Psycho-Babble Medication Thread 354178

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Amphetamines: sensitisation or tolerance or both?

Posted by Keith Talent on June 5, 2004, at 23:51:00

I've read some PubMed abstracts of studies from the New York State Psychiatric Institute that found that tolerance developed only to the euphoriant effects, whilst sensitisation developed to all the other effects (psychomotor activation, jitteriness, ability to concentrate, cardiovascular effects etc.).

Posts to Psycho-Babble seem to me to lean in favour of tolerance development over sensitisation, necessitating dose increases and/or drug holidays. Does anyone know if there is a single RIGHT answer to this question?

I ask because I am currently taking 40 mg per day (total) of dextroamphetamine (was first prescribed it two months ago). It has never been an adequate dose, so tolerance hasn't arisen as an issue, but if my psychiatrist raises the dose to, say 120 mg per day, which direction will things move in:

- tolerance developing such that I will ask for further dose increases
- sensitisation, leading me to complain about side effects getting worse, and asking for the dose to be reduced

?

There are some studies that found that tolerance develops, while others say that sensitisation develops.

My diagnoses are:

- Major Depressive Disorder
- Obsessive Compulsive Disorder
- Social Phobia

Current medications are:

- clonazepam 2 mg twice per day
- dextroamphetamine 20 mg in the morning, 10 mg six hours later and 10 mg six hours later still
- irbesartan 300 mg each morning
- sertraline 100 mg each morning

Any answers, advice, tips or pointers to research would be very much appreciated.

 

Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent

Posted by psychosage on June 6, 2004, at 1:08:27

In reply to Amphetamines: sensitisation or tolerance or both?, posted by Keith Talent on June 5, 2004, at 23:51:00

I really don't have an answer, but I don't doubt tolerance. I would assume sensitization would occur with long-term dosing or excessive dosing.

My question is why are you prescribed dextroamphetamine?

Hope you find an answer.

 

Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent

Posted by psychosage on June 6, 2004, at 2:39:27

In reply to Amphetamines: sensitisation or tolerance or both?, posted by Keith Talent on June 5, 2004, at 23:51:00

> I've read some PubMed abstracts of studies from the New York State Psychiatric Institute that found that tolerance developed only to the euphoriant effects, whilst sensitisation developed to all the other effects (psychomotor activation, jitteriness, ability to concentrate, cardiovascular effects etc.).
>
> Posts to Psycho-Babble seem to me to lean in favour of tolerance development over sensitisation, necessitating dose increases and/or drug holidays. Does anyone know if there is a single RIGHT answer to this question?
>
> I ask because I am currently taking 40 mg per day (total) of dextroamphetamine (was first prescribed it two months ago). It has never been an adequate dose, so tolerance hasn't arisen as an issue, but if my psychiatrist raises the dose to, say 120 mg per day, which direction will things move in:
>
> - tolerance developing such that I will ask for further dose increases
> - sensitisation, leading me to complain about side effects getting worse, and asking for the dose to be reduced
>
> ?
>
> There are some studies that found that tolerance develops, while others say that sensitisation develops.
>
> My diagnoses are:
>
> - Major Depressive Disorder
> - Obsessive Compulsive Disorder
> - Social Phobia
>
> Current medications are:
>
> - clonazepam 2 mg twice per day
> - dextroamphetamine 20 mg in the morning, 10 mg six hours later and 10 mg six hours later still
> - irbesartan 300 mg each morning
> - sertraline 100 mg each morning
>
> Any answers, advice, tips or pointers to research would be very much appreciated.
>

You may have come across this, but this is a very detailed report about stimulant adverse effects.

I am not sure how it is regarded, but at least it is fully comprehensive about every possible downfall of stimulant use.

http://www.breggin.com/Newstimulants.pdf

 

Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent

Posted by jodeye on June 6, 2004, at 22:36:45

In reply to Amphetamines: sensitisation or tolerance or both?, posted by Keith Talent on June 5, 2004, at 23:51:00

> I've read some PubMed abstracts of studies from the New York State Psychiatric Institute that found that tolerance developed only to the euphoriant effects, whilst sensitisation developed to all the other effects (psychomotor activation, jitteriness, ability to concentrate, cardiovascular effects etc.).
>
Do you have the links to these abstracts? I do not know how to search PubMed for studies by a particular institute. I am very interested in reading them.

I have read preclinical data stating that memantine can prevent stimulant sensitization. I have also read AndrewB's testimonials of memantine or acamprosate preventing stimulant tolerance. It almost seems as if AndrewB's prevention of stimulant tolerance could have also been a prevention of stimulant sensititization, allowing him to take higher doses. Oh well... I'm done rambling.

