![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by jerrympls on December 23, 2004, at 17:05:36
My doc is starting me on Metyrapone, a cortisol inhibitor, in adjunct to the Cymbalta I'm on. He was impressed with recent studies showing it helped with depression. However, I haven't been able to find a pharmacy that carries the medication (in the US). I did find out that the manufacturer - Novartis - has labeled it "for compassionate use" - whatever that means? Anyway, the pharmacist said I'd have to call Novartis directly to ask how to get the med. I just tried to call and they're closed - so I'll have to wait until next week. I've posted an article about the studies below.
Jerry
--------------------------
Cortisol synthesis inhibitors accelerate antidepressant effectThe cortisol inhibitor metyrapone appears to be an effective adjuvant treatment for major depression, accelerating the onset of antidepressant action, study findings show.
"Alterations of the hypothalamic-pituitary-adrenal axis are the most consistent pathological endocrine findings in depression," observe Holger Jahn (University Hospital Hamburg-Eppendorf, Germany) and colleagues.
"Preclinical studies nurture the hope for new therapeutic strategies based on steroid-synthesis inhibition, but clinical data about the antidepressive efficacy of these compounds are mainly confined to small open-label trials and case reports."
To investigate further, the researchers randomly assigned 66 patients with major depression and Hamilton Rating Scale for Depression (HAM-D) scores of 18 points or higher to receive 1 g/day of metyrapone or placebo for the first 3 weeks of a 5-week course of antidepressant treatment with either nefazodone or fluvoxamine.
After 3 weeks, 23 of 33 patients receiving metyrapone had a positive treatment response, defined as a 30% reduction in HAM-D scores, compared with 13 of 30 patients taking placebo. After 5 weeks, 19 and 10 patients, respectively, were considered responders, based on a 50% reduction in HAM-D scores.
Moreover, the onset of antidepressant action, defined as the time point at which at least a 20% reduction in HAM-D scores occurred, was more rapid among the participants taking metyrapone, beginning in the first week compared with after 2 weeks for those receiving placebo.
Metyrapone was generally well tolerated, with only nausea and headaches reported significantly more often during metyrapone than placebo treatment. Adverse events tended to be mainly due to the serotonergic antidepressant therapy.
Although cortisol levels remained largely unchanged, the plasma levels of corticotropin, the cortisol precursor 11-deoxycortisol, and the neurosteroid dehydroepiandrosterone increased, confirming that metyrapone intervened with cortisol synthesis.
"Although steroid-synthesis inhibitors are not quite ready for routine clinical application, the findings of this study clearly warrant further studies aimed at identifying subgroups of depressed patients who will benefit most from this approach and surrogate markers to find the optimal dosing regimen," the researchers conclude in the Archives of General Psychiatry.
Posted by jerrympls on December 23, 2004, at 17:07:32
In reply to Cortisol synthesis inhibitors-NEWS for depression, posted by jerrympls on December 23, 2004, at 17:05:36
Here's a link to one study:
http://archpsyc.ama-assn.org/cgi/content/abstract/61/12/1235
Posted by SLS on December 23, 2004, at 19:24:14
In reply to Cortisol synthesis inhibitors-NEWS for depression, posted by jerrympls on December 23, 2004, at 17:05:36
Hi Jerry.
Can you provide the link for this study? I want to show it to my doctor. I will be very interested to see how difficult it will be for you to get metyrapone. Its sole use at the moment is as a test for adrenal function. It is not meant to be a prescription medication. I guess that's why it was suggested to you that it might only be available on a compassionate use basis.
Thanks for your input.
- Scott
> My doc is starting me on Metyrapone, a cortisol inhibitor, in adjunct to the Cymbalta I'm on. He was impressed with recent studies showing it helped with depression. However, I haven't been able to find a pharmacy that carries the medication (in the US). I did find out that the manufacturer - Novartis - has labeled it "for compassionate use" - whatever that means? Anyway, the pharmacist said I'd have to call Novartis directly to ask how to get the med. I just tried to call and they're closed - so I'll have to wait until next week. I've posted an article about the studies below.
