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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by Denise528 on October 3, 2002, at 12:26:12
Hi,
Does anyone have any guesses to how long it will take for the above drugs to be on the market? Are we talking years or decades?
Denise
Posted by glenn on October 3, 2002, at 14:10:03
In reply to Substance P drugs and CRF antagonists?, posted by Denise528 on October 3, 2002, at 12:26:12
Hi there,
As far as I know the only substance p drug was dropped due to ineffectiveness, though there may be more, crf antagonists I beleive are in phase 2 testing , ie antalarmin and astressin, perhaps one of our american friends can say how long it takes from there to availability as I am from England so im not sure of their timetable.
There are meds which act on cortisol which is one of the things crf drugs will affect, but they tend to be problematic, ie mifepristone, ketoconazole and I beleive thalidoimide- a fine bunch!
glenn
Posted by LostboyinNC2 on October 3, 2002, at 16:10:10
In reply to Substance P drugs and CRF antagonists?, posted by Denise528 on October 3, 2002, at 12:26:12
> Hi,
>
> Does anyone have any guesses to how long it will take for the above drugs to be on the market? Are we talking years or decades?
>
> DeniseDenise, none of these drugs will be on the market for at the absolute minimum of five more years. More likely ten years...if they are ever FDA approved that is. Basically I wouldnt count on any truly novel antidepressants for at least ten more years. Mostly its just going to be more "me too" SSRI type serotonin antidepressants, variations on a theme basically. They have been talking about substance P ADs forever now, same thing for CRD-Antagonists. Most of these things never materialize in the real world, as there is very little political pressure to fix severe mental illness. If we had an AIDS like political campaign to wage war on mental illness, things might be different, but unfortunately, reality sucks.
Eric LOSTBOYinNC
Posted by pfinstegg on October 3, 2002, at 18:46:36
In reply to Substance P drugs and CRF antagonists?, posted by Denise528 on October 3, 2002, at 12:26:12
Hi
I am very interested in Substance P and CRH antagonists, too, as I have abnormally high 24-hour cortisol levels and do not suppress with the Dexamethasone suppression test, as you're supposed to. From what I have found out so far, these drugs are only in phase 2, and some have been discontinued due to serious side effects, so it's going to be a number of years before they are available and safe.
However, there are some other safe things that we can do, or will be able to do fairly soon, if we
have high cortisol levels underlying the depressive symptoms, which half of us do. As for drugs, tianeptine, while not sold in the USA, has been used throughout Europe for 5 years. The studies done in France show it to be safe and on a par with Paxil and Prozac for effectiveness- about 70%. I have taken it for 6 weeks, and can say that it is the most effective AD I have taken. I now have many days when I feel happy and normal- the depression gone, and the anxiety and social phobia either gone, or at manageable levels. And the less-good days seem like normal "down days"- not a huge crash like before. There are NO side effects! It acts by putting a barrier between the high cortisol levels and your brain- the hippocampus particularly. I'm also taking fish oils 4 gm., alpha-lipoic acid 100 mg.,and phosphadatylserine 200 mg.,which are all suppose to lower cortisol a little bit, plus all the regular vitamins. Because of having such high cortisol levels, I am also seeing an endocrinologist - we are following the cortisol, thyroid and estrogen levels, trying to get everything as close to normal as it can be without taking anything with potentially dangerous side effects such as ketonozodole or bromocriptine.There is something interesting for the not too distant future: mefipristone, or RU-486- the "morning-after" pill. It has been used on 8 unipolar depressed patients with psychotic features at Stanford. Five of these patients, who were extremely sick, went into complete remission with 7 days of treatment. Since mefipristone is very close to progesterone chemically, they still have to figure out how to use it. But the FDA thought it was so promising for severe depression that they "fast-tracked" it in August. It reduced the extremely high cortisol levels those 5 patients had to near-normal.
After having been severely depressed for 8 years, I am just now beginning to understand that cortisol may play a basic role- especially in those of us who have had childhood neglect and abuse; I guess these painful events put us into a chronic post-traumatic stress syndrome, which sooner or later dysregulates our HPA axis.
