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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 5 to 29 of 29. Go back in thread:
Posted by qbsbrown on November 3, 2006, at 22:36:02
In reply to Re: My first one worked..., posted by notfred on November 3, 2006, at 22:31:13
I would venture to guess that they know how they work (trust me, with that much money) (eg serotonin reuptake), but are unallowed to say that due to liability etc political issues.
But i don't know why about the poop out.
Posted by notfred on November 3, 2006, at 23:07:08
In reply to Re: My first one worked..., posted by qbsbrown on November 3, 2006, at 22:36:02
> I would venture to guess that they know how they work (trust me, with that much money)
Have you read a monograph for any AD ?
CLINICAL PHARMACOLOGY
Pharmacodynamics: Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the re-uptake of serotonin. While the mechanism of action of bupropion, as with other antidepressants, is unknown, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms.
Posted by notfred on November 3, 2006, at 23:22:18
In reply to Re: My first one worked..., posted by qbsbrown on November 3, 2006, at 22:36:02
> I would venture to guess that they know how they work (trust me, with that much money)
Actually it is quite common that we do not fully understand how a lot of meds work. We only have theories on the biochemical causes and processes
of MI. Given the low success rate of RI's it does not seem that RI theory fits very well. Otherwise
AD's should be very effective.Here is Geodon monograph:
The mechanism of action of ziprasidone, as with other drugs having efficacy in schizophrenia, is
unknown.As with other drugs having efficacy in bipolar disorder, the mechanism of action of ziprasidone in bipolar disorder is unknown.
Posted by qbsbrown on November 3, 2006, at 23:35:32
In reply to Re: My first one worked..., posted by notfred on November 3, 2006, at 23:07:08
Yes, I've read them all, and i still think that they know what they think is going on. They're only allowed to speculate due to liability issues. That's a bunch of crap.
Posted by notfred on November 3, 2006, at 23:58:17
In reply to Re: My first one worked..., posted by qbsbrown on November 3, 2006, at 23:35:32
My first AD worked, too. Tofrinil (imipramine).
Horrid sweating though. The next one, Adapin (doxepin), worked as well and did not have this side effect.> Yes, I've read them all, and i still think that >they know what they think is going on. They're >only allowed to speculate due to liability issues. >That's a bunch of crap.
Well, they do know what the meds do, infact most of our theories of MI come from research into drugs that effect MI. However this has not given us the root cause of MI. Otherwise AD's and AP's
would have high success rates.If they knew what was the real cause of MI I would think they would come out with a treatment. That would be big $$, esp. after a few patent extenders. However they do not research the causes of MI, just new meds that do the same as the other RI's and dopamine effecting drugs.
Posted by ronaldo on November 4, 2006, at 4:19:08
In reply to How many ADs did you try before one worked???????, posted by qbsbrown on November 3, 2006, at 21:26:05
> I was curious as to what the average was. I think they have what, about a 20 percent chance of working, so would that be 1/5????
>
> I was lucky and had paxil working great for about 4 years. Now looking for my next one. On to Zoloft.
>
> BrianHi Everybody,
I tried 3 different AD's and none of them worked for me. They still left me depressed. They were, in chronological order: Amitryptiline; Trazadone; Prozac. I suspect I wasn't given the full therapeutic dose. Was my GP frightened of pushing me over the hypermanic tipping point? Just how long does one have to take an AD before one gets a result? Weeks or months?
I suspect that I was not depressed at all and that I was suffering from flat affect brought on by the 900 mg Lithium I take. I am bipolar though that dx is not definite, I might also be schizo-affective. Some pdocs say one, some say the other. I am pretty sure that I suffer the negative symptoms for schizophrenia, though none of the positive symptoms. I wish they could come to some consensus.
One thing for sure, whether it is flat affect or depression, it still leaves me pretty miserable.
Can anyone tell me what is a therapeutic dose on the above AD's? and how long one has to take them before one starts to feel better?Periodically I get so fed up that I decide to quit all my medications which leaves me ill and back to the drawing board except that I do not have the assistance from my pdoc that I need. In my case the s/e's often seem to outweigh the therapeutic effects.
