Piracetam - OK got curious -some stuff I found out about it

[Guest guest]

2 articles about this drug...did those of you that give this stuff to

your kids know that you can't just stop it -you have to reduce a drop

at a time -and that there may be changes in dosages around the dates

of a flight?! I'm sure there's much more out there on this stuff or

what Dr. Leshin calls " a drug in search of a disease. "

Piracetam and Down syndrome

Summary by Len Leshin, MD, FAAP

Piracetam is what I refer to as " a drug in search of a disease. " A

best-selling drug in Europe and Japan, a large portion of sales is to

normal adults looking for cognitive enhancement. It is not a drug of

first choice for any disease process yet, though current research is

looking into myoclonus, sickle cell disease, stroke and Raynaud

syndrome.

Piracetam became a controversial topic in the mid-1990s when a

parent group began advocating its use for Down syndrome. There was

notable publicity due to two ABC news shows about it and internet

advocacy on the part of the parent group. However, the company

licensing it, UCB Pharma in Belgium, has discouraged its use in

children with Down syndrome. In July 1998, UCB Pharma specifically

denied all rumors that it will fund or has plans to fund any study

with children with Down syndrome in the United States or elsewhere.

Many advocates of its use in Down syndrome claim that UCB Pharma's

reluctance stems more from economic motives than scientific; however,

UCB Pharma has obtained " orphan drug " status for piracetam in the US,

and is currently planning a controlled trial of piracetam and

myoclonus in the US. If given approval by the FDA for myoclonus, UCB

Pharma would have several years of exclusivity of the drug in the

US.

I have listed below the studies that involve children with Down

syndrome. I have a separate page for other research on piracetam.

Lobaugh NJ et al. Piracetam does not enhance cognitive abilities in

moderate to high-functioning 7 to 13 year-old children with Down

syndrome. Presented at the PAS/SPR meeting in San Francisco May 3,

1999; published in Archives of Ped and Adol Med, April 2001, 155

(4):442-448.

" Piracetam, a drug reported to enhance cognitive performance in many

neurobehavioural conditions, has become popular in the treatment of

children with Down Syndrome (DS). However, reports of its efficacy in

DS have been anecdotal, not from evidence-based studies. Some

caregivers have noted no effect of piracetam, while others claim

substantial improvement in cognitive functioning. To address the need

for objective analysis, we conducted a double-blind placebo-

controlled crossover study assessing the cognitive and behavioral

effects of piracetam in children with DS. Patients and Study Design.

Children with DS (n = 25, 13 males, 6.5 - 13 yrs) and their parents

participated. The first phase of the study was a baseline cognitive

assessment. Children were then randomly assigned to one of two four-

month treatment arms: Piracetam. Placebo or Placebo. Piracetam.

Children were retested at the end of the two treatment phases.

Children received 80-100 mg/kg piracetam per day in capsules. Placebo

was administered in the same manner. Test Battery. The test battery

included 16 tasks assessing attention, learning, memory, verbal

fluency, perceptual and spatial abilities, processing speed, fine

motor skills, and executive function. Both standardized and

experimental tasks were included. Secondary outcome measures were

questionnaires completed by parents and teachers at each of the three

phases. Results. Eighteen children (7 - 13 yrs) completed the study,

5 withdrew, and 2 could not complete the battery at baseline testing.

The mean mental age for the final sample was 4.2 ± .7 years (Stanford

Binet). The 16 tasks yielded 75 measures and the parent and teacher

questionnaires had 80 and 24 items, respectively. Piracetam did not

show significant effects over placebo on any outcome measure. All

significant interactions (p's < 0.05) with drug order or the

covariate were examined further to ensure drug effects were not being

masked. That analysis did not alter the results. Piracetam

administration was associated with CNS stimulatory effects:

aggressiveness (n=4), agitation (n =3), sexual arousal, (including

masturbation in public, n=2), irritability (n=1), and poor sleep

(n=1). Conclusion. Piracetam has received a great deal of attention

in the popular press purporting its efficacy in improving cognitive

function in children with Down Syndrome. In this study, we were

unable to substantiate these claims, even at doses associated with

adverse effects. Neither cognitive nor behavioural measures

demonstrated improvement under piracetam. Due to the serious adverse

effects, it is unlikely that larger doses can be tolerated. "

©1999 Pediatric Academic Societies

Fialho J Dromia and Piracetam: a useful association in the treatment

of Down syndrome. Tempo Medico 30:944, 1977. (The original was

published in Spanish; an English version was reprinted in a book

whose specifics are unknown to me.) 26 children with DS between 3

months and 12 years were given Dromia (mixture of pyriglutine and 5-

hydroxytryptophan) alone, and then a combination of Dromia and

Piracetam. The children were then evaluated based on their muscle

tone, motor development, mental development, speech, affective-social

development, scholastic achievement and EEG trace. The author

concludes that the combination of the two drugs caused an improvement

in all aspects, but especially speech. There were no side effects

noted. (Unfortunately, this is a terrible study. There were no

controlled subjects, the investigator does not tell how he evaluated

the above categories and does not say if the subjects, parents, or

investigators were " blinded " as to which children were getting one or

both drugs.)