All the very best to you in finding what will work for you- there are so many differing answers!
Pfinstegg
Posted by Bob on October 3, 2002, at 18:49:47
In reply to Re: Substance P drugs and CRF antagonists?, posted by glenn on October 3, 2002, at 14:10:03
> Hi there,
> As far as I know the only substance p drug was dropped due to ineffectiveness, though there may be more, crf antagonists I beleive are in phase 2 testing , ie antalarmin and astressin, perhaps one of our american friends can say how long it takes from there to availability as I am from England so im not sure of their timetable.
> There are meds which act on cortisol which is one of the things crf drugs will affect, but they tend to be problematic, ie mifepristone, ketoconazole and I beleive thalidoimide- a fine bunch!
> glennGlenn:
Why are drugs like mifepristone and ketoconazole "problematic"? I'd be especially interested to hear your opinion concerning mifepristone, as my pdoc was willing to try me on it.
Posted by Pfinstegg on October 3, 2002, at 19:15:11
In reply to Re: Substance P drugs and CRF antagonists?, posted by pfinstegg on October 3, 2002, at 18:46:36
Hi
If your p-doc is willing, why not give mefipristone a try according to the 7-day protocol used at Stanford? Do you know if your cortisol levels are high? it brings them down to normal, although I guess no-one knows whether that's why it works so well. Being a female hormone, the use has to be short, but some of the Stanford patients were male and had no problems. It's been used, very short-term, by millions of women and is considered extremely safe. If you do try it, please let us know!
Pfinstegg
Posted by Phil on October 3, 2002, at 19:21:26
In reply to Re: Substance P drugs and CRF antagonists?, posted by pfinstegg on October 3, 2002, at 18:46:36
Never thought of that. Great post. My pdoc will be reading it if it's okay with you..I'll show her the post only, no names.
Posted by Bob on October 3, 2002, at 19:24:25
In reply to for Bob- mefipristone, posted by Pfinstegg on October 3, 2002, at 19:15:11
> Hi
>
> If your p-doc is willing, why not give mefipristone a try according to the 7-day protocol used at Stanford? Do you know if your cortisol levels are high? it brings them down to normal, although I guess no-one knows whether that's why it works so well. Being a female hormone, the use has to be short, but some of the Stanford patients were male and had no problems. It's been used, very short-term, by millions of women and is considered extremely safe. If you do try it, please let us know!
>
> Pfinstegg
I may indeed give it a try. I have familiarized myself somewhat with the Stanford study, but have wondered about longer term treatment. Where did you hear that it cannot be used long term because it is a female hormone? My pdoc found a study where it had been used long term in a man with Cushings disease. No, I don't know what long term is in this case.I'm supposed to have my cortisol levels checked next week.
Posted by pfinstegg on October 3, 2002, at 19:43:18
In reply to Re: for Bob- mefipristone » Pfinstegg, posted by Bob on October 3, 2002, at 19:24:25
Hi Bob,
I actually don't know whether it can be used safely for longer periods. I guess I just assumed that it couldn't be because it is a female hormone,and because the use at Stanford was so brief. But it's not estrogen, which would be feminizing, so maybe it can be. And I didn't know that it had been used longer term for a man with Cushing's Disease- that's fascinating.
Just brainstorming here, but maybe this is the kind of drug which can be used long-term in a stop-start fashion, the way they use various anti-androgens in men with prostate cancer.
I do hope you will let us know what you decide upon- I think there are hundreds of us who will really appreciate knowing! And the best of luck to you.
