Posted by NewQuestions on February 4, 2009, at 14:25:08
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by SLS on February 3, 2009, at 17:40:42
I just read this on another site. It may explain some of the problems I am having:
In my humble opinion, discontinuation syndrome is a form of hypothalamic-pituitary-adrenal (HPA) axis dysregulation. One way to look at it is as induced hypercortisolemia or even pseudo-Cushings Syndrome. See Gillespie, et al, Hypercortisolemia and Depression, Psychosomatic Medicine 67:S26-S28 (2005), full text available at http://www.psychosomaticmedicine.org...plement_1/S26:
"...More than 40 years ago, a significant number of patients with depression were noted to exhibit both hypersecretion of cortisol (1,2) and its metabolites (3). The observation that patients with Cushings disease or syndrome often experienced severe depression and anxiety, and the increased production and secretion of glucocorticoids such as cortisol in healthy people exposed to stress, in part contributed to the modern stress-diathesis hypothesis of depression in which excess secretion of cortisol is thought to play a significant pathophysiologic role in the etiology of depression....
... Currently, several novel approaches to the treatment of depression are being evaluated based on the present understanding of HPA axis dysregulation in mood disorders. The CRF-1 receptor antagonist R121919 has shown promise in the treatment of depression (43) but was subsequently withdrawn from clinical trials due to hepatotoxicity. More recently, the glucocorticoid receptor antagonist, mifepristone (RU486), has been reported to be effective in the treatment of psychotic depression (44). These compounds may be effective in treating depression through the interruption of reverberating neuroendocrine loops involving the HPA axis and several areas of the brain (prefrontal cortex, amygdala, hippocampus, and hypothalamus) that become excessively activated in response to stress driven perhaps by hypersecretion of CRF. Such interruption of a positive feedback loop may allow the system to return to a more adaptive set point associated with remission of depression (45)...."
One of the researchers looking at glucocorticoid receptor antagonists as described above is Dr. Owen Wolkowitz at the University of California San Francisco (See Wolkowitz and Reus, Treatment of Depression With Antiglucocorticoid Drugs, Psychosomatic Medicine 61:698-711 (1999), see full text at http://www.psychosomaticmedicine.org...full/61/5/698).
Aside from antiglucorticoids, including RU486 aka the abortion pill, Drs. W. and Reus discussed high doses of the glucocorticoid dexamethasone:
"...If short-term, high-dose dexamethasone treatment proves to have antidepressant effects, how might this be reconciled with antiglucocorticoids having similar effects? Antiglucocorticoids and dexamethasone administration could both have antidepressant effects via 1) their common effect of lowering cortisol levels (with resultant upregulation of brain corticosteroid receptors); 2) altering levels of other adrenal steroid hormones; or 3) increasing ACTH levels (with short-term, high-dose dexamethasone treatment, this might occur after dexamethasones acute inhibitory effects are terminated and the suppressed adrenal axis signals increased ACTH output). Additionally, recent evidence suggests that dexamethasone is actively excluded from brain and does not replace endogenous corticosteroids at hippocampal mineralocorticoid and glucocorticoid receptor sites (144). Its behavioral effects, therefore, may result from indirect effects of dexamethasone-induced ACTH suppression on the balance between the two corticosteroid receptor types in the hippocampus (144). Long-term dexamethasone treatment has also been shown to result in an increase in glucocorticoid receptor mRNA levels in hippocampus, an effect that parallels changes observed over the course of antidepressant treatment (33, 145)...."
Steroids are used to treat many illnesses, including autoimmune diseases, and people do take them for quite a while. Doctors do know how to use them, but they usually prescribe them in very high doses that have serious side effects. Note that I have been emphasizing a LOW DOSE approach.
I believe the HPA axis dysregulation resulting from discontinuation syndrome makes us hypersensitive -- we don't need much of anything to tip into HPA overdrive. A physiological dose rather than a therapeutic dose of anything can go a long way with us. The large doses of steroids that doctors usually prescribe are way, way too strong. Taking the hyperreactivity of the HPA axis into account, a tiny bit of something could help break the cortisol feedback loop -- "the self-propagating response" -- and help the HPA axis stabilize.
poster:NewQuestions
thread:874312
URL: http://www.dr-bob.org/babble/20090203/msgs/877993.html