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Re: Multiple drug exposures and treatment resistence

Posted by bleauberry on April 24, 2010, at 18:10:06

In reply to Multiple drug exposures and treatment resistence, posted by SLS on April 24, 2010, at 11:53:56

Interesting article, but they don't really get to what really matters...WHY or HOW does it happen? What is happening?

This is probably a topic we have all wondered about over the years. Probably a lot of theories going around. Here are some of mine:

1. As the immune system can eventually recognize and reject a particular molecule, it learns how to do that with the medication molecule.

2. Gene instructions are changed upon first exposure to a drug. They do not revert back to their original baseline after discontinuation of the drug. They remain altered. Reintroduction of that drug would have no effect because the changes already previously happened.

3. In an attempt to maintain homeostasis, the body is very pliable and creative at figuring out how to do that. For example with me, when my adrenals were burned out, my lifelong borderline hyperthyroidism went to borderline hypothyroid in a short timeframe. Since the adrenals couldn't be turned up, the thyroid was instead turned down to match it, so as to be in balance. Low balance, but balance. The body did what it could to adapt to weak adrenals by turning down the volume on everything else.

When we increase serotonin, or whatever, by a mechanism which is not natural, the body does what it can to get that serotonin back down to where instructions say it should be. The genes don't know or care if we are depressed or not, they have instructions to follow. In the attempt, the enzymes that convert tryptophan to serotonin are changed. Serotonin production drops. It doesn't matter that we block reuptake or mao, because there just isn't much there to work with. The body already turned the volume on the neuros way down. Now we need a drug just to keep the levels up at genetic baseline, which happens to be too low and we stay depressed.

Possibly the receptors become sensitized to the artificially increased serotonin, and stay that way. No amount of serotonin will cause them to budge. They have sort-of developed resistance to serotonin, basically rejecting it, ignoring it, rather than receiving it.

4. Biochemical damage. We have no idea what damage the meds do to neurons, genes, dendrites, or receptors. Skeptics claim they are deformed and destroyed, and their numbers and densities are greatly diminished. While fans claim the meds are neuroprotective. I think this needs a lot more research.

5. The genes can be fooled once, but not every time. Perhaps on first exposure to a drug, the genes do change, and opposed to #2 above, the genes do revert back to baseline instructions after discontinuation. But, on followup exposure they now recognize the drug molecule as an imposter. The drug can increase serotonin all it wants to, but the genes this time are saying, "we're up to your tricks this time, and we are not doing all the downstream adaptation stuff you tricked us into last time around".

6. There is an underlying disease or insult, where serotonin (or whatever) is low as a result. Lyme, heavy metals, whatever, anything. Upon the first exposure to a drug, that deficiency is corrected. However, the disease is not corrected. It continues to progress. Later, as the drug is attempted again, the disease has progressed far enough that the drug is not potent enough to do what it did the first time. Or even if it is, there is now more widespread damage well beyond a simple deficiency.

I have a feeling that of all the theories I can muster up, I think the genetic ones are probably on target. I say that because there is at least one drug that seems to defy the phenomemon of not working a second, third, or fourth time around. That one is Tramadol.

People who respond well to it can stop, go through withdrawals, and restart it with complete effectiveness again. Over and over. They can take drug holidays, return to it, and it works again. If tolerance develops, they can take time off, return to it, and it works again. We all know we can't do that with lexapro, zoloft, or practically anything else. So somehow tramadol is able to work in harmony with genetics. I don't think this holds true 100% of the time, but for most longterm tramadol users they seem to point at that feature as being the thing that makes it stand out from all other antidepressants (though it isn't normally viewed as an antidepressant by clinicians). It happened to be horrible for me, but so many people say it is the best and only real antidepressant on the market.

For sure, none of the drugs I've ever taken work again and none feel at all like they did the first time I took them. I can dream up all the theories I want to, but I know I will never know the answers in my lifetime.

As I usually comment, I think it is important to look outside the box. When neurotransmitter manipulating drugs don't work, then manipulate something else....adrenals, thyroid, blood sugar, pathogen load, food choices, heavy metal load...anything and everything to take a load off the body. Somewhere within that realm lies something that is making the whole depression thing worse than anything else we usually talk about here. My opinion.


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poster:bleauberry thread:944856
URL: http://www.dr-bob.org/babble/20100416/msgs/944914.html