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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by Hordak on April 11, 2018, at 18:41:08
There is a certain irony here:
"Ugh, tricyclics! Low selectivity for the serotonin transporter over the noradrenaline transporter, and what's with all the antagonism at histamine, alpha and 5HT2A receptors? Dirty stuff! Thankfully this is the 90's, and we have Selective Serotonin Reuptake Inhibitors!"
"...eh, maybe you do need a bit of a noradrenaline boost on top. Thankfully this is 2000, and we have SNRI's!"
"...and maybe it would be nice to have some histamine/5HT2-antagonism-mediated anti-anxiety action, too. It's 2010, try some Seroquel or Mirtazapine on top of your antidepressant!"
"...and we do want some alpha1-adrenergic receptor antagonism to normalize the HPA axis! And some FIASMA / BDNF would be nice. R&D, get started! It's 2018!"
"...or just have a tricyclic."
:=D ;=)
I would not be surprised if they try to market anticholinergics as new groundbreaking anxiolytics in a few years from now... *lol*
Posted by Hordak on April 11, 2018, at 19:21:29
In reply to pharmaceutical industry and their 'reinventions'., posted by Hordak on April 11, 2018, at 18:41:08
Posted by Christ_empowered on April 11, 2018, at 19:27:09
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by Hordak on April 11, 2018, at 19:21:29
one of Szasz's many criticisms of psychiatry was that the whole industry moves based more on dogma and trends than on facts and science.
got problems in the 50s? Dexamyl. 60s? Librium. 70s? Triavil.
Its not just treatment that follows trends, its diagnosis, too, like "pediatric bipolar" and whatever personality disorder is currently en vogue.
for example, my diagnosis is "Bipolar I." Up until the 90s or so, it would have been some flavor "Schizophrenia." If I was poor and/or a minority, it would still be "Schizophrenia."
so there you go.
Posted by rjlockhart37 on April 11, 2018, at 22:40:10
In reply to pharmaceutical industry and their 'reinventions'., posted by Hordak on April 11, 2018, at 18:41:08
it's always going to be that way, they improve treatments with newer drugs. I notice that previous generation doctors had different views treatment, were almost in 2020, the younger doctors have new treatment ideas no matter how previous generation pdocs did, they have newer meds, and also can reuse older meds that have lost patents, and redo their marketing. Evekeo was once benzedrine in the 1940s, it was popular using it for task force in the military to keep the soldiers alert and keep going during war....then they discontinued benzedrine and started using dexedrine
things change, even though past use of medications and antidepressants got pushed aside, the new generation of doctors could reuse the older treatments with more intelligence and insight, but always have to be aware of major red flags that happened in the past with them
Posted by rjlockhart37 on April 11, 2018, at 23:17:03
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by rjlockhart37 on April 11, 2018, at 22:40:10
like they could make new anti-depressants that work totally diffrent than others, they already have with Viibryd and serotonin modulators, instead of serotonin reptake inhibtors
and like using older meds, and repatening them, that would work, but the older psychiatric meds were harsh, not sure if they would really ever want to repatent ones that cause tartive dykansia......
but others.... dexamyl was a depression drug, they withdrew it from the market because it was being abused too much, and thought it wasn't fit as an anti-depressant but say like putting low dose methylphenidate with librium, which is known to not be so euphoric, its sutle in it's actions and not euphoric very much, that could be a repatent
Posted by SLS on April 12, 2018, at 7:36:04
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by rjlockhart37 on April 11, 2018, at 22:40:10
Excellent post!
- Scott
> it's always going to be that way, they improve treatments with newer drugs. I notice that previous generation doctors had different views treatment, were almost in 2020, the younger doctors have new treatment ideas no matter how previous generation pdocs did, they have newer meds, and also can reuse older meds that have lost patents, and redo their marketing. Evekeo was once benzedrine in the 1940s, it was popular using it for task force in the military to keep the soldiers alert and keep going during war....then they discontinued benzedrine and started using dexedrine
>
> things change, even though past use of medications and antidepressants got pushed aside, the new generation of doctors could reuse the older treatments with more intelligence and insight, but always have to be aware of major red flags that happened in the past with them
Posted by Hordak on April 12, 2018, at 10:29:52
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by rjlockhart37 on April 11, 2018, at 23:17:03
> like they could make new anti-depressants that work totally diffrent than others, they already have with Viibryd and serotonin modulators, instead of serotonin reptake inhibtors
How the f*ck is Vilazodone totally different?
It's an SSRI with some 5HT partial agonism...
