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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by elanor roosevelt on December 14, 2006, at 20:53:58
I can't seem to find a link to it but the wall sreet journal carried an article today about new medical approaches to depression titled:
Targeting Depression: Some Promising Treatments Take Different Path Than Prozac, Aim at Body's Response to Stress.In the article they make the point that stress causes the increase of production of a protien called CRF, which in turn triggers the release of hormones, including cortisol which can predispose people to to depression by damaging nerve-cell connections.
AD sales for last year were $12.6 bilion.
Anyway, I will watch for a reprint. I have a hard copy.
Posted by Phillipa on December 14, 2006, at 22:00:27
In reply to wsj article on depression, posted by elanor roosevelt on December 14, 2006, at 20:53:58
Does that mean if your cortisol levels are considered normal by an endo you're not depressed? And would that mean that cutting down on stress cuts down on depression? Love Phillipa
Posted by stargazer on December 14, 2006, at 23:16:16
In reply to Re: wsj article on depression » elanor roosevelt, posted by Phillipa on December 14, 2006, at 22:00:27
Can't you remember how you felt when you were in a very stressful situation and your heart starts pounding, you may sweat or feel flushed, that reaction is to increased cortisol. Now think of that level of stress not going away, I can remember saying to myself at times, try and relax, stay calm, the stress is gone, but your body continues to feel like it is being threatened, aka fight or flight reaction.
That is a situation that can lead to becoming depressed. I say that we need at least an equal amount of stress and relaxation in our lives for a stable healthy life. If the stress reaction is turned on all the time, it will inevitably lead to either medical or psychological burnout, depending on your genetic makeup. My faulty mechanism is the inability to buffer even mild stress effectively and where the right AD helps to do this. It's a feeling like you are missing a part, but with the right med, the stress is seen for what it is and handled in a logical and rationale way.At least that's how it feels to me...SG
Posted by Phillipa on December 14, 2006, at 23:25:09
In reply to Re: wsj article on depression, posted by stargazer on December 14, 2006, at 23:16:16
Exactly I wake-up this way during the night. Sweating and that's when I take more meds that don't work. This means to me that some doc has to do something other than tell me that stress will kill me like my GP did whom I don't like. Maybe the endo will help as he works at the large hospital here that has a huge more than one psych unit. Love Phillipa
Posted by dessbee on December 15, 2006, at 7:42:59
In reply to wsj article on depression, posted by elanor roosevelt on December 14, 2006, at 20:53:58
I think you are referring to corticotropin releasing factor also called CRH - corticotropin releasing hormone.
CRH is a part of the HPA-axis (Hypothalamic-Pituitary-Adrenal Axis). CRH triggers release of ACTH (adrenocorticotropin), which triggers release of cortisol, which inhibits release of CRH.
HPA-axis is a feedback system, like a thermostat for stress. Stress could be anything from a chemical, a bacteria or social environment.http://www.biology.ucr.edu/people/faculty/Garland/HPA_axis.jpg
http://cti.itc.virginia.edu/~psyc220/kalat/JK367.fig12.6.HPA_axis.jpg
It is interesting that animal models show that low glucocorticoid receptor density in the forebrain produces depression-like changes in adrenal axis regulation and behavior. Cortisol is a Glucocorticoid receptor agonist and act on these receptors to inhibit CRH release. So low glucocorticoid receptor density makes HPA-axis less sensitive and more cortisol is needed for feedback inhibition. Depression is like a thermostat gone haywire initiating a stress cascade.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=544280
In my mind SSRI only alleviates depression, it is not the true cure of depression. It only modulates the HPA-axis indirectly.
CRF1 receptor antagonists will probably be a far better antidepressant since it intervenes the HPA-axis directly, blocking the pathogenesis of a depression.
The most optimal treatment for depression would most likely be a therapy that increases Glucocorticoid receptor expression/density; this would hopefully heal the depression at its core, maybe the true etiology of a depression.
Posted by med_empowered on December 15, 2006, at 9:16:16
In reply to Re: Corticotropin Releasing Factor » elanor roosevelt, posted by dessbee on December 15, 2006, at 7:42:59
I think this is interesting...like the the use of RU486 for psychotic depression.
It seems like other docs have been talking about this for a while...like using low-dose naltrexone to boost endogenous opioids. And obviously, megavitamin combos and stress reduction techniques...its nice of Big Pharma to deign to take an interest, now that the market for reuptake inhibitors has grown stale.
