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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 23 of 23. This is the beginning of the thread.
Posted by Bill L on January 8, 2002, at 14:56:16
The recent special double issue of Newsweek has an interesting article on new antidepressants being tested. The magazine is not dated. It has a graphic of September 11 on the cover. The researchers anticipate that the new drugs may eventually replace the SSRI's and other current drugs.
The new drugs block cortisol. Cortisol is thought to cause shrinkage of a part of the brain known as the hippocampus. (I used to think that was a college for hippos). Autopsies show diminished hippocampuses (or is it hippocampi?) in depressed people. The idea is that the cortisol blocking drug will work better than current drugs with less side effects.
There are other drugs that could more directly prevent shrinkage of the neurons in the brain but these drugs taken orally cannot be absorbed. Also, even if injected, they cannot cross the blood brain barrier. The corisol blocking drug however can be taken orally.
This new drug caused less depression in rats. If you read the article it goes into detail of how one measures depression in rats. Apparently depressed rats drown more easily than happy rats.
Posted by bob on January 8, 2002, at 15:45:29
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
Did they happen to mention whether this drug is closer than 5 to 10 years away from FDA approval? It seems to me like all these promising drugs, like substance-P etc... never seem to materialize. They've been talking about some of these things for years and years. Reboxetine was in the UK years ago (at least 5) and they've been chasing FDA approval here in the US for, I think, about 3 years, maybe more. It's amazing how long some of this stuff takes.
Posted by bob on January 8, 2002, at 16:03:01
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
When you say that the new drug "blocks cortisol", does that mean it increases the blood levels of it, or decreases it? I've read some articles which suggest a link between high levels of cortisol in the blood and depression, so I'm assuming that blocking cortisol would have an overall effect of reducing blood levels.
Posted by Bill L on January 9, 2002, at 11:32:04
In reply to Re: Newsweek Article - new drugs » Bill L, posted by bob on January 8, 2002, at 16:03:01
Decreases it. I should have been more careful with the wording since SSRI's block the reuptake of serotonin which increases the extracellular serotonin. More specifically, the drug being investigated inhibits CRF (corticotrophin releasing factor). Both CRF and cortisol inhibit a chemical in the body which is responsible for facilitating the proliferation of neurons.
As for the time frame of when it could be on the market, I don't remember the article mentioning one.
> When you say that the new drug "blocks cortisol", does that mean it increases the blood levels of it, or decreases it? I've read some articles which suggest a link between high levels of cortisol in the blood and depression, so I'm assuming that blocking cortisol would have an overall effect of reducing blood levels.
Posted by Bekka H. on January 9, 2002, at 12:23:57
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
Thank you for this information. You did mention that the issue of Newsweek is not dated, and I was about to ask you the date. Do you know whether it's still available on the newstands? By the way, Tianeptine also prevents the hippocampal atrophy caused by elevated corticosteroids. Tianeptine is a serotonin reuptake ENHANCER. It's mechanism of action is exactly the opposite of SSRIs and yet, its clinical efficacy is comparable to many other widely used antidepressants. Unfortunately, it is only available overseas. Perhaps your doctor can help you get it.
Posted by OldSchool on January 9, 2002, at 13:51:48
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
> The recent special double issue of Newsweek has an interesting article on new antidepressants being tested. The magazine is not dated. It has a graphic of September 11 on the cover. The researchers anticipate that the new drugs may eventually replace the SSRI's and other current drugs.
>
> The new drugs block cortisol. Cortisol is thought to cause shrinkage of a part of the brain known as the hippocampus. (I used to think that was a college for hippos). Autopsies show diminished hippocampuses (or is it hippocampi?) in depressed people. The idea is that the cortisol blocking drug will work better than current drugs with less side effects.
>
> There are other drugs that could more directly prevent shrinkage of the neurons in the brain but these drugs taken orally cannot be absorbed. Also, even if injected, they cannot cross the blood brain barrier. The corisol blocking drug however can be taken orally.
