This may
sound like a very odd subject for my blog.
In 2002 US President George Bush first used the term “Axis of Evil” to refer collectively to Ian, Iraq and North Korea. Later that year the then-Undersecretary of State John Bolton gave a speech entitled "Beyond the Axis of Evil"; in it he added three more nations to be grouped together: Cuba, Libya and Syria. Finally, in 2005 Bush’s Secretary of State came up with “Outposts of tyranny” to refer to Cuba, Belarus, Burma and Zimbabwe.
Periactin/Cyproheptadine
The full study is listed later in this post.
Pentoxifylline
Herbal medicine and women's mental health
Autism spectrumdisorders: etiology and pharmacotherapy
ONLY
ABSTRACT
Herbal Medicine in the Treatment of Alzheimer’sdisease
Cyproheptadine in the
treatment of autism
Conclusion
All three drugs would seem worthy of further investigation, but particularly Piracetam and Periactin. Both seem to be widely used with children and were/are OTC.
In 2002 US President George Bush first used the term “Axis of Evil” to refer collectively to Ian, Iraq and North Korea. Later that year the then-Undersecretary of State John Bolton gave a speech entitled "Beyond the Axis of Evil"; in it he added three more nations to be grouped together: Cuba, Libya and Syria. Finally, in 2005 Bush’s Secretary of State came up with “Outposts of tyranny” to refer to Cuba, Belarus, Burma and Zimbabwe.
Many readers of my blog are from the US and may think that not much good
can be going on in Iran. The reality is
quite the reverse, at least in the field of autism.
In spite being under all kinds of economic sanctions, Iran has generated a
substantial body of insightful research.
There are 75 million Iranians which is just under the population of Germany. I do not recall seeing much German research
into autism.
One
particular researcher, Shahin Akhondzadeh, has done several very interesting
studies. His CV lists 128 research papers, including autism, ADHD,
schizophrenia, Alzheimer’s and other conditions. He also writes about herbal medicine for
mental health, which I know is popular among readers of this blog, so I included
links to some of those papers.
Piracetam, Periactin/ Cyproheptadine
& Pentoxifylline
Akhondzadeh
is unusual in that he actual makes repeated clinical trials of existing drugs
that the science shows could be effective.
In the case of autism he trialled three interesting drugs (with similar names):-
·
Piracetam
·
Periactin/Cyproheptadine
·
Pentoxifylline
Unfortunately
his three trials combined them with an anti-psychotic. But I think it is still interesting to look
at the net impact of each of the three drugs.
I did just that.
You have to
look at the data and compare the impact after 8 weeks to be consistent and you have to adjust for
the fact that in the Periactin/Cyproheptadine trial at week 0 the placebo group
was out of line with the trial group.
Net improvements:-
Piracetam 7
points on ABC
Periactin/Cyproheptadine 7 points on ABC
Pentoxifylline 3 points on ABC
This tells us
that Piracetam and Periactin had the greater incremental impact over the
antipsychotic and that the change was 7 points on the aberrant behaviour checklist (ABC). The ABC is a symptom checklist for assessing
problem behaviors in individuals ages 6 to 54. It is a 58 item checklist. There are five subscales: a) Irritability and
Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d)
Hyperactivity and Noncompliance and e) Inappropriate Speech.
I have
written about this drug in my recent post on Serotonin. Periactin is an old first generation H1
antihistamine that happens to have additional anticholinergic,
antiserotonergic
properties. It is the effect on
serotonin that appears to reduce aberrant behaviours in autism
Periactin is
available OTC in the UK. In the US it is
sometimes prescribed to increase appetite.
The link to Akhondzadeh’s
full study is later in the post.
Piracetam
Piracetam was first synthesized in 1964 by scientists at the Belgian
pharmaceutical company UCB; struck by its apparent ability to boost mental
functioning in even healthy individuals and by its safety, they coined the term
nootropic to describe
it and other substances. Piracetam (trade name "Nootropil") was
launched clinically by UCB in the early 1970s, and currently is in use in many
European countries.
Akhondzadeh
writes:-
In
addition to serotonergic abnormalities, the strongest evidence implicates the
glutamatergic and GABAergic systems are important biochemical factors in autism.
One current hypothesis is that autism is a hypoglutamatergic disorder. This
hypothesis is based on neuroanatomical and neuroimaging studies and supported
by similarities between symptoms produced by N-methyl-D-aspartate (NMDA)
antagonists in healthy subjects and those seen in autism. If there is deficient
glutamatergic transmission in autism, the most logical treatment would of
course be a glutamatergic agent. In the treatment of schizophrenia, that has
many similarities with autism either D-cycloserine (glycine agonist) or Piracetam
showed promising results. Indeed, autism and schizophrenia have some
similarities regarding the role of serotonin and glutamate in their
pathophysiology.
