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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by FredPotter on March 19, 2007, at 19:00:29
It's generally agreed that SSRIs have their effect not by selective serotonin reuptake inhibition per se, but by increased serotonin causing increased BDNF and a general cascade leading to regeneration of neurons in critical brain areas (I don't think it's been observed to happen, it's just whistling in the dark). This process would take about 6 weeks which is why SSRIs and SNRIs take as long as they do (sic)
However I've recently stopped Effexor cold turkey and amidst all the other symptoms, I feel very depressed, agitated and drowsy.
So what happened? Less setotonin around, as well as norepinephrine, therefore less new BDNF, but wait! The regeneration of neurons has already occurred. They're not going to die off suddenly just because serotonin concentration has dropped.
Do neuroscientists know what they're on about? even roughly?
Fred
Posted by linkadge on March 19, 2007, at 19:47:30
In reply to Current theories must be wrong, posted by FredPotter on March 19, 2007, at 19:00:29
A lot of it is just speculation. Only a portion of studies show that antidepressants increase BDNF in any sustained way.
More recently some have shown that antidepressants increase neuronal turnover more than they do neurogenesis, ie they increase neuronal generation and elimination.
But you are right, what happens after the drug is withdrawn. If any increased signalling capacity was gained, the brain will probably not be able to utilize it. Well hopefully you won't remain like me. Ie. brain perma-f*cked, and unable to respond normally to any pleasurable stimulii.
Antidepressant withdrawl for me, was like experiencing the exact opposite to every positive benifit I gleaned, for about the same length of time as I was on them.
Linkadge
Posted by FredPotter on March 19, 2007, at 20:41:15
In reply to Re: Current theories must be wrong, posted by linkadge on March 19, 2007, at 19:47:30
Thanks Linkadge that makes a lot of sense. Another theory I read, was that you have to eat a lot of SSRI before, crossing the blood-brain- barrier very reluctantly, it accumulates enough to start doing its stuff as an effective reuptake inhibitor. Unfortunately I don't know if the passage across the B-B-B *is* slow.
This theory would however explain withdrawal symptoms, and why Effexor, the patron saint of withdrawal sympom producers, does this part of the process so well. It will function somewhat at lower levels, but if you stop completely, like me, then wath out! Added to this the Effexor (I took XR) breaks down and gets washed away very quickly, thus pointing up that this theory may be the right one. I think it has a half-life of about 7 hours, as against Prozac which is weeks (is it 5?). Prozac is therefore not noted for withdrawal effects (I don't know this I'm just guessing if this theory is true).
IF this is all true, then a better AD would be one that gets in there quick, but one which can be turned off with another drug so a second candidate can be used if the first one doesn't work. Then we could at least zoom through 'em all, like a wallpaper sampler, till we get one we like. Then there's the MAOIs. They also take up to 6 weeks to work. So is it the drug that is slow to cross the BBB and get to an effective dose, or is it serotonin, norepinephrine, dopamine etc that are slow to build up?
Another . . . is it a race between getting the stuff in, inhibiting reuptake of monoamines and outdoing those pesky receptors that down-regulate on the receiving neuron, because there appears to be a high concentration of neuroreceptors about. The brain, or at least, the relevant bits were happy all along it seems with us in a dangerously depressed/anxious state.
Just some thoughts. More like hot air I expect.
Fred
Posted by Quintal on March 19, 2007, at 20:54:30
In reply to Re: Current theories must be wrong » linkadge, posted by FredPotter on March 19, 2007, at 20:41:15
Probably Fred.
Q
Posted by Phillipa on March 19, 2007, at 21:55:31
In reply to Re: Current theories must be wrong » FredPotter, posted by Quintal on March 19, 2007, at 20:54:30
Fred the thinker. And a wonderful person in my eyes. Love Phillipa
Posted by Ken Blades on March 21, 2007, at 3:22:49
In reply to Current theories must be wrong, posted by FredPotter on March 19, 2007, at 19:00:29
I think neuroscientists just throw theories in the
air and see which one sticks to the wall...they'll know how these drugs work in about 200 years.Effexor withdrawal is something I wish I had never
experienced, and I wish I had never TAKEN Effexor
in the first place. It was the last AD I had been
on before I started Parnate about two years later.
Like Linkadge, I am convinced that Effexor left my
neurochemistry/neuroanatomy permanently altered,
which may be why Parnate has no AD effect for me.
It has a great antianxiety effect in my case and
has for all intents and purposes eliminated my
social anxiety.Maybe Effexor is 'THE' thing for a lot of people, but I shudder when I see another person starting it.
Ken
Posted by tessellated on March 21, 2007, at 19:30:21
In reply to Re: Current theories must be wrong » FredPotter, posted by Ken Blades on March 21, 2007, at 3:22:49
effexor is a phenethlyamine chemically related to ecstacy.
short half life and potent 5HT release.in my experience parnate is absolutely effective in a not dissimilar fasion to amphetamines. it has a potent life-affirming effect, though the withdrawl, in my research, and experience, is similar to amphetamine w/drawl due to its dopaminergic agonism; and the residual dopamine receptor regulation.
i've not tried effexor, but parnate withdrawl has caused me major problems and though it does not supress appetite; in my experience it alters (over weeks) dopaminergic transmission. if one is to administer over 80mg/24hrs, i would recommend caution not disimilar to amphetamine w/drawl.
the best and worst times in my life have been parnate related.
Posted by Deniseuk190466 on March 22, 2007, at 4:23:04
In reply to Current theories must be wrong, posted by FredPotter on March 19, 2007, at 19:00:29
Fred,
Not that I have a clue about chemistry or biology but your points are exactly my points on an older thread. I can't see how this theory can be true given the fact that some people respond to medication and then later on the medication seems to stop working.
Surely the new neurons have developed so why would the medication stop working???
Denise
Posted by FredPotter on March 22, 2007, at 17:35:22
In reply to To Fred, posted by Deniseuk190466 on March 22, 2007, at 4:23:04
Hi Denise in the UK. How is my old home? You're right. The new neural circuitry is in place but stops working. Often "they" then talk about receptors downregulating because neurotransmitter (fill in gap) is in plentiful supply.
Another explanation is that what we took as working was a placebo effect, Placebo effects tend fade. As this fading may not be an issue in a 6 week clinical trial, it might be the drug is better than we thought
Fred
Posted by deniseuk190466 on March 24, 2007, at 14:07:41
In reply to Re: To Denise » Deniseuk190466, posted by FredPotter on March 22, 2007, at 17:35:22
Hi Fred,
Well your old home country is looking pretty bleak and grey (well at least to me right now).
I definately don't think that when I took ADs and they worked (infact I know) it wasn't a placebo affect. The effects were far too profound.
I do think though, based on my experience, that when they do really work then you can take them and come off them and feel pretty much ok. It's when they don't work properly that you get the problems coming off them. I had five great years on prothiaden, came off it when it seemed to stop working, and didn't feel as bad as I expected to, the same thing with Seroxat, I had three good medication free years. However, when my depression hit again and the drugs I tried didn't work as effectively, it was hell coming off them. I feel depressed on medication but off it I feel suicidal so I'm caught between a rock and a hard place.
Denise
This is the end of the thread.
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