![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 28. This is the beginning of the thread.
Posted by temoigneur on June 16, 2005, at 1:32:41
Full article: http://bjp.rcpsych.org/cgi/content/full/177/5/390
excerpt on therapeutic approaches,FUTURE THERAPEUTIC TARGETS
TOP
ABSTRACT
INTRODUCTION
HYPOTHALAMIC-PITUITARY-ADRENAL...
ANTIDEPRESSANTS, MOOD...
PRIMARY CONSEQUENCES OF...
FUTURE THERAPEUTIC TARGETS
Clinical Implications and...
REFERENCES
As discussed above, there is robust evidence of a dysfunction in HPA autoregulatory mechanisms in mood disorders, and it has been proposed that the consequent hypercortisolaemia is in some way integral to the pathogenesis of affective symptoms and cognitive deficits. It is therefore not surprising that research into potential treatments of mood disorders has focused on strategies designed to modulate the effects of hypercortisolaemia and/or the mechanisms underlying it.Dehydroepiandrosterone
One strategy for counteracting the effects of hypercortisolaemia, used with some success in the treatment of depression, makes use of the adrenal steroid dehydroepiandrosterone (DHEA; Bloch et al, 1999; Wolkowitz et al, 1999a). Although the physiological function of DHEA and its sulphated metabolite (DHEA-S) is unclear, these circulating corticosteroids have been shown to possess antiglucocorticoid properties, and high cortisol/DHEA ratios are reported to be associated with persistent depression (Goodyer et al, 1998). However, although DHEA does possess antiglucocorticoid activity, it is partially metabolised to testosterone and oestrogen, which have mood effects of their own and may contribute to DHEA's antidepressant effect (Wolkowitz et al, 1999a).Steroid synthesis inhibitors
Raised levels of cortisol can be lowered pharmacologically by inhibitors of steroid synthesis, and drugs of this class have been used with some success in the treatment of unipolar depression. Ravaris et al (1988) were the first to report that daily doses of ketoconazole reduced both cortisol levels and depressive symptoms within 72 hours in a case of treatment-resistant depression. Since then there have been a number of systematic studies and case reports investigating the use of not only ketoconazole but also metyrapone and aminoglutethimide as antidepressant therapies; as yet, however, the results of these studies are inconsistent (see Murphy, 1997, for review). This inconsistency is emphasised by two recent double-blind studies. Thus, while Wolkowitz et al (1999b) found a marked reduction in depressive symptoms following ketoconazole treatment in patients suffering from major depression, Malison et al (1999) found no therapeutic effect of the drug in a similar patient group. It is worth noting that in the former study, ketoconazole was effective in hypercortisolaemic but not normocortisolaemic patients with depression (Wolkowitz et al, 1999b). Unfortunately, one of the main factors which limits the use of steroid biosynthesis inhibitors as antidepressive therapy is the high incidence of side-effects resulting from generalised steroid biosynthesis inhibition.Corticotropin-releasing hormone antagonists
On the basis of the evidence for oversecretion of CRH in mood disorders, blockade of CRH receptors has been proposed as an approach to normalising hypercortisolaemia. Preclinical studies do indeed indicate that CRH antagonists will be of use in clinical conditions related to HPA hyperactivity, particularly anxiety disorders. Clinical investigations into the use of these compounds in many psychiatric conditions are presently underway and we await their results (see Holsboer, 1999, for review).Type II glucocorticoid receptor (GR) agonists
An alternative strategy for lowering circulating cortisol is activation of the GR-mediated negative-feedback mechanism that regulates cortisol levels. Sub-acute doses of dexamethasone (e.g. 3-4 mg daily for 4 days) have been reported to show antidepressant efficacy (Arana et al, 1995; Bodani et al, 1999). At this dose dexamethasone is thought not to enter the central nervous system and consequently central GRs are spared activation by this exogenous glucocorticoid. Activation of GRs at the level of the pituitary does occur, leading to a lowering of endogenous cortisol. If dexamethasone treatment does indeed act by lowering endogenous cortisol, then it would be interesting to correlate its therapeutic efficacy with the response of patients in the DST. Finally, it should be added that an advantage of the brief course of administration advocated by these studies is a reduction of the side-effects associated with longer-term dexamethasone treatment.Type II glucocorticoid receptor (GR) antagonists
Paradoxically, as well as GR agonists, GR antagonists have also been advocated as potentially of therapeutic benefit for mood disorders. This is based on the ability of the GR antagonist to block any detrimental effects of the raised levels of circulating cortisol and on the ability of an antagonist to up-regulate its receptor. Thus, administration of a GR antagonist might be predicted to have an acute antiglucocorticoid activity, while also causing a compensatory up-regulation of GR number, leading to enhanced negative feedback on the HPA axis. Preliminary clinical studies using the GR antagonist RU-486 (mifepristone) have been encouraging, even though some clinical efficacy may have been obscured by the prolonged administration of the drug (Murphy et al, 1993). However, animal work suggests that GR numbers can be increased rapidly (within hours) and it is possible that normal feedback is maintained after administration of the antagonist has ceased. This indicates that a brief (i.e. a few days) period of administration of antagonist may be adequate to increase number and normalise HPA function. This might reduce problems of non-compliance and side-effects associated with longer-term administration (Laue et al, 1990). A number of new, selective GR antagonists are currently being developed, although preliminary reports suggest that some of these drugs may lack ability to up-regulate the receptors (Bachmann et al, 1999).An evaluation and critique of case reports and clinical trials of some of the treatments outlined above has recently been reported (Wolkowitz & Reus, 1999). The cumulative evidence makes a strong case implicating GRs in the pathogenesis of affective disorders and suggests targeting these receptors in development of new therapies. We predict that drugs designed specifically to up-regulate GRs will be integral to future therapeutic strategies and may provide a long-awaited paradigm shift in the treatment of unipolar and bipolar mood disorders.
