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Dr. Bob is Robert Hsiung, MD,
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Posted by Pfinstegg on October 20, 2002, at 0:41:06
In reply to Pfinstegg going on about cortisol again g » Pfinstegg, posted by Seamus2 on October 19, 2002, at 21:56:52
I have read three reports which unfortunately suggest that the longer you live, the more likely it is that you'll get a dysregulated HPA axis, depending, of course, on your own genetic susceptibility, the amount of stress you have encountered, and the resources you call upon to deal with it. Also, people get dysregulated in varying degrees, some to a minor extent, and it is always potentially reversible, because the hippocampus is designed to repair itself throughout life. In its extreme form, it's still not a common or usual event, and more people than not in their 80's and 90's have still got it all together, cortisol-wise.
Just speculating- I think that in the future preventive treatments after highly traumatic events, including childhood trauma, will probably be so much better that long-term breakdown in the HPA axis will become much less common. This could make incredible changes for the better in treating all the mood disorders.
But for those of us coping with it now- at least it's human rather than rat years!
Madame C
Posted by Pfinstegg on October 20, 2002, at 1:00:10
In reply to Re: Pfinstegg going on about cortisol again g, posted by Pfinstegg on October 20, 2002, at 0:41:06
for the helpful information about Remeron and trimipramine, and the Medline links. I'm going to try to go into relaxation mode now, because the new sniper shooting here in Washington has probably gotten that cortisol up even higher than usual! I really do appreciate the information, and plan to follow up.
Pfinstegg
1
Posted by NikkiT2 on October 20, 2002, at 15:50:50
In reply to Re: Remeron and cortisol, posted by Pfinstegg on October 19, 2002, at 18:15:13
Thanks for that.. I might push for the other test.. but I'm in the UK and they don't like doing tests willy nilly here!!!
I've read a fair amount on it, and do exibit all the symptoms.. buffolo hump, stretch marks, very thick torsoe, terrible weight gain (though have lost 14lbs this month, but am doing 800 cals a day and 8g fat) etc
From what I've read, I'm quite convinced I have a cortisol problem!!! But I oculd just be a hypochondriac!!
Nikki
Posted by linkadge on October 20, 2002, at 19:12:40
In reply to Re: Remeron and cortisol » Pfinstegg, posted by NikkiT2 on October 20, 2002, at 15:50:50
Do people with pure cushings syndrome
have mental problems as well ?Linkadge
Posted by Seamus2 on October 20, 2002, at 20:10:36
In reply to Re: Pfinstegg going on about cortisol again g, posted by Pfinstegg on October 20, 2002, at 0:41:06
I was under the impression the HPA disregulation occured as a result of trauma only during childhood, and wondered at what age the same trauma would have no effect.
Instead of picking your brain, maybe it's time I did a little research on my own.
Regards,
Seamus
Posted by Pfinstegg on October 20, 2002, at 23:30:34
In reply to Re: Pfinstegg going on about cortisol again g, posted by Seamus2 on October 20, 2002, at 20:10:36
From what I have read, depression and anxiety are hallmarks of "real" Cushing's disease as well as the "pseudo" form.
That's such an interesting question about when the stress has to occur to dysregulate the HPA axis most readily. I don't know, but I'm assuming that the most vulnerable time is surely infancy and childhood. In one of the studies from Germany, baby tree shrews were separated from their mothers for three hours each day, and within several weeks had elevated cortisol and abnormally small hippocampuses. What is so interesting about tianeptine is that when the baby shrews were given it daily and separated in the same way, the cortisol and hippocampuses remained normal- it stress-proofed them!
I saw one article about Holocaust survivors- how much trouble they have with chronic depression: the article included reports that their cortisol tends to be permanently elevated. I get the impression that HPA dysregulation doesn't happen all at once, but is set in motion by trauma, and then in some people takes on a life of its own, with the brain slowly becoming less and less able to down-regulate the cortisol. But then there are lots of other people who undergo the same kinds of trauma. which may or may not be followed by depression, and recover permanently, with or without treatment. In Europe, particularly, they are studying how social support may play a crucial role in enabling people to get back to normal. It makes one think about how important Psychobabble may be to us all.
I'm doing a Medline search now to try to find out more about which AD's affect cortisol favorably. There is more information than I had thought, and it seems that all classes of AD's can have that effect when they are successful- the tricyclics, SSRI's and even the mood stabilizers.
I'm pleased that there are others here who are interested in this besides me..
