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Re: Ketoconazole for depression

Posted by Ant-z on November 17, 1999, at 9:46:18

In reply to Re: Ketoconazole for depression, posted by Adam on November 16, 1999, at 15:49:46

> Wow, that's new to me. I remember this conversation I had with a dermatologist years ago where there was some
> excitement about ketoconazole because it appeared to be an antiandrogen, and maybe could be used for baldness,
> though it seemed doubtful; not in a shampoo, because it wasn't absorbed well, and not orally because chronic
> treatment caused so many problems with drug interactions, but maybe in a cream. Don't know what happened to that
> idea. The cortisol/steroid connection is interesting vis-a-vis its "antiandrogen" properties. Anyway, it is, I
> guess, a very potent inhibitor of some CYPs, and is sometimes used in research for that purpose alone.
> > Ketoconazole (oral) has actually been investigated for its usefulness in major depression. The results of controlled trials are equivocal. It is thought that a disturbance in CRH - ACTH - cortisol function may play a part in, or be a result of, major depression.
> >
> > Cortisol is secreted by the adrenal glands and is said to be a "stress" hormone. What this means is that in a healthy person, the experience of stress will cause levels of cortisol to rise in the blood-stream. I don't know what function cortisol has in a stressful situation, but I imagine it has its benefits. One measure of cortisol function is the dexamethasone-suppression test (DST). When given dexamethasone (fake cortisol?), the rate of cortisol secretion is suppose to be suppressed so as to keep blood-levels stable. In many people with major depression, this control system seems to be out-of-whack. Levels of cortisol can be abnormally high. In addition, the production of cortisol is not suppressed by dexamethasone. In the past, this has been used as a diagnostic test for depression. I don't know if it is anymore.
> >
> > Ketoconazole has properties other than those that act as an antifungal. Among them is the ability to inhibit the biosynthesis of cortisol (antiglucocorticoid). It is used in diseases in which excessive levels of cortisol occur (hypercortisolemia). Cushings disease is an example of this.
> >
> > If elevated levels of cortisol in the blood-stream cause or contribute to depression, shutting down the cortisol factories (adrenal glands) should help. Right? Well...
> >
> > I'm glad the *topical* ketoconazole thread was running. I had no idea that cytochrome P450 inhibition was another of ketoconazole's properties. Is it possible to compensate for this by adjusting the dosage of those drugs with which it competes?
> >
> > Anyway, you can find articles in the literature regarding the use of ketoconazole in major depression and treatment-resistant depression. The most recent one I found on Medline is from October 1999.
> >
> >
> > - Scott

I recently had the DST cortisol test, and it came back my cortisol level is low. The endocronologist(sp?) said that he's not convinced that this is causing my fatigue/depression/muscle-tiredness. After reading the DHEA post, I might consider experimenting with this substance, seeing that the symptoms it was so helpful with are my biggest problem.(Anhedonia, fatigue, emotional numbness).I'm also considering thyroid augmentation, even though my levels were in the normal range.
If anyone has any input or suggestions I would love to hear them. Thanx, Ant-z




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