Posted by linkadge on December 15, 2006, at 10:36:34
In reply to Re: Corticotropin Releasing Factor, posted by med_empowered on December 15, 2006, at 9:16:16
In terms of controlling haywire HPA axis activity, the SSRI's are not terrably good.
The TCA's and mirtazapine are better, and Tianeptine is better yet.
Imipamine and other TCA's but not SSRI's have effects on the HPA axis gene expresson. Perhaps why they are more effective for certin melancholic depression.
The best way to tame overactive HPA axis is just some plain old marajuanna. Don't think its the THC, but some other constituents have significant effect on the HPA axis.
Linkadge
Posted by med_empowered on December 15, 2006, at 15:52:44
In reply to Re: Corticotropin Releasing Factor, posted by linkadge on December 15, 2006, at 10:36:34
yeah...I wish pot didn't make me so anxious. Turns out certain component are good for about everything--anxiety, depression, pain, nausea, possibly even psychosis.
Posted by Maxime on December 15, 2006, at 17:42:53
In reply to Re: Corticotropin Releasing Factor, posted by med_empowered on December 15, 2006, at 15:52:44
Last year my PDOC put me on a cortisone steroid to try and produce and anti-depressant effect. He said that some people respond to the med and then the good mood stays. You can only be on it for 10 days. After 7 days I felt better. Then after I stopped it I CRASHED. I don't remember the name of the med though.
Maxime
Posted by stargazer on December 15, 2006, at 20:30:07
In reply to Re: Corticotropin Releasing Factor, posted by Maxime on December 15, 2006, at 17:42:53
Wasn't there a test they used to do for depression called DMT, Dexamethasone Suppression Test. I can barely remember anything about it but they injected the drug and then did tests to see how your adrenals responded.
Does anyone else remember this? At least it was something that had a biological basis to it that was felt to play a role in depression.
Stargazer
Posted by linkadge on December 15, 2006, at 21:13:51
In reply to Re: Corticotropin Releasing Factor, posted by stargazer on December 15, 2006, at 20:30:07
Yeah, but its not used routenly because, if I'm not wrong, a good portion of depressed patients don't show abnormalities on the DST.
Linkadge
Posted by elanor roosevelt on December 15, 2006, at 22:56:27
In reply to Re: Corticotropin Releasing Factor, posted by linkadge on December 15, 2006, at 21:13:51
the article mention CRF1 antagonist,Agomelatine,Metabolic glutamate receptor 5 antagonists and Mifepristne.
i think the pharma companies will continue to milk the ssri business
they don't work very wll but it is easy to get approval for them
Posted by dessbee on December 16, 2006, at 12:13:21
In reply to Re: Corticotropin Releasing Factor, posted by elanor roosevelt on December 15, 2006, at 22:56:27
Lately I have seen more and more psychiatrist admitting that SSRI is no more efficient in alleviating depression compared to older AD.
The only advantage is that SSRI have fewer side effects and there is less risk of overdose.I have heard that only 25% who get a SSRI prescription actually goes to a pharmacy and collects it. That is alot of money lost for SSRI business. The 'collect rate' for AD prescriptions will probably improve when ADs become better at doing its job.
Posted by dessbee on December 18, 2006, at 7:34:06
In reply to Re: Corticotropin Releasing Factor, posted by stargazer on December 15, 2006, at 20:30:07
It seems like it is not a reliable test for diagnosing depression.
Found this:
"The sensitivity of the DST (rate of a positive outcome, or nonsuppression of cortisol) in major depression is modest (about 40%-50%) but is higher (about 60%-70%) in very severe, especially psychotic, affective disorders, including major depression with psychotic as well as melancholic features, mania, and schizoaffective disorder."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=3310667
"This test is performed when overproduction of cortisol is suspected. The low-dose test can help differentiate healthy people from those who produce too much cortisol. The high-dose test can help determine if the abnormality is in the pituitary gland (Cushing's Disease).
The secretion of ACTH from the pituitary gland is normally regulated by the level of cortisol in the blood plasma. ACTH stimulates the adrenal cortex to produce cortisol. As plasma cortisol levels increase, ACTH secretion is suppressed. As cortisol levels decrease, ACTH increases.
Dexamethasone is a synthetic steroid similar to cortisol, which suppresses ACTH secretion in normal people. Therefore, giving dexamethasone should reduce ACTH levels, resulting in decreased cortisol levels. People with pituitary glands which produce too much ACTH will have an abnormal response to the low-dose test, but a normal response to the high dose."
This is the end of the thread.
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