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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by Denise190466 on May 27, 2007, at 15:09:29
Now and then (lots) I look up studies on the internet for depression and to see if they are any closer to making breakthroughs in finding out what actually causes it.
The problem I have is a) my concentration is not great at the best of times and b) I have no idea about chemistry and find some of the language hard to absorb.
I also get confused by what seems to me like conflicting findings. For instance one study says that P11 proteing helps depression in rats by increasing localisation of 5HT1B receptors at the cell surface and then another study says that drugs like prozac exert their affects by decreasing 5HT2B receptors?????
Then I read another study which says that most of the beneficial affects of antidepressants comes from their action on the 5HT6 receptor.
Then they talk about BDNF and then nicotine receptors.
I know there is more than one way of skinning a cat I just wish it was a bit more straight forward.
So I get really confused and also it doesn't seem very encouraging when they can't seem to come to an agreement about how antidepressants actually work. Afterall if they are no closer to finding out how antidepressants work then how can they understand why they don't work? Or am I just being stupid and wanting things to be dead simple.I just feel like once you hit a resistant stage it feels like taking a car to the garage, not knowing what's wrong with it but trying to sort out the problem in a totally random way. putting more oil into it just because there is a lack of oil when the problem relates to the engine itself.
Are they any closer than they were five years ago to understanding the mechanics of depression and what causes it (biologically) than they were five years ago?
I do often feel discouraged and don't want to carry on but then I think well you never know maybe they will have found a cure in five years, so it's worth hanging on for another five years but then when I search the internet I feel more discouraged than ever.
Denise
Posted by Racer on May 27, 2007, at 15:22:58
In reply to I'm confused., posted by Denise190466 on May 27, 2007, at 15:09:29
>
>
> I also get confused by what seems to me like conflicting findings. For instance one study says that P11 proteing helps depression in rats by increasing localisation of 5HT1B receptors at the cell surface and then another study says that drugs like prozac exert their affects by decreasing 5HT2B receptors?????Those aren't conflicting results -- all the different serotonin receptor types do different things, so upping one sort, while downing others might lead to similar results.
>
> Then I read another study which says that most of the beneficial affects of antidepressants comes from their action on the 5HT6 receptor.And then there are the studies suggesting that SSRIs do their magic by upregulating dopamine receptors...
The bottom line, really, is that no one knows, but a lot of people are working on figuring it out. Don't feel discouraged -- unless you want to ;-) -- because you don't understand it all. There's a lot of information out there, and a lot of the studies haven't yet been replicated. My guess is that, eventually, it'll turn out that there are a constellation of biochemical disorders with similar symptoms, all of which are currently lumped together under the name "Depression." That would explain a lot about why people react so differently to antidepressants.
As for what it all means to us, one answer is: nothing. More drugs are coming out, slowly, and there are a lot of existing drugs out there, and we can try them all without knowing anything about the underlying actions or pathologies. The other answer, of course, is that knowing more may help increase our confidence in our doctors, or help us feel better about our response/lack of response to medications.
Really, though, here's what I would say to you: if reading these studies does not help you feel better, or if you find yourself feeling worse after reading them, don't read them. That's a behavioral option open to you for improving your mood. If, on the other hand, you find that you feel better, or more energized by reading them, then by all means -- read away!
Practically speaking, it might help for you to take a basic biopsych class, or even just do a bit of research on what is currently known about the actions of the various serotonin receptors. That way, you might be better able to put those studies in context.
Good luck.
Posted by Phillipa on May 27, 2007, at 19:06:54
In reply to Re: I'm confused. » Denise190466, posted by Racer on May 27, 2007, at 15:22:58
I'm with you makes no sense. Love Phillipa
Posted by linkadge on May 27, 2007, at 19:30:04
In reply to I'm confused., posted by Denise190466 on May 27, 2007, at 15:09:29
>I also get confused by what seems to me like >conflicting findings. For instance one study >says that P11 proteing helps depression in rats >by increasing localisation of 5HT1B receptors at >the cell surface and then another study says >that drugs like prozac exert their affects by >decreasing 5HT2B receptors?????
Well, the 5-ht1b and 5-ht2b receptors are totally different receptor subtypes. So this may not be a contradictory finding.
>Then I read another study which says that most >of the beneficial affects of antidepressants >comes from their action on the 5HT6 receptor.Bottom line, they don't know. One person studies the effects of these drugs on one set of receptors, and another studies another set.
>Then they talk about BDNF and then nicotine >receptors.
>I know there is more than one way of skinning a >cat I just wish it was a bit more straight >forward.The brain is probably one of the most complex things that mankind has ever studied.
>So I get really confused and also it doesn't >seem very encouraging when they can't seem to >come to an agreement about how antidepressants >actually work.Of course its discouraging. Especially when more than half of all clinical trials fail to show that antidepressants are better than placebo.