Pfinstegg
Posted by Pfinstegg on October 3, 2002, at 19:58:28
In reply to Re: Substance P drugs and CRF antagonists? » pfinstegg, posted by Phil on October 3, 2002, at 19:21:26
Hi Phil,
I'm so happy you thought my post was helpful. Although I do have a scientific background, all this stuff is really as new to me as anyone else. What little information I have comes from various web sources, just like everybody else. My post name comes from a favorite hiking destination in Switzerland- you can use it! (not that it will get you anywhere, unless you want to take a gorgeous, not too difficult hike among beautiful glaciers and snow-capped mountains)
Pfinstegg
Posted by Bob on October 3, 2002, at 23:00:00
In reply to Re: for Bob- mefipristone, posted by pfinstegg on October 3, 2002, at 19:43:18
> Hi Bob,
>
> I actually don't know whether it can be used safely for longer periods. I guess I just assumed that it couldn't be because it is a female hormone,and because the use at Stanford was so brief. But it's not estrogen, which would be feminizing, so maybe it can be. And I didn't know that it had been used longer term for a man with Cushing's Disease- that's fascinating.
>
> Just brainstorming here, but maybe this is the kind of drug which can be used long-term in a stop-start fashion, the way they use various anti-androgens in men with prostate cancer.
>
> I do hope you will let us know what you decide upon- I think there are hundreds of us who will really appreciate knowing! And the best of luck to you.
>
> Pfinstegg
Well, at the moment, it remains as one of my options to try. I'm on Lithium and Celexa right now, and the only thing that has made me more tired in my life has been Depakote therapy. Like I said, I need to get a cortisol level. If it turns out that it's not high, I'm not sure how we will proceed. Regardless, if I end up trying it, I will post on this board has to how it turns out.FYI, I read that mifeprestone was actually developed as a cortisol suppression drug. It was only later that it was marketed as an abortion pill due to it's abortifacent properties.
Posted by Pfinstegg on October 3, 2002, at 23:30:30
In reply to Re: for Bob- mefipristone » pfinstegg, posted by Bob on October 3, 2002, at 23:00:00
That's very interesting about mefipristone originally being developed to lower cortisol. I'm learning a lot of very useful information from you. As you learn more, please keep posting.
Pfinstegg
Posted by glenn on October 4, 2002, at 5:40:58
In reply to Re: Substance P drugs ... Mifepristone » glenn, posted by Bob on October 3, 2002, at 18:49:47
Bob , if your doc will give you mifepristone go for it!
You must have a great doc, the problems are twofold, firstly cost in the uk it costs £43 for 3 pills! none of our docs will spend that amount
secondly it is the anti abortion drug and has to cope with that identity, it also hasnt yet i beleive been fully tested long term.
However that said id take it!
glenn
Posted by Phil on October 4, 2002, at 6:18:22
In reply to Phil- re mefipristone, posted by Pfinstegg on October 3, 2002, at 19:58:28
Posted by pfinstegg on October 4, 2002, at 8:27:47
In reply to Re: Got an extra room?? (nm) » Pfinstegg, posted by Phil on October 4, 2002, at 6:18:22
Posted by Denise528 on October 4, 2002, at 11:06:29
In reply to Re: Substance P drugs and CRF antagonists?, posted by glenn on October 3, 2002, at 14:10:03
Hi Glenn,
What happened to Netamiftide? I thought that was a new substance P drug being developed by Innapharma and which held great promise as being a fast acting highly effective antidepressant? Has that been dropped now?
See http://www.innapharma.com/lead_compound.htm
Denise
Posted by dave40252 on October 4, 2002, at 17:21:47
In reply to Substance P drugs and CRF antagonists?, posted by Denise528 on October 3, 2002, at 12:26:12
Posted by EarlyWakening on October 4, 2002, at 19:58:18
In reply to Substance P drugs and CRF antagonists?, posted by Denise528 on October 3, 2002, at 12:26:12
In addition to psychotic depression,
Mifepristone is now being studied for Bipolar disorder. It looks like this avenue is building up some steam.
-------------------------------------Mifepristone to Treat Bipolar Depression
This study is currently recruiting patients.
Sponsored by
National Institute of Mental Health (NIMH)
PurposeThis two-part study will investigate: 1) the effectiveness of the experimental drug mifepristone in treating depression in patients taking a mood stabilizer drug; and 2) how certain hormones and mifepristone cause changes in mood, thinking and memory in some depressed patients with bipolar depression. Normal healthy subjects will be included in Part 2 to obtain data for comparison with patients.
