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Re: Questions re cortisol levels:SLS

Posted by SLS on September 17, 2005, at 8:19:57

In reply to Questions re cortisol levels:SLS, posted by Cecilia on September 17, 2005, at 1:19:09

Hi Cecilia.

First, I think it is important to determine what time of day depression is the worst for you. If mornings are clearly worse, you might have a more melancholic depression, which is usually associated with high cortisol. You might also want to rule out bipolar disorder by retrospective analysis or life-charting to see if there were any manic, hypomanic, mixed-states, or rapid-cycling cyclothymia. Bipolar depression can look very much like atypical depression. However, like melancholic depression, it involves a hyperactive HPA axis. Chronic hypercortisolemia is circular, and can lead to a downregulation of cortisol receptors in the hippocampus and thus further allow for hypercortisolism. The whole thing is more complicated than it looks on the surface. The system might try to release more CRH (same as CRF) in order to raise cortisol even further. Too much CRH in the brain seems to be depressogenic.

I think it is nice to have a DST (dexamethasone suppression test) performed, but I'm not sure how the results of such a test would influence treatment decisions.

The HPA axis can be manipulated by using:

1. Cortisol synthesis inhibitors (chronic treatment)
- ketaconozole
- metyrapone
- aminoglutethimide

2. Cortisol receptor antagonists (8 day treatment)
- mifepristone

3. Cortisol receptor agonists (4 day treatment)
- dexamethasone

4. CRH receptor antagonists (chronic treatment)
- in early development

I am looking at using all of these to treat my bipolar depression. It is quite possible that using either mifepristone or dexamethasone, drugs that on the surface seem to have opposite effects, might help to reset the HPA axis in the same direction by shocking it to function normally. Then again, perhaps mifepristone will be found to be especially effective when treating melancholic, psychotic, or bipolar depression, while dexamethasone will be found to be better suited to treating true unipolar atypical depression.

Not enought data yet.


- Scott

 

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