Do any of you Scientific types know anything (studies or facts) about why medications lose their effectiveness over time?

I'll check back from time to time

Thanks in advance!

dopamine recepters get less sensitive to dopamine cause there is more then usual
med breaks could prevent tolerance or reverse it

hey swedes well the brains a remakeable thing it atapess very quikely its its streghth an weaknesss the way life is today ........><....deps on whiotch part the brain the dopamines is working on sertoinesing has seemly effcts on works an fads an when you caut dwon angain it works better like A T P AN DIEECET HORRMONS thats cos water lose there go up an dwon an drugs that used to control sometimes dont work as well cos building up a tollencset to it .....when more is done to make persic drungs to the persons dna then tolerance will be less or maybe eraccataked dorm

This is also a topic of great interest to me. I wonder about Shire's claims about Adderall or Adderall XR not losing effectiveness over time (tolerance) when I experience this myself quite dramatically. What percentage of people taking it can maintain a constant dose, and what is the best way to deal with the tolerance effect? Does alternating with Ritalin work?

Thanks in advance for any good info on this, as I see discussion of sensitization and gene expression and NMDA and you-name-it tossed around, without any good summary.

dopamine recepters get less sensitive to dopamine cause there is more then usual
med breaks could prevent tolerance or reverse it
That makes sense. After all the drugs are just controlling the symptoms so it's an ongoing battle to maintain that fragile balance

Well, even the top experts in the field say that it is a mystery why SSRI's and other psycoactive drugs work in the first place. Brain chemistry is such a mystery. This would explain the almost constant tweeking that goes on with drug treatment.

drugs that used to control sometimes dont work as well cos building up a tollencset to it .....when more is done to make persic drungs to the persons dna then tolerance will be less or maybe eraccataked dorm
Thanks Dorm, so it's the same idea as all the talk about misuse or overuse of antibiotics here in America.

Below are the listings for the two articles I found that actually discussed tolerance and efficacy. I only have access to the abstracts, which I will post if people want. They're very heavy in pharmaceutical and chemical language so I only understood a bit of what I was reading, maybe other's here can make more sense of them. Most of the other articles that were long term noted that there was no loss of efficacy after 5 years, medically speaking. Not sure if that helps but here you go.

Evidence for tolerance following repeated dosing in rats with ciproxifan, but not with A-304121.Life sciences. (Life Sci) 2006 Aug 29; 79(14): 1366-79

New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder.Expert opinion on drug delivery. (Expert Opin Drug Deliv) 2005 Jan; 2(1): 121-43

Below are the listings for the two articles I found that actually discussed tolerance and efficacy. I only have access to the abstracts, which I will post if people want.
Please post the abstracts. Thanks!

Thanks Proscrire
I'm going to use the abstracts and hunt down the articles at the library

There are threads that say quite strongly that "tolerance" is the wrong word, and that there's no "tolerance" effect for these meds. See, for example:
http://www.addforums.com/forums/showpost.php?p=345748&postcount=4
http://www.addforums.com/forums/showpost.php?p=345773&postcount=7

Also, one poster said at http://www.addforums.com/forums/showthread.php?p=180473#post180473 : "Tolerance and sensitization appear to be related to the interval between doses. Therefore, . . . skipping a day or two over the weekend could worsen tolerance."

I've also seen evidence that repeated doses of amphetamine actually increase the response to the drug (ie primes the PKc receptors that induce reverse dopamine uptake). The reason why addicts continuously increase the dosage is dopamine receptor downregulation (ie the body gets used to the higher levels of dopamine).

I'd imagine that this is less likely to happen with ADHD because the brain can always adapt and release more dopamine to compensate (and receptors can upregulate as well). The reason why releasing more dopamine doesn't work without meds is excess reuptake, but as long as you've got meds inhibiting or reversing uptake, the brain ought to be able to even things out without serious tolerance effects.

On the other hand, it is very possible for the body to begin to excrete these drugs faster, as well as adapting to the peripheral effects like increased heart rate or body temperature. The thing is, I've been taking the same dose of around the clock Adderall XR since February without any serious tolerance effects, and the actual dose in my body at any given time (15mg, since they're 30mg XRs) is not much greater than the 10mg doses I started taking 2 years ago. The main reason for increasing the dosage from 10 to 15 also was not tolerance but rather that it was found to be more effective.

The thing is, a tolerance effect should be much greater than that. Tolerance in addicts is such that my dosing schedule should have turned into several grams a day after two years.

Part of it may be due to the fact that these doses are designed to try to get the brain functioning normally, in equilibrium. Substance abuse involves making the brain function abnormally, resulting in a number of natural responses to try to return to equilibrium, such as neuroreceptor downregulation or reductions in vesicular stores or reductions in endogenous neurotransmission. These responses often evoke a need to consume more to receive the same effect.

If the right dose creates a more normalized response, there is often little need to continuously increase the dosage. There is often a decision to increase the dosage occasionally to counter increased excretion, or sometimes a decision to increase the dosage to receive increased effects if the patient has adapted to the peripheral effects or side effects to allow for a higher dose.

I've been on low-dose Adderall for about 2 years now. It seems to me that as the side effects have continued to diminish, the positive effects stay the same.

it be good in the next few years when they tail make drugs to the person biogol we wont have such porblems or will we only time will tell ive been on bett blokers an i have found that if you lower the dose by even 10mg the said effcts are really bad an this is said to be an noe additvce drug so i woulders what the drugs that some take for add adhd have on brian over the longteam? dorm