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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by glenn on October 22, 2002, at 11:33:36
Hi , thanks for answering.
I think I agree with all you have said, I guess the question I am left with is what , if any are the treatment implications for dexamethasone suppressable hypercortisolaemic depression ( what a mouthful from now its got to be dshd,) as opposed to non dshd - if any?
I found your post about the fear factor in not having scans very relevant, I also have always relied on my brain to sort things out, its a bit scary if it starts fighting you so to speak!
I also wonder if I was a little scared by the idea that the dexa test if successful means your hpa axis is ok, cos if mine is ok Im not sure where that leaves me.
Im very pleased to have this forum to discuss and get information, so please keep up the good work,
Heres to cracking the cortisol puzzle!Glenn
Posted by Pfinstegg on October 22, 2002, at 21:42:10
In reply to To Pfinstegg, posted by glenn on October 22, 2002, at 11:33:36
Yes, the whole treatment question is a big puzzle. My endocrinologist does not want to rush in to using ketanozodole or mefipristone- the two he's considering, but wants to see how I do on my present self-designed cortisol-lowering regime, which consists, as I've mentioned, of tianeptine, Omega-3's, alpha-lipoic acid, phosphadatyl-serine and SAM-e. I am actually a lot better emotionally after 2 months of this, so he's interested in finding out whether what I'm already doing has lowered the cortisol any, or made me into at least a partial DST suppressor- he's doing the tests every two months to find out. One trouble with this regime- it's expensive as hell!
Having read a little more since I last posted, I am finding out about the gradual nature of this problem, which can take many years to develop. Apparently, infant or childhood stress sets the HPA axis a little high, so that subsequent stresses cause it to deliver a little more CRH and cortisol than normal. The only sign that this is happening at first is an elevated hypothalamic CRH, which is not a test that anyone ever gets! The next thing that happens is that the ACTH production by the pituitary begins to get high (no-one gets this one either); only after that does the cortisol production by the adrenals get high. Then, it has to stay high for a sustained period in order to damage the CR 2-3 receptors in the hippocampus, which are the receptors which normally take up the cortisol, returning the blood levels to normal and signalling the hypothalamus to stop producing CRH. Once you have enough damage to your hippocampal receptors to prevent cortisol uptake, you've got HPA axis dysregulation. The fact that you have high 24-hour levels, but suppress well means that you are in mid-stage in this progression; however, you do need the best possible treatment plan to prevent going on to be a non-suppressor. The few articles that I have found which actually show what reduces serum cortisol include a real collection of things: the best medications are apparently tianeptine and the tricyclics, with the SSRI's having a only a slightly positive effect on cortisol. Lithium and other mood stabilizers apparently don't affect the HPA system. rTMS and ECT sometimes have a normalizing effect, and, in one study I came across, dialectical behavior therapy actually lowered cortisol quite a lot!
Well, however we manage do it, here's to getting it down!
Pfinstegg
Posted by Pfinstegg on October 23, 2002, at 18:26:22
In reply to Re: To Pfinstegg » glenn, posted by Pfinstegg on October 22, 2002, at 21:42:10
Actually, I made a couple of mistakes and over-simplifications in my last post to you. On further reading, the cortisol-hippocampus situation is more complex than I had realized. For example, most antidepressants, including lithium (which I had mistakenly excluded), the tricyclics, SSRI's and oddballs like tianeptine all have a beneficial effect on the hippocampus, even though they don't lower the serum or CSF cortisol itself. Cortisol is supposed to make the hippocampus produce excitatory amines, like glutamate and NMDA, which stop the hippocampus from producing new dendrites and new neurons (in rats, about 4000 new neurons are produced per day when the rats are unstressed). The new neurons and dendrites are thought to be vital for memory and spatial learning. All the ADs, not just the SSRI's, are thought to increase neurotransmission at the 5HTA-1 receptors, which, by damping down glutamate and NMDA in some way not yet well understood, protect the hippocampus so that it can keep on producing new dendrites and some new neurons. Having read more about hippocampal shrinkage, it is not quite as bad as I had thought: the neurons don't actually die, usually, but they become smaller through loss of their dendrites and poorer metabolic functioning- also probably through loss of the supporting glial cells (white matter).
