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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 4 to 28 of 28. Go back in thread:
Posted by Maximus on June 16, 2005, at 8:12:18
In reply to Interesting article - HPA dysfunction in mood diso, posted by temoigneur on June 16, 2005, at 1:32:41
Hi,
Yes, with the mental illness, HPA axis is very often dysfunctional. But we need something to "reset" the glucocorticoid receptors and not just a cortisol reducer.
Exemple: Atypical depression and Bipolar depression share overlapping symptoms (low cortisol, etc.) Give them RU 486 or Remeron and they get worse quickly. But you can reverse their neurovegetative symptoms very fast in including Prednisone in their treatment. But the tricky part is that adrenals heal very very slowly.
Posted by SLS on June 16, 2005, at 8:43:57
In reply to Stanford Psychotic Majr Depression, posted by temoigneur on June 16, 2005, at 2:42:21
You need to be careful in interpreting the Shatzberg study. Positive effects were noted more for the psychotic cognition than the depressed affect.
- Scott
Posted by ed_uk on June 16, 2005, at 8:50:06
In reply to Re: Prednisone in atypical depression, posted by Maximus on June 16, 2005, at 8:12:18
Hi Maximus!
Prednisone's a strange drug. Some people get euphoric on it, others develop severe depression. Some people even get psychotic.
~Ed
Posted by Maximus on June 16, 2005, at 9:08:31
In reply to Re: Prednisone in atypical depression » Maximus, posted by ed_uk on June 16, 2005, at 8:50:06
> Hi Maximus!
>
> Prednisone's a strange drug. Some people get euphoric on it, others develop severe depression. Some people even get psychotic.Yes Ed. But i bet that those who get depressed on it have already a high level of cortisol. Just a guess.
Posted by ed_uk on June 16, 2005, at 11:16:34
In reply to Re: Prednisone in atypical depression » ed_uk, posted by Maximus on June 16, 2005, at 9:08:31
Hi Maximus!
>Yes Ed. But i bet that those who get depressed on it have already a high level of cortisol. Just a guess.
I think it's probably a matter of dose. At the very high doses used to treat inflammatory/autoimmune disorders, prednisone frequently causes psych adverse effects.
Kind regards,
Ed.PS. Was nice to see you on 'social' :-)
Posted by ed_uk on June 16, 2005, at 18:02:25
In reply to Re: Prednisone in atypical depression, posted by Maximus on June 16, 2005, at 8:12:18
Hi again Maximus :-)
Thanks for posting this.......
Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have long been implicated in major depression with hypercortisolaemia reported in typical depression and hypocortisolaemia in some studies of atypical depression. We report on the use of prednisone in treatment-resistant depressed patients with reduced plasma cortisol concentrations. Six patients with treatment-resistant major depression were found to complain of severe fatigue, consistent with major depression, atypical subtype, and to demonstrate low plasma cortisol levels. Prednisone 7.5 mg daily was added to the antidepressant regime. Five of six patients demonstrated significant improvement in depression on prednisone augmentation of antidepressant therapy. Although hypercortisolaemia has been implicated in some patients with depression, our findings suggest that hypocortisolaemia may also play a role in some subtypes of this disorder. In treatment-resistant depressed patients with fatigue and hypocortisolaemia, prednisone augmentation may be useful.
.........I think it's really interesting.
Some interesting stuff.............
Mol Psychiatry. 2002;7(3):254-75.
Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states.Gold PW, Chrousos GP.
Clinical Neuroendocrinology Branch, Intramural Research Program, NIMH/NIH, NIH Clinical Center, Room 2D-46-1284, Bethesda, MD 20892-1284, USA. philgold@codon.nih.gov
Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction.
Biol Psychiatry. 1997 Aug 1;42(3):165-74.Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression.
Geracioti TD Jr, Loosen PT, Orth DN.
Psychiatry Service, Veterans Affairs Medical Center, Cincinnati, Ohio 45220,USA.
