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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by denise1966 on September 15, 2005, at 11:39:09
Hi,
I've asked some of these questions before and didn't really get an answer so I assume nobody really knows. But here they are again if anyone does, otherwise I guess I'm going to have to do a lot of searching on the web.
Was just wondering if any of you knowledgeable people out there can answer these questions:-
If you have low levels or normal cortisol levels does this mean that CRF Antagonists will not work for you when they edventually come out?
Also if you have been a suppressor to the dexamethasone suppression test does this mean that you're cortisol levels are normal?
If you do have high cortisol levels then wouldn't that manifest itself in physical symptoms.
One thing I have noticed about when I suffer from depression is that my immune system is very strong, I never get coughs, colds or any infections and yet I smoke like a trooper. Whether that's because I go out less and because I'm too depressed to get stressed about the usual things I don't know but could it be that my cortisol levels are low?
Also, when will these CRF Antagonists be out and has anyone been on any of the trials?
Thanks.....Denise
Posted by Racer on September 15, 2005, at 12:57:59
In reply to CRF Antagonists More Questions, posted by denise1966 on September 15, 2005, at 11:39:09
For what it's worth, here are the answers that I know to your questions:
>
> Also if you have been a suppressor to the dexamethasone suppression test does this mean that you're cortisol levels are normal?In general, yes. When you're given dexamethasone, your cortisol levels are supposed to be suppressed. I'm sure that there are higher and lower levels within that, but the general answer is "Yes."
>
> If you do have high cortisol levels then wouldn't that manifest itself in physical symptoms.Absolutely! Have you ever seen someone who's been taking steroids for a while? (Prescribed steroids, like prednisone, that is. I don't know how the anabolic steroids work in this regard.) The "Moon Face" and so on? They look a bit swollen, and tend to be a bit fragile. That's called Cushing's Syndrome, and if it's caused naturally it can be Cushing's Disease. It's very common in some breeds of dogs and in horses. (So common in horses that it's sometimes called "Old Horse Disease.") When cortisol levels are chronically high, aside from the characteristic changes to body shape, tendons and ligaments tend to get weaker, and muscles waste. Other symptoms such as depression are also common.
Cushing's Disease in animals is caused by a benign pituitary tumor, which I believe is analogous to Acromegaly in humans. I'm only partly sure of that, though, because I've also seen references to Cushing's Disease in people, and surgery to correct it.
>
> One thing I have noticed about when I suffer from depression is that my immune system is very strong, I never get coughs, colds or any infections and yet I smoke like a trooper. Whether that's because I go out less and because I'm too depressed to get stressed about the usual things I don't know but could it be that my cortisol levels are low?Probably not, although you'd need some extensive testing to find out. How does stress affect you? Do you get ramped up when something stressful or startling occurs? Cortisol is secreted by your adrenal glands and is a stress related hormone. It's what gives you the impetus to get out of bed in the morning -- cortisol levels start to rise around 3 to 4 AM in most people, so that by the time you wake up, you've got the gumption to get up. (That figure, by the way, tends to be pretty consistent regardless of sleep patterns. It's why shift work is so difficult, and why most people get to feeling so cold around that time.)
>
Them's all the things I know about any of this. I hope it helps until someone who knows more comes along...
Posted by linkadge on September 15, 2005, at 16:07:35
In reply to I can only answer a bit of this.... » denise1966, posted by Racer on September 15, 2005, at 12:57:59
I do not know how a drug like this would work if you do not exhibit high levels of cortisol. Perhaps you would need to have it measured more than once to see how your cortisol varies over time.
Nicotine can actually lower cortisol, so smoking may have a HPA axis effect in this regard.
Linkadge
Posted by SLS on September 15, 2005, at 18:43:36
In reply to CRF Antagonists More Questions, posted by denise1966 on September 15, 2005, at 11:39:09
I don't think your questions have yet been investigated adequately to give answers to.
CRH receptors are present in different areas of the brain that are not at all related to HPA axis regulation. In other words, it is worth giving a CRH antagonist a try despite normal HPA function.
Do you have unipolar atypical depression? There is some thought that atypical depressives have a tendency to be hypocortisolemic, and that using dexamethasone as therapy might be effective in such circumstances.