Pfinstegg
Posted by SLS on October 21, 2002, at 1:18:12
In reply to Pfinstegg going on even more- Linkadge and Seamus, posted by Pfinstegg on October 20, 2002, at 23:30:34
Dear Pfinstegg,
For what it's worth - I agree with almost everything you have written. Cortisol is a MF. Reregulation of the HPA-axis during the course of an affective episode might be resistant to direct pharmacological targeting.
Ketoconazole?
Regarding antidepressants: That you specified "when they work" is most insightful and crucial. There are such smart people here (myself excluded). By comparison, lithium and Depakote reverse hippocampal shrinkage independent of therapeutic activity, albeit via mechanisms independant of cortisol. It involves a decrease in the production of neurotoxins and an increase in the production of neuroprotectants and neurotrophins.
------------------------------------------Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression
Tom Bschor, M.D.1, Mazda Adli, M.D.2, Christopher Baethge, M.D.2, Uta Eichmann2, Marcus Ising, Ph.D.3, Manfred Uhr, M.D.3, Sieglinde Modell, M.D.3, Heike Künzel, M.D.3, Bruno Müller-Oerlinghausen, M.D.2, Michael Bauer, Ph.D., M.D.4
1 Department of Psychiatry, Technische Universität Dresden, Dresden, Germany
2 Department of Psychiatry, Freie Universität Berlin, Berlin, Germany
3 Max-Planck Institute of Psychiatry, Munich, Germany
4 Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles (UCLA), Los Angeles, California, USA
"Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a DHDRS of ³ 50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared to the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium."------------------------------------------
I am almost convinced that my severe depression is very much due to an overproduction of cortisol in childhood and adolescence as a result of protracted psychosocial stress. I am also convinced that the severity of my condition - particularly cognitive deterioration (dementia) - is due to period lasting about a year of mammoth stress and trauma at age 20 when my fiancé dumped me and my life fell apart.My hippocampus must look like decaying almond, and my prefrontal cortex a ring of dehydrated tripe.
I have no doubt that cortisol and HPA dysregulation are fundamental to the induction, and possibly the perpetuation, of affective illness.
Sincerely,
Scott
Posted by Pfinstegg on October 21, 2002, at 14:16:31
In reply to Re: Pfinstegg going on even more- Linkadge and Seamus » Pfinstegg, posted by SLS on October 21, 2002, at 1:18:12
Oh, I know what you mean- I feel like I've got such a shrunken hippocampus and left prefrontal, too, and for the same reasons as you. Even though I am seeing an endocrinologist and he is exploring with me and my psychiatrist how he can lower the cortisol and,hopefully, get me so I suppress on the DST test, I decided that I did NOT want to know what my MRI or PET scan looked like. I was afraid it might take away my hope and will to keep fighting if it was very abnormal; I'm counting on my brain to help me out of this, and I need to keep up my confidence in it! So I refused those tests.
After that bit of cowardice, I am moving towards deciding on a treatment. Our two best choices seem to be ketanozodole and mefipristine. Although I am older, my physical health is so far excellent, so I have time to decide carefully, However, I am aware that cortisol levels as high as mine will lead eventually to various illnesses, such as hypertension, Syndrome "X" ( diabetes precursor) and all sorts of sequelae from decreased immune resistance.
I appreciated the report about lithium and its special method of action. Thank you, you smart person!
Pfinstegg
Posted by linkadge on October 21, 2002, at 18:51:54
In reply to Re: Pfinstegg going on even more- Linkadge and Seamus, posted by Pfinstegg on October 21, 2002, at 14:16:31
It seems to me that levels of cortisol have
a mood sustaining effect untill they have
dropped off.What I mean is that my depression was always
most pronounced after stressful situations
subsided. From Monday To Friday I would feel
like crap, but it seemed the cortisol kept
me going. On Friday night I would always drop
right off a cliff. When the stressor situations
subsided, then the really evil thoughts would
set in. Those were the times I really felt depressed. Mon-Fri I was irritable and edgy, angry and unhappy but not sadness depressed.
I would never cry during the school year, but as soon as exams were over I would cry for the next
month.The two things I noticed when I was treated, was improvement in resiliance and recovery time.
If I got little sleep the night before I could still function - it didn't feel like the end of the world. And after exams it would only feel like a couple of days before I could say I was happy again.Omega 3 has also seemed to make my mood more
even. I take 4gs per day, and have also noticed
improvement in the physical symptoms of depression. Achs and pains, irritablility. Sickness and the rest.When untreated I felt so responsive to the enviroment, like everything just penetrated
into my soul. A screeching car tire would
freek me out. Taking a bad step would send
a surge of adreneline into me. I now feel
as if there is an invisible barrier about me.
