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Re: Cortisol, Remeron, tianeptine, mifepristone

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:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12185405&dopt=Abstract

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:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12242054&dopt=Abstract

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


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poster:Skeezix thread:124268
URL: http://www.dr-bob.org/babble/20021019/msgs/124601.html