult.

Reward in a bottle; never. The ability to function and see the world as it is; yes.

I find the hardest thing about taking longterm medication is dealing with past regrets, and trying to come to a place where you're comfortable with it.
I can hold down a job, read a book; form my own thought structure, not have crippling anxiety and I'm not suicidal. I have a much wider view in the world.

I was talking to my father not long ago and I realized it was one of the first times he took me as an equal. For a A type personality male that's important.

I have taken Dex for 2 years, Concerta 1. Another regret is I didn't start a lot ALOT earlier.
Maybe I can achieve some of the dreams I have. Without hope where all cactus.

Kunga Dorji
07-11-15, 07:16 PM
Though it does feel as though supplying 'reward' in a bottle will serve to prevent us from changing society so life itself supplies 'reward'.

I wonder how much more quickly we'd have arrived at a solution to eg asthma if we didn't have 'rescue' inhalers to keep us going ? A partially overcome problem is kicked down the priority list.

What is the basis to asthma ?
Still working under the assumption that there's an underlying metabolic change perhaps to SCFAs from gut biome digested soluble fibre.

Supplemented by SCFAs from fasting, SCFAs from duration exercise, SCFAs from ketogenic metabolism + SCFAs generated by melanin.

That realisation'd solve the world's obesity + T2D prolems overnight.


So here's the catch.
You and I and many others realise this, but the information is being actively suppressed in the US in particular as the FDA comes down hard on any claims that any nutrients have any particular health benefits here. The power here in terms of media and political control rests with the wealthy pharmaceutical industry.

So- we can't drag every human on this planet kicking and creaming into awareness of and ability to act on current knowledge.

How do we actually do this work?
This isn't going to change if we just sit here repeating the same old themes, preaching to the converted.

I have the advantage of being in clinical practice with a virtually exclusive focus on ADHD.

Many patients are deeply conditioned to accept the current conventional wisdom.

So are many doctors, and the penalties for being found to be too "different" include loss of one's Medical Registration.

I find it takes most patients about 10 consultations, going often into considerable detail, to get one individual to be open to new approaches.

So this is a serious question- how do we go from just repeating the same old thing to actually changing outcomes and helping ourselves, those near to us, and humanity in general live happier, more functional lives?

Kunga Dorji
07-11-15, 07:36 PM
Watching the aberrant behaviour of my family leaves a certain mark on your psyche. Then struggling through school and the massive blows to ones self esteem, that settle ones outlook when one becomes an adult.

Yep- can relate to this.
All of us need to grasp though, that our relatives are really rather silly very often. If we should believe them when they talk rubbish or we feel responsible for rescuing them if they are not able to be open minded to new ways of dealing with their problems then we are still a bit mad ourselves.


Reward in a bottle; never. The ability to function and see the world as it is; yes.


The outcomes of those better observed and regulated decisions are a reward in themselves- as is the lifting of the brain fog and the ability to be still and enjoy sitting in the sun under a tree. I couldn't do those things before I started stimulants.

We need to be careful about using perjorative terms like "reward in a bottle".

They are inaccurate - and they have infiltrated our culture from sources that profit from the suffering of untreated ADHD individuals.


I find the hardest thing about taking long term medication is dealing with past regrets, and trying to come to a place where you're comfortable with it.

Yes for most of us that is the case.


I decided some time ago that the most practical thing to do was to act as though reincarnation is a real thing and that I have chosen this rebirth for the advantages and opportunities for rapid spiritual growth inherent in such a path.

My choice to make that decision had nothing to do with whether or not I believed in reincarnation.

I made that choice because it was clear to me that that was an adaptive belief to hold. I ceased being the victim of my adverse experiences and started seeing each one as a learning opportunity- always asking myself-- what is the lesson i need to learn here?

This approach really does work- as it draws us away from useless dwelling on losses. However you have to work at it for years until it becomes second nature to think like that.


I can hold down a job, read a book; form my own thought structure, not have crippling anxiety and I'm not suicidal. I have a much wider view in the world.

Keep at it-- it really does get much better.


I was talking to my father not long ago and I realized it was one of the first times he took me as an equal. For a A type personality male that's important.

I am still waiting for that conversation!
It is hard for parents to stop parenting and see their offspring's strength.
I terminated my relationship with my psychoanalyst this week (on friendly terms), for exactly those reasons. I am confident in myself, and it is time for me to move on and be independent.
I keenly await the day when my children surpass my achievements.


I have taken Dex for 2 years, Concerta 1. Another regret is I didn't start a lot ALOT earlier.
Maybe I can achieve some of the dreams I have. Without hope where all cactus.

Maybe you will find even better dreams and aspirations.
Hope is always present and opportunities lie in wait in every direction.

One needs to be mentally still to see them coming though.
The stimulants do help achieve that.

Kunga Dorji
07-11-15, 07:45 PM
P { margin-bottom: 0.21cm; }A:link { } While there has been concern about the safety of stimulant medication both for treatment of ADHD and for other indications, current evidence suggests that these concerns may not only be overstated, they may be totally wrong, and , in many situations, long term cause of stimulants may be so beneficial that to deny access to the may be irresponsible.



So- where do we go with this information. This is an extract form a conversation I am having with another health professional:


Finally the question of nutrition and appropriate supplementation is also relevant.

The ADHD category is quite broad and contains many very different individuals with very different mixes of causative factors.

My patients also struggle financially and the functional pathology tests are not cheap and not covered by Medicare.


From my point of view I am highly interested to develop some sort of decision tree that will rationalise pathology ordering.


The other issue of note is the question of ensuring conditions that maximise the potential of neuroplastic brain development.

Demonstrating neuroplastic changes is a core theme of many papers on mindfulness and I find mindfulness meditation of core importance in managing ADHD (even in patients who can only do 5 minutes at a time!).

Equally physical rehabilitation exercises targetting especially the faulty loops involving cerebellum and basal ganglia is of critical importance in providing the right kind of neuroplastic brain growth.


Equally, recent metanalyses have clearly shown that psychostimulant use, when tolerated, actually accelerates neuroplastic brain development and also, interestingly slows neuronal degeneration in Parkinson's disease ( the opposite of what we have worried about).


So the logical next step to me is to focus on optimising diet and nutrition to provide maximal nutritional support for neuroplastic brain development.

I am about to post that on a closed user group of health professionals.

We will see where we go with that. Things are looking more promising.

Fortune
07-11-15, 09:19 PM
While stims may be demonized unfairly, a large and possibly;e main way they are used is to help people make themselves credulous herded animals without much knowledge.