>
> Jerry
>
> --------------------------
>
>
> Cortisol synthesis inhibitors accelerate antidepressant effect
>
> The cortisol inhibitor metyrapone appears to be an effective adjuvant treatment for major depression, accelerating the onset of antidepressant action, study findings show.
>
> "Alterations of the hypothalamic-pituitary-adrenal axis are the most consistent pathological endocrine findings in depression," observe Holger Jahn (University Hospital Hamburg-Eppendorf, Germany) and colleagues.
>
> "Preclinical studies nurture the hope for new therapeutic strategies based on steroid-synthesis inhibition, but clinical data about the antidepressive efficacy of these compounds are mainly confined to small open-label trials and case reports."
>
> To investigate further, the researchers randomly assigned 66 patients with major depression and Hamilton Rating Scale for Depression (HAM-D) scores of 18 points or higher to receive 1 g/day of metyrapone or placebo for the first 3 weeks of a 5-week course of antidepressant treatment with either nefazodone or fluvoxamine.
>
> After 3 weeks, 23 of 33 patients receiving metyrapone had a positive treatment response, defined as a 30% reduction in HAM-D scores, compared with 13 of 30 patients taking placebo. After 5 weeks, 19 and 10 patients, respectively, were considered responders, based on a 50% reduction in HAM-D scores.
>
> Moreover, the onset of antidepressant action, defined as the time point at which at least a 20% reduction in HAM-D scores occurred, was more rapid among the participants taking metyrapone, beginning in the first week compared with after 2 weeks for those receiving placebo.
>
> Metyrapone was generally well tolerated, with only nausea and headaches reported significantly more often during metyrapone than placebo treatment. Adverse events tended to be mainly due to the serotonergic antidepressant therapy.
>
> Although cortisol levels remained largely unchanged, the plasma levels of corticotropin, the cortisol precursor 11-deoxycortisol, and the neurosteroid dehydroepiandrosterone increased, confirming that metyrapone intervened with cortisol synthesis.
>
> "Although steroid-synthesis inhibitors are not quite ready for routine clinical application, the findings of this study clearly warrant further studies aimed at identifying subgroups of depressed patients who will benefit most from this approach and surrogate markers to find the optimal dosing regimen," the researchers conclude in the Archives of General Psychiatry.
Posted by jerrympls on December 23, 2004, at 19:31:51
In reply to Re: Cortisol synthesis inhibitors-NEWS for depression » jerrympls, posted by SLS on December 23, 2004, at 19:24:14
> Hi Jerry.
>
> Can you provide the link for this study? I want to show it to my doctor. I will be very interested to see how difficult it will be for you to get metyrapone. Its sole use at the moment is as a test for adrenal function. It is not meant to be a prescription medication. I guess that's why it was suggested to you that it might only be available on a compassionate use basis.
>
> Thanks for your input.
>
>
> - Scott
>Here's the link
http://archpsyc.ama-assn.org/cgi/content/abstract/61/12/1235
Posted by SLS on December 24, 2004, at 10:00:08
In reply to Re: Cortisol synthesis inhibitors-NEWS for depression » jerrympls, posted by SLS on December 23, 2004, at 19:24:14
Hi Jerry.
Thanks to supplying the link for the article.
Check this out:
http://www.patient.co.uk/showdoc/30003048/
It appears that metyrapone is available in England for the treatment of various conditions. You can do the rest of the math. :-)
- Scott
> > My doc is starting me on Metyrapone, a cortisol inhibitor, in adjunct to the Cymbalta I'm on. He was impressed with recent studies showing it helped with depression. However, I haven't been able to find a pharmacy that carries the medication (in the US). I did find out that the manufacturer - Novartis - has labeled it "for compassionate use" - whatever that means? Anyway, the pharmacist said I'd have to call Novartis directly to ask how to get the med. I just tried to call and they're closed - so I'll have to wait until next week. I've posted an article about the studies below.> Can you provide the link for this study? I want to show it to my doctor. I will be very interested to see how difficult it will be for you to get metyrapone. Its sole use at the moment is as a test for adrenal function. It is not meant to be a prescription medication. I guess that's why it was suggested to you that it might only be available on a compassionate use basis.