Hypersecretion of corticotropin-releasing hormone (CRH) and resulting hypercortisolism have been implicated in the pathogenesis of major depression. To test this CRH hypersecretion hypothesis, cerebrospinal fluid (CSF) was continuously withdrawn from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter (placed at 8:00 AM), and immunoreactive CRH concentrations were determined at 10-min intervals in 10 depressed patients, the majority of whom exhibited at least one "atypical" symptom, and in 15 normal volunteers. CSF CRH was low, plasma adrenocorticotropin (ACTH) tended to be low, and plasma cortisol was normal in the depressed patients..........
J Psychiatry Neurosci. 2002 Jan;27(1):47-51.Low-dose dexamethasone challenge in women with atypical major depression: pilot study.
Levitan RD, Vaccarino FJ, Brown GM, Kennedy SH.
Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont. Robert_Levitan@camh.net
OBJECTIVE: To examine if atypical depression may be associated with hypersuppression of the hypothalamic-pituitary-adrenal (HPA) axis. METHOD: Eight women with atypical major depression and 11 controls with no history of psychiatric illness, matched on age and body mass index, were challenged with low-dose dexamethasone (0.25 mg and 0.50 mg in random order and 1 week apart). Dexamethasone was self administered at 11 pm, and plasma cortisol samples were drawn at 8 am and 3 pm on the following day. RESULTS: After the 0.50-mg dexamethasone challenge, mean suppression of morning cortisol was significantly greater in patients with atypical depression (91.9%, standard deviation [SD] 6.8%) than in the controls (78.3%, SD 10.7%; p < 0.01). CONCLUSION: These preliminary data add to the growing body of literature that suggests atypical depression, in contrast to classic melancholia, may be associated with exaggerated negative feedback regulation of the HPA axis.
~Ed
Posted by Maximus on June 16, 2005, at 19:04:47
In reply to Atypical depression » Maximus, posted by ed_uk on June 16, 2005, at 18:02:25
Ed, very good studies, indeed.
"Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment".
Hummm, that remembers someone ;-) I think that the natural course of the mental (most pathologies) illness (years?) leads ineluctably to the dreaded adrenal burnout.
Although that appears logic to me (adrenal burnout), it is a pure presumption.
Hopefully, more and more scientists have re-oriented their research on glucocorticoides receptors in the brain. In the future, that could lead to a powerfull co-treatment of these disorders.
Posted by ed_uk on June 16, 2005, at 19:22:18
In reply to Re: Atypical depression » ed_uk, posted by Maximus on June 16, 2005, at 19:04:47
Hi Max!
>Hopefully, more and more scientists have re-oriented their research on glucocorticoides receptors in the brain.
I hope so too. We really need some novel treatments.
Kind regards,
Ed.
Posted by EERRIICC on June 17, 2005, at 20:40:04
In reply to Interesting article - HPA dysfunction in mood diso, posted by temoigneur on June 16, 2005, at 1:32:41
Thanks for posting this information!
Is it true that HPA disfunction is most directly manifested by lowered or increased levels of a person's cortisol?
I suffer from unipolar depression but my cortisol levels, both "immediate" and "24-hour", are normal. Will future treatments that are geared towards regulating HPA disfunction not be helpful for people who suffer from depression but do not have abnormal cortisol levels?
I know you may not be able to answer these kind of questions but I'd appreciate your opinion.
Thanks,
Eric
Posted by Maximus on June 17, 2005, at 21:08:41
In reply to Cortisol_testing » temoigneur, posted by EERRIICC on June 17, 2005, at 20:40:04
> I suffer from unipolar depression but my cortisol levels, both "immediate" and "24-hour", are normal. Will future treatments that are geared towards regulating HPA disfunction not be helpful for people who suffer from depression but do not have abnormal cortisol levels?
Hi Eric,
I think that these futures "reseters" of the HPA axis will constitute a robust add-on to our present medication. However if your HPA axis is already normal, it just makes sense that they will not touch it.