How does this work? Please explain using established features of stimulants that are well-understood because of the extensive research establishing both their utility in treating ADHD and their safety. How on Earth do stimulants make people "credulous herd animals?"

Stimulants are demonized unfairly. One of the ways they are unfairly demonized is in the claim that they're used to make people docile and credulous.

dvdnvwls
07-11-15, 11:10 PM
Certainly in my own situation I am less docile and less credulous with a stimulant.

eeyore: I honestly and without irony believe that it actually takes a docile and credulous person to swallow the stories you're being told, and that you've got some things backwards.

Hathor
07-11-15, 11:58 PM
It is not the stims themzelves that get u herded, but what you pay attention to when on them. I am on a tablet and cant handle typing so will explain tomorrow if Kunga does not beat me to it.

dvdnvwls
07-12-15, 12:03 AM
It is not the stims themzelves that get u herded, but what you pay attention to when on them. I am on a tablet and cant handle typing so will explain tomorrow if Kunga does not beat me to it.

I don't mind if it's Kunga or anyone else telling you the stories, I stand by what I said.

SB_UK
07-12-15, 04:39 AM
So - strictly on topic of the positive effects (stress relief and elimination of negative downstream consequences of exposure to chronic stress in an immoral society) of stimulant medication.

These are the consequences of stress.

When used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults.
Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry 77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013 (https://dx.doi.org /10.1016%2Fj.biopsych.2014.09.013).
PMID 25499957 (https://www.ncbi.nlm.nih.gov /pubmed/25499957).
Ilieva IP, Hook CJ, Farah MJ (January 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". J. Cogn. Neurosci.:

Stress affects many memory functions and cognitive functioning of the brain.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907136/
Taken together, the evidence indicates that high levels of catecholamine release initiated by the amyg dala during stress switch the brain from thoughtful, reflective regulation by the PFC to more rapid reflexive regulation by the amygdala and other subcortical structures (BOX 1 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907136/#BX1)). These mechanisms might save our life when we are in danger and need to react rapidly, but they can be detrimental when we need to make choices that require thoughtful analysis and inhibitory control.Basal ganglia
And from above.

J neurosci 2006
Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity.

-*-

Summary of posts above - Question - Long term safety of stimulant medication.
From KD, EEyore, Peripheral, DVD and Fortune- stimulant medication mimics the reward activation / punishment deactivation axes.Human beings have a need for 'programming (SEEKING)' which uses reward / punishment to take us from birth to wisdom.
Is reward activation / punishment deactivation taking the individual closer to the state of morality (enforced moral consistency) ?
Dependent on how much stress the individual is under and how the individual uses stimulant medication (what they pay attention to) - stimulant meds can either be useful or not.
However - give a global shift to free education/voluntaryism - we'd eliminate the aspect of the environment (psychosocial stress) which propels their need.

Cavanagh, J. F.; Frank, M. J.; Allen, J. J. B. (7 May 2010). "[psycho]Social [di]stress reactivity alters [dopamine as carrot and stick] reward and punishment learning ". Social Cognitive and Affective Neuroscience [B]6 (3): 311–320. doi (https://en.wikipedia.org/wiki/Digital_object_identifier):10.1093/scan/nsq041 (https://dx.doi.org/10.1093%2Fscan%2Fnsq041).

As ever - prevention is immeasurably better than cure.

Kunga Dorji
07-12-15, 07:45 AM
ADDForum Members.

Rewards are found in the environment.

There are many reward systems in the brain.

The general role of dopaminergic system is seeking the rewards in the environment.



P

Actually quite incorrect.
The majority of dopaminergic innervation involves the basal ganglia (the fronto-striatal system) not the nucleus accumbens ("reward centre"). The basal ganglia are primarily involved in the process of deciding whether to stay with the current task, switch to another one or just stop and observe for a bit.

If you wish to fully inform yourself on this subject the most current texts that I am aware of are "Subcortical Structures and Cognition" (Koziol L.F. and Budding D. E. )Springer Press 2009 )and "ADHD as a Model of Brain-Behaviour Relationships (Koziol L.F. ,Budding D. E. and Chidikel D.) Springer Press 2013

Panksepp is actually a little behind the front line of neurology research in this department.
His appraoch is very useful as it correlates with an experiential reality, but the more precise approach made possible bu the intimate understanding of the correlation between cortical structures and the loops involving them and the major subcortical structures has radically altered our understanding of the problem presented by "ADHD".

I can't blame him- keeping up with all this is a BIG job!

someothertime
07-12-15, 08:44 AM
Kunga, thanks once again for your ongoing actions and sharing of contemporary science and law. Your posts once again highlight the disparity between lawmakers, researchers, prescribers and regulators.

A review of the data presented from Prof Alistair Vance of the Royal Children's Hospital yielded the following figures:
Out of every 100 children with ADHD, about 66 will still be diagnosable as ADHD , about 5 will have full resolution of their ADHD and the remaining 29 or so will have symptoms but fall below diagnostic thresholds.

This is very interesting.

My experience in ADHD suggests that many of that group will fall back into diagnosable ADHD if hit by a crisis.

Agreed.

My overall observations as a GP (about 20 years in the same practice watching many of my middle aged and elderly patients slip into dementia), suggest to me that the ADHD pattern may be a precursor to neurodegenerative disorders – such as Alzheimer's and Caparisons. In this setting symptoms like restless legs may be a prodrome of conditions such as Parkinson's disease.

I think there is some correlation in the *pattern* and degeneration..... or at the very least, presentations mimicking patterns.

Given my current awareness of the field of evidence based neuroscience (formerly called functional neurology) and a field that specialises in neurological rehabilitation, there is every reason to believe that this would be a predicted outcome of lifelong ADHD. Given my personal experience of rehabilitation provided by practitioners of functional neurology it is clear that this downhill slide can not only be halted, it can be reversed.

I suspect not such predictable outcomes here. If anything, lifelong ADHD neurology may equip a portion ( substantial ) of individuals with adequate in effect, alternative pathways and neurological resilience. It is interesting you mention crisis above.... as i feel this would be one of the predictors and triggers to this resilience or lack of.

Either way, the convergence of the two feilds is sure to yeild benefits in both camps.


Thanks once again.

mildadhd
07-12-15, 01:01 PM
Actually quite incorrect.
The majority of dopaminergic innervation involves the basal ganglia (the fronto-striatal system) not the nucleus accumbens ("reward centre"). The basal ganglia are primarily involved in the process of deciding whether to stay with the current task, switch to another one or just stop and observe for a bit.