Posted by ed_uk on December 24, 2004, at 10:22:40
In reply to Re: Cortisol synthesis inhibitors-NEWS for depression, posted by SLS on December 24, 2004, at 10:00:08
>It appears that metyrapone is available in England for the treatment of various conditions. You can do the rest of the math. :-)
What did I tell you!!!
Happy Christmas (Eve) Scott!
Ed.
Posted by Dave001 on December 24, 2004, at 16:48:35
In reply to Re: Cortisol synthesis inhibitors-NEWS for depression, posted by SLS on December 24, 2004, at 10:00:08
> Hi Jerry.
>
> Thanks to supplying the link for the article.
>
> Check this out:
>
> http://www.patient.co.uk/showdoc/30003048/
>
> It appears that metyrapone is available in England for the treatment of various conditions. You can do the rest of the math. :-)
>Adrenal steroid inhibitors have been around for a long time. Aminoglutethimide (Cytadren in the U.S.) is one such example that's cheap and easily available. Adrenal steroid production is blocked by inhibiting the enzyme desmolase. Aminoglutethimide blocks aromatase as well, an enzyme responsible for the conversion of testosterone to estrogen.
I don't see why anyone would want to mess around with systemic cortisol levels unless they have Cushing's Syndrome or some other condition causing pathophysiologically high cortisol levels. Either that or a death wish. I would be very careful.
Dave
Posted by SLS on December 24, 2004, at 17:36:30
In reply to Re: Cortisol synthesis inhibitors-NEWS for depress, posted by Dave001 on December 24, 2004, at 16:48:35
- Scott
Posted by jerrympls on December 24, 2004, at 21:24:49
In reply to Re: Cortisol synthesis inhibitors-NEWS for depress, posted by Dave001 on December 24, 2004, at 16:48:35
> > Hi Jerry.
> >
> > Thanks to supplying the link for the article.
> >
> > Check this out:
> >
> > http://www.patient.co.uk/showdoc/30003048/
> >
> > It appears that metyrapone is available in England for the treatment of various conditions. You can do the rest of the math. :-)
> >
>
> Adrenal steroid inhibitors have been around for a long time. Aminoglutethimide (Cytadren in the U.S.) is one such example that's cheap and easily available. Adrenal steroid production is blocked by inhibiting the enzyme desmolase. Aminoglutethimide blocks aromatase as well, an enzyme responsible for the conversion of testosterone to estrogen.
>
> I don't see why anyone would want to mess around with systemic cortisol levels unless they have Cushing's Syndrome or some other condition causing pathophysiologically high cortisol levels. Either that or a death wish. I would be very careful.
>
> DaveThe HPA system is VERY much involved with mood, emotion, etc. IN fact, there are many new meds in the works that target the HPA axis. It's not simply about cortisol levels. See Scott's post.
Jerry
Posted by Cairo on December 25, 2004, at 8:32:47
In reply to Re: Cortisol synthesis inhibitors-NEWS for depress » Dave001, posted by jerrympls on December 24, 2004, at 21:24:49
The question is whether you have high cortisol or a down regulated HPA axis:
http://www.neurotransmitter.net/Gold.pdf
Cairo
> The HPA system is VERY much involved with mood, emotion, etc. IN fact, there are many new meds in the works that target the HPA axis. It's not simply about cortisol levels. See Scott's post.
>
> Jerry
Posted by jerrympls on December 27, 2004, at 14:18:08
In reply to Re: Cortisol synthesis inhibitors-NEWS for depress, posted by Cairo on December 25, 2004, at 8:32:47
> The question is whether you have high cortisol or a down regulated HPA axis:
>
> http://www.neurotransmitter.net/Gold.pdf
>
> Cairo
>
>
> > The HPA system is VERY much involved with mood, emotion, etc. IN fact, there are many new meds in the works that target the HPA axis. It's not simply about cortisol levels. See Scott's post.
> >
> > Jerry
>
>Hey thanks for the info! I'll take to my doc!
Jerry
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.