If something comes in, It has to pass my
contious thought before it gets to me
emotionally.My inital point is that I think high while high cortisol levels do dammage the brain, I think they have some sort of sustaining effect. I would alsways get physically sick after exams when the stress subsided.)
Linkadge
Posted by susan C on October 21, 2002, at 19:13:35
In reply to Re: Pfinstegg going on even more- Linkadge and Seamus, posted by Pfinstegg on October 21, 2002, at 14:16:31
hi
I just got tested for this, and am now running as fast as my little verapamil/depakote enhanced legs can carry me to understand and catch up to what you are saying. Now I can click the "notify you of later follow-ups to this thread" box and know no bit of your investigations will be missed.
Thank you, puff, puff,
mouse
Posted by Pfinstegg on October 21, 2002, at 19:54:46
In reply to Cortisol's sustaining effect, posted by linkadge on October 21, 2002, at 18:51:54
Hi.. the first thing I just can't help saying is that I have such admiration and respect for how far you have come, and how much you have accomplished in getting some control over what sounds like a very tough original situation. Am I right in thinking from a previous post that you are in grad school now and making it OK?
I wonder, too, whether cortisol has gotten me through tough situations; I bet it has, being the agent for responding to danger, real or perceived. Then , of course, there's always adrenaline! I've had the same collapse after stressful events as you in the past; I still do, although not nearly as severely. I'm pretty sure it's the medications and the Omegas helping.
I saw something interesting about people whose cortisol was tested immediately after a major trauma (rape). They were tested as soon as they started to show signs of PTSD, and the cortisol levels were extremely LOW, as if they had just completely exhausted their physical coping mechanisms.
take care,
Pfinstegg
Posted by Pfinstegg on October 21, 2002, at 20:18:11
In reply to Re: Pfinstegg going on even more, posted by susan C on October 21, 2002, at 19:13:35
Hi.. glad you are reading the posts! We are all learning together as we go along, and as you can see, lots of posters have been contributing extremely helpful ideas, references and medical summaries. I've found it to be so rewarding and useful to do this together.
Just to give you an idea of how rapid the learning curve has been for me - if I hadn't started reading Psychobabble, it would never have occurred to me that cortisol was probably the reason that I was treatment-resistant despite having taken a lot of ADs. I didn't even know that it was important, and I was amazed to find out that my own cortisol was so high.
Now, to find out how best to get it down to normal..
Pfinstegg
Posted by Skeezix on October 21, 2002, at 22:07:56
In reply to Re: Remeron and cortisol, posted by Pfinstegg on October 19, 2002, at 18:15:13
Greetings Pfinstegg, all...You can add me to the cortisol club. My urine free cortisol is high, though I suppress normally with dexamethasone. I am trying to find out more about mifepristone, and I have some personal experience with Remeron and tianeptine. Read on if you are interested...
There is some preliminary evidence that Remeron may suppress cortisol and ACTH. See:
Unfortunately, this study has a number of limitations. First, cortisol and ACTH were measured for only 12 hours following a single 15 mg dose of Remeron, so it isn't clear whether or not the cortisol suppression is sustained with long-term use. Second, the subjects of this study were all healthy volunteers with normal baseline cortisol levels. Third, the effect of higher doses was not studied, and it is possible that Remeron's noradrenergic effects at higher doses could counteract it's cortisol-suppressing effects.
Remeron may reduce cortisol through 5-HT2 and/or H1 receptor antagonism. Cyproheptadine, an antihistamine with 5-HT blocking properties has been used to treat Cushing's disease in animals. Some of the atypical anti-psychotics also block these receptors which could explain why they are effective for some depressions.
I have been trying Remeron on myself to see if it will lower my own cortisol. A recent 24-hr urine free cortisol was about 25 percent lower than my baseline level, however, it was still well above normal. Also, my baseline cortisol measurement was done on a day when I was under a lot of physical and emotional stress, so it doesn't surprise me that the second reading was lower. My mood has improved only slightly on Remeron, and when the norephinephrine effects kicked in it was definitely too stimulating, so I am in the process of tapering down.
Though tianeptine may have protective effects, it appears to suppress the HPA axis only at very high doses:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1660816&dopt=Abstract
This was done on rats and required doses of 10 mg/kg -- about 15-20 times more than the typical human dose (37.5 mg/day, if I remember correctly). I tried tianeptine a few years back and it didn't do much for me, though it sounds like you're getting some relief from it, Pfinstegg. Have you been able to check your cortisol levels since you've been on it to see if there is an effect?