Posted by Cairo on June 18, 2005, at 11:46:06
In reply to Interesting article - HPA dysfunction in mood diso, posted by temoigneur on June 16, 2005, at 1:32:41
I think there are subtypes of depression, some with high cortisol, some with low, some with normal. I myself have cortisol levels that come back "normal", but I believe that the feedback loop or receptors or something is messed up so that my HPA axis is hypofunctioning and can't mount an effective response to stress of any kind. My TSH was creeping up, but addition of Unithroid brings it to "normal" (less than 2), but with no relieve of atypical symptoms or Fibromyalgia symptoms.
Giving cortisol is fraught with problems long term, though I've heard of doctors using low "pulse" doses when needed. My doc won't even go there.
http://www.dr-bob.org/babble/20030525/msgs/230047.html
http://www.neurotransmitter.net/Gold.pdfCairo
Posted by Maxime on June 18, 2005, at 21:20:09
In reply to Dexamethasone in the treatment of depression » temoigneur, posted by ed_uk on June 16, 2005, at 7:04:42
My pdco tried me on this. I had to take it for 10 days and then stop. On the 8th day I finally started to feel good. But then when i had to stop the med on the 10th day, I crashed big time.
Maxime
> J Psychopharmacol. 1999;13(2):196-7.
>
> The use of dexamethasone in elderly patients with antidepressant-resistant depressive illness.
>
> Bodani M, Sheehan B, Philpot M.
>
> Maudsley Hospital, London, UK.
>
> Many depressed patients do not respond to first-line antidepressant treatment. Dexamethasone is a synthetic steroid which may have antidepressant properties. Its use in two elderly patients with resistant depression is reported. Both patients appeared to benefit from the treatment. The possible modes of action of this treatment, and its potential benefits to the elderly, are discussed.
>
>
>
> Am J Psychiatry.
>
> Dexamethasone for the treatment of depression: a randomized, placebo-controlled, double-blind trial.
>
> Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425-0742.
>
> OBJECTIVE: The authors' goal was to assess dexamethasone for the treatment of depression. METHOD: Thirty-seven outpatients (11 men and 26 women) meeting DSM-III-R criteria for major depressive disorder were randomly assigned to receive either placebo or 4 mg/day of oral dexamethasone for 4 days. Baseline Hamilton depression scale scores were compared with scores obtained 14 days after the first dose of study medication. Data were analyzed by using two-sample t tests, chi-square methods, and Fisher's exact test. RESULTS: Seven (37%) of the 19 patients given dexamethasone but only one (6%) of the 18 patients given placebo responded positively. No adverse events or side effects were reported, and all patients who entered the study completed it. CONCLUSIONS: A brief course of oral dexamethasone (4 days) was significantly more effective than placebo within 14 days for the treatment of depression in a randomized, double-blind study of depressed outpatients.
>
>
> J Clin Psychiatry. 1991 Jul;52(7):304-6.
>
> Dexamethasone for the treatment of depression: a preliminary report.
>
> Arana GW, Forbes RA.
>
> Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425-0742.
>
> BACKGROUND: This preliminary uncontrolled trial of intravenous dexamethasone addresses the question of the utility of a glucocorticoid for the treatment of depression. METHOD: Patients with a DSM-III-R (SCID confirmed) diagnosis of major depression or bipolar disorder, depressed type, and a Hamilton Rating Scale for Depression (HAM-D) score of greater than or equal to 20 were selected. Baseline HAM-D scores were compared with scores within 10 days after intravenous infusion of dexamethasone; data were analyzed by t tests. Control subjects (no psychiatric illness and HAM-D scores less than 5) were given intravenous dexamethasone to test for its mood-altering effect. RESULTS: The mean HAM-D scores in 16 depressed subjects 10 days after intravenous dexamethasone dropped by 56% (p less than .0001), and 75% of the patients experienced a greater than 50% reduction in HAM-D scores. Additionally, 6 nonpsychiatric, nondepressed control subjects were given intravenous dexamethasone and found to have no changes in mental status examination. CONCLUSIONS: Intravenous dexamethasone may be an effective treatment for depressive illnesses. Because this was an uncontrolled, unblinded trial, further studies need to be done in nonpsychiatric and psychiatric controls to ascertain the validity of this finding.