If you wish to fully inform yourself on this subject the most current texts that I am aware of are "Subcortical Structures and Cognition" (Koziol L.F. and Budding D. E. )Springer Press 2009 )and "ADHD as a Model of Brain-Behaviour Relationships (Koziol L.F. ,Budding D. E. and Chidikel D.) Springer Press 2013



I will look into your recommendations.

Not sure what you think is incorrect about Prof Panksepp's work? some examples would be great.

Rather than incorrect, I think we are talking past each other.

I take ADHD medication.

If we want to understand the medications that may partially help us self regulate our emotional response systems, (raw emotions) we must understand the neurophysiology (biology) of the unconditioned primary emotional response systems involved, as well.

The topics I am layhumanly presenting are only off topic, if the mind research ignores the brain research.

https://en.m.wikipedia.org/wiki/Dopaminergic_pathways

If the dopaminergic pathways (SEEKING system) is the reward system?

What about good feelings we get from different chemistries mammalian primary social emotional response LUST system, CARE system, GRIEF system, PLAY system, etc..?

Oxytocin etc.



The three dominant brain systems in addiction--the opioid attachment-reward system, the dopamine-based incentive-motivation apparatus and the self-regulation areas of the prefrontal cortex--are exquisitely fine-tuned by the environment...the fourth brain-body system implicated in addiction: the stress-response mechanisms.

-Gabor Mate M.D., "In The Realm Of Hungry Ghosts", p188.



P

Kunga Dorji
07-12-15, 06:52 PM
How does this work? Please explain using established features of stimulants that are well-understood because of the extensive research establishing both their utility in treating ADHD and their safety. How on Earth do stimulants make people "credulous herd animals?"

Stimulants are demonized unfairly. One of the ways they are unfairly demonized is in the claim that they're used to make people docile and credulous.

They have only ever made me more independent minded and determined to be myself-- as I am sure you are well aware Fortune ;)

You are also well aware that I would be the last person to advocate a drug only approach, and that often now, I do not need stimulants at all. So am hardly one eyed about the matter.

I would go further than you on this one though.
It is an interesting anomaly that psychostimulants, which bring clarity and help us se cause and effect are demonised while alcohol, which makes us dopey and unable to think is licenced and taxed and approved of socially.
Dexamphetamine costs 5 cents a tablet to make and has a very low side effect rate.

There have been comprehensive comparative studies of risks associated with drug use.
Alcohol is far and away the worst. Even street speed not Ice)- with all its associated hazards has a harms ratio about 40% of that of alcohol.
Untreated ADHD is very strongly associated with addictive behaviours and numerous other harms.

The drug laws and the antipathy to use of stimulants in ADHD make no sense to me except that they keep a series of markets going very profitably.

We need to be measured in our criticisms of their use- as they are life saving for many of us.
I could not be as well and as happy as I am without them.

Eeyore does have a point though- often ADHD kids are destabilised by bad teachers - and often the response is to simply treat the child.
I pay a great deal of attention to this-I see many school reports and you can tell so clearly from a school report which teacher was warm and encouraging.
It matters much more to ADHD children that more settled and stable children.

Kunga Dorji
07-12-15, 07:04 PM
It is not the stims themzelves that get u herded, but what you pay attention to when on them. I am on a tablet and cant handle typing so will explain tomorrow if Kunga does not beat me to it.

Attention has to be combined with intention.
BTW- I totally get what you are saying about difficulty using tablets.
The eye coordination thing is a really big issue in ADHD, and ties in closely with all the other stuff I have brought to attention here.

At the risk of hijacking my own thread- take a look at this:
http://www.npr.org/templates/story/story.php?storyId=128977924

and realise that Susan Barry, a well known neuroscientist who was born with a squint that needed surgery, was stuck in a class with all the troublesome ADHD kids.

I am working on some new material and will post it when it is finished-- but too much time on line is hard for me too :)

More later.

SB_UK
07-13-15, 04:36 AM
Dopamine in Reward, punishment
Dopamine in Seeking
Dopamine in Loops

Abstract

Dopamine neurons located in the midbrain play a role in motivation that regulates approach behavior (approach motivation). In addition, activation and inactivation of dopamine neurons regulate mood and induce reward and aversion, respectively. Accumulating evidence suggests that such motivational role of dopamine neurons is not limited to those located in the ventral tegmental area, but also in the substantia nigra. The present paper reviews previous rodent work concerning dopamine's role in approach motivation and the connectivity of dopamine neurons, and proposes two working models: One concerns the relationship between extracellular dopamine concentration and approach motivation. High, moderate and low concentrations of extracellular dopamine induce euphoric, seeking and aversive states, respectively. The other concerns circuit loops involving the cerebral cortex, basal ganglia, thalamus, epithalamus, and midbrain through which dopaminergic activity alters approach motivation. These models should help to generate hypothesis-driven research and provide insights for understanding altered states associated with drugs of abuse and affective disorders.

http://www.ncbi.nlm.nih.gov/pubmed/25907747

Midbrain (substantia nigra - black hole - 1d - unidirectional ie positive transmission good - rewarding)

https://upload.wikimedia.org/wikipedia/commons/thumb/5/54/EmbryonicBrain.svg/375px-EmbryonicBrain.svg.png

Model of evolution - 1 continuous structure - black hole surrounded by male, female archetype - forming 1 structure

/ | \

mildadhd
07-13-15, 12:36 PM
Stimulants have sensitized my brain.

Motivation lacks even more without.

But I can't focus enough to read and understand much of SB_UK's or anyone else's post's when I do not take medication.

The doctor was very clear, that I might need to take it for the rest of my life.

Taking medication is a very serious decision, and non stimulant treatments should always considered before taking medication.

When life is not as distressful, I don't require as much medication.


P

Lunacie
07-13-15, 01:03 PM
Stimulants have sensitized my brain.

Has a doctor told you this?

In what way have stimulants sensitized your brain?



Taking medication is a very serious decision, and non stimulant treatments should always considered before taking medication.

Stimulants have been proven to be as safe, and usually more effective,
than other treatments.

Why should they NOT be tried first?

mildadhd
07-13-15, 01:11 PM
Has a doctor told you this?

In what way have stimulants sensitized your brain?



Stimulants have been proven to be as safe, and usually more effective,
than other treatments.

Why should they NOT be tried first?

Taking stimulants results in neural growth.

When I stop taking stimulants, the neural growth wants the medication.

P

Abi
07-13-15, 01:13 PM
Thread temporarily closed for staff review.