Mifepristone definitely looks interesting, though I'm still trying to get more information on how it affects the HPA axis in the long run. Here is one recent study published on the treatment of (psychotic) depression with mifepristone:The results are promising, though after reading the entire study I had more questions than answers. First, it isn't clear if any of the subjects in the study even had high cortisol to begin with! Only 4 PM serum cortisol was measured, which is not terribly meaningful. Since mifepristone is a glucocorticoid antagonist it will block feedback to the hypothalamus and pituitary resulting in a rapid *increase* in cortisol output while taking the drug. It isn't clear from this study what happens to cortisol levels after the drug is discontinued. The authors measured 4 PM cortisol 21 days after discontinuation but didn't publish the results. Not very helpful...
Well, that's enough rambling for now. Hope this is of interest.Skeezix
Posted by Shawn. T. on October 21, 2002, at 22:24:14
In reply to Re: Cortisol, Remeron, tianeptine, mifepristone, posted by Skeezix on October 21, 2002, at 22:07:56
These are the best reviews that I know of with regards to cortisol and stress. Note that cortisol exists in humans while corticosterone is the rat equivalent. These two are referred to as glucocorticoids. Synthetic glucocorticoids include dexamethasone and prednisone, which differ in terms of potency and half-life.
http://edrv.endojournals.org/cgi/content/full/21/1/55http://bmj.com/cgi/content/full/315/7107/530
http://content.nejm.org/cgi/content/full/338/3/171?ijkey=2ayL2HP0PzdXQ
http://edrv.endojournals.org/cgi/content/full/22/4/502
http://www.psychosomaticmedicine.org/cgi/content/full/61/5/698
Also, on the topic of PKC epsilon & anxiety... chronic dexamethasone causes PKC epsilon levels to increase in the hippocampus.
http://jneurochem.highwire.org/cgi/content/full/72/1/380?ijkey=9NylfUX3.p4rg
Shawn
Posted by Pfinstegg on October 22, 2002, at 0:27:37
In reply to Re: links to cortisol/stress reviews, posted by Shawn. T. on October 21, 2002, at 22:24:14
Thanks for the great references- I'm copying them out. I wasn't aware of how MUCH tianeptine those tree shrews were given in order to protect their brains from the cortisol. It's great to have scientifically able people who can evaluate the design of these experiments with a critical eye. What you say makes the human doses seem pretty insignificant- still, so far I feel confident that the tianeptine is helpful. I just saw the endocrinologist (it took 2 months to get an appointment), but now that I am there, he is planning to do a 24-hour urinary cortisol and a combined CRF-DST suppression test every two months, to see if what I am doing now- 37.5 mg tianeptine, 4 gms. Omega 3, and relational psychotherapy- will have any effect on the cortisol over the next few months. If it doesn't, he is thinking over the pros and cons of using mefipristone or ketanozodole- how long to give them, and at what doses.
Whether the levels improve or not, I promise to post the results..after going on about cortisol at such length here, I would really be letting you down if I didn't..
Pfinstegg
Posted by linkadge on October 22, 2002, at 11:12:36
In reply to Re: Cortisol's sustaining effect » linkadge, posted by Pfinstegg on October 21, 2002, at 19:54:46
I am in university now and doing well.
I have a little problem with being
spaced out with the celexa but my
concentration is still 100X better than
before with the anxiety.Linkadge
Posted by Skeezix on October 22, 2002, at 20:46:38
In reply to Skeezix and Shawn on glucocorticoids, posted by Pfinstegg on October 22, 2002, at 0:27:37
Hi PfinsteggI was wondering if you know anything about the availability of mifepristone at this time. If a doctor is willing to prescribe it (and it sounds like your doctor might be), can/will a pharmacy be able to provide it in the amounts needed to treat depression?
Also, I didn't mean to imply in my previous post that tianeptine isn't a useful drug, just that it isn't clear whether or not it reduces cortisol in humans. It's great that you're getting good results!
Skeezix
Posted by Pfinstegg on October 22, 2002, at 22:51:43
In reply to Re: Skeezix and Shawn on glucocorticoids » Pfinstegg, posted by Skeezix on October 22, 2002, at 20:46:38
Hi Skeezix..mefipristone is very hard to get. Your doctor has to be registered with Danco Laboratories, which markets it as Mifeprix, and has to order it directly; you can't get it through a pharmacy. However, endocrinologists and gynecologists can register, and are able to get enough for a one-week treatment.