....Alan
Posted by Phillipa on November 4, 2006, at 9:54:25
In reply to Re: How many ADs did you try before one worked???????, posted by ronaldo on November 4, 2006, at 4:19:08
Ronaldo same here I wish I'd had a positive experience with one but the benzos were the only positive one. Love Phillipa
Posted by blueberry on November 4, 2006, at 10:11:44
In reply to My first one worked..., posted by Racer on November 3, 2006, at 22:07:00
My first one was paxil and it worked starting at about 2 weeks and then progressively improved a little bit more continuously over about a 3 month period. I was on it for over a year and was safely free from depression the whole time.
It was not until after I got off it (to see how I would do) that I realized a lot of the "anti-depressant" effect was actually "anti-emotion" effect, or "flat" effect. Good emotions as well as the bad ones had all been kind of flattened down and tamed to neutral. It was admittedly a whole lot better than dealing with the severe major depression I had started with.
Since moving on to other meds, such as zoloft or prozac or st johns wort and others, I've discovered they all seem to work fairly well beginning at about 2 weeks, but they all have individual characteristics and personalities that make them different from each other.
Other psychiatric meds that are not ssris, such as benzos, wellbutrin, stimulants, antipsychotics, and mood stabilizers, all seemed to be helpful to me in one way or another but were helpful much faster than ssris, many being quite helpful beginning the very first day.
Posted by madeline on November 4, 2006, at 12:15:12
In reply to How many ADs did you try before one worked???????, posted by qbsbrown on November 3, 2006, at 21:26:05
My first one worked - Prozac.
I'm still on it and have been for many years. However, it can and does "poop out" which means my psychiatrist and I start jockeying with the dose for a couple of months, then back to the original dose.
I'm also on trazadone for sleep and that has some AD action as well.
Posted by linkadge on November 4, 2006, at 13:48:00
In reply to Re: My first one worked..., posted by qbsbrown on November 3, 2006, at 22:36:02
We do not know that they work via serotonin uptake inhibition.
The reason being that we have agents that are capable of inhibiting the uptake of serotonin with no antidepressant potential. We also have agents like tianeptine that are serotonin uptake acellerators which are just as effective as SSRI's.
Common denominators? All of the SSRI's enhance the action of the potent gabaergic neurosteroid alloprenanaolone. Certain SSRI's and tianeptine also have analgesic/opioid like activity.
So, in total I don't think we have a clue.
Linkadge
Posted by linkadge on November 4, 2006, at 13:56:06
In reply to Re: My first one worked..., posted by qbsbrown on November 3, 2006, at 23:35:32
If they knew what was going on, they would be able to create better agents.
Theres no evidence that serotonin uptake is altered in depression. Actually, no, thats not true. There has been some evidence that serotonin uptake is altered in depression, unfortunately it is altered in a way that does not fit with SSRI theory. Ie a few large studies of SERT genes revealed that medication free, depression prone had lower baseline uptake of serotonin.
The way they discover these agents is kind of a crap shoot. Potential molecule, shock a bunch of mice, and throw them in water. See if the agent reverses the behavior. If so..step two of process.
Do you think these mice are selected because they have abnormalities in their serotonin/norepinephrine? Of course not.
The fact that all of our current antidepressants work the same way is not evidence that this mechanism is target, it just means that scientists are only good enough to refine accidentally discovered drugs.
Linkadge
Posted by ed_uk on November 4, 2006, at 14:48:27
In reply to How many ADs did you try before one worked???????, posted by qbsbrown on November 3, 2006, at 21:26:05
>I was curious as to what the average was. I think they have what, about a 20 percent chance of working, so would that be 1/5????
My first AD worked eventually (for anxiety), but only after two dose increases and a long wait. 20mg Paxil to 30mg then 40mg.
Ed
Posted by madeline on November 4, 2006, at 16:55:35
In reply to Re: My first one worked..., posted by linkadge on November 4, 2006, at 13:56:06
Penicillin immediately comes to mind. Then coumadin, then too many come to mind to list.
About 10 years ago "rational drug design" was all the rage. It failed miserably.
Then massive screenings (still ongoing).
Basically, I think it is very safe to say that we know very little about what we are doing when it comes to drug discovery and development.
While there are a few instances where knowing the fundamental mechanism of disease progression has led to successful therapy (read gleevec), overall it's still a big crap shoot.
It's just like what billy joel said "some of the most creative things I have ever done have been my mistakes"
So, take it easy on us, we are doing the best we can.