Posted by temoigneur on June 16, 2005, at 2:42:21
In reply to Interesting article - HPA dysfunction in mood diso, posted by temoigneur on June 16, 2005, at 1:32:41
PSYCHOTIC MAJOR DEPRESSION (PMD)
http://psychoticdepressionalgorithm.stanford.edu/default.asp?main=main.asp
Click here for a detailed discussion of PMD, or click on one of the section titles below to see more details about that specific topic.
Clinical Features
Psychotic or delusional marked by the presence of hallucinations or delusions that occurs only coincident with the depressed mood symptoms.
Paranoid delusions may be the most common delusions.
Delusions appear to be more common than hallucinations.
Patients with PMD tend to demonstrate greater agitation, early and middle insomnia, depressed mood and guilt, and absence of diurnal variation, and greater cognitive impairment then patients with non-psychotic major depression disorder (MDD).
Diagnostic Criteria
Diagnostic Criteria for Major Depression with Psychotic Features
Adapted from Diagnostic and Statistical Manual of Mental Disorders
Fourth Edition DSM-IV
Published by the American Psychiatric AssociationDifferential Diagnosis
The most important differential diagnosis is with MDD.
PMD patients tend NOT to exhibit elements of a formal thought disorder that characterize schizophrenia.
Presence of bizarre delusions ("Aliens have planted a receiver in my head") appears to be less common in PMD than in schizophrenia.
Course
Episodes of PMD tend to be discrete and time limited.
Patients generally function well between episodes, both interpersonally and vocationally.
The psychosocial impairment does not typically approach that seen in schizophrenia.
PMD patients are more likely than MDD patients to be hospitalized in any given episode.
The average age of onset is in the 30s and 40s.
No difference between MDD and PMD patients in the risk of suicide.
Pathophysiology
PMD tends to be marked by the following:A marked abnormality of the hypothalamic pituitary adrenal (HPA) axis.
High levels of urinary free cortisol, basal serum cortisol levels, and high serum corticotropin releasing factor (CRF) levels.
High levels of unconjugated dopamine and the dopamine metabolite homovanillic acid (HVA) after dexemethasone administration.
Higher levels of tyrosine hydroxlase activity that can contribute to higher dopamine levels and activity.
Poorer sleep efficiency, reduced REM sleep, diminished slow wave sleep, and a higher percentage in stage one sleep.
Higher levels of serotonin metabolites (5-HIAA), and higher rates of platelet serotonin reuptake.
Treatment
PMD is less likely than MDD to respond to placebo and to monotherapy with either antidepressants or antipsychotics.
Only 25-40% of patients respond to tricyclic antidepressants.
Typical antipsychotics alone appear to be ineffective in the treatment of PMD, although they do help with the psychotic symptoms
Atypicals alone may also be ineffective in PMD.
Combination of an antidepressant and an antipsychotic appears to be necessary for the treatment of PMD.
Recommended Treatment Strategies
First line strategy might be the combination of an atypical agent and either an Selective Serotonin Reuptake Inhibitor (SSRI) or venlafaxine.
A second line strategy might be the combination of a tricyclic antidepressant (TCA) with an atypical antipsychotic or the use of amoxapine.
ECT may have a more reliable track record in improving symptoms than pharmacological treatments.
Experimental Treatment Strategies
Current studies looking at on glucocorticoids antagonists, such as C-1073 (mifepristone or RU 486), which works by blocking the GR II receptor in the brain.
Transcranial Magnetic Stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression.
Posted by ed_uk on June 16, 2005, at 7:04:42
In reply to Interesting article - HPA dysfunction in mood diso, posted by temoigneur on June 16, 2005, at 1:32:41
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 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.
Go forward in 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.