There is an excellent NY Times article from today's Science section, posted here by Sjb, which gives an overview of the use of mefipristone- well worth reading!
Pfinstegg
Posted by McPac on October 23, 2002, at 0:59:04
In reply to Re: Skeezix and Shawn on glucocorticoids » Skeezix, posted by Pfinstegg on October 22, 2002, at 22:51:43
The following substances may be helpful for some:
Tryptozen.
Basically a milk protein developed by the French and actually patented, it has some anti cortisol properties and some research. It is primarily marketed as anti stress and anxiety.
Try the following link:
http://www.pnt-200.com/pnt200.html
Relora.A mixture of two Chinese herbs which has been found to reduce cortisol and substantially increase dhea. Again it is primarily marketed as anti stress and anxiety but it is interesting that Owen Wolkowicz has successfully used dhea to treat depression.
A good link is:
http://relora.com/News/pr3.htm
As is:
http://www.solanova.com/info_relora.asp?slno=0
Posted by Pfinstegg on October 24, 2002, at 1:24:52
In reply to Re: Cortisol, Remeron, tianeptine, mifepristone, posted by Skeezix on October 21, 2002, at 22:07:56
That was such a good post of yours with the references: I've just now had time to look at them. The study of mefipristone didn't include lots of things we'd like to know- like how long the effects last, and exactly what happens with the cortisol. My endocrinologist says that it has to be considered as a short-term treatment, which will get the cortisol down well, but probably won't keep it down; for that, we'd have to have a different plan, involving ADs.
He said that in the 1980's he was able to obtain enough of mefipristone to treat some Cushing's syndrome patients, both men and women, for periods as long as a year, without much in the way of side effects, but this is just not possible to do now.
Keep posting as you find out things!
Pfinstegg
Posted by Skeezix on October 24, 2002, at 20:48:18
In reply to Re: Cortisol, Remeron, tianeptine, mifepristone » Skeezix, posted by Pfinstegg on October 24, 2002, at 1:24:52
Thanks, Pfinstegg. I've learned quite a bit from your posts as well! You're probably aware of this, but someone posted a link recently to the current trial of mifepristone in bipolar patients. It looks like this will be a much more thorough study in terms of measuring the hormonal effects and monitoring long-term results.It's also great that you have such a progressive endocrinologist!
Skeezix
Posted by Pfinstegg on October 24, 2002, at 22:27:04
In reply to Re: Cortisol, Remeron, tianeptine, mifepristone » Pfinstegg, posted by Skeezix on October 24, 2002, at 20:48:18
Yes, isn't that exciting?- it's a big study run by NIH, with trials taking place there and at other centers. I haven't come across a study yet for unipolar depression, but I bet there will be one soon. As you probably know, mefipristone has been "fast-tracked" by the FDA as a promising treatment for depression; past experience with using it in Cushing's has given quite a good safety profile. It will be fun keeping an eye on how it progresses!
Pfinstegg
Posted by linkadge on October 25, 2002, at 12:47:24
In reply to new trials of mefipristone » Skeezix, posted by Pfinstegg on October 24, 2002, at 22:27:04
I know this drug would be beneficial
for my mother who is bipolar. She
identifies anxiety as the source of
all her problems. She went into a depression
and then mania following many major life
stressors. I myself have linked my depression
to major life stressors as well. I think
some people were built to just secrete cortisol
by the galon.Linkadge
Posted by Pfinstegg on October 25, 2002, at 22:17:01
In reply to Re: new trials of mefipristone, posted by linkadge on October 25, 2002, at 12:47:24
I couldn't agree more. In addition to our genes playing a huge role, apparently high cortisol in a pregnant woman can set the HPA axis of her fetus to "high", thus setting the stage for the individual to react to events with cortisol overproduction all through life. Gosh...
Pfinstegg
Posted by SLS on October 26, 2002, at 23:32:54
In reply to Re: new trials of mefipristone » linkadge, posted by Pfinstegg on October 25, 2002, at 22:17:01
> I couldn't agree more. In addition to our genes playing a huge role, apparently high cortisol in a pregnant woman can set the HPA axis of her fetus to "high", thus setting the stage for the individual to react to events with cortisol overproduction all through life. Gosh...
>
> Pfinstegg
Wow Pfinstegg, I hadn't thought of that. That's brilliant. Where can I find more information about this - or is the idea your own?Wow.
- Scott
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