>
> This new drug caused less depression in rats. If you read the article it goes into detail of how one measures depression in rats. Apparently depressed rats drown more easily than happy rats.These cortisol blocking drugs are called CRF-Antagonists. Frankly Im not that excited about CRF-Antagonists. I expect we will see these drugs marketed along with the much hyped substance P antidepressants about the time that the SSRIs all lose their patents and become available generic.
Id be much more excited to see this new selegiline MAOI patch become FDA approved. I think that would be a much more successful antidepressant, particularly if the patch allows you to skip the MAOI diet as the claim is being made. Id like to see more dopaminergic antidepressants developed and marketed.
All currently available antidepressants already have an indirect effect on the hippocampus, particularly if the ADs work well. Any successful antidepressant prevents further atrophy of the hippocampus.
Posted by OldSchool on January 9, 2002, at 13:55:00
In reply to Re: Newsweek Article - new drugs » Bill L, posted by bob on January 8, 2002, at 15:45:29
> Did they happen to mention whether this drug is closer than 5 to 10 years away from FDA approval? It seems to me like all these promising drugs, like substance-P etc... never seem to materialize. They've been talking about some of these things for years and years. Reboxetine was in the UK years ago (at least 5) and they've been chasing FDA approval here in the US for, I think, about 3 years, maybe more. It's amazing how long some of this stuff takes.
Yes, it is ridiculous how there is no sense of expedition with the development and FDA approval of these new antidepressants. We need better treatments NOW, today...not five or ten years from now. FDA...what a crock.
Posted by IsoM on January 9, 2002, at 14:11:27
In reply to Re: Newsweek Article - new drugs, posted by Bill L on January 9, 2002, at 11:32:04
Interesting idea, Bill. A lot of health problems can be traced to a too steady release of cortisol hormones in response to modern man's fairly steady levels of stress. I read years ago a book called "Why Zebras Don't Get Ulcers" by neurobiologist Robert Sapolsky. While the title sounds 'cute', it's a fairly serious look at the effects of stress hormones on people.
I remember when I was younger & discovered the reason salmon's bodies changed so radically & why they died after spawning was due to a flood of cortisol-type hormones degrading their entire systems. They died from stress basically! I always wanted to block the stress hormones in salmon to see what would happen & if death was still programmed in them.
Thanks for the info on this new approach to depression!
*************************************************************************************************
> Decreases it. I should have been more careful with the wording since SSRI's block the reuptake of serotonin which increases the extracellular serotonin. More specifically, the drug being investigated inhibits CRF (corticotrophin releasing factor). Both CRF and cortisol inhibit a chemical in the body which is responsible for facilitating the proliferation of neurons.
>
> As for the time frame of when it could be on the market, I don't remember the article mentioning one.
>
> > When you say that the new drug "blocks cortisol", does that mean it increases the blood levels of it, or decreases it? I've read some articles which suggest a link between high levels of cortisol in the blood and depression, so I'm assuming that blocking cortisol would have an overall effect of reducing blood levels.
Posted by Bekka H. on January 9, 2002, at 15:35:45
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
> The recent special double issue of Newsweek has an interesting article on new antidepressants being tested. The magazine is not dated. It has a graphic of September 11 on the cover. The researchers anticipate that the new drugs may eventually replace the SSRI's and other current drugs.
>
> The new drugs block cortisol. Cortisol is thought to cause shrinkage of a part of the brain known as the hippocampus. (I used to think that was a college for hippos). Autopsies show diminished hippocampuses (or is it hippocampi?) in depressed people. The idea is that the cortisol blocking drug will work better than current drugs with less side effects.
>
> There are other drugs that could more directly prevent shrinkage of the neurons in the brain but these drugs taken orally cannot be absorbed. Also, even if injected, they cannot cross the blood brain barrier. The corisol blocking drug however can be taken orally.
>
> This new drug caused less depression in rats. If you read the article it goes into detail of how one measures depression in rats. Apparently depressed rats drown more easily than happy rats.
**************************************************Unfortunately, I don't have a citation right in front of me, but I've read that about 50% of depressed people have elevated corticosteroid levels. Question: Are the elevated corticosteroid levels the chicken or the egg?
