Posted by Questionmark on January 19, 2004, at 11:04:11
In reply to A question/concern about 5-HT reuptake inhibition, posted by Ame Sans Vie on January 9, 2004, at 10:05:23
> First I want to make it very clear that unless I find out that SSRIs invariably cause cancer, stroke, or brain aneurysm, I'm sticking with my Prozac, lol. With that said, there's something that's been bugging me a little bit since early this morning. Obviously there is a reason for the reabsorbtion of neurotransmitters into their originating neurotransmitter after attempting to cross the synapse. I have to wonder then, is it possible that drugs which inhibit the reuptake of serotonin (or dopamine, norepinephrine, whatever) are creating undue stress on our brains which are trying to protect themselves from overload through this reabsorbtion process? I mean, are we forcing more of a certain neurochemical to cross our synapses than our brains can (healthily) handle? This question particularly applies to those who are helped significantly by reuptake inhibiting drugs, of course, as their response to these classes of medications are possibly indicative of a deeper problem than they directly address... i.e. their neurons aren't equipped to handle "normal" (perhaps "adequate" would be a better word) neurotransmission, and so it seems logical that a defense mechanism in the brain would set off, resulting in an increased amount of 5-HT/DA/NE to be "returned to sender" and reabsorbed. If this is in fact the case, I really have to wonder if forcing these chemicals across the synapse is really such a bright idea.
>
> Of course, this is all just conjecture. And I understand that, were any pharmaceutical company to develop a different style of antidepressant, MAOIs excepted, that Paxil, Anafranil, Strattera, Wellbutrin, etc would all be just bad memories for many of us. In other words, I realize that these types of drugs are used for depression today simply because there isn't much else to turn to, and at some point during my lifetime I expect to see the mental illness riddle finally solved completely. But since many of us have to take these drugs in the meantime, I can't help but wonder... are we creating undue stress in our nervous systems?Ame (/Mike[?]), you brought up a really good question. It's one i wonder about a great deal at different at different points-- esp. when i got off Paxil and felt like absolute s**t for months on end.
i have a partial answer to your question, i believe (if you hadn't thought of this before at least). In regard to why we have any reuptake process at all (which is not exactly what you asked, but a sort of indirect variation maybe), i'm sure it's as a safeguard. I.e., if we did not, and then we had a high release of a certain neurotransmitter-- whether from some emotional response or an exogenous substance or what have you-- then the continued presence of that neurotransmitter in the synapse could produce toxic reactions in the postsynaptic neuron. Plus there would then be insufficient amounts of that transmitter in the PREsynaptic terminal, which would then eventually result in an under-supply of that neurochemical in the synapse.
(i hope that at least somewhat helped in answering your question, and wasn't just obvious information. Sorry if the latter).
As far as whether or not antidepressants (and other psychoactive meds) are somehow detrimental or something-- since they disrupt the naturally occurring processes of the brain-- i don't know. But i really wonder. However, i think the fact that no one fully knows the answer to this question shows that the psychiatric industry is far more naive and liberal in prescribing potent psychotropic drugs that it should be. i know so many people on some SSRI it's not even funny. There are so many people drugged up these days-- many of whom don't even have any specific psychiatric diagnosis, or if they do, just some mild case of Seasonal Affective Disorder or PMDD or irritability or dissatisfaction with life or what have you. i'm not saying these meds aren't needed or worthwhile sometimes-- oftentimes even, maybe-- but i do think they are overprescribed and we need to be much more careful and judicious with them. And don't even get me started on the outrageous number of children who are (forced, no less, to be) on potent psychostimulants, and pretty d*mn high doses no less, in this country.
ANYway!... (sorry, the caffeine is 'causing' me to ramble this morning). i think maybe the sustained overstimulation of certain receptors that antidepressants create does cause excessive [chemical] stress to certain neurons/brain areas. The fact that we feel "good" or better as a result of these drugs does not negate this possibility any more than the use of a euphoriant drug temporarily results in feeling "good" or better as well-- even if this drug could cause some amount of brain damage and/or causes physiological dependence (e.g., cocaine, morphine, alcohol, barbiturates, MDMA, amphetamines, benzodiazepines, etc.). The main difference, as far as i can tell, is that with the last example (of using euphoriant drugs occasionally and w/ temporary duration) one is just getting "messed up" occasionally or, say, with the shorter acting drugs, even once a day. So during the time that s/he is not using the respective drug, s/he can notice how s/he feels without it in his/her system-- and can feel the withdrawal or come-down or what have you. However, with the typically prescribed psychiatric medication schedule-- esp. with SSRIs or benzos (since they usually have effects that last all day)-- one is getting the effects every day and oftentimes *all* day. So any come-down ("rebound") effect is more effectively bypassed and dependence (via noticing withdrawal) is goes unnoticed indefinitely until the person tries to finally go off the drug.
Also, maybe there is a good reason for why, in certain people, neurotransmitter reuptake and/or enzyme metabolization at the "normal" (drug-free) activity/levels for that particular person occurs when s/he has a "psychiatric disorder" or whatever-- and needs to have reuptake inhibition, enzyme inhibition, or neurotransmitter agonism or sometimes antagonism in order for him/her to feel well. (Sorry for the run-on!) Maybe it is because through genetics and, to some degree, the habituated behavior and responses to various environmental stimuli, a person's brain (or certain neural pathways) gets adjusted to acting in a specific manner, and then its "normal" activity (neurochemically) gets refined to being ABnormal (psychologically/behaviorally). Thus, without some extensive, sufficient behavioral and cognitive therapy (and/or changes and/or exercises), or without some adequate pharmacological intervention, this person will likely stay "disordered" or "abnormal" indefinitely. For (a simplified) example, say a child-- say even one who is neurogenetically healthy-- is raised in a home in which one or both the parents are extremely concerned and strict with being clean and germ-free. This child's brain could then quite easily develop in a manner that would eventually result in OCD-type thoughts and behavior being his/her normal state. (This kind of change in neurobiological normalcy would not, i would assume, have to take place in childhood either. It's just more extreme, fast, and easy in childhood.)
Anyhow, those are my two many cents. Sorry for the length and the unneeded conjecture. Can't help it. But let me know what yous think.Oh, also, in response to Mattd:
he/you said, "This is what has always perplexed me. If the net serotonergic transmission returns to equilibrium after a sufficient amount of exposure to say, fluoxetine, how is it even working? Why doesn't it just poop out for everybody? It doesn't, though.
This is not to say it *isn't* working, it's just always puzzled me, and up to this point I haven't seen a convincing explanation."
Thats a really good question too. i'm convinced, though, that the net neurotransmitter (whichever is directly involved) transmission does not completely return to equilibrium. Be it the receptors or intracellular processes, i believe something must still be occurring different than normal. Or, maybe as someone else said, there have simply been changes in other neurotransmitter systems.
OK thats all!!
poster:Questionmark
thread:298512
URL: http://www.dr-bob.org/babble/20040118/msgs/302725.html