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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by SLS on October 10, 2023, at 9:21:54
"Deemed"
The FDA was about to approve zuranalone for Major Depressive Disorder, when a clinical study reported that the trial failed to meet the requirements to be deemed effective. There are more independent investigations reporting the efficacy of zuranolone than there are reporting failure.
Zuranolone is already approved for PPD. It's pharmacology is novel as an antidepressant. It is hard to justify not prescribing it off-label if a patient has been refractory to all other treatments. I haven't seen any concerns regarding dangerous side effects. Of course, I haven't been exposed to all of the information available.
Anyway, it is potentially one more tool in the toolbox. Just as psilocybin (microdoses?) is, despite not being approved by the FDA.
I've written at length several times in the past that the paradigm for clinical trials as they have been performed over the last 25 years has sabotaged the pharmacopeia of psychiatric drugs. I don't doubt that the zuranolone clinical trials are equally flawed. Have you ever wondered why the placebo response rate has doubled since the 1980s, while the response to active compound has gone down? In a nutshell, this is the consequence poor selection criteria or not enforcing a good one. As a consequence, I don't pay attention to failed clinical trial anymore.
- Scott
Posted by undopaminergic on October 11, 2023, at 3:58:58
In reply to Zuranalone is 'deemed' ineffective for MDD by FDA., posted by SLS on October 10, 2023, at 9:21:54
In my view, it's worth making a new drug available (if not toxic) simply because of its having a novel mechanism of action. If it does, it's almost certain to be useful in *some* cases.
-undopaminergic
Posted by SLS on October 11, 2023, at 11:23:14
In reply to Re: Zuranalone is 'deemed' ineffective for MDD by FDA. » SLS, posted by undopaminergic on October 11, 2023, at 3:58:58
> In my view, it's worth making a new drug available (if not toxic) simply because of its having a novel mechanism of action. If it does, it's almost certain to be useful in *some* cases.
>
> -undopaminergic
>\
Agreed. Unfortunately, zuranolone might be acting more like a sex steroid than any of the established antidepressants. I didn't realize this until you put up your post. It motivated me to take another look at zuranolone in the context of it possibly being specific for PPD. I decided to check if it was derived from, or acted like, a neuroactive sex-steroid. That might account for zuranolone being specific for PPD, and ineffective in MDD.Well, it turns out that zuranolone is indeed a neuroactive steroid that is chemically related to allopregnanolone, a sex hormone precursor. Both zuranolone and allopregnanolone act as a positive allosteric modulators of GABA-A receptors. I don't have time to think about this right now. I have to get ready for a move.
I am disappointed by what I found today.
- Scott
Posted by undopaminergic on October 12, 2023, at 4:13:49
In reply to Re: Zuranalone is 'deemed' ineffective for MDD by FDA. » undopaminergic, posted by SLS on October 11, 2023, at 11:23:14
> > In my view, it's worth making a new drug available (if not toxic) simply because of its having a novel mechanism of action. If it does, it's almost certain to be useful in *some* cases.
> >
> > -undopaminergic
> >\
>
>
> Agreed. Unfortunately, zuranolone might be acting more like a sex steroid than any of the established antidepressants.
>Why is that unfortunate?
> I didn't realize this until you put up your post. It motivated me to take another look at zuranolone in the context of it possibly being specific for PPD. I decided to check if it was derived from, or acted like, a neuroactive sex-steroid. That might account for zuranolone being specific for PPD, and ineffective in MDD.
>
> Well, it turns out that zuranolone is indeed a neuroactive steroid that is chemically related to allopregnanolone, a sex hormone precursor. Both zuranolone and allopregnanolone act as a positive allosteric modulators of GABA-A receptors. I don't have time to think about this right now. I have to get ready for a move.
>Neurosteroids can be useful, although I've had no luck with them myself. I tested pregnenolone (not allo-) a long time ago. I was also going to try DHEA (dehydroepiandrosterone), but it got stuck in customs.
-undopaminergic
Posted by SLS on October 14, 2023, at 15:34:27
In reply to Re: Zuranalone is 'deemed' ineffective for MDD by FDA. » SLS, posted by undopaminergic on October 12, 2023, at 4:13:49
> Neurosteroids can be useful, although I've had no luck with them myself. I tested pregnenolone (not allo-) a long time ago. I was also going to try DHEA (dehydroepiandrosterone), but it got stuck in customs.
What were the results for you?
For now, I would like to forget about endogenous neurosteroids. Your question is a good one, and I'm not sure of anything.
I would request that perform as much research as is necessary to answer the question the following question:
Can zuranolone and/or ganaxolone serve as treatments for Major Depressive Disorder or Bipolar Depression?
Take a look at this and tell me what you think. Both zuranolone and ganaxolone are approved by the FDA. However, neither drug is approved for depression. One would have to review the history of published research regarding zuranolone. You might want to do exactly the same with ganaxolone in order to see if there is reason to believe that it, too, might serve as an antidepressant.
Perhaps zuranolone can be prescribed off-label.
I won't have enough time to do this myself. I just got married and have a lot to do to renovate a house, sell it, and move to North Carolina.
I hope you for considering doing this. We might be looking at a good TRD drug. I no longer trust modern Phase III clinical trials. I have been railing against these trials since 2000. I will address with this some time in the future. Bug me about it in the futre.
The results of your research could change lives.
Take care of yourself.
- Scott
Posted by Jay2112 on December 1, 2023, at 21:46:00
In reply to Zuranalone is 'deemed' ineffective for MDD by FDA., posted by SLS on October 10, 2023, at 9:21:54
I tried the hormone it is based on...pregnalone (sp??) when it was available OTC here in Canada. Just made me MORE nervous. The anxiety effect over-powered the GABA effect. Just junk, IMHO.
Jay
This is the end of the thread.
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