Posted by Bekka H. on January 9, 2002, at 15:58:31
In reply to Re: Newsweek Article - new drugs, posted by OldSchool on January 9, 2002, at 13:55:00
> > Did they happen to mention whether this drug is closer than 5 to 10 years away from FDA approval? It seems to me like all these promising drugs, like substance-P etc... never seem to materialize. They've been talking about some of these things for years and years. Reboxetine was in the UK years ago (at least 5) and they've been chasing FDA approval here in the US for, I think, about 3 years, maybe more. It's amazing how long some of this stuff takes.
>
> Yes, it is ridiculous how there is no sense of expedition with the development and FDA approval of these new antidepressants. We need better treatments NOW, today...not five or ten years from now. FDA...what a crock.
*************************************************
The problem, as I see it, is that the pharmaceutical lobby in Washington has too much influence on politicians and on the FDA. The pharmaceutical companies just don't want the competition that some of these other antidepressants would create. Your mental health and mine are the last things on the list of priorities of greedy drug company CEOs.
Posted by OldSchool on January 9, 2002, at 16:00:30
In reply to Re: Newsweek Article - new drugs, posted by Bekka H. on January 9, 2002, at 15:35:45
>
> Unfortunately, I don't have a citation right in front of me, but I've read that about 50% of depressed people have elevated corticosteroid levels. Question: Are the elevated corticosteroid levels the chicken or the egg?
My depression was actually corticosteroid induced (prednisone). Never have been the same since I was on a twenty day prednisone cycle in late 1997. I think the prednisone burned out my brain and created a severe clinical depression.Old School
Posted by IsoM on January 9, 2002, at 16:47:02
In reply to Re: Newsweek Article - new drugs, posted by Bekka H. on January 9, 2002, at 15:35:45
Posted by Bekka H. on January 9, 2002, at 17:26:23
In reply to Elevated Levels Becomes A Vicious Circle (nm) » Bekka H., posted by IsoM on January 9, 2002, at 16:47:02
IsoM, I don't see your message.
Posted by IsoM on January 9, 2002, at 19:12:32
In reply to Re: Elevated Levels Becomes A Vicious Circle, posted by Bekka H. on January 9, 2002, at 17:26:23
> IsoM, I don't see your message.
There was no message - that's why the subject line had (nm).
I just meant that it doesn't matter what came first sometimes. The elevated cortisol levels can cause depression & depression raises cortisol levels. So no matter what the initial reason was, it can be self-perpetuating & a hard cycle to break. Looking for one reason is often limiting what we learn.
Posted by Bekka H. on January 9, 2002, at 20:17:04
In reply to Re: Elevated Levels Becomes A Vicious Circle » Bekka H., posted by IsoM on January 9, 2002, at 19:12:32
> > IsoM, I don't see your message.
>
> There was no message - that's why the subject line had (nm).
>
> I just meant that it doesn't matter what came first sometimes. The elevated cortisol levels can cause depression & depression raises cortisol levels. So no matter what the initial reason was, it can be self-perpetuating & a hard cycle to break. Looking for one reason is often limiting what we learn.
Oops! Thanks for the information!
Posted by finelinebob on January 10, 2002, at 11:56:56
In reply to Re: Elevated Levels Becomes A Vicious Circle, posted by Bekka H. on January 9, 2002, at 20:17:04
In Noonday Demon, Solomon talks a lot about the blurred line between anxiety and depression and the effect of sustained elevated cortisol levels. First thing that occured to me was "Where are the meds/treatments that address this specifically?"
Tied up in FDA approval, of course.
I don't think it's just a matter of postponing competition for current meds ... it also leads to a justification of the high prices for these meds when they do come out.
grrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr...
flb
Posted by Dr. Bob on January 10, 2002, at 19:15:33
In reply to Re: Elevated Levels Becomes A Vicious Circle, posted by finelinebob on January 10, 2002, at 11:56:56
Posted by Noa on January 10, 2002, at 19:30:31
In reply to Re: Elevated Levels Becomes A Vicious Circle, posted by finelinebob on January 10, 2002, at 11:56:56
Ah, those familiar growls...Good to have you back.