Abi
07-13-15, 01:39 PM
MODERATOR NOTE

Thread reopened.

Please stick to the topic: The Safety of Long-Term Use of Stimulants.

Thank you.

Kunga Dorji
07-15-15, 02:29 AM
Kunga, thanks once again for your ongoing actions and sharing of contemporary science and law. Your posts once again highlight the disparity between lawmakers, researchers, prescribers and regulators.

A review of the data presented from Prof Alistair Vance of the Royal Children's Hospital yielded the following figures:
Out of every 100 children with ADHD, about 66 will still be diagnosable as ADHD , about 5 will have full resolution of their ADHD and the remaining 29 or so will have symptoms but fall below diagnostic thresholds.

This is very interesting.

My experience in ADHD suggests that many of that group will fall back into diagnosable ADHD if hit by a crisis.

Agreed.

My overall observations as a GP (about 20 years in the same practice watching many of my middle aged and elderly patients slip into dementia), suggest to me that the ADHD pattern may be a precursor to neurodegenerative disorders – such as Alzheimer's and Caparisons. In this setting symptoms like restless legs may be a prodrome of conditions such as Parkinson's disease.

I think there is some correlation in the *pattern* and degeneration..... or at the very least, presentations mimicking patterns.


There are a couple of reasons to think not- I suspect that restless leg syndrome is an early presenting feature of Parkinson's.

Also there are a number of high profile ADHD individuals who have progressed to Parkinson's and there has been suspicion of an association for some while- especially with the cluster of problems that arose after the Spanish Flu outbreak in 1918.
. However- by the time most people present with Parkinson's there is little hope of getting a clear picture of their past psychological profile.

In Middle aged adults untreated ADH is very socially isolating- and decreased social interaction is an independantly variable risk factor for Alzheimers and also for chronic depression (another risk factor for Alzheimer's !). Again it is hard to get at the past history at that stage though. In any case I am inclined to do whatever is necessary to mitigate those risks.
Given my current awareness of the field of evidence based neuroscience (formerly called functional neurology) and a field that specialises in neurological rehabilitation, there is every reason to believe that this would be a predicted outcome of lifelong ADHD. Given my personal experience of rehabilitation provided by practitioners of functional neurology it is clear that this downhill slide can not only be halted, it can be reversed.

I suspect not such predictable outcomes here. If anything, lifelong ADHD neurology may equip a portion ( substantial ) of individuals with adequate in effect, alternative pathways and neurological resilience. It is interesting you mention crisis above.... as i feel this would be one of the predictors and triggers to this resilience or lack of.

Either way, the convergence of the two fields is sure to yield benefits in both camps.
Both good points.
The functional neurology field is evolving rapidly- and it is still hard to find a practitioner who has mastered it.
Also- perseverance is required.
Five and a half years since the first treatment on my neck and 6 and 1/2 years since starting stimulants, I am still improving.
However- it is too easy to forget to do the homework and exercises that are required to make that sort of work succeed, and ADHD individuals can give up quickly if there is not initial success.

Re resilience- any ADHD individual with any degree of success in any field has to learn to congratulate themselves for having pulled it off against the barrier of unstable attention. I can assure you though that as attentional stability improves that toughness that has allowed us to get anywhere at all- turns to our advantage.

The big sea change in trauma therapy is to move from "Post traumatic stress to post traumatic growth". That is what separates a good practitioner from a bad one.

In my work my first and most important goal is to get any individual to see the times that they have done well.

My big lightbulb moment in this area came in the field of social skills. I was quite socially isolated most of my life and though "I just could not do it".
I failed to observe that when seeing patients I was actually very good at it.

That sort of thing can be found in virtually any ADHD individual.

Kunga Dorji
07-15-15, 02:31 AM
Stimulants have sensitized my brain.

Motivation lacks even more without.

But I can't focus enough to read and understand much of SB_UK's or anyone else's post's when I do not take medication.

The doctor was very clear, that I might need to take it for the rest of my life.

Taking medication is a very serious decision, and non stimulant treatments should always considered before taking medication.

When life is not as distressful, I don't require as much medication.


P

Re the latter- same for me too.
However I am sure that the issue is not chronic stimulant use- there will be another factor contributing to the problem. I will email you.

Kunga Dorji
07-15-15, 07:48 AM
I will look into your recommendations.

Not sure what you think is incorrect about Prof Panksepp's work? some examples would be great.

Rather than incorrect, I think we are talking past each other.

I take ADHD medication.

If we want to understand the medications that may partially help us self regulate our emotional response systems, (raw emotions) we must understand the neurophysiology (biology) of the unconditioned primary emotional response systems involved, as well.

The topics I am layhumanly presenting are only off topic, if the mind research ignores the brain research.

https://en.m.wikipedia.org/wiki/Dopaminergic_pathways

If the dopaminergic pathways (SEEKING system) is the reward system?

What about good feelings we get from different chemistries mammalian primary social emotional response LUST system, CARE system, GRIEF system, PLAY system, etc..?

Oxytocin etc.






P

You know all these models that talk about the reward pathway or the seeking/lust/play modes are just working models generated in the heads of a very tiny and non representative individuals who happen to hold senior positions in academic institutions. These models are not even based on up to date understandings of human neurology and physiology.
Panksepp's model provokes new ways of thinkng about things, but it is really just another model.

Current understandings in evidence based neuroscience are far more precise than these models.

I mean really- I cant think of more than a few times when my

Amotivational states in which there are no "reward seeking behaviours'

A failure in "reward seeking" behaviour is really rather unusual-- thee are only a few situations-- severe infections or severe depression where the high levels of inflammatory cytokines (esp Interleukin 6) drive withdrawal type sickness behaviours, hypothyroidsim--(where there are very few behaviors of any kind) and a few rather unusual syndromes involving the dorsolateral prefrontal cortex are the main ones I can think of.

daveddd
07-15-15, 12:11 PM
There are a couple of reasons to think not- I suspect that restless leg syndrome is an early presenting feature of Parkinson's.

Also there are a number of high profile ADHD individuals who have progressed to Parkinson's and there has been suspicion of an association for some while- especially with the cluster of problems that arose after the Spanish Flu outbreak in 1918.
. However- by the time most people present with Parkinson's there is little hope of getting a clear picture of their past psychological profile.

