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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by denise1904 on November 23, 2004, at 10:23:58
Hi,
Can somebody offer some possible opinions. About 8 years ago I was taking 20mg of Seroxat (Paxil) daily and getting a really robust response. I decided to give it a try without antidepressants and about 4 years ago started feeling unwell again. I tried going back on Seroxat along with many other antidepressants and I felt just as bad if not worse.
Anyway two years ago the psychiatrist decided to put me back on Seroxat only this time at a higher dose and they are working but not half as well, I feel tired alot of the time but am extremely grateful I'm not as bad as I was.
I just don't understand why they don't work like they used to anymore, as it wasn't even as though I had developed a tolerance to them before I came off them. I actually came off them partly so as not to develope a tolerance to them.
I've had my thyroid and T3 levels checked (their ok), I've tried rTMS hoping this would make the Seroxat work like it used to, I don't drink any more than I used to (which is very little), nothing majorly bad has happened to me this time round, so I just don't get it.
I'm trying to think about this logically, and all I can think is that it could be one of the following reasons, Can somebody let me know what they think?
1) I've got less serotgenic neurons than I used to have, so am not making as much.
2) Tryptophan or whatever makes Serotonin is not crossing my blood brain barrior as well as it used to.
3) There is a problem with my serotonin transporter sites.
4) I've now got too many Serotonin post synaptic receptors.
Any other ideas?
I realise that I'm probably over-simplifying things and I know it's just not that simple (how I wish it was).
Can somebody advise please on what the other possibilities could be?Thanks.......Denise
Posted by linkadge on November 23, 2004, at 11:18:32
In reply to I just don't get it! Need advise please, posted by denise1904 on November 23, 2004, at 10:23:58
Take 1mg of folic acid with your seroxat if you are not already. Low folic acid levels can severely inhibit the AD responce of a medication.
There are several studies that showed that prozac nonresponders responded when folic acid was added.
Linkadge
Posted by King Vultan on November 23, 2004, at 12:37:39
In reply to I just don't get it! Need advise please, posted by denise1904 on November 23, 2004, at 10:23:58
> Hi,
>
> Can somebody offer some possible opinions. About 8 years ago I was taking 20mg of Seroxat (Paxil) daily and getting a really robust response. I decided to give it a try without antidepressants and about 4 years ago started feeling unwell again. I tried going back on Seroxat along with many other antidepressants and I felt just as bad if not worse.
>
> Anyway two years ago the psychiatrist decided to put me back on Seroxat only this time at a higher dose and they are working but not half as well, I feel tired alot of the time but am extremely grateful I'm not as bad as I was.
>
> I just don't understand why they don't work like they used to anymore, as it wasn't even as though I had developed a tolerance to them before I came off them. I actually came off them partly so as not to develope a tolerance to them.
>
> I've had my thyroid and T3 levels checked (their ok), I've tried rTMS hoping this would make the Seroxat work like it used to, I don't drink any more than I used to (which is very little), nothing majorly bad has happened to me this time round, so I just don't get it.
>
> I'm trying to think about this logically, and all I can think is that it could be one of the following reasons, Can somebody let me know what they think?
>
> 1) I've got less serotgenic neurons than I used to have, so am not making as much.
>
> 2) Tryptophan or whatever makes Serotonin is not crossing my blood brain barrior as well as it used to.
>
> 3) There is a problem with my serotonin transporter sites.
>
> 4) I've now got too many Serotonin post synaptic receptors.
>
> Any other ideas?
>
> I realise that I'm probably over-simplifying things and I know it's just not that simple (how I wish it was).
>
>
> Can somebody advise please on what the other possibilities could be?
>
>
>
> Thanks.......Denise
>
>
It could just as easily be some kind of issue with norepinephrine or dopamine. These two systems are important components of one's overall mood and are not well served by SSRIs. There is a school of thought that people tend to have better long term success using a drug that works on both serotonin and norepinephrine. I suppose that would be my belief also.Todd
Posted by smokeymadison on November 23, 2004, at 12:45:10
In reply to Re: I just don't get it! Need advise please, posted by King Vultan on November 23, 2004, at 12:37:39
i have been warned time and time again not to off antidepressants that are working b/c sometimes after being off of them for a while they don't work when trying to go back on them. i suggest that you try another SSRI or wellbutrin, which i find very helpful because it does not cause weight gain or sexual side effects. good luck!
Posted by linkadge on November 23, 2004, at 13:54:52
In reply to Re: I just don't get it! Need advise please, posted by smokeymadison on November 23, 2004, at 12:45:10
Sometimes after going back on an AD we expect to have the same sucess right away.
For instance I was on celexa, and it took me about 6 months to start feeling like myself again. (While I did have some relief in a few weeks).
Anyhow after stoping and restarting it, I expected to feel like myself right away. Unfortunately it took another 6 months for me to really feel *better*.