>
Posted by ed_uk on June 18, 2005, at 21:29:37
In reply to Re: Dexamethasone in the treatment of depression » ed_uk, posted by Maxime on June 18, 2005, at 21:20:09
Hi Maxi :-)
Did you have your cortisol level measured prior to treatment? Was it abnormal?
Love,
Ed xxx
Posted by Maxime on June 19, 2005, at 22:49:00
In reply to Re: Dexamethasone in the treatment of depression » Maxime, posted by ed_uk on June 18, 2005, at 21:29:37
> Hi Maxi :-)
>
> Did you have your cortisol level measured prior to treatment? Was it abnormal?
>
> Love,
> Ed xxxNo, silly pdoc. He said he should have had it measured first. He said the idea of taking the med is that it "lifts" you and most people will stay that way. I did not. In fact, the crash was worse than if I hadn't taken it all.
Maxime
Posted by 4WD on June 19, 2005, at 23:21:22
In reply to Re: Dexamethasone in the treatment of depression » ed_uk, posted by Maxime on June 19, 2005, at 22:49:00
> > Hi Maxi :-)
> >
> > Did you have your cortisol level measured prior to treatment? Was it abnormal?
> >
> > Love,
> > Ed xxx
>
> No, silly pdoc. He said he should have had it measured first. He said the idea of taking the med is that it "lifts" you and most people will stay that way. I did not. In fact, the crash was worse than if I hadn't taken it all.
>
> Maxime
Hmpppphh! I've never heard of a drug that you can take for a short while, stop abruptly and have it remain in effect.Marsha
Posted by EERRIICC on June 19, 2005, at 23:24:09
In reply to Re: Cortisol_testing » EERRIICC, posted by Maximus on June 17, 2005, at 21:08:41
I guess what I'm wondering is if low or high cortisol levels are the sole indicator of HPA disfunction; or is depression in and of itself the main indicator?
Posted by ed_uk on June 20, 2005, at 10:42:06
In reply to Re: Dexamethasone in the treatment of depression » ed_uk, posted by Maxime on June 19, 2005, at 22:49:00
>He said the idea of taking the med is that it "lifts" you and most people will stay that way.
Sounds too good to be true!
Ed xxx
Posted by Elroy on June 21, 2005, at 17:54:27
In reply to Re: Cortisol_testing » Maximus, posted by EERRIICC on June 19, 2005, at 23:24:09
I believe that the dysfunction of the HPA Axis can also be manifested by increased levels of your adrenaline hormones (epinephrine, norepinephrine, etc.).
It seems that in my case I had elevated levels of the adrenaline homones from years of chronic stress and low-level anxiety (work related and lawsuit related). At some point those hormones actually DECREASED as the cortisol production took over.
If you have anxiety problems or a very active, agitated type of depression that could clearly be the case...
And might be worth having those adrenaline hormone levels checked...
The protocols being tested for re-setting the HPA Axis as relates to excessive cortisol secertion probably wouldn't be of any effect in that scenario though.
Elroy
X
X
X> I guess what I'm wondering is if low or high cortisol levels are the sole indicator of HPA disfunction; or is depression in and of itself the main indicator?
Posted by Jordann on June 30, 2005, at 14:51:02
In reply to Re: Prednisone in atypical depression » Maximus, posted by ed_uk on June 16, 2005, at 11:16:34
I've been dealing with depression for over a decade. My symptoms include fatigue, excessive daytime sleeping, depressed mood, low productivity, and inability to concentrate. I've been feeling absolutely wonderful for the past week or two. I was just sitting here at my desk contemplating how on earth I could feel so incredible. Then I scratched my arm. Poison oak. I've been taking prednisone for the past two weeks. I thought hey, why not, so I googled prednisone and depression and found this site. As I said, I have not felt this good in years. I think there may be something to what you guys are discussing.
