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!
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> 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.
poster:djmmm
thread:337215
URL: http://www.dr-bob.org/babble/20040417/msgs/337256.html