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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by temoigneur on June 4, 2005, at 15:14:27
I have severe anxiety/ mod. depression. OCD; I was reading how cortisol levels may be implicated in mood disorders, Namy psychotic depression - it caught my attention, because one of my main symtpoms is the need to punish myself for some sin I've committed. In my case I have poor/no intuition, and I only learn that my attempts to rectify the 'delusions/obsessions' through rituals, purging are useless, by trying every option, - it's like if I do nothing i think I'll be given over to suicide, and when i do muster the courage to do whatever it is to satisfy the punishing impulse, I realize it was pointless, for about 1 sec, and then it repeats. Here's the par. from the Mifepristone article, I realize I'm rekindling an old debate from a couple weeks ago, but this could have earth shattering implications for anxiety and depression, here's the paragraph that especially caught my attention, the article, and a link to the discussion two weeks back. Any imput, on cortisol lowering drugs, would be wonderful.
RU-486 - Mifepristone
Tested for Treatment of DepressionThe New York Times reported that Corcept Therapeutics is testing the controversial abortion pill, Mifepristone (formerly known as RU-486, brand name, Mifreprex), in clinical trials for the treatment of severe depression.
The article uncritically transcribed the sponsors' optimistic pitch about "encouraging findings" : "Of the 30 patients in the recent study, those who took mifepristone for seven days at dosages higher than those used for abortions showed substantial and rapid improvement in their symptoms, the researchers found. The drug produced only mild side effects in the study."
However, toward the end of the article we learn that one of the 30 patients, "a 49-year-old man, had died during the study." (not exactly a "mild side effect") We also learn that this patient "had been taking 11 other medications in addition to mifepristone...the man died from congestive heart failure, brought on by high blood pressure and heart disease."
The Times reporter accepted on faith the sponsors' claim: "it was unlikely that the death was related to his participation in the clinical trial."
Not reported by the Times, is the fact that the FDA issued Dear Doctor letters on April 19, 2002, warning about reported severe adverse drug reactions in patients taking Mifepristone: several reports of ruptured ectopic pregnancies--including a death from hemorrhage; two cases of sepsis (one fatal); and a heart attack in a 21 year old woman.
http://www.fda.gov/medwatch/SAFETY/2002/mifeprex_deardoc.pdf
http://www.fda.gov/cder/drug/infopage/mifepristone/mifepristone-qa_4_17_02.htm#1
Two questions arise--though neither was raised by The Times reporter:
1. Did the NY Times ascertain whether the dead man had been taking antidepressants and / or anti-psychotics as well as the abortion pill? If so, he was at increased risk inasmuch as those drugs, singly and in combination, are known to produce heart failure and high blood pressure.
Whatever the merit of the theory promoted by investigators and the sponsoring company, the study design--and inclusion of patients taking drug cocktails--does not appear to meet scientific or safety standards.
2. Was the scientific merit and safety of this experiment evaluated by independent medical experts and an independent institutional review board?
Critics might say that this study is an illustration of how conflicts of interest corrupt the integrity of clinical trials. [See also, AHRP Infomail, Duke Survey of Clinical Trials: Conflicts of Interest Violate Ethics, Oct 27, 2002]
~~~~~~~~~~~~~~~~~~~http://www.nytimes.com/2002/10/22/health/psychology/22PILL.html?pagewanted=print&position=top
THE NEW YORK TIMES
October 22, 2002
Abortion Pill May Help Treat Severe Form of Depression
By ERICA GOODE
Mifepristone, once called RU-486, is best known as the abortion pill.But some scientists believe that the drug may eventually serve another, far less controversial, purpose: treating a particularly fierce and intractable form of depression.
Two small studies, the latest appearing last month in the journal Biological Psychiatry, have found that mifepristone is effective in helping people whose severe depression is accompanied by delusional beliefs or hallucinations. Of the 30 patients in the recent study, those who took mifepristone for seven days at dosages higher than those used for abortions showed substantial and rapid improvement in their symptoms, the researchers found. The drug produced only mild side effects in the study.