Patients between 18 and 75 years of age who require treatment for severe bipolar depression may be eligible for this study. Candidates will be screened for eligibility with a physical examination, medical and psychiatric history, laboratory tests, and various neuropsychiatric evaluations. Participants will undergo the following tests and procedures:
Bipolar Patients
Patients will be hospitalized at the NIH Clinical Center for 3 to 4 weeks. They will slowly be tapered off all psychiatric medications, except Depakote (valproate) or lithium, or both. They will then begin taking a placebo (sugar pill) and begin baseline testing as described below. At the end of the baseline studies, patients will be randomly assigned to receive mifepristone pills or to continue placebo. After 1 week on medication, the treatment will be switched-that is, those taking placebo will be switched to mifepristone and vice versa. This treatment will continue for 1 week. During the study, patients will undergo the following additional procedures:
- ..........................Condition Treatment or Intervention Phase
Bipolar Disorder Drug: Mifepristone Phase IIMEDLINEplus related topics: Bipolar Disorder
Study Type: Interventional
Official Title: Antiglucocorticoid Therapy in Bipolar Depression with Mifepristone (RU486)Further Study Details:
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances and may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU 486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on lithium, valproate, or both after washout of prior antidepressants will have a detailed neuroendocrine assessment. Patients (n=75) will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls (n=35) will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.
EligibilityGenders Eligible for Study: Both
Accepts Healthy Volunteers
Criteria
INCLUSION CRITERIA FOR BIPOLAR PATIENTS:
Patients must meet the following inclusion criteria in order to participate in the study:
a) Male or female inpatients in need of treatment for severe bipolar depression.
b) 18-75 years of age.
c) Women of childbearing potential must be using an adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method (women who are on an OCP will be kept on it others must agree to use only a barrier method).
d) DSM-IV diagnosis of bipolar depression I/II, severe, with or without psychotic features.
e) A current major depressive episode of at least 6 weeks' duration.
f) Score of greater than or equal to 28 on the first 24-item HAM-D at the prestudy visit and at the first baseline phase visit.
g) Score of 20 or greater on the HAM-D (24) at the end of the baseline period(s) (i.e., at randomization no more than 20% less than entry enrollment criteria).
h) Score of greater than or equal to 4 on the CGI-BP scale at the prestudy and first visit and end of baseline phase.
i) Judged to be in good physical health on the basis of medical history, physical examination, and laboratory screening.
j) Able to understand procedures and agree to participate in the study by giving written informed consent.
k) On lithium and/or valproate for at least 4 weeks (2 levels 1 wk apart).
l) However patients not on a mood stabilizer can have this started as an outpatient or inpatient for 4 weeks as discussed above.
m) Able to come off of prior drugs and PRN zolpidem and lorazepam by start of baseline.
EXCLUSION CRITERIA FOR BIPOLAR PATIENTS:
Patients will be excluded from the study if they meet any of the following criteria:
a) Women who are pregnant, intending to become pregnant in the next month or breast-feeding.
b) Treatment with any of the following therapies within the specified interval prior to baseline: Fluoxetine - 2 weeks; Investigational compounds - 4 weeks; MAOIs - 1 week; Other antidepressants - 1 week.
c) Contraindication or history of hypersensitivity to mifepristone as well as cortisol, and CRH.
d) Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
e) Have evidence of any disorder that represents a contraindication to the use of mifepristone (such as adrenal disease or a condition requiring chronic corticosteroid administration).
f) History of Addison's Disease, Cushing's Disease, insulin dependent diabetes, or other uncompensated endocrine conditions.
g) Evidence of infection, severe liver, respiratory, or renal disease.
h) Have clinically significant cardiovascular disease, e.g., angina, valve disease, arrhythmia, cardiac failure.
i) Anemia (hemoglobin less than 10 g/dL or hematocrit less than 30%).
j) Have a known clotting defect or are receiving anticoagulants.
k) Rapid cycling in the last year (defined as greater than 6 episodes).
l) History of porphyries.
