![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 53 to 77 of 89. Go back in thread:
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 The CRF-1 receptor antagonist R121919 has shown promise in the treatment of depression (43) but was subsequently withdrawn from clinical trials due to hepatotoxicity.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.
Posted by Garnet71 on February 4, 2009, at 15:18:55
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 4, 2009, at 14:25:08
Hey New Questions,
I keep coming back to this thread too. I have to admit that I cannot read that whole thing right now. Do you think this is worth bringing to my endochronologist next week, or would she just roll her eyes if I presented it?
Is the pituitary gland that one at the base of your neck? I was going to start a new thread about a symptom I've had for a few months now-lots of fluid sounds and sensations coming from the back of my neck/base of my head. Or does everyone have that?
Maybe someone will come along and interpret the article you posted. I hope you are closer to finding a solution to your health issues!!
Thanks,
Garnet
Posted by SLS on February 4, 2009, at 15:55:00
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.
Maybe we can put our humble heads together and come up with a more comprehensive theory. I feel that something must precede the HPA dysregulation. I suggest that the withdrawal syndrome is the result of neural hyperactivity in several areas of the brain, including the amygdala, the fear center of the brain, thus producing anxiety as one of the symptoms. I think it might be the kindling of glutamatergic pathways that leads to the persistence of withdrawal syndrome after discontinuation seen in some people.
It is my suggestion that it is a kindling effect that a rapid discontinuation of a SRI drug induces that makes one more sensitive to drugs subsequently.
Somewhere in here is, of course, serotonin. It is probably the loss of serotoninergic inhibition of glutamatergic pathways that allows for the withdrawal syndrome to manifest.
- Scott
Posted by NewQuestions on February 4, 2009, at 16:04:15
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by Garnet71 on February 4, 2009, at 15:18:55
Thanks Garnet. My sense is that you are not experiencing what I am experiencing. My body has adapted to the drugs, I have become hypersensitive to them, I am now off of them and my body is stressed because of the withdrawal, and the HPA axis is not in balance. My sense with you is that you are still struggling to find the right drug to begin with. Therefore, the information might not be of much value to you.
Posted by SLS on February 4, 2009, at 16:32:45
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 4, 2009, at 16:04:15
> Thanks Garnet. My sense is that you are not experiencing what I am experiencing. My body has adapted to the drugs, I have become hypersensitive to them, I am now off of them and my body is stressed because of the withdrawal, and the HPA axis is not in balance. My sense with you is that you are still struggling to find the right drug to begin with. Therefore, the information might not be of much value to you.
There is always the "spit test". It is a quick way to get a cortisol level. In depression, cortisol is often elevated. This test used to be used routinely in the 1980s in some clinics.
There is also the dexamethasone-suppression test (DST) to evaluate the state of the HPA axis. The subject takes a single dose of dexamethasone, a corticosteroid. In a healthy person, this will produce a negative feedback loop that reduces (suppresses) the amount of ACTH released by the pituitary gland. This can be assayed in the blood. In many depressed people, ACTH secretion is not inhibited. So, dexamethasone non-suppression is an indication of major depressive disorder.
- Scott
Posted by SLS on February 4, 2009, at 16:36:58
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 4, 2009, at 14:25:08
Hi NQ.
I sometimes suggest that people make three lists:
1. Drugs that produced a positive response, regardless of the length of time or how robust.
2. Drugs that produced a negative response, making one's depression more severe.
3. Drugs that had no effect on depression.
What drugs have you had some sort of positive response in the past. Sometimes it is as simple as combining partially drugs to produce a full remission.
- Scott
Posted by Garnet71 on February 4, 2009, at 21:50:52
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 4, 2009, at 16:04:15
> Thanks Garnet. My sense is that you are not experiencing what I am experiencing. My body has adapted to the drugs, I have become hypersensitive to them, I am now off of them and my body is stressed because of the withdrawal, and the HPA axis is not in balance. My sense with you is that you are still struggling to find the right drug to begin with. Therefore, the information might not be of much value to you.