In Middle aged adults untreated ADH is very socially isolating- and decreased social interaction is an independantly variable risk factor for Alzheimers and also for chronic depression (another risk factor for Alzheimer's !). Again it is hard to get at the past history at that stage though. In any case I am inclined to do whatever is necessary to mitigate those risks.
Both good points.
The functional neurology field is evolving rapidly- and it is still hard to find a practitioner who has mastered it.
Also- perseverance is required.
Five and a half years since the first treatment on my neck and 6 and 1/2 years since starting stimulants, I am still improving.
However- it is too easy to forget to do the homework and exercises that are required to make that sort of work succeed, and ADHD individuals can give up quickly if there is not initial success.

Re resilience- any ADHD individual with any degree of success in any field has to learn to congratulate themselves for having pulled it off against the barrier of unstable attention. I can assure you though that as attentional stability improves that toughness that has allowed us to get anywhere at all- turns to our advantage.

The big sea change in trauma therapy is to move from "Post traumatic stress to post traumatic growth". That is what separates a good practitioner from a bad one.

In my work my first and most important goal is to get any individual to see the times that they have done well.

My big lightbulb moment in this area came in the field of social skills. I was quite socially isolated most of my life and though "I just could not do it".
I failed to observe that when seeing patients I was actually very good at it.

That sort of thing can be found in virtually any ADHD individual.


No expert here but i know people with s fragile x premutation (much more common then full mutation and mentally retarded) have a 91 % adhd rate. Then a very high risk of a tremor/ gate ataxia issue usually beginning in yheir mid 50s

Lunacie
07-15-15, 12:41 PM
Taking medication is a very serious decision, and non stimulant treatments should always considered before taking medication.


P

Asking again because this didn't get answered in your previous post.

Since these meds have a long history of being effective without a ridiculous
risk of serious side effects, why should they not be considered as a first line
treatment rather than trying all kinds of treatments that are not as effective
overall?

sarahsweets
07-15-15, 12:53 PM
.

Age of development is also a giant factor in what treatment approach to try first.


Which is why I am glad they lowered the acceptable earliest age for treatment with stimulants to age 4.

Kunga Dorji
07-16-15, 03:38 AM
No expert here but i know people with s fragile x premutation (much more common then full mutation and mentally retarded) have a 91 % adhd rate. Then a very high risk of a tremor/ gate ataxia issue usually beginning in their mid 50s


Here is at least 1 link:
https://en.wikipedia.org/wiki/Cerebellar_cognitive_affective_syndrome

Cerebellar cognitive affective syndrome


Psychiatric Disorders

There are a number of psychiatric disorders that are thought to be related to dysfunction of the cerebellum and that appear similar to symptoms of CCAS.[4] (https://en.wikipedia.org/wiki/Cerebellar_cognitive_affective_syndrome#cite_note-autogenerated6-4) It has been suggested that lesions in the cerebellum may be responsible for certain characteristics of psychiatric disorders, such as
schizophrenia, autism, depression, bipolar disorder, ADHD, developmental dyslexia, Down Syndrome and Fragile X Syndrome.

Much more to come here- as this is a central unifying concept that ties in a large number of facts that are otherwise hard to connect.

daveddd
07-16-15, 08:44 PM
"An increasingly recognized number of neuropsychiatric FXD have recently been identified that are caused by ‘premutation’ range expansions (55-200). These disorders are characterized by a spectrum of neuropsychiatric manifestations ranging from an increased risk of neurodevelopmental, mood and anxiety disorders to neurodegenerative phenotypes such as the fragile X-associated tremor ataxia syndrome (FXTAS)."

"Additional systematic studies have found a higher prevalence of adult ADHD in carriers compared to non-carriers"

"Children with the premutation are most likely to present with ASD or ADHD in boys and anxiety in girls. Those with ASD generally lack the dysmorphic features and intellectual disability seen in FXS. Adult carriers may present with psychiatric manifestations on the depression and anxiety spectra, often with an onset later in life than is typical in the general population. Finally, these same adult carriers are at increased risk of developing a progressive dementia with tremor, ataxia, and parkinsonism often accompanied by depression and anxiety."
from study

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086747/

Abi
07-17-15, 10:26 AM
Thread closed for staff review.

Abi
07-17-15, 11:34 AM
off topic material moved here: http://www.addforums.com/forums/showthread.php?t=170838

Thread reopened.

mildadhd
07-17-15, 12:41 PM
Asking again because this didn't get answered in your previous post.

Since these meds have a long history of being effective without a ridiculous
risk of serious side effects, why should they not be considered as a first line
treatment rather than trying all kinds of treatments that are not as effective
overall?

Just like I don't think all types of diabetics should take insulin as their first line of treatment.


P

Lunacie
07-17-15, 01:02 PM
Just like I don't think all types of diabetics should take insulin as their first line of treatment.


P

Some diabetics absolutely need to use insulin from the first diagnosis.
Suggesting that they try other things first could lead to death. :eek:

Some can start on insulin and find life hacks that let them go without.

Just because you start with stimulant meds or insulin as the first treatment
doesn't mean you'll have to keep taking it forever.

People with ADHD are also at great risk and need to take their treatment
seriously.

mildadhd
07-17-15, 01:49 PM
You know all these models that talk about the reward pathway or the seeking/lust/play modes are just working models generated in the heads of a very tiny and non representative individuals who happen to hold senior positions in academic institutions. These models are not even based on up to date understandings of human neurology and physiology.
Panksepp's model provokes new ways of thinkng about things, but it is really just another model.

Current understandings in evidence based neuroscience are far more precise than these models.

I mean really- I cant think of more than a few times when my

Amotivational states in which there are no "reward seeking behaviours'

A failure in "reward seeking" behaviour is really rather unusual-- thee are only a few situations-- severe infections or severe depression where the high levels of inflammatory cytokines (esp Interleukin 6) drive withdrawal type sickness behaviours, hypothyroidsim--(where there are very few behaviors of any kind) and a few rather unusual syndromes involving the dorsolateral prefrontal cortex are the main ones I can think of.


I am also discussing overactivity of the SEEKING system.

I am not trying to derail your thread, I am trying to understand the brain systems involved in taking medication, to understand long term use of medication better.

There is lots of topics related to stimulant use I would like to discuss, so maybe it would be best to discuss them as separate thread topics.

I promise that I can explain how these topics relate to this thread topic, in time.

Please see thread, "What is a reward system?"

http://www.addforums.com/forums/showthread.php?p=1742890#post1742890



P

mildadhd
07-17-15, 02:03 PM
Some diabetics absolutely need to use insulin from the first diagnosis.
Suggesting that they try other things first could lead to death. :eek:

Some can start on insulin and find life hacks that let them go without.

Just because you start with stimulant meds or insulin as the first treatment
doesn't mean you'll have to keep taking it forever.