Maddie
Posted by bassman on November 4, 2006, at 17:42:42
In reply to Hey man, don't knock accidental discovery » linkadge, posted by madeline on November 4, 2006, at 16:55:35
I couldn't agree more. Gleevec was the poster child for knowing what you are doing in drug design-but a real exception. Now the main method is to make literally 100's of thousands of compounds a DAY and screen them for activity (CombiChem). Never in the history of pharmaceutical science have so many useless drugs been synthesized. The odd thing is that "breakthroughs" are methods that make MORE useless compounds per day. Odd field. :>}
I have this feeling that one day it will be discovered that the neurotransmitter hypothesis is just plain wrong and that AD's do something else that sometimes reduces depression. Right now, you probably could get burned at the stake in medical circles by suggesting such heresy.
Posted by qbsbrown on November 4, 2006, at 17:47:25
In reply to Re: Hey man, don't knock accidental discovery, posted by bassman on November 4, 2006, at 17:42:42
So venture a guess of how many ADs people try before one:::
Posted by bassman on November 4, 2006, at 17:56:13
In reply to Re: Hey man, don't knock accidental discovery, posted by qbsbrown on November 4, 2006, at 17:47:25
I'll play. My guess is 3-5 for an AD that can be taken for several months.
Posted by linkadge on November 4, 2006, at 18:25:57
In reply to Hey man, don't knock accidental discovery » linkadge, posted by madeline on November 4, 2006, at 16:55:35
Hey, nothing wrong with accidental discovery.
Linkadge
Posted by linkadge on November 4, 2006, at 18:27:17
In reply to Re: Hey man, don't knock accidental discovery, posted by bassman on November 4, 2006, at 17:42:42
There is a phospholipid theory too, as some of the SSRI's affect phospholipid ballance.
Linkadge
Posted by linkadge on November 4, 2006, at 18:30:00
In reply to Re: Hey man, don't knock accidental discovery » qbsbrown, posted by bassman on November 4, 2006, at 17:56:13
The problem with the hypothesis is that it could discard countless functional antidepressants that have no effect on the monoamines.
Linkadge
Posted by linkadge on November 4, 2006, at 19:17:05
In reply to Re: Hey man, don't knock accidental discovery, posted by linkadge on November 4, 2006, at 18:30:00
The effect of TCA antidepressants on phospholipids. Pertaining to how they might affect depresison.
Linkadge
Posted by halcyondaze on November 4, 2006, at 22:29:07
In reply to Re: Hey man, don't knock accidental discovery, posted by linkadge on November 4, 2006, at 19:17:05
> The effect of TCA antidepressants on phospholipids. Pertaining to how they might affect depresison.
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16118470
>
> LinkadgeI was just about to say that, Linkadge. Second messenger systems as the reason that ADs work is currently being studied by Maurico Fava. There is also some speculation that brain-derived neurotrophic factor (BDNF) is involved and is partially why SSRIs have been shown to reverse neuronal death in the hippocampus, something that turned science on its head. It was only after this discovery that medical schools began grudgingly admitting that "maybe neuronal regeneration is possible in some populations, such as those with depression who are treated with antidepressants."
Posted by linkadge on November 5, 2006, at 8:50:36
In reply to Re: Hey man, don't knock accidental discovery, posted by halcyondaze on November 4, 2006, at 22:29:07
Thats true, infact Tianeptine (serotonin uptake acellerator) is vastly superior to SSRI's in its capacity to prevent stress induced hippocampal atrophy.
Linkadge
Posted by fca on November 5, 2006, at 11:19:14
In reply to Re: Hey man, don't knock accidental discovery, posted by linkadge on November 4, 2006, at 19:17:05
3-5 plus augmentation is the national average for the treatment of BP disorder before there is relatively stable symptom remission and control ( I think).
Posted by ronaldo on November 9, 2006, at 3:07:41
In reply to Re: How many ADs did you try before one worked???????, posted by ed_uk on November 4, 2006, at 14:48:27
> >I was curious as to what the average was. I think they have what, about a 20 percent chance of working, so would that be 1/5????
>
> My first AD worked eventually (for anxiety), but only after two dose increases and a long wait. 20mg Paxil to 30mg then 40mg.
>
> EdHi Ed,
How long is a long wait?
...Alan
Posted by ed_uk on November 9, 2006, at 13:57:10
In reply to Re: How many ADs did you try before one worked??????? » ed_uk, posted by ronaldo on November 9, 2006, at 3:07:41
It was several months Ronaldo, I don't remember exactly.
Ed
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