Encouraged by such findings, Corcept Therapeutics, the small California pharmaceutical company that financed the second study, has applied to the Food and Drug Administration for approval to market mifepristone for psychotic depression, and two large clinical trials of the drug are in progress. (Danco Laboratories of New York manufactures and distributes mifepristone, sold as Mifeprex, for ending pregnancy.)
Dr. Joseph K. Belanoff, a psychiatrist and Corcept's chief executive, said the drug could be available within five years "if everything went well" and mifepristone was found to be safe, as used in the study, and effective for the disorder. Dr. Belanoff was also the lead author of the study published in the journal in September.
If mifepristone does reach the market, it will be the first medication specifically approved for psychotic depression, which psychiatrists say is the most difficult form of depression to treat.
The illness accounts for 15 percent to 19 percent of the cases of severe depression diagnosed in the United States, according to a study by Dr. Maurice M. Ohayon and Dr. Alan Schatzberg of the Stanford medical school to appear soon in The American Journal of Psychiatry. Dr. Schatzberg, Stanford's chairman of psychiatry, is a founder of Corcept and a shareholder in the privately held company.
Patients with psychotic depression often suffer from delusions, believing, for example, that they deserve punishment for imagined crimes or that they have terminal illnesses.
Psychiatrists have traditionally treated psychotically depressed patients with some combination of antidepressants, antipsychotic drugs and electroshock therapy, an approach that has yielded only moderate success. But the investigators hope that mifepristone, which patients would take for a short period then return to the usual course of treatment, will relieve symptoms more quickly and effectively.
A chemical compound used for abortions may seem an odd candidate for a depression drug. But mifepristone attracted the attention of researchers for good reason.
Mifepristone induces abortion by blocking the action of progesterone, a hormone necessary for implanting a fertilized egg in the lining of the uterus.
But in higher doses, the drug also blocks another hormone, cortisol, which is secreted by the adrenal glands and plays a critical role in the body's response to stress. Patients with psychotic depression, studies have shown, often have elevated levels of cortisol.
Dr. Anthony Rothschild, a professor of psychiatry at the University of Massachusetts Medical School, who has studied psychotic depression, said he and Dr. Schatzberg had hoped to test RU-486 as a treatment in the late 1980's.
"You just couldn't get it because of the political controversy," Dr. Rothschild said.
Dr. Dennis Charney, the director of the mood and anxiety disorders research program at the National Institute of Mental Health, said scientists at first assumed that the elevated cortisol levels found in some severely depressed patients were only indirectly related to their illness.
In the last few years, however, researchers have demonstrated that stress hormones can have a significant effect on brain areas involved in memory formation, emotion and other mental functions. The preliminary studies of mifepristone, said Dr. Charney, an author of a commentary accompanying the recent journal article, suggest that cortisol may be directly connected to the delusions and severe depression that patients experience.
Such research, he said, "suggests that cortisol may be mediating a lot of the symptoms associated with mood disorders."
Prednisone, a drug closely related to cortisol, can sometimes produce mood changes and psychosis as side effects, Dr. Charney noted.
Still, he said, more research is required before the effectiveness of mifepristone can be confirmed. The study published last month, for example, was not double-blinded, a protection that prevents the experimenters from knowing whether a patient is taking the drug being tested or a dummy pill.
Dr. Belanoff said the results of the first large double-blinded clinical trial, of 200 patients at 25 medical centers around the country, would be available early next year. A second trial is in the early stages.
Dr. Belanoff confirmed that one patient in the first clinical trial, a 49-year-old man, had died during the study. But he said an autopsy concluded that the man, who had been taking 11 other medications in addition to mifepristone, died from congestive heart failure, brought on by high blood pressure and heart disease, and that it was unlikely that the death was related to his participation in the clinical trial.
