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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 temoigneur on September 24, 2005, at 16:25:09
In reply to mifepristone stanford trial log day 3, posted by temoigneur on September 24, 2005, at 0:01:28
Mifepristone trail log day 4
This is the second day I've been receiving the placebo or mifep. Not too much to report - an increase in appetite and fatigue, also my thinking stills feels a little clearer, but this could well placebo as I was expecting that. Could the mifepristone be altering the action of some of the drugs, so that I could come off the dreaded mind numbing antipsychotics and 'dumbdrug clomipramine' ?
Posted by med_empowered on September 24, 2005, at 17:38:50
In reply to Re: mifepristone stanford trial log day 3 » temoigneur, posted by temoigneur on September 24, 2005, at 16:25:09
hey! THe other trials with mifepristone I read about used it in lieu of an antipsychotic for psychotic depression; apparently, the going theory now is that dopamine/serotonin dysregulation isn't a big part of psychotic depression, so alternative treatments will be useful...the results were apparently pretty impressive in that one (I think they used hospitalized psychiatric patients for that one). So...its entirely possible, assuming mifepristone does the trick for you, that you could ditch your current combo (btw--your combo seems kind of harsh. Have you asked your doc about maybe trying meds that are a little less hardcore?)
Posted by SLS on September 24, 2005, at 19:36:37
In reply to Re: mifepristone stanford trial log day 3, posted by temoigneur on September 24, 2005, at 16:19:11
> Scott, if I you let me babble mail you I could tell you more.. some inside info~~
I turned on my Babblemail. Let's see if this works.
- Scott
Posted by SLS on September 24, 2005, at 19:43:24
In reply to Re: mifepristone stanford trial log day 3 » temoigneur, posted by temoigneur on September 24, 2005, at 16:25:09
Hi.
> also my thinking stills feels a little clearer, but this could well placebo as I was expecting that.
One of the findings of a study performed in Britain demonstrated that mifepristone improved various aspects of cognition, including verbal fluency.
- Scott
Posted by EERRIICC on September 24, 2005, at 22:57:14
In reply to mifepristone stanford trial log day 3, posted by temoigneur on September 24, 2005, at 0:01:28
Are your cortisol levels high?
Could mef. work for depression that is not induced by high cortisol?
Best of luck in your trial; keep us posted!
Eric
Posted by med_empowered on September 25, 2005, at 16:34:44
In reply to Normal cortisol? » temoigneur, posted by EERRIICC on September 24, 2005, at 22:57:14
OK...so, hypothetically speaking...if super-high levels of cortisol are behind some forms of depression (Psychotic depression, possibly some cases of schizoaffective disorder), could you maybe treat these with high-dose Remeron? I mean..it does reduce cortisol. Maybe remeron+RU-486?
Posted by SLS on September 26, 2005, at 9:00:00
In reply to **CORTISOL**, posted by med_empowered on September 25, 2005, at 16:34:44
> OK...so, hypothetically speaking...if super-high levels of cortisol are behind some forms of depression (Psychotic depression, possibly some cases of schizoaffective disorder), could you maybe treat these with high-dose Remeron? I mean..it does reduce cortisol. Maybe remeron+RU-486?
The difference in cortisol production produced by Remeron is probably too subtle to be of any use in cases where the whole HPA axis is in overdrive. I think you need to shock the system to reregulate itself. Using either mifepristone or dexamethasone for brief, paroxsysmal, one-week courses of treatment probably acts to stress the system into changing gene expressions that control relevant receptor sensitivities, second messenger events, and secretory responses. In other words, a dysregulated HPA axis might need "shock therapy" to produce any meaningful changes.
Just guessing, of course.
- Scott
Posted by SLS on September 26, 2005, at 9:05:19
In reply to Re: **CORTISOL**, posted by SLS on September 26, 2005, at 9:00:00
> The difference in cortisol production produced by Remeron is probably too subtle to be of any use in cases where the whole HPA axis is in overdrive.
It will be interesting to see if the chronic application of a CRF antagonist will produce the kind of long-lasting changes in HPA axis function that we are looking for. Hopefully, there won't be a tendency towards "poop-out" as the system might try to recreate a dysfunctional homeostasis. Of course, CRF receptors are located in brain regions that are not involved in HPA axis regulation. Perhaps these sites will prove important in the treatment of depression.
- Scott
Posted by Sarah T. on September 26, 2005, at 20:21:39
In reply to Re: **CORTISOL**, posted by SLS on September 26, 2005, at 9:05:19
Hi Scott,
Do you know of any Mifepristone trials in the New York metropolitan area? If so, could you let me know about them?
Thanks.
Sarah
Posted by SLS on September 27, 2005, at 7:55:54
In reply to Re: **CORTISOL** » SLS, posted by Sarah T. on September 26, 2005, at 20:21:39
Hi Sarah.
> Do you know of any Mifepristone trials in the New York metropolitan area? If so, could you let me know about them?So far, I am not aware of any trials in the NY area. I live in New Jersey, and would gladly go into the city to participate in one. I think the NIMH in Maryland is still recruiting patients for bipolar depression. I would have considered it had they not required that I discontinue all my other medication. They will allow only for lithium and Depakote.