Also what Vultan said is true. Oftentimes a second mood disorder can have separate chemical imballences than the first, ie it responds to separate meds.
Linkadge
Posted by denise1904 on November 24, 2004, at 5:13:06
In reply to Re: I just don't get it! Need advise please, posted by linkadge on November 23, 2004, at 13:54:52
Hi,
Thanks to all of you for your responses, I just wish all of this wastn't so theoretical, I wish there was some sort of obvious proof.
Denise.
Posted by SLS on November 24, 2004, at 19:08:05
In reply to Re: I just don't get it! Need advise please, posted by denise1904 on November 24, 2004, at 5:13:06
> Hi,
>
> Thanks to all of you for your responses, I just wish all of this wastn't so theoretical, I wish there was some sort of obvious proof.
>
>
> Denise.
Have you ever tried adding lithium 300-600mg?
- Scott
Posted by denise1904 on November 26, 2004, at 3:24:23
In reply to Re: I just don't get it! Need advise please, posted by SLS on November 24, 2004, at 19:08:05
Hi Scott,
Yes, I've tried Lithium as an add on to Prozac, dothiapin and paxil, with paxil I went up to 600mg but to no avail.
Strange because I was expecting Lithium to be a really strong drug but I didn't feel as though I was taking anything. I've tried reducing my dose of paxil for a week down to 20mg but am starting to feel not so good, I'm managing to do my work but am withdrawing from people and social contact as much as I can. I'll probably end up going back up to 40mg tonight, it's not worth putting myself through.
How are you anyway, what have you been up to and what have you been trying, anything other than Cymbalta? Are you still going to try and get on RU486?
Also, I read somewhere and I can't find the site now that they are experimenting with new methods of ECT, have you heard anything about this? I'd have ECT without a shadow of a doubt if I thought it would work but the fact that rTMS didn't doestn't bode well.
Denise
Posted by denise1904 on November 26, 2004, at 6:39:53
In reply to Re: I just don't get it! Need advise please, posted by denise1904 on November 26, 2004, at 3:24:23
Scott,
Just to another thing to add to my previous thread. Why is adding lithium as an augmentor supposed to help, what's the theory behind this?
Thanks....Denise
Posted by SLS on November 26, 2004, at 8:32:37
In reply to Re: Scott ,another thing to add., posted by denise1904 on November 26, 2004, at 6:39:53
Hi Denise.
It's too bad that lithium didn't do the trick. It would have been a nice, simple fix. Lithium actually makes me feel significantly worse. If it hadn't, I would like to have remained on it, even if only to act to preserve hippocampal and cerebral tissue. As far as to why lithium acts to augment antidepressants, the simple explanation invariably involves a pro-serotonergic mechanism. That it acts so quickly, usually within 3-7 days, might argue against an effect on second messenger events. Many investigators speculate that lithium promotes an increase in the levels of extracellular serotonin. I wonder if it might act directly upon the G-protein coupled receptors, changing their sensitivity. Lithium does so many things, though, it is difficult to isolate its mechanism of action for augmentation.
I decided to discontinue Cymbalta two days ago. I had taken it for at least 12 weeks. I received a significant improvement during the second and third weeks, but nothing thereafter. Unfortunately, this is exactly the same pattern of response to antidepressants that I have experienced since beginning this odyssey 22 years ago.
RU-486 (mifepristone) might be the very next thing I try. I have to bug my doctor to do the paperwork necessary to get it. In the meantime, I will have allowed enough of a washout period from Cymbalta that I could start a MAOI. I have not decided which one I will go with yet. Probably Parnate.
I guess the logical question to ask you - and I apologize if you have already answered it - have you yet tried a tricyclic or MAOI? What are your primary symptoms?
- Scott
----------------------------------------------------------------------
Effect of subchronic lithium treatment on citalopram-induced increases in extracellular concentrations of serotonin in the medial prefrontal cortex.Muraki I, Inoue T, Hashimoto S, Izumi T, Ito K, Koyama T.
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. [email protected]
We investigated the effect of citalopram [a selective serotonin (5-HT) reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist), following treatment with subchronic lithium (p.o., 1 week) on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). Acute treatment with citalopram (3 and 30 mg/kg) led to significant increases in extracellular 5-HT concentrations. The subchronic lithium group showed significantly higher basal levels of extracellular 5-HT than normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment together with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Acute MKC-242 (1 mg/kg) treatment showed significant decreases in extracellular 5-HT concentrations, in both the normal diet and lithium diet groups to the same extent. The addition of lithium did not change the effect of the 5-HT1A agonist on extracellular 5-HT concentrations. This study suggests that lithium augmentation of the antidepressant effect of SSRI is mediated by the additional increases in extracellular 5-HT concentrations following the co-administrations of lithium and SSRI.