- Scott
Posted by Racer on September 15, 2005, at 19:42:40
In reply to Re: CRF Antagonists More Questions, posted by SLS on September 15, 2005, at 18:43:36
>
> Do you have unipolar atypical depression? There is some thought that atypical depressives have a tendency to be hypocortisolemic, and that using dexamethasone as therapy might be effective in such circumstances.
>
>
> - ScottI've actually read that using low-dose, short-term dexamethasone therapy can kick-start antidepressant response in treatment resistant depression. Have you thought of trying it?
Just another randome thing I read...
Posted by SLS on September 15, 2005, at 20:20:14
In reply to Re: CRF Antagonists More Questions » SLS, posted by Racer on September 15, 2005, at 19:42:40
> > There is some thought that atypical depressives have a tendency to be hypocortisolemic, and that using dexamethasone as therapy might be effective in such circumstances.
> I've actually read that using low-dose, short-term dexamethasone therapy can kick-start antidepressant response in treatment resistant depression. Have you thought of trying it?No, I haven't. However, you have. :-)
I'll put it on my list of things to try. Right now!
Thanks, Racer.
- Scott
Posted by denise1966 on September 16, 2005, at 13:42:36
In reply to I can only answer a bit of this.... » denise1966, posted by Racer on September 15, 2005, at 12:57:59
Hi Racer,
Thanks for answering some of my questions, I feel stressed most of the time, well on edge anyway, regardless of what's going on around me.
Anyway, thanks again....Denise
Posted by denise1966 on September 16, 2005, at 13:46:16
In reply to Re: I can only answer a bit of this...., posted by linkadge on September 15, 2005, at 16:07:35
Hi,
Thanks to you all for at least trying to answer my questions anyway.
I think I may have my cortisol levels checked anyway although I don't manifest any of the physical symptoms.
I do smoke a lot especially since being depressed.
Denise
Posted by Cecilia on September 17, 2005, at 1:19:09
In reply to Re: CRF Antagonists More Questions » Racer, posted by SLS on September 15, 2005, at 20:20:14
I`ve never had my cortisol level checked but I always assumed it was probably high because I`m depressed, stressed and overweight. It`s interesting that you said that cortisol levels tend to be low in people with atypical depression because both cortisol and atypical depression cause weight gain-you`d think they`d be high. I have atypical depression and my sleep and circadian rhythms are completely out of whack. I have extreme difficulty getting to sleep and extreme extreme difficulty waking up. No matter how much sleep I`ve had I wake up with overwhelming exhaustion and emotional pain. I have bizarre unpleasant dreams but no matter how bad they are I still want to sink back into them rather than wake up. I`ve been this way as long as I can remember but the older I get the worse it seems to be. But even if my cortisol levels were off I`m not clear what they could do. If they were low I certainly wouldn`t want to take steroids that would cause me to gain more weight and if they were high I really haven`t heard about anything to lower them that`s effective and not extremely toxic. And what if they`re low when they should be high and vise versa? Cecilia
Posted by Sarah T. on September 17, 2005, at 1:54:47
In reply to Re: CRF Antagonists More Questions » SLS, posted by Racer on September 15, 2005, at 19:42:40
Hi Racer,
When you say "short term," how short a term do you mean? Days? Weeks?
S.
Posted by SLS on September 17, 2005, at 8:19:57
In reply to Questions re cortisol levels:SLS, posted by Cecilia on September 17, 2005, at 1:19:09
Hi Cecilia.
First, I think it is important to determine what time of day depression is the worst for you. If mornings are clearly worse, you might have a more melancholic depression, which is usually associated with high cortisol. You might also want to rule out bipolar disorder by retrospective analysis or life-charting to see if there were any manic, hypomanic, mixed-states, or rapid-cycling cyclothymia. Bipolar depression can look very much like atypical depression. However, like melancholic depression, it involves a hyperactive HPA axis. Chronic hypercortisolemia is circular, and can lead to a downregulation of cortisol receptors in the hippocampus and thus further allow for hypercortisolism. The whole thing is more complicated than it looks on the surface. The system might try to release more CRH (same as CRF) in order to raise cortisol even further. Too much CRH in the brain seems to be depressogenic.