An unpublished feasibility study was conducted in 1999 at the Kennedy

Kriger Institute in Baltimore under the guidance of Dr.

Capone. Five school-aged children with DS were given piracetam and

compared to five children with DS not on piracetam. The piracetam was

given at 100 mg/kg body weight per day. After six months, the

children were assessed for auditory verbal memory, auditory non-

verbal memory, visual memory, and spatial working memory. There were

no statistically significant differences in the two groups. It should

be noted that this was a study that was set up more to prove to the

NIH that the study was doable and deserving to be funded on a large-

scale basis rather than to prove whether to not piracetam had any

measurable effects. A lack of funds kept this study from being

carried out to a point where the research could be published.

In 2002, Dr. Capone and his associates published their trial of

piracetam on trisomy mice: The effects of piracetam on cognitive

performance in a mouse model of Down's syndrome Physiology & Behavior

77: 403-409, 2002.

" Piracetam is a nootropic agent that has been shown to improve

cognitive performance in a number of animal model systems. Piracetam

is reported to be used widely as a means of improving cognitive

function in children with Down's syndrome (DS). In order to provide a

preclinical assessment of the potential efficacy of piracetam, we

examined the effects of a dose range of piracetam in the Ts65Dn mouse

model of DS. Ts65Dn mice are trisomic for a region of mouse

chromosome 16 with homology to human chromosome 21. Daily piracetam

treatment at doses of 0, 75, 150, and 300 mg/kg ip was initiated in 6-

week-old male Ts65Dn and euploid control mice. Following 4 weeks of

treatment, mice were tested in the visible and hidden-platform

components of the water maze and were placed overnight in

computerized activity chambers to assess effects on overall activity.

Piracetam treatment was continued through the 4 weeks of testing. In

control mice, 75 and 150 mg/kg/day piracetam improved performance in

both the visible- and hidden-platform tasks. Although low doses of

piracetam reduced search time in the visible-platform component in

Ts65Dn mice, all piracetam doses prevented trial-related improvements

in performance in Ts65Dn mice. The 300-mg/kg/day-piracetam dose was

associated with a reversal of the nocturnal spontaneous hyperactivity

in Ts65Dn. These data do not provide support for piracetam treatment

for individuals with DS. "

Advocates of piracetam have argued that choline must also be

supplemented with piracetam to get any effect, thus explaining the

results of the Toronto and s Hopkins studies. The main basis for

this belief are the following studies:

Bartus RT et al. Profound effects of combining choline and piracetam

on memory enhancement and cholinergic function in aged rats.

Neurobiol Aging Summer;2(2):105-11, 1981. Rats given both choline and

piracetam did better on a memory test than on choline or piracetam

alone.

Platel A et al. Habituation of exploratory activity in mice: effects

of combinations of piracetam and choline on memory processes.

Pharmacol Biochem Behav 21(2):209-12, 1984. Mice did better on memory

of their environment with the combination of choline and piracetam

than on either separately.

Mosharrof AH & Petkov VD. Effects of citicholine and of the

combination citicholine + piracetam on the memory. Acta Physiol

Pharmacol Bulg 16(1):25-31, 1990. Mice did better with memory

retention with the combination of citicholine and piracetam than the

compounds separately.

Friedman E et al. Clincal Response to choline plus piracetam in

senile dementia: relation to red-cell choline levels. New Eng J Med

1981 Jun 11; 304(24): 1490-1. This is actually a " letter " rather than

a full paper, and consisted giving 10 patients with presenile

dementia piracetam and choline for 7 days in a non-controlled study.

3 of the 10 had " marked improvement " cognitively, but no description

of the cognitive tests or whether the testing was blinded is

mentioned. The 3 who responded had higher choline red blood cell

levels than the 7 who didn't respond.

However, other studies show a lack of usefulness of the combination:

Ennaceur A & Delacour J. Effect of combined or separate

administration of piracetam and choline on learning and memory in the

rat. Psychopharmacology 92(1):58-67, 1987. Rats given choline alone

did better than rats given piracetam alone on memory test, and rats

given piracetam and choline together did worse than the other groups.

Growdon JH et al. Piracetam combined with lecithin in the treatment

of Alzheimer's disease. Neurobiol of Aging 7:269-276, 1986. Piracetam

was administered alone or with lecithin (phosphatidylcholine) in a

double-blinded test. No effect was seen, with or without lecithin, on

cognition or memory test scores.