People with ADHD are also at great risk and need to take their treatment
seriously.


Yes some types of diabetic's require insulin as part of their treatment.

But not all types of diabetic's should be treated with insulin.

Right?



P

Abi
07-17-15, 02:14 PM
I thought the topic was SAFETY of stimulants not EFFICACY, so isn't the whole insulin debate a bit of a straw man and diversion?

-Abi (as MEMBER)

Lunacie
07-17-15, 02:34 PM
Yes some types of diabetic's require insulin as part of their treatment.

But not all types of diabetic's should be treated with insulin.

Right?



P

Insulin is the first line treatment for diabetes type 1. No question.

Abi is right. The issue is not whether stimulants work as well for all three
types of ADHD.

They are perfectly safe to recommend and use as a first line treatment.

SB_UK
07-17-15, 02:42 PM
My first thread here was all about how long one could expect dexedrine to work for.
Totally amazing experience.

The problem with stimlant medication - is that it ceased to work fairly soon after.

So - all well and good if they're safe ... ... but they have to continue to be effective also.

This story is confused though by the idea that the effective meaning of life allies with the meds no longer working or leaving the system that the meds operate within to one side.

mildadhd
07-17-15, 02:46 PM
Insulin is the first line treatment for diabetes type 1. No question.

Abi is right. The issue is not whether stimulants work as well for all three
types of ADHD.

They are perfectly safe to recommend and use as a first line treatment.

Type one diabetic's definitely need insulin, ADHD is not so "acute".

My father is a type one diabetic, I have moderate ADHD.

Avoiding distress, family support, exercise and heathy eating, etc...are all as important as insulin in a type one diabetic's treatment. (Same applies to people with ADHD)

Treatment specific's for both ADHD and diabetes depends on the individual, and medication is never the only option.

Right?

Abi
07-17-15, 02:54 PM
Okay, it's Abi as Moderator now:

Enough about insulin and environmental interventions. Make your own thread if you wish to discuss these.

Lunacie
07-17-15, 03:30 PM
My first thread here was all about how long one could expect dexedrine to work for.
Totally amazing experience.

The problem with stimlant medication - is that it ceased to work fairly soon after.

So - all well and good if they're safe ... ... but they have to continue to be effective also.

This story is confused though by the idea that the effective meaning of life allies with the meds no longer working or leaving the system that the meds operate within to one side.

And for some people they do continue to work ... safely ... for a long time.
I'm sorry that didn't happen for you.



Type one diabetic's definitely need insulin, ADHD is not so "acute".

My father is a type one diabetic, I have moderate ADHD.

Avoiding distress, family support, exercise and heathy eating, etc...are all as important as insulin in a type one diabetic's treatment. (Same applies to people with ADHD)

Treatment specific's for both ADHD and diabetes depends on the individual, and medication is never the only option.

Right?

ADHD can also be "acute", or much more impairing than yours seems to be.

I don't think anyone in this thread has said anything stimulant meds being
the 'only' option.

I simply disagree that a treatment that has been tested to be safe should
only be tried after other, less well tested, treatments have been tried.

mildadhd
07-17-15, 04:20 PM
And for some people they do continue to work ... safely ... for a long time.
I'm sorry that didn't happen for you.





ADHD can also be "acute", or much more impairing than yours seems to be.

I don't think anyone in this thread has said anything stimulant meds being
the 'only' option.

I simply disagree that a treatment that has been tested to be safe should
only be tried after other, less well tested, treatments have been tried.

If your interested discussing the topics, please post in thread "what is a reward system".

http://www.addforums.com/forums/showthread.php?p=1742890#post1742890

Understanding what a reward system is very important to understanding the question of long term stimulant use.


P

Kunga Dorji
07-18-15, 06:00 AM
I am also discussing overactivity of the SEEKING system.

I am not trying to derail your thread, I am trying to understand the brain systems involved in taking medication, to understand long term use of medication better.

There is lots of topics related to stimulant use I would like to discuss, so maybe it would be best to discuss them as separate thread topics.

I promise that I can explain how these topics relate to this thread topic, in time.

Please see thread, "What is a reward system?"

http://www.addforums.com/forums/showthread.php?p=1742890#post1742890



P

Interesting question, but in the context of the original topic- not relevant and therefore a thread hijack.
( Consider this some gratis ADHD coaching:D )
Oops-- hijacked my own thread with a joke :eek:

Kunga Dorji
07-18-15, 06:08 AM
I thought the topic was SAFETY of stimulants not EFFICACY, so isn't the whole insulin debate a bit of a straw man and diversion?

-Abi (as MEMBER)

Technically you are quite correct but my original post contains data relevant to efficacy:


When used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults.
Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry 77 (11): 940950. doi:10.1016/j.biopsych.2014.09.013 (https://dx.doi.org /10.1016%2Fj.biopsych.2014.09.013).
PMID 25499957 (https://www.ncbi.nlm.nih.gov /pubmed/25499957).
Ilieva IP, Hook CJ, Farah MJ (January 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". J. Cogn. Neurosci.:


Working memory and executive function are key areas of impairment in ADHD- and stimulants are proven to improve them.

Now, effective use of any medication requires skill and judgement on the part of the prescribing practitioner and a therapeutic alliance in which the patient and the prescriber work together to ensure the best result.

I have seen some very poor prescribing practice and I have also seen some patients who will not do anything more than just take the medication. SOme patients continue try to stay up all night and continue to try and do more things than they can possibly do.

The trouble with the sort of big studies favoured by the medical establishment is that they are just not fine grained enough to produce meaningful efficacy data.

SO- actually getting a good result depends on this as well as the medication

SB_UK
07-18-15, 07:46 AM
The problems with efficacy/safety is that decreasing efficacy could lead to increasing dosage leading to decreasing safety ... ... so ... ... we need to define a schedule which prevents that from happening.

Presumably lifestyle change ie losing weight, becoming healthier, not eating carbs - should lead the T2Diabetic to reduce their insulin requirement.

We need to ensure that stimulant meds have the same sort of effect ie a lifestyle which eliminates need as opposed to drives increasing need.

To do this we need to know how to transcend the reward system that the stimulant medication is operating within - and it appears to be operating within a system which can best be described as craving / satisfaction of craving.

So the goal is to eliminate craving.
Eliminating the need to satisfy craving.

With reference back to the idea that the reward system (pleasure) is considered a part of the brain's pain network.

Kunga Dorji
07-21-15, 12:18 AM
And for some people they do continue to work ... safely ... for a long time.
I'm sorry that didn't happen for you.