I think it is nice to have a DST (dexamethasone suppression test) performed, but I'm not sure how the results of such a test would influence treatment decisions.
The HPA axis can be manipulated by using:
1. Cortisol synthesis inhibitors (chronic treatment)
- ketaconozole
- metyrapone
- aminoglutethimide2. Cortisol receptor antagonists (8 day treatment)
- mifepristone3. Cortisol receptor agonists (4 day treatment)
- dexamethasone4. CRH receptor antagonists (chronic treatment)
- in early developmentI am looking at using all of these to treat my bipolar depression. It is quite possible that using either mifepristone or dexamethasone, drugs that on the surface seem to have opposite effects, might help to reset the HPA axis in the same direction by shocking it to function normally. Then again, perhaps mifepristone will be found to be especially effective when treating melancholic, psychotic, or bipolar depression, while dexamethasone will be found to be better suited to treating true unipolar atypical depression.
Not enought data yet.
- Scott
Posted by Racer on September 17, 2005, at 13:02:39
In reply to Re: CRF Antagonists More Questions » Racer, posted by Sarah T. on September 17, 2005, at 1:54:47
> Hi Racer,
>
> When you say "short term," how short a term do you mean? Days? Weeks?
>
> S.The study I read about it was using either 2mg or 4mg dexamethasone -- I forget which, and don't have time to go through my files to find the article right now -- for four days. Very short term. I can't remember all the results, but that it was effective for most of the patients it was tried in.
Hope that helps. You might be able to find the article yourself through google, but I think it may have been in Science, which you'd need a subscription to.
Posted by Sarah T. on September 17, 2005, at 15:54:10
In reply to Re: CRF Antagonists More Questions » Sarah T., posted by Racer on September 17, 2005, at 13:02:39
Thanks for your reply, Racer. Scott's post, directly above yours, provides a good summary until I can find the SCIENCE article. I let my subscription to SCIENCE run out, but I have most of the back issues (clutter!). I will look for the article.
Posted by Declan on September 18, 2005, at 20:34:43
In reply to CRF Antagonists More Questions, posted by denise1966 on September 15, 2005, at 11:39:09
Denise, this is somewhat off tangent, but my progesterone is too high and my cortisol too low, perhaps because of inadequate levels of the enzymes 21-lyase and beta hydroxylase. For the same reason my testosterone is too low and my DHEA too high. At least that's what my doctor thinks.
Declan
Posted by Cecilia on September 25, 2005, at 3:56:10
In reply to Re: Questions re cortisol levels:SLS, posted by SLS on September 17, 2005, at 8:19:57
> Hi Cecilia.
>
> First, I think it is important to determine what time of day depression is the worst for you. If mornings are clearly worse, you might have a more melancholic depression, which is usually associated with high cortisol. You might also want to rule out bipolar disorder by retrospective analysis or life-charting to see if there were any manic, hypomanic, mixed-states, or rapid-cycling cyclothymia. Bipolar depression can look very much like atypical depression. However, like melancholic depression, it involves a hyperactive HPA axis. Chronic hypercortisolemia is circular, and can lead to a downregulation of cortisol receptors in the hippocampus and thus further allow for hypercortisolism. The whole thing is more complicated than it looks on the surface. The system might try to release more CRH (same as CRF) in order to raise cortisol even further. Too much CRH in the brain seems to be depressogenic.
>
> I think it is nice to have a DST (dexamethasone suppression test) performed, but I'm not sure how the results of such a test would influence treatment decisions.
>
> The HPA axis can be manipulated by using:
>
> 1. Cortisol synthesis inhibitors (chronic treatment)
> - ketaconozole
> - metyrapone
> - aminoglutethimide
>
> 2. Cortisol receptor antagonists (8 day treatment)
> - mifepristone
>
> 3. Cortisol receptor agonists (4 day treatment)
> - dexamethasone
>
> 4. CRH receptor antagonists (chronic treatment)
> - in early development
>
> I am looking at using all of these to treat my bipolar depression. It is quite possible that using either mifepristone or dexamethasone, drugs that on the surface seem to have opposite effects, might help to reset the HPA axis in the same direction by shocking it to function normally. Then again, perhaps mifepristone will be found to be especially effective when treating melancholic, psychotic, or bipolar depression, while dexamethasone will be found to be better suited to treating true unipolar atypical depression.