Piracetam
is a member of the nootropic class of drugs, which have cognition enhancing
effects, it appears to modulate AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic
acids)-sensitive glutamate receptors positively and has been used in many countries
in the management of dementia. Although its mode of action is not certain, it
is said to protect the cerebral cortex against hypoxia and has been used
following trauma or surgery and in a variety disorders including senile
dementia and behavioral disorders in children. In addition, it is used in the
treatment of dyslexia and some type of myoclonus in adults. Indeed. Piracetam
is the most studied nootropic in children.
Piracetam
was freely available in the US as a supplement until three years ago. You will see on the web that people were
using it, combined with another supplement called choline, to improve their
mental functioning. It had been shown to
work in rats, as you can see in this trial.
In the Ukraine it seems that Piracetam has long been given as a therapy in
autism. No mention of choline.The full study is listed later in this post.
Pentoxifylline
is a drug that targets the immune system, well established to play a key role
in autism. It is a
competitive nonselective phosphodiesterase inhibitor
which raises intracellular cAMP,
activates PKA, inhibits
TNF and leukotriene
synthesis, and reduces inflammation and innate immunity.
So it would
be fair to classify it as an immunological treatment
for autism.
It is hard
to find much about Pentoxifylline and autism.
It was trialled in the 1970s in Japan.
Japanese Journal
of Child Psychiatry, Vol 19(3), 1978, 137-144
Describes the
successful use of Pentoxifylline (150–600 mg/day) with 3–15 yr old children
with abnormal behaviour (e.g., self-mutilation, aggressiveness, and
hyperkinesis) and with autism. It is noted that while the drug was effective in
reducing symptoms of autism, developmental factors in the disorder should not
be ignored. (English abstract)
Unfortunately
I gave not found the full text version of Akhondzadeh’s study on this drug.
Autism in Iran
A paper
actually entitled “Autism in Iran”, makes very interesting reading and was
co-authored by Akhondzadeh.
Links to my selection of Akhondzadeh’s
Research
Autism spectrumdisorders: etiology and pharmacotherapy
ONLY
ABSTRACTHerbal Medicine in the Treatment of Alzheimer’sdisease
Cyproheptadine in the
treatment of autism
Authors: GUDARZI S., YASAMYM. and AKHONDZADEH S
Eur. Psychiatry, Vol.17, Year. 2002, Page: 230-231, NO ABSTRACT
Pentoxifylline is an oral medication that improves the symptoms of blood flow problems, such as intermittent claudication. Pentoxifylline is also used to improve blood flow to the brain, prevent strokes, reduce muscle pain during exercise, manage sickle cell disease, as well as relieve nausea and headaches associated with high-altitude sickness.Pentoxifylline allows blood to flow more easily.
ReplyDeleteInteresting. I once took a medicine to prevent altitude sickness when crossing the Himalayas, maybe this was it. I also found that Pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNF and leukotriene synthesis, and reduces inflammation and innate immunity. Perhaps the effect in ASD is caused by anti-inflammatory properties. It is a pity that such drugs are not fully investigated for ASD. It is another inexpensive generic drug, supposedly well tolerated.
DeleteI went to a neurologist (he's a professor and an epileptologist) in my country (asian developing), he has 37 years of experience and his son is a neuropsychiatrist in USA.
ReplyDeleteHe ordered an MRI(brain plain) everything was normal he gave my son 3 medicines and says that these are not branded and will be compounded in his office, he won't tell me what it is (medicine is not very tightly regulated here like developed countries, some doctors are strict and some like him are experimental and innovative, and the regulators don't care they just frown upon as you mentioned) what I can read from the prescription are these 3 names.
Seems like he is using some coded short terms so only him and his assistant can understand what the meds are
1. Torma or Topma (I dont think its topamax(topiramate) how can he do that without an EEG. I requested for an eeg he said no need) (once daily)
2. Neurotonic (once daily)
3. Sachet (once a week)
He says his assistant will provide the meds, dose for a month and come back with videos of your son, you will see a difference. Wouldn't tell me the generics or anything. I discussed this situation with another female neurologist and she called him Magic Man and said don't discuss him with me, this same female neurologist is mainstream and poor on research as I figured out (when I discussed some of the research she got annoyed and said why are you here go treat yourself) and said my son knows how to talk but does not want to talk she cant do anything and started about differently wired brains and genetics, and there is no such thing as normal or abnormal and referred me to a therapist and said shes got nothing for me in medicine.
Do you think I should go ahead and try the meds from the Magic Man, I know its shocking but that's the situation.