Posted by spike4848 on January 12, 2002, at 20:56:49
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
People with Cushing Syndrome have elevated cortisol levels .... also have higher rates of depression. Medication like ketoconazole and metapyrone can reduce levels of costisol in the body and have been tried for depression. They were case reports and open trials ... I don't know if there are any double blind studies. Actually ... I look that up now.
I have read scientists have injected cortisol into the CSF of rats ... right into the brain. It apparently caused severe depressive features in rats.
Spike
Posted by BarbaraCat on January 12, 2002, at 21:31:25
In reply to Newsweek Article - new drugs, posted by Bill L on January 8, 2002, at 14:56:16
When was the last time your Pdoc asked about what you were eating? How your thyroid was doing? Your levels of DHEA or free cortisone levels and circadian surges? What time you get to sleep? How do you breathe?
OK, I've been following the CRF factor cortisol/HPA axis trail for some time and, while in theory it's promising, I can assure you that cortisol is not the lynchpin in all this - it's the EFFECT, not the cause. Cortisol is released by the adrenals - the adrenal medulla in fact, in response to stress, as well as the circadian rhythm/sleep cycle and light. Cortisol converts to noradreneline, which then travels by way of the cerebral spinal fluid to find it's way into the limbic system which then releases a surge of norepinephrine. A normal and healthy response to stress and motivational energy is dependant upon a healthy CRF/HPA in-sync system. It's a very useful catabolic hormone without which you would feel little energy and you would not break down and excrete old debris out of your system. Cortisol should normally be higher in the a.m. and lower in the p.m. The problem occurs when the parasympathetic (the fight/flight branch of the nervous system) system is chronically overstimulated and gets stuck in hyperarousal and fear mode and keeps churning out cortisol, especially at bedtime when it should be at a low tide. There's also a school of thought that says that all this churning out of cortisol/noradrenaline depletes our adrendal reserve which has to be restored and recovered through recuperation. It's not as easy as taking a pill to block cortisol - it comes down to looking at our lifestyle and healing any underlying metabolic dysfunctions. We simply don't know how to decompress and disconnect from the intense stress we're bathed in, whether it be our jobs, relationships or our depressions, and this takes it's toll. There are ways to address the root of these problems rather than apply bandaids via drug therapy after the fact. What needs to be addressed and IS NOT in psychiatry is some in-depth knowledge and testing in basic body health and lifestyle counseling (along with brain imaging scans!). What vitamins/herbs/amino acids/hormones, in specific and tailored therapeutic doses might target and support underlying metabolic dysfunctions? Is DHEA supplementation called for? Is there a sleep cyle dysregulation that might be helped with melatonin? EPA in fish oils seem to help excess cortisol. Breath training for hyperarousal. There are many other systems in our miraculous bodies that need attention.
I'm NOT saying medication isn't called for - I'd be incoherent without it and have needed big-guns drug therapy to get me to a place to look beyond it. However, we cannot expect pharmacology to do it all. We can't expect our very busy PDocs or MD's to know all the answers either. Let's start being very curious about all possible sources of our imbalances and what body systems they affect. There are trained folks who can delve deeper into these branches of healthcare than most of our typical care team has time for. I have personally been helped tremendously by eventually dragging my poor sick bod into good naturopath's office.
> The recent special double issue of Newsweek has an interesting article on new antidepressants being tested. The magazine is not dated. It has a graphic of September 11 on the cover. The researchers anticipate that the new drugs may eventually replace the SSRI's and other current drugs.
>
> The new drugs block cortisol. Cortisol is thought to cause shrinkage of a part of the brain known as the hippocampus. (I used to think that was a college for hippos). Autopsies show diminished hippocampuses (or is it hippocampi?) in depressed people. The idea is that the cortisol blocking drug will work better than current drugs with less side effects.
>
> There are other drugs that could more directly prevent shrinkage of the neurons in the brain but these drugs taken orally cannot be absorbed. Also, even if injected, they cannot cross the blood brain barrier. The corisol blocking drug however can be taken orally.