m) Clinically significant abnormalities in physical exam, ECG, or laboratory assessments.
n) History of any disease which, in the investigator's opinion may confound the results of the study or pose an additional risk, including but not limited to, history of organic mental disorder, seizures, or mental retardation.
o) Substance dependence that is not in sustained full remission (DSM-IV definition).
p) History of PTSD (DSM-IV definition).
q) Other principal psychiatric diagnosis judged by the investigator to dominate the clinical presentation. In particular, patients with depressive symptoms more than 2 years in duration should be carefully evaluated to determine whether another psychiatric diagnosis exists which could interfere with efficacy and safety measurements.
r) History of nonresponse to greater than four trials of antidepressants for the current episode (not including mood stabilizers) will exclude subjects.Expected Total Enrollment: 110
Location and Contact Information
Maryland
National Institute of Mental Health (NIMH), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting
Patient Recruitment and Public Liaison Office 1-800-411-1222 mailto:[email protected]?subject=NCT00043654, 020251: 02-M-0251- Mifepristone to Treat Bipolar Depression
Posted by pfinstegg on October 4, 2002, at 21:06:04
In reply to What IS substance P? (nm), posted by dave40252 on October 4, 2002, at 17:21:47
Hi...Substance P is one a newly discovered group of neurotransmitters called neurokinins. It is, when at normal levels, an essential transmitter involved in emotional regulation and pain perception in the amygdala. However, if the levels become too high, it is thought to play an important role in the onset of depression.
Because of this, research interests have focussed on substance P antagonists, also called NK1 receptor antagonists- the site of blockade being the amygdala. Merck had one called MK-869; it was shown in laboratory animals to stimulate the growth of new neurons in the hippocampus, and to alleviate major depression. It was initially very exciting and promising: it acted independently of the serotonin, norepinephrine and dopamine systems, and had a good side effect profile- including no sexual side effects. However, it got bogged down in phase 2 because it wasn't clear that it was a really effective AD. Merck discontinued work on it, but is working on a more potent variant of it; they expect to file for FDA approval in 2002. Novartis is also testing a substance P antagonist called NKP608; they expect to file for approval in 2003. It sounds good, doesn't it- but we'll have to wait a while.
Pfinstegg
Posted by SLS on October 5, 2002, at 1:14:15
In reply to Re: Substance P drugs ... Mifepristone » glenn, posted by Bob on October 3, 2002, at 18:49:47
I came across something about mifepristone awhile back, but didn't follow up on it. What have you come up with and where on the Internet can I find out more about it?
I have been stuck in a refractory bipolar depression for over 20 years. HELP!
Check this out:
http://www.clinicaltrials.gov/ct/gui/show/NCT00043654?order=1
- Scott
Posted by pfinstegg on October 5, 2002, at 10:44:42
In reply to Re: More Indications for Mifepristone, posted by EarlyWakening on October 4, 2002, at 19:58:18
Hi...this was so interesting. The NIMH study for mefipristone in bipolar is following rapidly on the Stanford study using it for unipolar. It does take at least a month staying there, and everyone will get only a week's worth of mefipristone, just like they did at Stanford. It could be that that's all that is needed. Later on, if it's really effective, they will surely figure out ongoing treatment strategies.
Anyone going there will get such a terrific neurological and endocrine workup- much better than you could get anywhere else. It would help the people who participate understand all the subtle but sometimes catastrophic physical and cognitive changes which we know are there, but which just aren't understood well yet. If the bipolar depression is presently severe, you have the time available, and qualify, I think the knowledge you will gain, and the chance to get treated in a fundamentally new way based on your neurophysiology would make it really worth considering. Since mefipristone is an already approved drug, safe, and with an American manufacturer (Danco), if it worked well, you could possibly be able to begin taking it on a longer-term, probably intermittent basis with your pdoc getting guidance from NIMH as to how it should be used. Even at NIMH, there is no way they can know much about that yet, either, but they will certainly know more than anyone else!
In any event, this study is really going to be worth watching closely.
Pfinstegg
This is the end of the thread.
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