--------------------------
So NewQuestions, for me, I am almost convinced now (esp after hanging out here for a while!) that my problems are more endo related and a combination of long-term heavy stress, anxiety (which totally drains you physically & exhausts your system), ADD cognitive type, and just having had the PTSD/depressive episode almost a decade ago; also having the genetic disposition of these problems have all led up to my current state of well being. I also think use of anti-depressives does screw up your endo system, especially with all the other variables listed.I think back, and when the heavy depression dissipated, I was off drugs and was temporarily assigned to an extremely stressful job for one year. I won't go into too much detail..but it was a job that had a whole special shift and safety parameters due to its highly stressful nature. You could not even go to the bathroom for at least 6 hours after you started because if you missed one little detail...you could easily lose track of all the operations. Much of the time you had to make split-second decisions to decide what major issue you should make a decision on first, there was so much fired at you nonstop; it was multitasking on steriods. I kicked a$# at the job and loved it. I think I overdid it. I was medication free at the time.
Now that I look back, it was after this time I started feeling my worst and went back on ADs for severe anxiety.
So-I was thinking about if your situation relates to mine and remembered a class I once had. Economists have actually done research on your profession, and the little I saw concerned the newbies in your line of work who had to work rediculously long hours and put in like 500% for a few years until they reached a certain milestone for the firm. Of course, it's uphill from there. I forgot to ask you about that last time we spoke.
Have you been under a lot of chronic stress--long-term? I could be totally wrong, but I think your symptoms are more similar than when we discussed them last time.
I'm going to an endochronologist next week, and last we talked--you were thinking about doing the same. I've been medication-free for a couple of weeks now; don't want to skew any test results. It may (or may not) be a matter of getting treatment for multiple issues rather than letting a psychiatrist alone determine my destiny.
I'll check back on this thread and let you know how it goes! Until then, hang in there!
Posted by Garnet71 on February 4, 2009, at 21:55:11
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by Garnet71 on February 4, 2009, at 21:50:52
New Questions - forgot to say, if you want, I can email the professor who published that research and get a copy for you. It's very interesting :)
Posted by SLS on February 5, 2009, at 1:52:52
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by SLS on February 4, 2009, at 16:36:58
Forgot the word "effective".
"What drugs have you had some sort of positive response to in the past? Sometimes it is as simple as combining partially effective drugs to produce a full remission."
A good friend of mine was smart enough to do this. She had partial responses to Effexor and Wellbutrin given as monotherapy. She described Wellbutrin as giving her more energy, and Effexor as giving her the "wanna do's". In her mind, she superimposed the feelings that the two drugs produced separately and asked the doctor to be placed on both in combination. Bingo.She has since tweaked her regime by swapping Effexor for Lexapro and adding Geodon. Geodon can be energizing.
- Scott
Posted by SLS on February 5, 2009, at 1:54:57
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by Garnet71 on February 4, 2009, at 21:50:52
Posted by NewQuestions on February 5, 2009, at 9:35:50
In reply to Re: Long Term SSRI Use Has Destabilzed Me » SLS, posted by SLS on February 5, 2009, at 1:52:52
Assuming it is the glutamatergic pathways, how do I fix it? My most distressing symptons are cognitive decline (memory, abstract reasoning, learning) and lack of energy.
Posted by SLS on February 5, 2009, at 13:52:29
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 5, 2009, at 9:35:50
> Assuming it is the glutamatergic pathways, how do I fix it? My most distressing symptons are cognitive decline (memory, abstract reasoning, learning) and lack of energy.
That sounds like depression to me, my friend. Often, we confuse withdrawal for relapse. Is there anything that leads you to believe that you are not experiencing a relapse?
I think using anticonvulsants or benzodiazepines might help mitigate an ongoing withdrawal syndrome if kindling is to be avoided. Actually, a more rational approach is not to let the withdrawal syndrome develop in the first place. I believe this can be done with a flexible-dosing strategy. Please see: http://www.dr-bob.org/babble/wdrawl/20081229/msgs/877349.html
Please write back. I'd like to get to the bottom of this.
- Scott
Posted by NewQuestions on February 5, 2009, at 17:08:08
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by SLS on February 5, 2009, at 13:52:29
Winter 1994: start Zoloft, work up to 200mg, no atypical side effects
August 2002: Zoloft side effects change dramatically--more lethargic, less muscle energy, brain fog, confusion, heaviness, mentally lazy, nonrestful sleep, more withdrawn, physically grooming worsens. It was still "working" on my depression but the side effects were overwhelming. What was the cause? Is this poop out or something else?
Winter 2003: wean off zoloft and onto Lexapro--very difficult--seem to experience withdrawal effects from zoloft and SSRI side effects from Lexapro at same time--confusion, muscle energy, fogginess
Winter 2004: I finally got off zoloft, and some of the heaviness and confusion was gone. However, still experiencing similar side effects on Lexapro. Tapered from 20 mg to 10 mg of Lexapro and experience new clarity and energy. However, experienced withdrawal--nausea, lack of energy and anxieties come back. So I stayed on 10 mg of Lexapro and tried Cymbalta. Very energizing but caused anxiety. Wellibutrin and TCA's caused hypomania.