>
> This new drug caused less depression in rats. If you read the article it goes into detail of how one measures depression in rats. Apparently depressed rats drown more easily than happy rats.
Posted by Mitch on January 13, 2002, at 21:05:34
In reply to What about health? (or, Who's on first?), posted by BarbaraCat on January 12, 2002, at 21:31:25
We simply don't know how to decompress and disconnect from the intense stress we're bathed in, whether it be our jobs, relationships or our depressions, and this takes it's toll. There are ways to address the root of these problems rather than apply bandaids via drug therapy after the fact. What needs to be addressed and IS NOT in psychiatry is some in-depth knowledge and testing in basic body health and lifestyle counseling (along with brain imaging scans!).
While meds can offer a decent life that otherwise would be intolerable for people that need them-you have this horrific possible(?) scenario where making us insulated (med-wise) from these extreme stressors *allows some* to crank up the stress to even higher levels. Are we any better off as a society, if the *stakes* are just increased as a result of our ability to tolerate them?? In other words, what have we gained?
MItch
Posted by BarbaraCat on January 13, 2002, at 22:09:54
In reply to Re: What about health? (or, Who's on first?) » BarbaraCat, posted by Mitch on January 13, 2002, at 21:05:34
> While meds can offer a decent life that otherwise would be intolerable for people that need them-you have this horrific possible(?) scenario where making us insulated (med-wise) from these extreme stressors *allows some* to crank up the stress to even higher levels. Are we any better off as a society, if the *stakes* are just increased as a result of our ability to tolerate them?? In other words, what have we gained?
>
> MItchI couldn't agree with you more. What we're seeing is the result of total disconnection from our natural ways and means catching up with us. Medication, in my humble opinion, should allow us the focus and energy and hope to explore other means of raising our joy quotient rather than primarily offering a means to drive ourselves harder. When we get a little better, it's usually back to the same ol' same ol', but with renewed vigor. Something has got to give and it's our brains, our bodies and our souls. Some folks in this group are on 10 and more meds to try to attain some balance both chemically and in their day to day living abilities. I too have been on major med changes, cocktails, on and on. It took a major breakdown physically and psychically to really look at how I've been trying to cope with an unmanageable and frenetic life and how my body eventually just said 'that's it, I've had enough! Get me out of here!'. AD drugs don't work for me anymore for more than 1 month. In fact, as I pile more and more drug combos into my body, it rebels. What to do? I dunno. But little by little as I force myself to take those walks in nature, as I sit with my pain and try to feel safe in the moment, as I try to live a disgustingly clean life, I think all systems are beginning to breathe a teensy sigh of relief. I will always be on medication, I'm certain of it, but oh, I just want the energy, clarity, and motivation to steer my choices in the direction of Life and pure, radiant Health and well-being. And maybe eventually, even a means of financial support that doesn't leave me blasted.
> We simply don't know how to decompress and disconnect from the intense stress we're bathed in, whether it be our jobs, relationships or our depressions, and this takes it's toll. There are ways to address the root of these problems rather than apply bandaids via drug therapy after the fact. What needs to be addressed and IS NOT in psychiatry is some in-depth knowledge and testing in basic body health and lifestyle counseling (along with brain imaging scans!).
>
Posted by Mitch on January 14, 2002, at 9:39:14
In reply to Re: What about health? (or, Who's on first?) » Mitch, posted by BarbaraCat on January 13, 2002, at 22:09:54
I remember some comedy skit I heard on public radio about ten years ago. It had something to do about warning people not to take any meds not approved by your *supervisor* or *manager*! While I understand and support the idea of *enabling* people to "plug-in" to the economy and pay their taxes-contribute to the common pie (who otherwise would not), etc., we will probably be reorganizing our priorities. Maybe with the baby-boomer obsessive-compulsive-personalities (I am one of those at times!), losing some status--newer meds can have a chance to "catch-up" and surpass some of the ever-mounting stressors in society that is damaging us. You have to work both sides-some people are going to need meds no matter what, but you have to do what you can to promote a healthy psycho-social environment for yourself and others.
Mitch
This is the end of the thread.
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