--Jay

 

Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent

Posted by don_bristol on June 7, 2004, at 7:19:19

In reply to Amphetamines: sensitisation or tolerance or both?, posted by Keith Talent on June 5, 2004, at 23:51:00

> I've read some PubMed abstracts of studies from the New York State Psychiatric Institute that found that tolerance developed only to the euphoriant effects, whilst sensitisation developed to all the other effects (psychomotor activation, jitteriness, ability to concentrate, cardiovascular effects etc.).
>


Do you have any links to those Pubmed reports?

Thank you.

 

Re: Amphetamines

Posted by Keith Talent on June 7, 2004, at 14:24:05

In reply to Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent, posted by psychosage on June 6, 2004, at 1:08:27

> My question is why are you prescribed dextroamphetamine?

It helps with:
- the anergic component of the Major Depressive Disorder, especially as I have the atypical variety
- Social Phobia (has a prosocial effect)

 

Re: Amphetamines:

Posted by Keith Talent on June 7, 2004, at 14:33:58

In reply to Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent, posted by psychosage on June 6, 2004, at 2:39:27

> You may have come across this, but this is a very detailed
> report about stimulant adverse effects:

> http://www.breggin.com/Newstimulants.pdf

Thanks for the reference, psychosage. While it mainly focusses on children, it is certainly chilling to consider the range of toxicities that these agents can cause. If I had any children, I would certainly only consider stimulant therapy as a last resort, for any indication.

I'm curious as to the funding source of the study, as some epidemiological studies have found that funding source was one of the key determinants of (drug evaluation) study outcome. You can probably imagine that Uncle Sam and the HMOs would want these drugs to be painted in as bad a light as possible, while drug companies and psychiatrists would tend to lean in the other direction.

This is a fascinating area of research, where the complexities of biological systems come into clear focus.

 

Re: Amphetamines:

Posted by Keith Talent on June 7, 2004, at 14:38:31

In reply to Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent, posted by jodeye on June 6, 2004, at 22:36:45

> Do you have the links to these abstracts? I do not know how to search PubMed for studies by a particular institute. I am very interested in reading them.

I don't know how to give you direct links, but here is how I found the material:

Go to:

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?CMD=Display&DB=pubmed

Basically, I used the MeSH Database search under PubMed Services (on the left column). If you don't know how to use this, just cut and paste from below:

Search PubMed for ("Dextroamphetamine/administration and dosage"[MeSH] OR "Dextroamphetamine/pharmacology"[MeSH] OR "Dextroamphetamine/therapeutic use"[MeSH]) AND "Drug Tolerance"[MeSH]

Limits: only items with abstracts, Human

Sort by: Pub Date
Show: 50

Display Abstract

-> should give 22 articles

Use your browser to find new york state psychiatric institute -> article 2 (PMID: 11441429)

There are plenty of other interesting articles as well, and you can play around with the Limits settings to see animal studies or limit it to only randomised controlled trials, for example.

> I have read preclinical data stating that memantine can prevent stimulant sensitization. I have also read AndrewB's testimonials of memantine or acamprosate preventing stimulant tolerance. It almost seems as if AndrewB's prevention of stimulant tolerance could have also been a prevention of stimulant sensititization, allowing him to take higher doses. Oh well... I'm done rambling.

I'd heard memantine talked about to preventing and/or reversing stimulant tolerance, but not acamprosate. The latter is used to reduce ethanol cravings, right?

Happy reading Jay,

Keith

 

See reply to jodeye (nm)

Posted by Keith Talent on June 7, 2004, at 14:39:43

In reply to Re: Amphetamines: sensitisation or tolerance or both? » Keith Talent, posted by don_bristol on June 7, 2004, at 7:19:19

 

Re: direct links

Posted by Dr. Bob on June 7, 2004, at 22:40:26

In reply to Re: Amphetamines:, posted by Keith Talent on June 7, 2004, at 14:38:31

> I don't know how to give you direct links

See:

http://www.ncbi.nlm.nih.gov/entrez/query/static/linking.html#Retrieve

Bob

 

Talent + Dr. Bob = The Missing Link!

Posted by jodeye on June 8, 2004, at 11:38:09

In reply to Re: direct links, posted by Dr. Bob on June 7, 2004, at 22:40:26

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=11441429&dopt=abstract

I also saw an example for creating a Search link, although I could not find how to include your limits into the URL (abstracts, human).

Now on to the abstracts...

--Jay

 

Re: Talent + Dr. Bob = The Missing Link! » jodeye

Posted by Keith Talent on June 9, 2004, at 8:10:28

In reply to Talent + Dr. Bob = The Missing Link!, posted by jodeye on June 8, 2004, at 11:38:09

I'm glad that I could be of some assistance.


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