- Scott
Posted by Sarah T. on September 28, 2005, at 1:57:25
In reply to Re: **CORTISOL**, posted by SLS on September 27, 2005, at 7:55:54
Hi Scott,
Thanks very much for the information. I don't want to travel far for this, and I wouldn't qualify for the NIMH study.
I guess it is nearly impossible to try an investigational drug if you're not enrolled in a study.
I would hate to travel far to participate in a study, only to find out later that I had been given the placebo.
Have you ever looked into transcranial magnetic stimulation? Pfinstegg has posted quite a few messages about it over the past few years.
Sarah
Posted by SLS on September 28, 2005, at 2:20:11
In reply to Re: **CORTISOL** » SLS, posted by Sarah T. on September 28, 2005, at 1:57:25
Hi Sarah.
> Have you ever looked into transcranial magnetic stimulation? Pfinstegg has posted quite a few messages about it over the past few years.
Yes. rTMS is getting closer and closer to the top of my list through the process of attrition.
How about yourself?
- Scott
Posted by denise1966 on September 28, 2005, at 3:47:04
In reply to Re: **CORTISOL** » Sarah T., posted by SLS on September 28, 2005, at 2:20:11
Hi,
Are they just doing these studies on people with depression AND with high level of cortisol only. I was reading about the one they did here in England and it wasn't even restricted to people with high level of cortisol which seems a bit silly really.
If the theory is that high levels of cortisol contribute towards depression then you would have thought they would have included only people with high levels to either prove or disprove the theory.
Denise
Posted by Pfinstegg on September 28, 2005, at 20:56:41
In reply to Re: **CORTISOL** » Sarah T., posted by SLS on September 28, 2005, at 2:20:11
I am in the lucky 50 percent of people who respond really well to TMS. As to the cortisol aspect, my 24-hour totals are normal; however, they do not go down to low levels in the evening, as they should. I'm also a DST non-suppressor. I feel so much better for a few weeks after treatment that I'm assuming that my cortisol function is more normal: however, I haven't had it checked right after; I'm a bit afraid to, in case I find it hasn't made any change, but I will in the future.
I have been reading from Mark George, and also hearing from Mark Hutto, who treats me, that the type of depression is not the most important factor in who responds well to TMS. In particular, people with bipolar tend to respond well; Mark George has a study showing good remissions with patients with severe bipolar with one weekly TMS treatment, plus medications. These were patients who did not respond to medications alone. I have MDD, probably kind of atypical, and I respond extremely well to four TMS treatments every two months. In fact, I feel great after two treatments, but have two extra for "insurance", since I have to travel quite a long way to get them.
Next July, Neonetics will be ready with a new, improved TMS machine, which will be more precise in its delivery of the EM impulses, and also, according to Dr. Hutto, will not cause as much pain as the present one does. I think FDA acceptance is expected at about the same time.
Posted by Sarah T. on September 28, 2005, at 23:27:23
In reply to Re: **CORTISOL** » Sarah T., posted by SLS on September 28, 2005, at 2:20:11
> Hi Sarah.
> > Yes. rTMS is getting closer and closer to the top of my list through the process of attrition.>
> How about yourself?> > - ScottHi Scott,
Yes, I am seriously looking into rTMS now. I am also going to speak with my doctor AGAIN (!) about Mifepristone.My 24-hour urinary cortisol has risen steadily over many years, but the greatest increases occurred this year. My late night salivary cortisol was in the normal range, but I'm uncertain whether I did the test correctly. Each lab that offers that test seems to have a different set of instructions. Have you done the salivary cortisol test?
Sarah
Posted by ravenstorm on September 29, 2005, at 11:24:28
In reply to Re: **CORTISOL** TMS » SLS, posted by Sarah T. on September 28, 2005, at 23:27:23
I am interested in mifepristone as well. I have unusally high progesterone and severe depression/anxiety that is not responsive to anything since paxil withdrawal. A hormone researcher came into work the other day and she mentioned trying to reset my hormones with mifepristone, but I know of no doctor who will go along with this. I know I need to get my cortisol checked etc but I am so depressed etc I just don't have the gumption to keep getting tested etc.
I admire how you all keep going. I just stop going to the doctor/psychiatrist because I feel too hopeless and at this point there really isn't anything I can take anyway because my stomach is so bad.
Posted by Cecilia on September 30, 2005, at 4:40:56
In reply to Re: **CORTISOL** TMS, posted by ravenstorm on September 29, 2005, at 11:24:28
I`m still confused about cortisol. I always thought that stress, depression, anxiety etc. raise cortisol levels so in theory any successful treatment would lower them. It`s a chicken or the egg situation-even if your cortisol`s high, if you`re already depressed how would you know if elevated cortisol caused the depression or depression caused the elevated cortisol? Cecilia
Posted by temoigneur on September 30, 2005, at 23:50:18
In reply to Re: **CORTISOL** TMS, posted by ravenstorm on September 29, 2005, at 11:24:28
> I am interested in mifepristone as well. I have unusally high progesterone and severe depression/anxiety that is not responsive to anything since paxil withdrawal. A hormone researcher came into work the other day and she mentioned trying to reset my hormones with mifepristone, but I know of no doctor who will go along with this. I know I need to get my cortisol checked etc but I am so depressed etc I just don't have the gumption to keep getting tested etc.