ADHD can also be "acute", or much more impairing than yours seems to be.

I don't think anyone in this thread has said anything stimulant meds being
the 'only' option.

I simply disagree that a treatment that has been tested to be safe should
only be tried after other, less well tested, treatments have been tried.

Lunacie,
I agree with you here.
Children are one matter- and there are well established protocols for when stimulants should be tried in children.
In adults though, the issue is that non stimulant treatments require perseverence over a long period.
I see few adults who are together enough, with enough social support to do well on non stimulant treatment unless they have the support of stimulants first.

sarahsweets
07-21-15, 04:45 AM
We need to ensure that stimulant meds have the same sort of effect ie a lifestyle which eliminates need as opposed to drives increasing need.

To do this we need to know how to transcend the reward system that the stimulant medication is operating within - and it appears to be operating within a system which can best be described as craving / satisfaction of craving.

So the goal is to eliminate craving.
Eliminating the need to satisfy craving.
Just so I understand....
Are you saying need as in need for medication?
Are you saying that meds only work because they deal with the reward system? What do you mean by that?
Are you saying that a need for meds is simply a craving and that eliminating meds would eliminate craving?
I am just trying to wrap my head around this.

SB_UK
07-21-15, 06:48 AM
1. So the T2D lifestyle operates to change the individual so less medication is required. I know pre-diabetes can be completely overcome with lifestyle changes - partly interested in knowing whether insuln requiring T2D can also.
Son't know.

2a/b. The Barliman/Peripheral conversation above was of dopamine in reward centres (pleasure) and dopamine in basal ganglia (pain alleviation). KD mentioned that quantitatively dopaminergic innervation is of greater level in the basal ganglia than reward centres.
Just copying their ideas.

3a. Operates within the same paradigm as craving.
So - take the meds and we all know it results in appetite suppression ie reduced need for food.
Often made the comment of interesting that dex/ritalin operate on timings roughly equivalent to the 3 meals a day - 3 to 4 hours efficacious.
Noted that dexedrine COMPLETELY eliminated (I couldn't have even if I wanted to) smoke cigarettes.

3b. No eliminating the need for meds occurs through overcoming the reward system which has CRAVING as a central part.

The general suggestion that wisdom represents the elimination of CRAVING - through ahhh!!!

- cerebral learning of physical world handling, non-abstract language and understanding (abstract) completing.

Lunacie
07-21-15, 11:56 AM
The problems with efficacy/safety is that decreasing efficacy could lead to increasing dosage leading to decreasing safety ... ... so ... ... we need to define a schedule which prevents that from happening.

Presumably lifestyle change ie losing weight, becoming healthier, not eating carbs - should lead the T2Diabetic to reduce their insulin requirement.

We need to ensure that stimulant meds have the same sort of effect ie a lifestyle which eliminates need as opposed to drives increasing need.

To do this we need to know how to transcend the reward system that the stimulant medication is operating within - and it appears to be operating within a system which can best be described as craving / satisfaction of craving.

So the goal is to eliminate craving.
Eliminating the need to satisfy craving.

With reference back to the idea that the reward system (pleasure) is considered a part of the brain's pain network.

I believe this has been pointed out before, but it apparently needs repeating.

When properly dispensed, properly taken, properly overseen, meds treat
ADHD and make the brain work somewhat normally.

It's only when they are obtained improperly, taken improperly, and not
overseen by a doctor that the person may take too much and try for reward
or pleasure rather than simply helping their brain work better.

IMO there is nothing wrong with craving a better-functioning brain.

dvdnvwls
07-21-15, 12:34 PM
IMO there is nothing wrong with craving a better-functioning brain.

In fact, many spouses in the Non-ADD Spouse Support section of this forum come on there just to complain that their ADHD spouse doesn't seem to crave a better-functioning brain, and this is (in their opinion, as far as I can tell) a horrible shame.

SB_UK
07-21-15, 01:07 PM
When properly dispensed, properly taken, properly overseen, meds treat
ADHD and make the brain work somewhat normally.


How many years have you taken meds for ?

What's your dosage ?

I stepped up and could not exceed (was limited at) 60 mg per day D.

Lunacie
07-21-15, 01:19 PM
How many years have you taken meds for ?

What's your dosage ?

I stepped up and could not exceed (was limited at) 60 mg per day D.

Fish oil works well enough for me that I don't need to take stimulants. Which
is a good thing because I don't have health insurance to pay for doctor visits
and expensive meds.

But ...

This isn't about my personal experience. It's about research showing that
these meds are safe and effective long term.

And although it's great that other countries have national health care, they
haven't approved more than a couple of meds for ADHD.

I do wonder if a higher dose, or a different med, would have worked better
for you. Unfortunately, dosing is still based on research on children, not on
adults. Doses that work for children may not be enough for adults.

SB_UK
07-21-15, 04:08 PM
Tried ritalin, straterra and dexedrine - no other options.
Ritalin - awful.
Straterra - nowhere near the effect of dexedrine
Dexedrine - it worked for a while
Also lots of schizophrenia and depression meds - which prescribing medics appeared to like (less controversial than stimulants ??) - ALL awful

I'll repeat that it doesn't matter how safe something is, unless it works.
And from a strictly scientific perspective = if a med goes from working well to not working at all - it wouldn't be scientific to shrug one's shoulders
- because something has changed courtesy of meds -

and it's important to know whether the change which has occurred to alter med reactivity - is change for the better or worse.

Abi
07-22-15, 11:33 AM
Fish oil discussion moved here (http://www.addforums.com/forums/showthread.php?t=170926)

Lunacie
07-22-15, 11:41 AM
How many years have you taken meds for ?

What's your dosage ?

I stepped up and could not exceed (was limited at) 60 mg per day D.

I don't take stimulants (I take Omega 3).

I'm sorry the meds didn't keep working for you. No one seems to know why
some are good on a low dose while other require a higher dose.

My granddaughter stopped taking Concerta for the same reason. She was at
the max dose and it was only effective for 4-5 hours, not a full school day.

Unfortunately, studies have not been done on what the maximum dose for
adults would be. Adults are still being dosed based on studies done on children.

acdc01
07-23-15, 05:52 AM
My overall observations as a GP (about 20 years in the same practice watching many of my middle aged and elderly patients slip into dementia), suggest to me that the ADHD pattern may be a precursor to neurodegenerative disorders such as Alzheimer's and Caparisons. In this setting symptoms like restless legs may be a prodrome of conditions such as Parkinson's disease.
Given my current awareness of the field of evidence based neuroscience (formerly called functional neurology) and a field that specialises in neurological rehabilitation, there is every reason to believe that this would be a predicted outcome of lifelong ADHD. Given my personal experience of rehabilitation provided by practitioners of functional neurology it is clear that this downhill slide can not only be halted, it can be reversed.