>
> Not enought data yet.
>
>
> - ScottScott, my depression is much much worse when I wake up (which is usually in the afternoon since my part time job is evening shift- I don`t think there is ANY way I could function if I had to work days.) But I definitely think I have atypical depression. I can definitely relate to the "leaden paralysis" where the idea of getting out of bed seems physically impossible, the rejection sensitivity, overeating, oversleeping (and then of course not being able to get to sleep when I finally drag myself to bed at sunrise, though even when I`ve had to get up early I still find it extremely difficult to get to sleep the following night). I have a LOT of anxiety but I really can`t recall any time in my life where I could possibly be considered manic or hypomanic. Unless you can be bipolar with a daily cycle, where you wake up in extreme emotional pain and gradually get, I don`t know, not happy, certainly, but more detached from the pain. 7 years of therapy only made my depression worse and no med has ever helped. I can`t even wrap my mind around the concept of happiness, I look at all the pain in the world and the idea of happiness seems beyond absurd; I just wish there were something to lessen the intensity of the pain of those hours after awakening. Cecilia
Posted by SLS on September 25, 2005, at 8:37:29
In reply to Re: Questions re cortisol levels:SLS, posted by Cecilia on September 25, 2005, at 3:56:10
Hi Cecilia.
> Scott, my depression is much much worse when I wake up (which is usually in the afternoon since my part time job is evening shift- I don`t think there is ANY way I could function if I had to work days.)
What hours do you work? How long have you been working these hours?
Do you wake up too early and lie awake with anxiety or is it necessary for you to use an alarm?
If you didn't have to work, and your sleep/wake cycle were free-running, what do you think your cycle would look like?
> (and then of course not being able to get to sleep when I finally drag myself to bed at sunrise, though even when I`ve had to get up early I still find it extremely difficult to get to sleep the following night).
You might profit from working with your circadian rhythm. That your body is still cued by sunrise might hurt rather that help your situation the way things are now. I think you should either take a sleep aid and get to sleep as soon as possible before sunrise or not go to bed until well after sunrise. If you are able to fall asleep before sunrise, set your alarm for 7:00am or 8:00am and get up for a little while, expose yourself to bright light, and perhaps drink some juice or get something to eat before going back to bed. Hopefully, you can find some way to synchronize your Y clock with your X clock sleep/wake cycle. It might even be a good idea to try taking melatonin at 2:00am. If that makes things worse, then try taking it at 8:00am.
> But I definitely think I have atypical depression. I can definitely relate to the "leaden paralysis" where the idea of getting out of bed seems physically impossible,
People often confuse psychomotor retardation with leaden paralysis. Do your limbs actually feel heavy or is it that you seem to have trouble initiating movement or do things in slow motion?
> the rejection sensitivity
I don't think this is any longer considered to be of diagnostic value.
> overeating, oversleeping
That is pretty typical of atypical depression. However, it is also typical of bipolar depression.
> I have a LOT of anxiety but I really can`t recall any time in my life where I could possibly be considered manic or hypomanic.
How old were you when your illness started?
Were you irritable or angry early in the course of your illness?
> Unless you can be bipolar with a daily cycle,
You can. It is called ultra-dian cycling. It seems to be fairly rare, though.
> where you wake up in extreme emotional pain and gradually get, I don`t know, not happy, certainly, but more detached from the pain.
Now THAT sounds like unipolar endogenous (melancholic) depression.
If you haven't tried a tricyclic antidepressant yet, I would consider doing so. If you have tried tricyclics, which ones were they, and what were the dosages used and for how long?
> 7 years of therapy only made my depression worse and no med has ever helped. I can`t even wrap my mind around the concept of happiness, I look at all the pain in the world and the idea of happiness seems beyond absurd; I just wish there were something to lessen the intensity of the pain of those hours after awakening.
Does this include anxiety?