Even after all this time there is still debate as to how and why they work, or even *if* they work.
>Afterall if they are no closer to finding out >how antidepressants work then how can they >understand why they don't work? Or am I just >being stupid and wanting things to be dead >simple.It would be nice if somebody made a real breakthrough that was capable of producing meaningful clinical improvement to patients. I don't really trust the system at this current time though. Its not about health it is about $.
>Are they any closer than they were five years >ago to understanding the mechanics of depression >and what causes it (biologically) than they were >five years ago?I would personally say no, or at least not much.
In the past 5 years we have learned that antidepressants may make people more suicidal, that their efficacy has been way overblown and their side effects have been disguised.
One might even argue that psychiatry is weaker now than what it was 5 years ago. I mean sales for antidperessants are down since then.
>I do often feel discouraged and don't want to >carry on but then I think well you never know >maybe they will have found a cure in five years, >so it's worth hanging on for another five years >but then when I search the internet I feel more >discouraged than ever.
Hey I agree with you. It would be nice to believe there is going to be a breakthrough. I guess the same thing goes for any dabilitating disease.Linkadge
Posted by linkadge on May 27, 2007, at 19:31:17
In reply to Re: I'm confused. » Denise190466, posted by Racer on May 27, 2007, at 15:22:58
>And then there are the studies suggesting that >SSRIs do their magic
Magic ??
Linkadge
Posted by deniseuk190466 on May 28, 2007, at 12:10:15
In reply to Re: I'm confused. » Denise190466, posted by Racer on May 27, 2007, at 15:22:58
Racer,
Sorry I misquoted before. I meant to say that
then another study says that drugs like prozac exert their affects by decreasing 5HT1B receptors not 5HT2B receptors. So there are two studies one suggesting that depression is caused by decrease in 5HT1B receptors and another saying by an increase in 5HT1B receptors.Yes I guess you are right I should do some sort of basic course, if only I had the inclination.
I sort of scour the internet out of a feeling of desperation, in some ways it helps relieve the frustration and makes me feel like I'm being proactive and fighting the apathy to some degree.
Denise
Posted by deniseuk190466 on May 28, 2007, at 12:14:43
In reply to Re: I'm confused., posted by linkadge on May 27, 2007, at 19:30:04
Linkadge,
I misquoted that first paragraph should have said
>I also get confused by what seems to me like >conflicting findings. For instance one study >says that P11 proteing helps depression in rats >by increasing localisation of 5HT1B receptors at >the cell surface and then another study says >that drugs like prozac exert their affects by >decreasing 5HT1B receptors
not 5HT2B receptors.
And you are right I guess most people with deabilitating illnesses search for possible breakthroughs.
I wish they knew (I sound like a child sometimes) how the same drugs that worked so well for me years ago could make me feel so suicidal this time round. I know my depression is worse this time around I just hadn't counted on such a paradoxical reaction to antidepressants.
Anyway, here is hoping they get closer to the answers soon, like tomorrow :-)
Denise
Posted by linkadge on May 28, 2007, at 14:05:36
In reply to Re: I'm confused., posted by deniseuk190466 on May 28, 2007, at 12:10:15
This still may not be a contradiction. There are postsynaptic and presynaptic receptors for 5-ht1b.
The presenyaptic receptors are autoreceptors. By downregulating the presynaptic 5-ht1b autoreceptors, you diminish the inihibition on serotonin release, and thus promote more serotonin release.
The postsynaptic 5-ht1b receptors are controlled by p11, and activation of these receptors may be responsable for AD effect. So p11 increasing the expression of these receptors might be benificial.
So it may have been that one study was referring to the downregulation of 5-ht1b autoreceptors, wherase the other was referring to the increase in post-synaptic 5-ht1b receptors.
Linkadge
Posted by Racer on May 28, 2007, at 14:49:07
In reply to To Linkadge, posted by deniseuk190466 on May 28, 2007, at 12:14:43
>
>
> I wish they knew (I sound like a child sometimes) how the same drugs that worked so well for me years ago could make me feel so suicidal this time round. I know my depression is worse this time around I just hadn't counted on such a paradoxical reaction to antidepressants.
>I'm sorry you're struggling so much, Denise. I wonder, though, if you had any thoughts about what I wrote above, vis a vis life changes or aging having something to do with the variation in your response this time around? I realize it's easier sometimes to look for a biochemical explanation, but if there's something involved which isn't biochemical, you might have more control over it...
Good luck.
Posted by linkadge on May 28, 2007, at 19:30:56
In reply to Re: To Linkadge » deniseuk190466, posted by Racer on May 28, 2007, at 14:49:07
If I recall, you once said you had a really good response to the TCA dothepin? When is the last time you have tried a TCA? You dothapin or doxapin. Amitryptaline too might be similar.
