Posted by Larry Hoover on February 6, 2009, at 11:46:48
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 4, 2009, at 14:25:08
> In my humble opinion, discontinuation syndrome is a form of hypothalamic-pituitary-adrenal (HPA) axis dysregulation.
>
> 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.For some depressives, this may be true. It's long been recognized that abnormalities in both baseline HPA function, and in its response to stimulation, are associated with mood disorders. In contrast to your thoughts, I think the evidence shows that antidepressant therapy often fails to normalize HPA function during treatment, and in that respect its failure is due to its having been an inappropriate treatment. Depression is a heterogenous disorder, and one lone treatment strategy just doesn't meet every need.
The following study looked at 235 inpatient depressives, and sought correlations between HPA-axis function and a large number of potential influences upon it.
Pharmacological and Nonpharmacological Factors Influencing HypothalamicPituitaryAdrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test
(full-text link)
http://www.nature.com/npp/journal/v28/n12/full/1300280a.htmlI've pulled some selected quotes from it, and I'll make some comments as I go through them.
"The reactivity of the HPA-axis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms....peak cortisol values range from 3.9 to 332.4 ng/ml (mean/SD=62.6/55.3)."
I think this is an amazingly important finding. There is roughly 100-fold difference in peak cortisol response across this sample population of acutely depressed patients. Depressive symptomatology is not a predictor of HPA activity or sensitivity.
"We first investigated whether the type of current antidepressant treatment affected the outcome of the Dex-CRH test. In all, 32 patients did not receive any medication at the time of the Dex-CRH test. The other patients were divided according to the class of the administered antidepressants, the largest groups being selective serotonin reuptake inhibitors (SSRIs) (N=58), tricyclic antidepressants (N=37), and mirtazapine (N=27). A general linear model showed no significant effect of type of antidepressant treatment on any of the Dex-CRH test parameters."
This finding doesn't rule out the possibility that some individuals were significantly influenced by treatment modality, but overall, no effect of acute antidepressant treatment was observed.
"A partial correlation analysis showed no correlation of any of the investigated Dex-CRH test parameters with the number of antidepressant treatment trial in the index episode or overall."
The number of times a person was treated with antidepressants did not influence HPA function.
"Nonparametric analysis showed significant differences between patients whose episode started under an established psychopharmacotherapy (n=36) vs patients who were not treated (n=160) at the time of the onset of the current episode."
Subjects whose depression relapse occurred while medicated had enhanced HPA activity. So, rather than medication per se, medication failure is an acute trigger of HPA activity.
"We could not show an association of presence or absence of antidepressant treatment, the type of antidepressant treatment or of the number of previous ineffective antidepressant treatment attempts before hospitalization and the results of the Dex-CRH test, indicating that the reported normalizing effect of antidepressant treatment on the Dex-CRH test is actually dependent on clinical improvement and not just a pharmacological side effect."
Remission of symptoms during treatment is associated with normalization of HPA parameters, and that is independent of prior experiences.
In discussing the finding that relapse during treatment led to exaggerated HPA response, they said:
"One possible explanation of this effect may be that patients relapsing without an established pharmacotherapy are also more likely to have no medication at the time of the test. Indeed 26 patients in this group vs only two in the treated group were medicated at the time of the test."I point this out simply to emphasize that this finding may be due to selection bias alone. These subjects ended up in the trial because they were experiencing relapse during treatment. They may be atypical.
There was then substantial discussion in the paper about some physiological HPA regulatory parameters that may be influenced by antidepressants, but they then say:
"It is also conceivable that patients with a recurrent depressive disorders, who are more likely to relapse under pharmacotherapy, represent a biologically distinct subgroup of patients, featuring enhanced cortisol and ACTH responses in the Dex-CRH test."They make the atypical subject argument more concise.
What seems to come through for me, reading this paper and others in a similar vein, is that HPA dysfunction is a fundamental characteristic of depression. It remits when depression remits. It also precedes, and therefore predicts, relapse. For those individuals with exaggerated HPA response, treatment selection ought to be a primary concern. I think it's a failure in the typical diagnostic process that HPA function is not fully assessed prior to, and during, treatment. This study found 100-fold HPA variability in its subjects. I strongly suspect that HPA function is relatively stable in each individual, despite the variability within the group. What you bring into depression (HPA function trait) stays with you in treatment, remission, or relapse. Specific treatments may be appropriate or inappropriate for an individual, but are not the cause of the HPA dysfunction itself. In my opinion.
Lar
poster:Larry Hoover
thread:874312
URL: http://www.dr-bob.org/babble/20090203/msgs/878461.html