>
> I admire how you all keep going. I just stop going to the doctor/psychiatrist because I feel too hopeless and at this point there really isn't anything I can take anyway because my stomach is so bad.Hi Sarah, I'm the one who just completed the eight day mifepristone trial. Although I'm on very heavy medications and haven't felt too much, the doctor said that many people find that after going on mifepristone for a short period, than switching medications they find that their medications work much better than they previously did. In my case, Prozac worked brilliantly then pooped out four montsh later, so I'm hoping to restore original efficacy, I just have to get off the numbing regimen of medications I'm on now. Hang in there the study Coordinator at Stanford, said that hopefully mifepristone would be approved in a year - maybe that's pie in the sky.... I'll post developments.
Posted by Sarah T. on October 1, 2005, at 0:13:42
In reply to Resensitizing system to SSRI's and mifepristone » ravenstorm, posted by temoigneur on September 30, 2005, at 23:50:18
Hi, Temoigneur!
What an interesting name you have! Thanks very much for your help. I look forward to reading updates from you.
Sarah
Posted by ravenstorm on October 1, 2005, at 9:34:57
In reply to Re: Resensitizing system to SSRI's and mifepristone » temoigneur, posted by Sarah T. on October 1, 2005, at 0:13:42
Are there any trials for this drug for hormones/anxiety/depression or does it have to be psychotic depression to get into a trial?
Posted by 4WD on October 2, 2005, at 0:13:21
In reply to Re: Cortisol, posted by Cecilia on September 30, 2005, at 4:40:56
> I`m still confused about cortisol. I always thought that stress, depression, anxiety etc. raise cortisol levels so in theory any successful treatment would lower them. It`s a chicken or the egg situation-even if your cortisol`s high, if you`re already depressed how would you know if elevated cortisol caused the depression or depression caused the elevated cortisol? Cecilia
Good question. My former pdoc said high cortisol could cause anxiety. The endocrinologist said anxiety caused the high cortisol.Marsha
Posted by denise1966 on October 5, 2005, at 8:53:46
In reply to Resensitizing system to SSRI's and mifepristone » ravenstorm, posted by temoigneur on September 30, 2005, at 23:50:18
Hi,
This sounds really promising, do they know why antidepressants would work after taking this drug.
Also, are they just including people with high cortisol levels in the trial? Are your baseline cortisol levels high or were they?
Thanks....Denise
Posted by sregan on October 5, 2006, at 16:33:30
In reply to Re: **CORTISOL**, posted by SLS on September 26, 2005, at 9:00:00
> Using either mifepristone or dexamethasone for brief, paroxsysmal, one-week courses of treatment probably acts to stress the system into changing gene expressions that control relevant receptor sensitivities, second messenger events, and secretory responses.
Scott,
When a neuro-receptor is blocked the effect is immediate. If you block NMDA then you feel less anxious. With the HPA negative feedback I get confused on what is doing what. A glucocorticoid receptor antagonist should INCREASE circulating glucorticoids because if the receptors are blocked then the monitoring mechanism thinks they are LOW and need to be increased? So it actually increases CRH->cortisol?
Shawn
Posted by SLS on October 5, 2006, at 18:21:34
In reply to Re: **CORTISOL** » SLS, posted by sregan on October 5, 2006, at 16:33:30
> > Using either mifepristone or dexamethasone for brief, paroxsysmal, one-week courses of treatment probably acts to stress the system into changing gene expressions that control relevant receptor sensitivities, second messenger events, and secretory responses.
>
> Scott,
>
> When a neuro-receptor is blocked the effect is immediate. If you block NMDA then you feel less anxious. With the HPA negative feedback I get confused on what is doing what. A glucocorticoid receptor antagonist should INCREASE circulating glucorticoids because if the receptors are blocked then the monitoring mechanism thinks they are LOW and need to be increased? So it actually increases CRH->cortisol?
Exactly. I would expect adrenal exhaustion as a possibility if treatment were continued for too long. I'm not sure, though.
- Scott
Posted by sregan on October 5, 2006, at 20:28:57
In reply to Re: **CORTISOL**, posted by SLS on October 5, 2006, at 18:21:34
>A glucocorticoid receptor antagonist should INCREASE circulating glucorticoids because if the receptors are blocked then the monitoring mechanism thinks they are LOW and need to be increased? So it actually increases CRH->cortisol?
>
>
> Exactly. I would expect adrenal exhaustion as a possibility if treatment were continued for too long. I'm not sure, though.
>
>
> - ScottI just read that the GC is an inhibitory receptor and in animal studies of chronic stress GCs become stimulatory rather than inhibitory on HPA axis.
In the normal model GC/MR stimilation from plasma glucortocoids causes an inhibitory effect on CRH. For HPA dysfunction in the chronic stress model antagonising the GC receptor makes sense as glucortocoids are causing a stimulatory effect perpetuating the cycle.
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