The TCA's can be good drugs for some, and there is evidence that they can be better AD's for many.
Clomipramine, for example, is a TCA, but it is often assumed to be a SSRI. Clomipramine was much better than any SSRI I tried. SSRI's didn't even come close to clomipramine.
Linkadge
Posted by Cecilia on May 29, 2007, at 6:38:54
In reply to I'm confused., posted by Denise190466 on May 27, 2007, at 15:09:29
No one has a clue how any of these drugs work (for the lucky ones they do work for). The SSRI"s and tianeptine have exactly opposite modes of action, but approximately the same percentage of responders. Cecilia
Posted by Sigismund on May 29, 2007, at 20:23:44
In reply to Re: I'm confused., posted by Cecilia on May 29, 2007, at 6:38:54
What's more, Cecilia, both drugs seem to have very roughly similar, rather than opposite, effects.
Maybe?
Posted by deniseuk190466 on May 30, 2007, at 9:19:20
In reply to Re: I'm confused. » deniseuk190466, posted by linkadge on May 28, 2007, at 14:05:36
Thanks Linkadge,
This makes sense now. What do you mean by increasing the expression of these receptors though, making them more reactive??
Denise
Posted by deniseuk190466 on May 30, 2007, at 13:16:06
In reply to Re: To Linkadge » deniseuk190466, posted by Racer on May 28, 2007, at 14:49:07
Hi Racer,
Thanks but I really can't think of any dramatic life changes which may have expected my response this time round. In fact from the outset things were better than they had ever been before.
My weight is the same, I don't have any thyroid issues. I haven't had any children, I hadn't divorced, I hadn't lost anyone close to me so it just doesn't make any sense.
The only thing is that years ago when my depression first started (at 17) I was convinced I had health problems, never associated it with depression and I pursued that line of thinking. I went to the doctors searching for an answer and nothing. I wasn't suicidal then just scared that I was going to die. Then I finally just accepted the way I felt and sort of got on with it. Then at 24 when I seemed to get worse and the doctor prescribed this pill (prothiaden) and I took it, I felt like somebody had truly unlocked the door to my prison and I was finally free, it worked so well. I had the answer and I always thought it would be the answer if I ever got depressed but not so. When I finally came off antidepressants its strange but I never felt as bad as I had done before going on them.
This time round it hasn't been so easy and I'm no longer scared of dying but more scared of carrying on living like this and not knowing why I feel the way I do.
The only thing I can think is that depression gets worse and more severe the older you get. It's progressive, it must be.
Anyway, thanks for asking.
Denise
Posted by deniseuk190466 on May 30, 2007, at 13:18:08
In reply to Re: Try a TCA again? » Racer, posted by linkadge on May 28, 2007, at 19:30:56
Linkadge,
I'm not sure if your post was to me or Racer but you are right I did once have a really good response to prothiaden (tricyclic) but when I tried it this time round at about 4 times the amount it didn't work so I've tried that one.
Thanks anyway.
Denise
Posted by linkadge on May 30, 2007, at 19:11:50
In reply to Thanks Linkadge, posted by deniseuk190466 on May 30, 2007, at 9:19:20
>This makes sense now. What do you mean by >increasing the expression of these receptors >though, making them more reactive??
Basically. More reactive / more of them.
Linkadge
Posted by linkadge on May 30, 2007, at 19:14:30
In reply to Re: Try a TCA again? Linkadge, posted by deniseuk190466 on May 30, 2007, at 13:18:08
Have you considered the possability that you may be "over" dosing ?
Occasionally, lower doses can work better. Somtimes if the dose gets too high you can feel more rotten for different reasons alltogether.
Linkadge
Posted by deniseuk190466 on June 1, 2007, at 14:52:21
In reply to Re: Try a TCA again? Linkadge » deniseuk190466, posted by linkadge on May 30, 2007, at 19:14:30
Thanks Linkadge but I've definately found that I feel worse on lower doses. God I sound like such a junkie.
But thanks anyway.
Denise
Posted by elanor roosevelt on June 5, 2007, at 0:08:39
In reply to Re: Try a TCA again? Linkadge, posted by deniseuk190466 on June 1, 2007, at 14:52:21
so, will you try a new TCA?
please keep posting
next TCAs are under consideration
Posted by deniseuk190466 on June 7, 2007, at 10:29:07
In reply to TCA s?, posted by elanor roosevelt on June 5, 2007, at 0:08:39
Hi,
I might do, although only in addition to an SSRI.
Like I said though, I've already tried maximum dose prothiaden (I think called Doxepin) and it didn't work this time round.
Denise
This is the end of the thread.
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