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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by Ame Sans Vie on April 17, 2004, at 15:25:28
I found this article listed on BioMedNet, but no abstract is available. If anyone out there can get the abstract/full article, I'm sure a lot of people would be interested to read it!
_________
Tolerance to antidepressant treatment may be overcome by ketoconazole. Report of two cases [Letter to the Editor]
Nicoletta Sonino
Tolerance to antidepressant drugs treatment is an important clinical problem which may manifest as resistance or loss of clinical effect (Baldessarini et al., 2002). Resistance occurs when a patient, after...
Journal of Psychiatric Research, 2003, 37:2:171-173
Posted by linkadge on April 17, 2004, at 16:28:34
In reply to Article: Ketoconazole prevents AD poop-out?, posted by Ame Sans Vie on April 17, 2004, at 15:25:28
I wonder if it is something about this particular medication or if is something that might be shared by other antifungal medication.
Strange that something like this would work.
Linkadge
Posted by SLS on April 17, 2004, at 19:15:21
In reply to Re: Article: Ketoconazole prevents AD poop-out?, posted by linkadge on April 17, 2004, at 16:28:34
> I wonder if it is something about this particular medication or if is something that might be shared by other antifungal medication.
>
> Strange that something like this would work.
>
> Linkadge
Ketoconazole inhibits the secretion of cortisol.
- Scott
Posted by djmmm on April 17, 2004, at 19:57:34
In reply to Article: Ketoconazole prevents AD poop-out?, posted by Ame Sans Vie on April 17, 2004, at 15:25:28
> I found this article listed on BioMedNet, but no abstract is available. If anyone out there can get the abstract/full article, I'm sure a lot of people would be interested to read it!
>
> _________
>
>
> Tolerance to antidepressant treatment may be overcome by ketoconazole. Report of two cases [Letter to the Editor]
> Nicoletta Sonino
> Tolerance to antidepressant drugs treatment is an important clinical problem which may manifest as resistance or loss of clinical effect (Baldessarini et al., 2002). Resistance occurs when a patient, after...
> Journal of Psychiatric Research, 2003, 37:2:171-173something related....
Glucocorticoid Antagonists
As elevated corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH)/cortisol activity is frequently associated with depression, consideration has been given to treatments that reduce glucocorticoid function. Positive open clinical trials have been reported for amino glutethamide, ketoconazole, and metapyrone in treatment-resistant depressed patients (58) and ketoconazole in hypercortisolemic depressed patients (85). Animal model studies using either normocortisolemic animals or the hypercortisolemic Fawn-hooded rat strain that manifests depressionlike behavior (4) have not yet been completed.
also...
Corticosteroid modulation of 5-HT receptors has important implications for the pathophysiology and treatment of mood disorders, and perhaps suicide. This may be one of the mechanisms by which stressful events can precipitate depressive episodes in some (genetically) vulnerable individuals and or precipitate suicidal behavior. Another implication is that altered 5-HT levels or metabolism do not necessarily have to be present for 5-HT receptor abnormalities to occur. Based on the animal data, it is apparent that specific 5-HT receptors may be directly regulated in response to alterations of corticosteroid levels. Thus, in depressed patients normal levels of serotonin and its metabolites may not necessarily reflect normal central 5-HT activity.
An important therapeutic implication of this model is the prediction that agents that can reduce the stress response, and/or decrease LHPA activation, will be useful in the pharmacological treatment of anxiety, depression and perhaps suicidal behavior. In fact, patients with MDD who are resistant to antidepressant treatment, have been reported to improve after receiving steroid suppression agents, like ketoconazole (Murphy et al 1991; Wolkowitz et al 1993). However, these agents have many side effects, and are often difficult for patients to tolerate. In this respect, CRH receptor antagonists, which are currently under development, may provide us with a new therapeutic weapon to treat these patients (De Souza 1995, Chalmers et al., 1996). These compounds could be used in conjunction with antidepressants, as adjuvants or augmenting agents, and may decrease treatment resistance. This agents may also be useful in monotherapy, since preventing hypercortisolemia may be translated into an improvement of monoaminergic receptor function. The use of modern biochemical and pharmacological tools, coupled with our increased understanding of the neurobiology of depression, should allow us to test these hypotheses, first in animal models and then directly in patients with affective illness.
and...
CRH antagonists might be antidepressants,19 although there have been a few hypothalamic-pituitary-adrenal axis negative findings. Inhibitors of cortisol synthesis, such as ketoconazole20 or metyrapone,21 have an antidepressant effect. Vasopressin also stimulates corticotropin (ACTH) secretion, but vasopressin antagonists have not been clinically studied. Urocortine has a strong affinity for the two types of CRH receptors, as well as for the protein that binds CRH; it could therefore serve as a target for new antidepressants.
Posted by cubbybear on April 18, 2004, at 4:35:54
In reply to Article: Ketoconazole prevents AD poop-out?, posted by Ame Sans Vie on April 17, 2004, at 15:25:28
So, you ARE out there! Did you see my post for you a few days ago (re: Are MAOIs and anti-cholinergic drugs contraindicated?)? I directed it to you because I've known about your expertise with so many meds. Can you reply?
cubbybear
Posted by Rick on April 21, 2004, at 0:10:13
In reply to Article: Ketoconazole prevents AD poop-out?, posted by Ame Sans Vie on April 17, 2004, at 15:25:28
I put the title of the article you cited in quotes, popped it into the Google search box, and came with a short report on it (see below). While the report is pretty topline, it's clear that the passages cited by djmmm do relate.
I wonder what AD's were used? Ketoconazole is a heavy-duty inhibitor of some CYP450 enzymes, so I wonder if some of the poop-out reversal could have simply been due to inhibiting the AD's metabolism and thus effectively increasing the dose.
Rick
http://www.advancesinlifescience.com/features_17.htm
Breaking the mould of resistant depression
06 May 2003 - Features EditorCould an old antifungal open up a new way to tackle the problem when antidepressant drugs stop working?
The development of tolerance to antidepressant treatment is an important clinical problem affecting about one third of patients treated for depression. This can show up as a loss of clinical effect, for example an antidepressant, which was working becomes less effective. In some cases, patients may develop resistance after a period of time off treatment, failing to respond to an antidepressant which had been effective previously.
Until now there has been no satisfactory explanation nor a way to improve treatment of antidepressant intolerance or resistance. Now Nicoletta Sonino, endocrinologist at the Department of Mental Health in Padova working together with Giovanni A. Fava at the University of Bologna in Italy, have described a novel way to tackle the problem.
Their work was based on assessing the hypothalamic-pituitary-adrenal (HPA) axis in such patients -they found their HPA axis seemed to be overactive. The breakthrough came from using a treatment to bring down the level of steroids in the blood. One way to do this is by giving patients ketoconazole. This is an agent which is often used for treatment of systemic fungal infections, including thrush. Ketoconazole is also known to block adrenal steroid production. Sonino and Fava found that ketoconazole was effective in reversing the tolerance to antidepressants in two carefully studied cases.
Clearly, a larger scale investigation will be needed, but the pioneering work by Sonino and Fava opens up a new avenue for helping a large number of patients to overcome depression when tolerance or resistance to medication is a problem.
Peer reviewed publication and reference:
Sonino N, Fava GA: Tolerance to antidepressant treatment may be overcome by ketoconazole. Report of two cases. J Psychiat Res 2003 ; 37 : 171-173
Keywords : Antidepressant Tolerance Resistance Ketoconazole Antifungal agent Steroid biosynthesis inhibitor HPA axis Clinical reversal of tolerance
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