Next, tried Remeron which made me feel better, smarter, more cognitive energy, relieved the inner-tension but it made me incrediably tired during the day. I tried prozac (small dose) and for the first 4 weeks, it was great. It stimulated me and gave me cognitive energy. However, it suddenly sent me into a suicidal depression, which didn't go away until over a month later, i.e., when the prozac with its long half life exited my body. Yes, it was the drug, it was not environmental.
In September 2006, tried remeron again and it gave me a numbing depression. (Same drug different effect--did the prozac adverse reaction change me?) All of the benzos gave me a similar numbing depression (except Ativan). Then I tried effexor. Effective against depression but was hypersentitive to it. It caused jitterines, lack of inner well-being, some cognitive impairment. Worsened anxiety. Started to take Ativan regular to conteract jitteriness.
In November 2007, I stopped effexor. This was the first time I was off a sertonin boosting drug in 12 years. After a couple of months, I got depressed with feelings of hopelessness. I was also more obsessive, including sexually and extremely nervous. Tried a small dose of Lamictal and it seemed to help a little.
In April 2008, I tried stablon. It did not work and may make me worse.
In June 2008, I increased lamictal but it caused major cognitive impairment. Not only could I not finish sentences, but I couldn't even think. People thought I had ADD. In retrospect, the cognitive impairment maybe a delayed withdrawal symptom, due to lack of a sertonin drug (last dose in November of 2007) and not from the lamictal.
In July 2008, weaned off lamictal and start taking MAOI Parnate. Parnate helped with the depression, but the side effects were overwhelming including blurry vision, weakness, dry mouth, spiders crawling on skin, swollen ankles, insomnia, day time sleepiness, drugged feeling, apathetic, confusion, memory and learning impairment and extreme irritability. My guess at the time was the confusion was caused by the norepinhperine.
I went down to 1 pill (10 mg?) around the middle of November and immediately felt better. Then I tried a small dose of Adderall. I felt an adrenaline boost and I had more energy including cognitive energy. However, the adrenaline boost wore off and I felt the same confusion I felt on a higher dose Parnate.
Since reducing Parnate, noticed sexual obssession. Read online that some people who take Parnate experience sexual obsessions.
Last dose of Parnate was on December 18, 2008.
In January, 2009, I tried small dose of Inostiol--helped with obsessiveness but made me more depressed, especially in morning; tried small dose of 5-HTP--saw immediate improvement in skin and hair (retained oils), and helped with obsessiveness and anxiety, but made me depressed. Bad reactions to small doses of magnesium and choline too.
I am now off of everything except 1 mg Ativan.
Current symptoms:
Derealisation and depersonalisation (for 2 or 3 years)
irritability (last couple of years)
Vision problems, foggy vision, focus problems (more recent)
Cognitive problems, foggy brain, memory and concentration problems, inability to learn or think abstractly (memory, inability to learn and abstract reasoning within last year)
sexual obsessions (recent)
Muscle weakness, fatigue, low stamina (had this since Zoloft pooped out)
Apathy, lack of emotions (had this since Zoloft pooped out)
Sticky skin, waxy hair, skin rashes (had this since Zoloft pooped out)
Horrible sensations like heavy head, head pressures (more recent)
can't handle stress, racing thoughts (2 or 3 years)
Worse anxiety and depression than pre-ADs--its a physical anxiety (last year)
Dizziness in different ways, vertical and horizontal; major internal restlessness (2 or 3 years)
Inability to enjoy everyday things, including music, movies, etc (2 or 3 years)
personality change (gradually changed)I am extremely hypersensitive to sound, drugs, amino acids and B vitamins. Arguably, the hypersenitivity started when zoloft pooped out.
The only thing I take is 1 mg Ativan. The confusion and cognitive issues could a side effect of the Ativan but they are so extreme, I think they are related to the withdrawal.
WHAT IS HAPPENING TO ME?
Posted by SLS on February 5, 2009, at 17:43:19
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 5, 2009, at 17:08:08
NQ.
First of all - relax. Nothing is happening to you that hasn't happened to others. You are not doomed!
It will take me awhile to digest your whole post. I'm currently having trouble reading.
> Wellibutrin and TCA's caused hypomania.