Have any studies been done that prove/disprove the link between Alzeheimers and ADHD? I thought I read that there had been studies and no link was found. But there was one type of dementia which ADHDers did have a greater change of getting.

Why do you think rehabilitee will reverse the downhill slide? Is it your opinion that the medication keeps the brain from deteriorating further or because of the social isolation aspect? ADHD leads to social isolation which is a higher risk factor for Alzheimers.

SB_UK
07-23-15, 06:54 AM
Have any studies been done that prove/disprove the link between Alzeheimers and ADHD? I thought I read that there had been studies and no link was found. But there was one type of dementia which ADHDers did have a greater change of getting.

Why do you think rehabilitee will reverse the downhill slide? Is it your opinion that the medication keeps the brain from deteriorating further or because of the social isolation aspect? ADHD leads to social isolation which is a higher risk factor for Alzheimers.

Thanks -
apparently ADHD and Dementia with Lewy Body #2 to Alzheimer's and similar to Parkinson's.
Similar to Parkinson's.
https://www.psychologytoday.com/blog/the-distracted-couple/201411/adhd-and-dementia-what-s-the-connection

Assuming close relationship between Parkinson's and DLB

From a parallel thread:
wikiP/MPTP
MPTP causes permanent symptoms of Parkinson's disease (https://en.wikipedia.org/wiki/Parkinson%27s_disease) by destroying dopaminergic neurons (https://en.wikipedia.org/wiki/Neuron) in the substantia nigra (https://en.wikipedia.org/wiki/Substantia_nigra) of the brain (https://en.wikipedia.org/wiki/Brain).

and

D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease.http://www.ncbi.nlm.nih.gov/pubmed/12975474

-*-

Assuming that Parkinson's and DLB occur by similar mechanisms.
Death of DA cells of the SN.

Suggestion - mitochondrial destruction - no energy generating facility - cell death.

Why ? First suggestion - over-use.

Too much usage of the neurones involved in the pleasure/pain primitive reward strategy.

What happens with over-use of mitochondria ?
Excess ROS formation - cell death.

ROS, mitochondria and the regulation of autophagyhttp://www.ncbi.nlm.nih.gov/pubmed/17804237
"Here, we review recent reports suggesting a regulatory role for ROS of mitochondrial origin as signaling molecules in autophagy, leading, under different circumstances, to either survival or cell death. We then discuss the relationship between mitochondria and autophagosomes and propose that mitochondria have an essential role in autophagosome biogenesis."

-*-


Problems with this idea.

We don't want to eliminate ROS (if necessary for peroxisome proliferation) and we don't want to generate too much ROS.
Note connection to eustress vs distress ie eustress supplies an appropriate level of stress to a system (peroxisome and mitochondrial proliferation/hormesis) - and distress does the opposite.
Autophagy - presumably more important for non-neuronal than neuronal cells which aren't as mitotically capable.
Autophagy - a key mechanism in peripheral housekeeping - but do we really want to be autophaging nerves - as opposed to re-connecting.

^
| depends on age ?
http://www.intropsych.com/ch02_human_nervous_system/neural_evolution.html

Cell death is a normal part of nervous system development. In some parts of the brain, more than half of the neurons generated during embryonic development die before a baby is born. To survive, a neuron requires a survival signal to turn off a built-in "suicide program." The suicide program within each cell is called programmed cell death or apoptosis . One neuron's loss is likely to be another neuron's gain, however. Neighboring neurons compete to fill the space left by a cell that has died due to apoptosis, and in some cases cell death actually stimulates the growth of new cells (Lasley, 2000).
How does the brain arrive at its adult form?
Evidently the brain arrives at its mature adult form by producing more nerve cells than it needs, then killing off the ineffective ones bit by bit while allowing successful neurons to grow. In children below the age of 7, new cells are added much faster than existing ones are killed. The number of neurons in the human brain peaks around age 7. After that, the total number of neurons decreases gradually for the remainder of a person's life. Certainly don't want to destroy the DA nerves of the SN if leading to Parkinson's + Dementia.

-*-

General suggestion

Pursuit of the craving (pleasure/pain) paradigm ramps up usage of the DA nerves of the SN triggering autophagy through ROS ?

What do meds do ?
Make the DA we produce go a bit further.

Would meds increase the likelihood of Parkinson's/Dementia ?
Presumably - they're supporting usage of the primitive reward system and so make life bearable within an inappropriate reward system. So it'd be unfair to blame the meds - better to blame the need to perform non-rewarding tasks.

Noting.
Mount Athos - where there is no psychosocial stress - no money, no jobs, no hierarchy - flat organizational, collaborative, equality
- and very elderly men present - there is no Parkinson's or Dementia of any sort.

-*-

- Concluding -
Pursue intrinsically rewarding (DA reward centre) + not distressful tasks (DA basal ganglia) ie plus carrot minus stick for appropriate level functioning of the DA expressing cells of the SN ?

SB_UK
07-23-15, 07:42 AM
Naughty !!

We are trying to identify safe and effective strategies for exploiting autophagy upregulation in order to enhance the removal of the toxic intracytoplasmic proteins ... [which] ... are features of many late-onset neurodegenerative diseases, called proteinopathies. These include Alzheimer’s disease, Parkinson’s disease, tauopathies, and polyglutamine expansion diseases (like Huntington’s disease (HD) and various spinocerebellar ataxias (SCAs)). http://www.cimr.cam.ac.uk/research/principal-investigators/principal-investigators-q-z/rubinsztein

Appropriate autophagy.

The ketone set of fat consumption, soluble fibre consumption, endurance exercise, carloric restriction, intermittent fasting and neuromelanin-mediated gamma ray conversion.

Short-term fasting induces profound neuronal autophagyhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/

acdc01
07-23-15, 09:53 AM
Thanks SB_UK. So the study suggested there was no link between ADHD and Alzheimers but there was a link with DLB dementia. It also pointed out one study doesn't confirm a hypothesis though and no other studies have been done on the matter. Hopefully they do more studies.

Abi
07-23-15, 10:12 AM
This Thread is now permanently closed.

Due to the excellent nature of the OP And *some* of the responses, it will be stickied.

If you would like to contribute more ON TOPIC material to this thread, ie. About the safety of stims or lack thereof, please PM me and I will arrange for your post to be included.