So shrinking hippocampuses, at least potentially, are reversible - good news!. Apparently, researchers haven't yet begun to do long-term studies of various ADs, cortisol levels and hippocampal size, but there is now much pressure from neurophysiologists to do so, both on the traditional ones and on the newer ones.
I also discovered that it isn't all about high cortisol! a recent NIH publication indicated that there is evidence that atypical depression involves LOW, rather than high cortisol, and should be treated with activating medications, rather than ADs, mentioned in the last paragraph, that indirectly modify the effects of high cortisol. Apparently the easiest way to tell if you have atypical is to notice when you feel best- it's morning for atypical, and evening for typical.
Pfinstegg
Posted by Skeezix on October 23, 2002, at 21:00:43
In reply to Re: To Pfinstegg- Glenn, posted by Pfinstegg on October 23, 2002, at 18:26:22
> I also discovered that it isn't all about high cortisol! a recent NIH publication indicated that there is evidence that atypical depression involves LOW, rather than high cortisol, and should be treated with activating medications, rather than ADs, mentioned in the last paragraph, that indirectly modify the effects of high cortisol. Apparently the easiest way to tell if you have atypical is to notice when you feel best- it's morning for atypical, and evening for typical.
Interestingly, low cortisol and DST hypersuppression have also been associated with post-traumatic stress disorder and borderline personality disorder. Chronic fatigue syndrome may also involve low cortisol.
Posted by Jerrympls on October 23, 2002, at 21:49:08
In reply to To Pfinstegg, posted by glenn on October 22, 2002, at 11:33:36
So - what if one sees a "good" endocrinologist - tests are taken and results clearly indicate a problem with cortisol ,et al? What meds can pdocs use? What meds WILL pdocs use? My doc is very supportive as far as investigating the cortisol side of things - but he's unsure what meds - if any - can be safely used to help straighten things out. he's a very good pdoc too. I'm certain if I gave him some solid research he'd try it.
?
Posted by Pfinstegg on October 23, 2002, at 22:28:17
In reply to Re: So - what if you DO have a prob. w/ cortisol?, posted by Jerrympls on October 23, 2002, at 21:49:08
Well, there's no easy answer. I am presently taking tianeptine, which doesn't lower cortisol, but does protect the hippocampus from it. The hope is that it will allow the hippocampus to slowly regain a more normal size, start branching out dendrites and making a few new neurons, and that, if you continue taking it over an extended period, you may regain a more normal amount of D2-3 receptors, which will allow the hippocampus to take up the cortisol again, and thus tell the hypothalamus to stop pumping out so much CRH- in other words, the hope is that you can reverse the HPA dysregulation, entirely or partly.
No-one knows if this is possible to do, but I do have a very interested endocrinologist who wants to follow the cortisols and the DST every 2 months to see. If this fails, and he feels my general health is becoming endangered, he said he will consider ketanozodole or mefipristone- short courses of them- he's just considering now, not committed!
Some articles which might be helpful to you are:
1.Prevention of stress-induced morphological and cognitive consequences, McEwen et al, Laboratory of Neuroendocrinology, Rockefeller University, NY, Eur Neuropsychpharmacol, 1997 Oct, 7 Suppl 3:,S323-8 (reasons for using tianeptine)
2.Antiglucocorticoid treatment of depression: double-blind ketanozodole, Biol Psychiatry 1999 Apr 15;45(8):1070-4 (from Wolkowitz, et al, University of California, San Francisco)
3.Rapid reversal of psychotic depression using mefipristone J Clin Psychopharmacol 2001 Oct; 21(5):516-21 (from Belanoff, Schatzberg et al, Stanford University Medical Center)
As you can see, this will be a slow process for me, but I promised earlier that I will post my cortisol levels as I learn them, so you can see how this guinea pig is doing!
Pfinstegg
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