Easy decision here. Allow the hypomania and control it with an atypical AP or whatever it takes. Depakote even. Doctors only wished that such would happen to me. Yes. I think this is an experiment worth performing.
Maybe you could start with the AP first. Get settled. I would love to see you be able to handle Abilify 10-20mg. Whatever. Then, after you are at a stable dosage of the AP and get past the startup side effects, then add the drug of your choice that would otherwise produce a hypomania. The AP should prevent that from happening, and you will feel great and live happily everafter.
I guarantee it. Well, maybe not. But I like your chances. You'll have to work on the happily everafter part separately, but the process of the journey will be a joy.
I would try it. It is certainly safe.
- Scott
Posted by SLS on February 5, 2009, at 17:53:04
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 5, 2009, at 17:08:08
You might want to have your thyroid checked. You might be hyperthyroid.
- Scott
Posted by garnet71 on February 6, 2009, at 0:32:20
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 5, 2009, at 17:08:08
I'm not going to sugar coat this, NewQuestions. Sorry, it's for your own good.
If you are not planning to see an endochronologist, neurologist, rheuematologist and perhaps others, you may be self-sabotaging yourself. The last time we spoke, you said "I know, I should go to an endochronologist..., but..." But being the key word.
Edema, muscle weakness, and dizziness/tinnutis are symptoms that should never be overlooked, or viewed under the lone lens of psychiatrists.
As you know, the operationalization of the body occurs from the brain and ALL the other systems. and organs...you cannot seperate 'brain' issues with the others - if you go to a pdoc and have more medications pumped in your brain, don't expect to get better. There is something more going on.
PLEASE - don't go there.
Sorry to be so blunt.
Posted by SLS on February 6, 2009, at 5:22:31
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 5, 2009, at 17:08:08
Hi NQ.
As has been suggested, you could certainly go for endocrinological tests to rule out other explanations for your experiences. I would at least go for thyroid and cortisol testing. I'll be very interested to know the other tests the doctor orders.
Hyperthyroidism can sensitize NE receptors.
The antidepressant-induced mania is, I believe, a sign of bipolarity.
Which of the maniagenic drugs would you choose to take, and why? (Wellbutrin versus TCA)
- Scott
Posted by NewQuestions on February 6, 2009, at 8:34:17
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by SLS on February 6, 2009, at 5:22:31
At this point, I think the drugs are making me worse, not better. Two things appear to be going on:
1. My body is suffering from withdraw leading to increased cortiol production and HPA axis dysregulation. This causes the hypersentivity to the drugs and the drug agitation.
Of course, I could take the drugs REALLY REALLY SLOWLY. But there is something else happening
2. Once the drug kicks in, I am having paradoxical effects. Benzos, prosac and remeron make me MORE depressed. Cymbalta and Effexor make more MORE anxious. Wellbutrin and TCA's appear intolerable--one small dose makes my mind race and my heart pound.
Thus, it appears the only thing to do is take a really long drug holiday.
Tell me why I am wrong?
Posted by SLS on February 6, 2009, at 8:42:49
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 6, 2009, at 8:34:17
> At this point, I think the drugs are making me worse, not better. Two things appear to be going on:
>
> 1. My body is suffering from withdraw leading to increased cortiol production and HPA axis dysregulation. This causes the hypersentivity to the drugs and the drug agitation.
>
> Of course, I could take the drugs REALLY REALLY SLOWLY. But there is something else happening
>
> 2. Once the drug kicks in, I am having paradoxical effects. Benzos, prosac and remeron make me MORE depressed. Cymbalta and Effexor make more MORE anxious. Wellbutrin and TCA's appear intolerable--one small dose makes my mind race and my heart pound.
>
> Thus, it appears the only thing to do is take a really long drug holiday.
>
> Tell me why I am wrong?You're not.
I was under the impression that Wellbutrin and TCAs produced hypomania only. You didn't mention anything about additional side effects or that these drugs were otherwise intolerable.
If you can manage a drug holiday, then I don't see why it would not make sense to do so. I'm sure your system would welcome the opportunity to establish an equilibrium.
Good luck.
- Scott
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
Posted by SLS on February 6, 2009, at 12:32:59
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by Larry Hoover on February 6, 2009, at 11:46:48
Did you find any studies examining the dexamethasone suppression test (DST)? It might give a more pertinent measurement of HPA axis dysregulation than measuring blood or salivary cortisol levels.
I tested positive on both.