Posted by ed_uk on June 30, 2005, at 16:42:26
In reply to Re: Prednisone in atypical depression, posted by Jordann on June 30, 2005, at 14:51:02
Hi Jordan,
What dose of prednisone are you taking?
~Ed
Posted by Elroy on June 30, 2005, at 17:17:34
In reply to Re: Cortisol_testing » Maximus, posted by EERRIICC on June 19, 2005, at 23:24:09
Happened to re-visit this and wasn't sure that it had been properly answered.
I don't believe that depression - by itself with no other HPA Axis hormonal malfunctions indicated - would be considered a main indicator.
The HPA Axis controls the production of certain hormones (cortisol, DHEA, testosterone - via the HPAT Axis, the various adrenaline hormones, etc.). If the regulated hormones are being secreted consistently within normal ranges and over long-term observations, then an assumption would have to be made that there is no HPA Axis dysfunction. And adopting a mode of treatment specifically geared towards allieviating a dysfunctional HPA Axis (and then a particular, specific process within that HPA Axis operation) would be inappropriate.
As an example, the HPA Axis can be dysfunctional in the sense that burn-out has occurred and adrenal functioning is slowing down very significantly and cortisol levels are well below normal. That is Adrenal Fatigue and would be treated in a specific direction (with concurrent efforts hopefully to get the HPeA Axis re-set). That disorder can very definitely lead to depression.
The opposite of that would be hypercortisolism where the adrenal glands are pumping out way too much cortisol. That disorder would be treated in a different direction (but also hopefully with a goal of getting the HPA Axis to "re-set"). That disorder can definitely lead to not only depression (and some severe forms of depression), but also develop severe anxiety.
A thread you might want to scan through to get more detailed info...
http://www.dr-bob.org/babble/20050617/msgs/515432.html
Elroy
X
X
X
X> I guess what I'm wondering is if low or high cortisol levels are the sole indicator of HPA disfunction; or is depression in and of itself the main indicator?
Posted by Elroy on June 30, 2005, at 18:07:32
In reply to Re: Prednisone in atypical depression, posted by Jordann on June 30, 2005, at 14:51:02
Did you ever have your daily cortisol levels tested (via a 25-hr UFC - Urinary Free Cortisol - test)?
Your symptoms sounds very much like classical symptoms of low cortisol - which can also readily cause depression...
That method of treatment would probably *not* be a recommended protocol for someone who's depression was a result of the opposite problem: highly elevated cortisol....
Prednisone is an artificial form of cortisol and as such would - IMHO - simply add to the problems of one who was experiencing mental/emotional disorders (and - as in my case, unfortunately, also some uncomfotable physical effects also) due to highly elevated cortisol...
Elroy
X
X
X
X
> I've been dealing with depression for over a decade. My symptoms include fatigue, excessive daytime sleeping, depressed mood, low productivity, and inability to concentrate. I've been feeling absolutely wonderful for the past week or two. I was just sitting here at my desk contemplating how on earth I could feel so incredible. Then I scratched my arm. Poison oak. I've been taking prednisone for the past two weeks. I thought hey, why not, so I googled prednisone and depression and found this site. As I said, I have not felt this good in years. I think there may be something to what you guys are discussing.
Posted by iforgotmypassword on July 1, 2005, at 3:30:36
In reply to Re: Prednisone in atypical depression, posted by Jordann on June 30, 2005, at 14:51:02
do you remember how long it took to feel an effect and what dose you were on?
Posted by Jordann on July 1, 2005, at 12:18:22
In reply to Re: Prednisone in atypical depression, posted by iforgotmypassword on July 1, 2005, at 3:30:36
I was adjusting my dose based on how bad I was itching. I took between 30 and 60 mg per day. I felt not depressed within a day or two.
Posted by iforgotmypassword on July 3, 2005, at 19:53:29
In reply to Re: Prednisone in atypical depression, posted by Jordann on July 1, 2005, at 12:18:22
This is the end of the thread.
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