For the short term, it might be a good idea to experiment with a low dosage of an atypical neuroleptic (antipsychotic). You could start out with Zyprexa 5.0mg. This drug probably demonstrates the greatest efficacy as an antidepressant / mood-stabilizer. Unfortunately, weight gain is a problem. However, I think a short trial of Zyprexa (two weeks) would give you a good idea as to how well an AP strategy would work. You could then try switching to Seroquel or Abilify if the side effects of Zyprexa become problematic.
Are you bipolar? It is difficult to say if there is any bipolarity to your CNS biology. However, it sometimes serves well to consider treatment-resistance to standard antidepressants as a sign of a bipolar diathesis (cause), and that using mood-stabilizers would get you well.
- Scott
Posted by Cecilia on September 26, 2005, at 5:20:15
In reply to Re: Questions re cortisol levels:SLS » Cecilia, posted by SLS on September 25, 2005, at 8:37:29
> Hi Cecilia.
>
> > Scott, my depression is much much worse when I wake up (which is usually in the afternoon since my part time job is evening shift- I don`t think there is ANY way I could function if I had to work days.)
>
> What hours do you work? How long have you been working these hours?
>
> Do you wake up too early and lie awake with anxiety or is it necessary for you to use an alarm?
>
> If you didn't have to work, and your sleep/wake cycle were free-running, what do you think your cycle would look like?
>
> > (and then of course not being able to get to sleep when I finally drag myself to bed at sunrise, though even when I`ve had to get up early I still find it extremely difficult to get to sleep the following night).
>
> You might profit from working with your circadian rhythm. That your body is still cued by sunrise might hurt rather that help your situation the way things are now. I think you should either take a sleep aid and get to sleep as soon as possible before sunrise or not go to bed until well after sunrise. If you are able to fall asleep before sunrise, set your alarm for 7:00am or 8:00am and get up for a little while, expose yourself to bright light, and perhaps drink some juice or get something to eat before going back to bed. Hopefully, you can find some way to synchronize your Y clock with your X clock sleep/wake cycle. It might even be a good idea to try taking melatonin at 2:00am. If that makes things worse, then try taking it at 8:00am.
>
> > But I definitely think I have atypical depression. I can definitely relate to the "leaden paralysis" where the idea of getting out of bed seems physically impossible,
>
> People often confuse psychomotor retardation with leaden paralysis. Do your limbs actually feel heavy or is it that you seem to have trouble initiating movement or do things in slow motion?
>
> > the rejection sensitivity
>
> I don't think this is any longer considered to be of diagnostic value.
>
> > overeating, oversleeping
>
> That is pretty typical of atypical depression. However, it is also typical of bipolar depression.
>
> > I have a LOT of anxiety but I really can`t recall any time in my life where I could possibly be considered manic or hypomanic.
>
> How old were you when your illness started?
>
> Were you irritable or angry early in the course of your illness?
>
> > Unless you can be bipolar with a daily cycle,
>
> You can. It is called ultra-dian cycling. It seems to be fairly rare, though.
>
> > where you wake up in extreme emotional pain and gradually get, I don`t know, not happy, certainly, but more detached from the pain.
>
> Now THAT sounds like unipolar endogenous (melancholic) depression.
>
> If you haven't tried a tricyclic antidepressant yet, I would consider doing so. If you have tried tricyclics, which ones were they, and what were the dosages used and for how long?
>
> > 7 years of therapy only made my depression worse and no med has ever helped. I can`t even wrap my mind around the concept of happiness, I look at all the pain in the world and the idea of happiness seems beyond absurd; I just wish there were something to lessen the intensity of the pain of those hours after awakening.
>
> Does this include anxiety?
>
> For the short term, it might be a good idea to experiment with a low dosage of an atypical neuroleptic (antipsychotic). You could start out with Zyprexa 5.0mg. This drug probably demonstrates the greatest efficacy as an antidepressant / mood-stabilizer. Unfortunately, weight gain is a problem. However, I think a short trial of Zyprexa (two weeks) would give you a good idea as to how well an AP strategy would work. You could then try switching to Seroquel or Abilify if the side effects of Zyprexa become problematic.