- Scott
Posted by Larry Hoover on February 6, 2009, at 13:26:12
In reply to Re: Long Term SSRI Use Has Destabilzed Me » Larry Hoover, posted by SLS on February 6, 2009, at 12:32:59
> Did you find any studies examining the dexamethasone suppression test (DST)?
Recent ones? There are very few of those.
> It might give a more pertinent measurement of HPA axis dysregulation than measuring blood or salivary cortisol levels.
>
> I tested positive on both.
>
>
> - ScottWhat I found was that dexamethasone suppression/nonsuppression isn't used as a stand-alone test very often any more. Usually the "measure" they're looking for is a subsequent response to CRH post-dexamethasone. Or a change in baseline cortisol resulting from dexamethasone exposure.
I honestly wonder if they've yet got any idea of just what is they're looking at, or looking for.
Here is a bit of recent stuff, one abstract, and two links to full-text articles. The latter link raises some interesting considerations.
Regards,
LarScientificWorldJournal. 2006 Oct 31;6:1398-404.
Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior.Sher L.
Division of Neuroscience, Department of Psychiatry, Columbia University, New York, USA. LS2003@columbia.eduThe hypothalamic-pituitary-adrenal (HPA) axis controls the secretion of corticotropin-releasing hormone (CRH), corticotropin (adrenocorticotropic hormone, ACTH), and cortisol. The dexamethasone suppression test (DST) is the most frequently used test to assess HPA system function in psychiatric disorders. Patients who have failed to suppress plasma cortisol secretion, i.e., who escape from the suppressive effect of dexamethasone, have a blunted glucocorticoid receptor response. After CRH became available for clinical studies, the DST was combined with CRH administration. The resulting combined dexamethasone suppression-corticotropin-releasing hormone stimulation (DST-CRH) test proved to be more sensitive in detecting HPA system changes than the DST. There is a growing interest in the use of the DEX-CRH test for psychiatric research. The DEX-CRH test has been used to study different psychiatric conditions. Major depression, alcoholism, and suicidal behavior are public health problems around the world. Considerable evidence suggests that HPA dysregulation is involved in the pathogenesis of depressive disorders, alcoholism, and suicidal behavior. Over the past 2 decades, there has been a shift from viewing excessive HPA activity in depression as an epiphenomenon to its having specific effects on symptom formation and cognition. The study of HPA function in depression, alcoholism, and suicidal behavior may yield new understanding of the pathophysiology of these conditions, and suggest new approaches for therapeutic interventions. The combined DEX-CRH test may become a useful neuroendocrinological tool for evaluating psychiatric patients.
Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19014558Season of birth, clinical manifestations and Dexamethasone Suppression Test in unipolar major depression.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17683542
Posted by Alexanderfromdenmark on February 14, 2009, at 3:48:38
In reply to Re: Long Term SSRI Use Has Destabilzed Me » NewQuestions, posted by SLS on February 6, 2009, at 8:42:49
It's funny I should reád trhis. I'm having excactly the same problem post-lexapro, after I was on it for year. If you figure out how to fix it, please let me know.
Myself, I'm looking into the thyroid and the adrenals which a very important in the dopamine system.
Posted by NewQuestions on February 17, 2009, at 8:48:10
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by Alexanderfromdenmark on February 14, 2009, at 3:48:38
What is your drug history and symptoms?
Posted by Alexanderfromdenmark on February 17, 2009, at 16:12:49
In reply to Re: Long Term SSRI Use Has Destabilzed Me, posted by NewQuestions on February 17, 2009, at 8:48:10
Hi
I was on Lexapro for about a year, perhaps more and Lyrica(pregabalin) for six months. I was on them´for depression and anxiety I suppose. Before the meds, my symptoms were basicly chronic constipation, swinging levels of energy between fatigue or restlessness and insomnia and hypersomnia, and most thoughts inherent to depression and anxiety. But I still had a sex drive always, and I could still drink alchohol and basicly get on with it.
Now my symptoms after I discountinoued all medicaiton around 6 months ago,
Hi, my symptoms are
-Fatigue, all day
-Dry skin and hair(still there before meds)
-Dark Circles under eyes(were still there before meds)
-Impaired mental energy, concentration, focus, mood, attention, memory
-Chronic constipation(still there before meds)
-Water retention, bloating and increased fat in mid-section
-General feeling of dryness
-NO sexdrive and decreased ability to get and hold erections(very new, never a problem before SSRI usage)Basicly I think SSRI usage has knocked out my dopamine system, but I can never know of course. So right no I'm getting tests to get my endoctrine system checked out.
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