Even if mifepristone wins approval as a treatment for psychotic depression, the drug's controversial history may make it difficult to dispense, perhaps restricting its use to hospital wards. When, in 2000, the F.D.A. finally approved Mifeprex for abortions, it placed tight restrictions on its use. And the continuing debate over chemical abortion will probably ensure that similar restrictions are applied to mifepristone in any form, even one intended to help the most severely depressed patients.
and the link to the thread from a few days ago:
Posted by Mr.Scott on June 8, 2005, at 1:17:41
In reply to Anyone with Severe Anxiety/ mod Depression, posted by temoigneur on June 4, 2005, at 15:14:27
That was very interesting. Thanks for posting.
Scott
Posted by temoigneur on June 8, 2005, at 20:51:32
In reply to Re: Anyone with Severe Anxiety/ mod Depression » temoigneur, posted by Mr.Scott on June 8, 2005, at 1:17:41
I'm deliberating over ketoconazole for reducing cortisol with prozac - the thing is on clomipramine my anxiety an OCD is gone - but I feel vegetative, buzzed on a low grade euphoria - so I'm looking into ketoconazole /w prozac - there's a european researcher who writes about two successful long-er term treatments with ket. augmentation - studies seem fairly sparse but one in the journal of clin. psychiatry suggested that ketoconazole may have a limited effect in treatment resistant depression. My GP says it makes complete sense - because she knows that cortisol levels are disrupted in depression... So I'm weighing the pro's and cons, and with invaluable help from Ed_UK, trying to find a safe way to approach this - it can cause liver damage - cirrohsis, hepatitis - hopefully rarely. Also, I wrote the manufacturer of mifepristone, and they do have a compassionate access program for low/no cost it's at:
Mifeprex is approved for ending early pregnancy and is not approved for any other treatments. Danco does have a compassionate use program for treatment of other diseases with mifepristone. This program is run by Dr. Beth Jordan at the Feminist Majority. You should contact her for more information and to see if your patient might be eligible for the compassionate use program. She can be reached by phone at 703-522-2214 or by email at bjordan@feminist.org. Corcept is also researching mifepristone for psychotic depression, and their contact information is as follows: 650-688-8800 general number and perhaps www.corcept.com or info@corcept.com.
Posted by SLS on June 8, 2005, at 21:47:49
In reply to Mifepristone; compassionate access, +. » Mr.Scott, posted by temoigneur on June 8, 2005, at 20:51:32
Mifepristone is not easy to get, nor is it free. It is do-able, though. It is just time-consuming. There is a lot of paperwork to do, and the physician must follow the same procedure for each individual patient. Two applications go out:1. The feminist majority
2. The FDAI have already been assigned an IND number by the FDA to take mifepristone. Now, I must work with the feminist majority to actually procure the drug. You take 600mg of mifepristone for 7 days and then stop. You hope that you begin to respond to it by the end of the week, and then pray that the newly regulated brain stays that way indefinitely. Each person is allowed two treatments per year, so if relapses occur less than 6 months apart, you are left to agonize. Hopefully, this will all change once the drug receives any number of new indications, including psychotic unipolar depression, bipolar depression, and Cushings Disease. The feminist majority doesn't really care which new indication the drug is approved for, as long as they can help insure that it remains available in the US as an abortifacient. The cost of the medication is much reduced. They will sell it for $10 per 200mg or 300mg tablet, I can't remember which. So that becomes a total cost of between $140 and $210 for the one week treatment. That's a pretty cheap fix - as long as you stay fixed. My guess is that for people like me, there will need to be maintenance treatments in excess of the twice per year that is currently allowed.
I get the stuff in about a month if all goes well. Of course, by then, I may not need it. Trileptal might be the answer for me. I still have hope that it will be.
Presently taking:
Lamictal 150mg
Parnate 80mg
nortriptyline 100mg
Abilify 10mg
Trileptal 600mg
Caffeine PRN
- Scott
Posted by Mr.Scott on June 8, 2005, at 23:25:05
In reply to Re: Mifepristone; compassionate access, +., posted by SLS on June 8, 2005, at 21:47:49
Well...well...well
I see the Rx man tomorrow. I will mention it. I'm sure he knows as he's actually a great doctor. I fear he will say don't change anything since you're well, and he may be right...
However...If I could find an even easier softer way than what I do now (assuming it is easier and softer!) that would still be good. Thanks for the info.
Scott
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