>
> Are you bipolar? It is difficult to say if there is any bipolarity to your CNS biology. However, it sometimes serves well to consider treatment-resistance to standard antidepressants as a sign of a bipolar diathesis (cause), and that using mood-stabilizers would get you well.
>
>
> - ScottI`ve been working evenings or nights since 1978, so I`m defiitely not a morning person. I use 2 alarm clocks to wake up at 1230 in order to leave for work at 230. I usually take sleeping pills which of course makes waking up even harder but even when I`ve managed to get to sleep without them, waking up is excruciating-a combination of depression, anxiety and exteme exhaustion. It seems to get harder every year. When I was younger I used to force myself to get up and do things to try to overcome my depression and anxiety, but I no longer have any expectation that anything I do will make any difference, I just want to sleep all day. It has nothing to do with sunrise, I keep my curtains closed. Years ago I tried a light box for a month but didn`t notice any benefit from it. Melatonin made my insomnia worse, plus worse nightmares when I finally slept. I don`t think I ever have deep sleep, just endless unpleasant dreams. I really can`t say when my depression started, I don`t remember ever not being depressed. But it definitely worsened in college. I suppose I was angry at the time, but I`m not a person who often expresses anger-more the classic anger turned inward. I`ve tried a number of tricyclics but the only one I was ever able to get to a therapeutic level on was nortriptyline. I was able to stand that one by increasing very slowly, though there were still plently of side effects and no benefits. I did try a small dose of zyprexa for a couple of weeks-no benefit. Having recently been diagnosed with diabetes, I wouldn`t take it again-I can`t afford to gain any more weight. Mood stabalizers-I tried lithium as a augmentor to zoloft but gave it up fairly quickly because of the side effects. I tried lamictal for quite a long time with celexa and trazadone-no benefit. I tried neurontin as an augmentor to celexa-ironically I`m taking it again now for peripheral neuropathy-doesn`t work any better for that than it did for depression and anxiety. My doctor, who`s supposed to be the expert on treatment resistant depression at my HMO, basically just has the attitude "if you`re not willing to try ECT you must not really be depressed." And that`s the one thing I`m just too afraid to try. I`ve tried: Desipramine, imipramine, amitriptyline, Prozac, Nardil, zoloft, Paxil. welbutrin, Effexor, serzone, buspar, remeron, lithium, nortiptyline. celexa. neurontin, lamictal, trazodone, SAM-e, ritalin, dexedrine, parnate, amisulpride, reboxetine, adrafinil, lamictal, moclobemide, tianeptine, St. John`s wort, 5-HTP, trytophan, duloxetine, miilnacipran clonazepam, Xanax and rTMS. I`ve had no benefit from anything except the benzos and sleeping pills (temazepam and ambien). Cecilia
Posted by SLS on September 26, 2005, at 8:39:30
In reply to Re: Questions re cortisol levels:SLS, posted by Cecilia on September 26, 2005, at 5:20:15
I guess the only thing I don't see in your list is the use of Provigil during your waking hours to combat excessive sleepiness.
Cecelia, your situation is a frustrating one to have to live with. Have you ever tried to go 36 hours without sleep - total sleep deprivation? People who react to this by experiencing a brief antidepressant effect often respond to Wellbutrin.
- Scott
Posted by Cecilia on September 29, 2005, at 4:14:56
In reply to Re: Questions re cortisol levels:SLS, posted by SLS on September 26, 2005, at 8:39:30
I`ve gone 36 hours without sleep but never by choice-usually it was because I couldn`t sleep and then had to get up and go to work. And even then, when I finally got home, though exhausted I would still find it hard to fall asleep. It`s like my body can`t handle transitions-incredibly difficult to fall asleep, incredibly difficult to wake up. I`ve always been amazed that there are actually people who can fall asleep for naps. Somehow the sleep/wake part of my brain is wired wrong. I mean, I have plenty of psychological "issues" but this sleep problem is what makes me think there has to also be something physiological going on, though I doubt there will be a solution for it in my lifetime. Of course pdocs always assume that if their meds don`t work it`s purely psychological. Whereas you`d never hear an oncologist say that if a patient doesn`t respond to their drugs it`s because of the patient`s deep seated need to have cancer. Cecilia
This is the end of the thread.
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