Corona GL et al. Clinical and biochemical responses to therapy in

Alzheimer's disease and multi-infarct dementia. Eur. Arch. Psychiatr.

Neurol. Sci. 239:79-86, 1989. Patients with either AD or multi-

infarct dementia were given either piracetam or piracetam with

choline. This was not paired with placebos. Despite biochemical

changes, there was no change in memory performance.

It should be noted that the maker of piracetam, UCB Pharma, has never

incorporated choline as part of any of its research on humans with

Alzhemier's disease or myoclonus.

http://www.ds-health.com/piracet.htm

Piracetam Frequently Asked Questions

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Piracetam's (2-oxo-1-pyrrolidine acetamide) earliest use in Down

syndrome was in Spain and Portugal in 1974 in a comparative study,

using historic case controls, of Dromia (a 5-hydroxytryptophan

containing product) and Noostan (a brand of Piracetam) in 26 children

from age 3 months to 12 years of age (Fialho, 1977).

Piracetam is a cyclic derivative of GABA (gamma amino butyric acid, a

neurotransmitter) and enhances cognition under conditions of hypoxia

(lack of oxygen), enhances memory and some kinds of learning in non-

disabled persons, mitigates oxidative stress, returns fluidity to

brain membranes that have undergone hardening from lipid peroxidation

and allows for increased communication between the hemispheres of the

brain. It is reported to be an intelligent booster and a CNS (central

nervous system) stimulant with no known toxicity or addictive

properties. Its effects and safety are so impressive that piracetam

prompted the creation of a new pharmaceutical category called

nootropics.

Piracetam is available by mail overseas or by prescription in the USA

from a compounding pharmacy.

Piracetam is not FDA approved for OTC (over the counter) sale and has

been granted an orphan status in the USA. As of June of 2006,

piracetam is not regulated in the United States (it is neither a

controlled substance nor a prescription drug).

The Piracetam NDC code for insurance purposes is 38779017725.

Piracetam and Seizures

Piracetam is an anticonvulsant. There are no know medical reports

supporting the link between Piracetam and seizures. Infantile spasms

are common in Down syndrome.

Piracetam and Coumadin

Piracetam can cause lack of adhesion of platelets which can affect

clotting.

When a patient is on Coumadin therapy due to valve replacement,

Coumadin levels will need to be adjusted if the patient is on

Piracetam.

Piracetam and Surgery

Piracetam should be doubled 72 hours prior to surgery and removed 48

hours before the surgery is scheduled because of its blood thinning

properties. Because Piracetam increases acetylcholine receptors, it

allows the brain to handle the effects of anesthesia and cholinergic

drugs better, like atropine and scopalamine, that are given as part

of pre-operation medications. Resume Piracetam as soon as patient is

home.

Piracetam and Flying

Piracetam has the capability of maintaining high oxygen levels in the

brain even under periods of low oxygen stress such as flying.

Pressurized planes have periods of low partial pressure of oxygen due

to altitude. In addition, aircrafts are typically only pressurized to

the equivalent of 8,000-9,000 feet altitude, i.e., there is less

oxygen for a child that has a heart condition impairing oxygenation.

Increase Piracetam dosage by 50% the day before and the day of

flying.

Piracetam and Phosphocholine

Choline is necessary because one of the major effects of Piracetam is

the stimulation of increased numbers of acetylcholine receptors.

Without choline this step is inefficient and choline should be given

in conjunction with Piracetam within 8 hour timespan. A dosage of 250

mg of phosphocholine for every 20 pounds of weight, up to 800 mg, in

conjunction with Piracetam, is recommended for persons not on

NuTriVene-D®. The dosage can be doubled for adults up to 1600 mg.

Phosphocholine, also known as Phosphatidyl Choline or Lecithin, is

available from most health food stores.

Piracetam and Glutamate

While glutaminergic receptors are increased in Down syndrome [Arai,

Mizuguchi, & Takashima, 1996. Excessive glutamate receptor 1

immunoreactivity in adult Down syndrome brains. Pediatric Neurology,

15, 203-6] there is no evidence that Piracetam stimulates

glutaminergic receptors to any great extent. Their main stimulus is

on acetylcholine receptors.

Withdrawing Piracetam

Do not stop any drug that has psychotropic effects abruptly: first

reduce the dose of Piracetam by half for 2 days, then drop a dose

each day, until it is eliminated.

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Source: http://www.altonweb.com/cs/downsyndrome/piracefa.html

1. Cognitive Enhancement Research Institute Revised: October 20,

2006.

2. Lawrence G. Leichtman, M.D. FAAP, FACMG. Genetics and Disabilities

Diagnostic Care Center

http://www.altonweb.com/cs/downsyndrome/index.htm?page=piracefa.html

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