PMID: 11208912 [PubMed - indexed for MEDLINE]
Posted by denise1904 on November 26, 2004, at 9:07:51
In reply to Re: Scott ,another thing to add. » denise1904, posted by SLS on November 26, 2004, at 8:32:37
Hi Scott,
Yes have tried tryciclics already, actually prothiaden (I think you know it as dothiapen) was the first antidepressant I ever took when I was about 24 and it worked wonders at 75mgs.
However, when I tried it again about 3 years ago up to 300mg it didn't do anything apart from give me a seizure, it was either a seizure or I passed out not sure which but I ended up coming too at work with Paramedics around me.
This is what makes me think something has gone wrong futher down the line, all the drugs that used to work so effectively and quickly for me just don't seem to work as well anymore and there must be a reason somewhere for that.
Are you going to try Parnate again, didn't you once have a really good response on that?
Thanks for the explanation on Lithium although I do so much searching on these things and end up feeling more confused, they seem to be exploring so many different avenues and I just wonder if they're red herrings. I've read about them identifying 15 different regions on chromosones involved in depression and then somewhere else where they say they've identified 5 genes linked to it. Then you hear about possible roles of CRF, Nicotine receptors, BDNF, peptides, then I read a study where they found that People who had sever clinical depression when they died had significantly lower levels of FGFs (whatever they are).
You know when I was at school I never really took much interest in chemistry or any other subject for that matter and now I seem to spend half my time reading and trying to grasp these articles. I'm just about starting to understand the basics thanks to many people on this board, you included.
Did you go up to the highest dose on Cymbalta? sorry I seem to go on about myself for ages and then suddenly remember to ask you about yourself and what you're doing. It's called being self obsessed I suppose, although I'm not really.
Denise
Posted by linkadge on November 28, 2004, at 1:06:00
In reply to Re: Scott ,another thing to add., posted by denise1904 on November 26, 2004, at 9:07:51
Lithium is a 5-ht autoreceptor antagonist. Ie it blocks the serotonin thermostat so to speak, allowing more to be released. In this method it rapidly increases serotonin content. Pindolol is also a 5-ht autoreceptor antagonist, but has not gained the same recognition as an augmentation agent, perhaps because it does not share other properties of lithium.
Lithium alone increases BDNF, NGF,serotonin, decreases cortisol, and glutamate. It is also trophic to the grey matter and hippocampus.
Drawbacks, lithium can be a downer. It saps your brain of mood brightening inositol. Perhaps lithium + inositol would be a better augmentation agent.
I don't really love lithium myself, but its my only attempt to salvage my brain. I'm trying to do a lithium and exercise only routine.
Denise: I would add folic acid (1mg) to your paxil. I know it sounds simple, but folic acid turned my celexa from a nonresponce to a responce for over a year. Inositol can also increase the responsivness of gaba and serotonin receptors.
At one point I was able to down my celexa from 30mg to 10mg by taking 2g of inositol daily. Wherease other attempts to decrease celexa were in vain.
Another thing that really helped me was to eat loads of turkey and drink milk, tryptohpan loaded foods.
Also omega 3 plumps up the serotonin receptors. The serotonin receptors need omega 3 to work more flawlessly.
I would take your paxil +Folic Acid, Inositol, Omega 3, and high tryptophan diet. I think this would *really*
boost the effectivness of your paxil.P.S. I'm in a bit of a positive mood cause I did a total nights sleep deprivation. This works for me when nothing else works.
Linakdge
Posted by SLS on November 28, 2004, at 7:12:38
In reply to Re: Scott ,another thing to add., posted by linkadge on November 28, 2004, at 1:06:00
Thanks for such a concise and informative post.
:-)
- Scott
Posted by denise1904 on December 1, 2004, at 12:12:06
In reply to Re: Scott ,another thing to add., posted by linkadge on November 28, 2004, at 1:06:00
Hi Linkadge,
Thanks for the advice, I've started taking Fish Oil EPS and DHA at 2grams a day and I've just started taking Folic Acid too but I must admit don't really hold out much hope for the Folic Acid, I'm sceptical about any kind of supplements as I think you should really get what you need in your meals if you eat sensibly which I do.
How long did it take for the Folic Acid to make a difference with you and how did you know it was making a difference? I know when something is really working because things start to look different visually (less flat) and my sense of smell and hearing seem to become more acute.
Denise
Posted by denise1904 on December 1, 2004, at 16:07:03
In reply to To Linkadge, posted by denise1904 on December 1, 2004, at 12:12:06
Linkadge,
Hope your still feeling positive and didn't go back down after a good nights sleep.
I wanted to ask you something else as well as what I've asked you in the previous note.
I was reading about autoreceptors the other day and I assumed that they were completely different from pre-synaptic and post-synaptic receptors but from what you've just said they are not they are the same. Can you clarify for me and I'm sorry for the incessant questions. You think your brain is damaged :-)
Denise
This is the end of the thread.
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