Posted by rjlockhart37 on April 12, 2018, at 20:07:08
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by Hordak on April 12, 2018, at 10:29:52
i wrote that backwards, your right it's a agonist and repuptake
and vortioxetine...it's an agonist and antagonist of multiple serotonin receptors trazodone does the same thing, it blocks reuptake but also an antagonist of release, so thats not really totally new thing
i got confused reading saying "serotonin modulators" and thought it was a different term, it's the same thing an an SSRI but their also agonists
Posted by rjlockhart37 on April 12, 2018, at 20:20:13
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by rjlockhart37 on April 12, 2018, at 20:07:08
by the way i need to get 'totally' out of my vocabulary, i write it and don't even notice it
Posted by SLS on April 12, 2018, at 21:59:59
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by Hordak on April 12, 2018, at 10:29:52
> > like they could make new anti-depressants that work totally diffrent than others, they already have with Viibryd and serotonin modulators, instead of serotonin reptake inhibtors
>
> How the f*ck is Vilazodone totally different?
> It's an SSRI with some 5HT partial agonism...In what ways were you disappointed by vilazodone?
The brain, psychiatric disorders, and the drugs that are used to treat them are not fully understood. New properties of old drugs are discovered often enough such that it becomes easier to understand why two people can respond so differently to the same drug.
I tried vilazodone. It worked for me for awhile. It was a very clean drug. I didn't experience side effects typical of the classic SSRIs. Different is different. For each new drug that comes to market, a certain percentage of previously TRD patients will respond to it. If drug companies want to bring new drugs to market, what's the problem? Drugs with novel antidepressant properties are being worked on right now. Hopefully, we will soon see ketamine-like drugs without dissociative or psychotomimetic effects that can be taken orally. Personally, I would like to see hydroxynorketamine (HNK) looked at.
I'm grateful for anything new that comes along that might bring me to remission. The next drug that I am scheduled to try is vortioxetine. I have no reason to be optimistic, but it is different.
I don't know what you are searching for, but I hope you find it quickly.
- Scott
Posted by bleauberry on April 13, 2018, at 8:04:40
In reply to pharmaceutical industry and their 'reinventions'., posted by Hordak on April 11, 2018, at 18:41:08
...or we could take a different approach and remove the insult causing all of the neurochemical problems in the first place....but that isn't how medicine works.....The current medical system is designed to manage illness, not to restore wellness. They are not the same thing.
Here's an example:
A girl does 20 years of bipolar-like behavior - productive mild mania alternating with sluggish withdrawal type depression. Meds help manage it all but not really. She can't decide if it's a serotonin thing, norepinephrine thing, dopamine, whatever. No idea. One day the depression takes a deeper dive. It gets really dark, with trembling, terror, schizo-like, and she says she would jump off of a skyscraper if there was one to jump off of. On day 5 of this nightmare she is offered two pills - Azithromycin (wide spectrum general antibiotic) and Rifampin (narrow spectrum antibiotic targeting tuberculosis which she doesn't have, and targets Bartonella - the bacteria from ticks notoriously responsible for psychiatric symptoms.
In less than 24 hours her psychiatric state was 70% improved. The antibiotics totally arrested the event and set her back on normal footing.
So now she is looking at a longterm journey to get better. This time she knows her prescriptions will probably come from an LLMD instead of a psychiatrist. Not that there is anything wrong with the psychiatrist. Just that, as I said, their job really is to manage illness. We want more than that. We want to restore wellness.
I used to be a King of armchair quarterbacking with receptor sites, neurochemicals, synapses, agonists, antagonists, all that. The problem is that approach rarely restores wellness with anybody anywhere.
imo
> There is a certain irony here:
>
> "Ugh, tricyclics! Low selectivity for the serotonin transporter over the noradrenaline transporter, and what's with all the antagonism at histamine, alpha and 5HT2A receptors? Dirty stuff! Thankfully this is the 90's, and we have Selective Serotonin Reuptake Inhibitors!"
>
> "...eh, maybe you do need a bit of a noradrenaline boost on top. Thankfully this is 2000, and we have SNRI's!"
>
> "...and maybe it would be nice to have some histamine/5HT2-antagonism-mediated anti-anxiety action, too. It's 2010, try some Seroquel or Mirtazapine on top of your antidepressant!"
>
> "...and we do want some alpha1-adrenergic receptor antagonism to normalize the HPA axis! And some FIASMA / BDNF would be nice. R&D, get started! It's 2018!"
>
> "...or just have a tricyclic."
>
> :=D ;=)
>
> I would not be surprised if they try to market anticholinergics as new groundbreaking anxiolytics in a few years from now... *lol*
Posted by Hordak on April 13, 2018, at 18:10:01
In reply to Re: pharmaceutical industry and their 'reinventions'. » Hordak, posted by SLS on April 12, 2018, at 21:59:59
> > > like they could make new anti-depressants that work totally diffrent than others, they already have with Viibryd and serotonin modulators, instead of serotonin reptake inhibtors
> >
> > How the f*ck is Vilazodone totally different?
> > It's an SSRI with some 5HT partial agonism...
>
> In what ways were you disappointed by vilazodone?I am not disappointed in it, because I haven't tried it, but it's nothing "new".
Take an old SSRI and add Buspirone and you get Vilazodone.>Drugs with novel antidepressant properties
If they only were "novel"... ;=)
Posted by SLS on April 14, 2018, at 0:41:12
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by Hordak on April 13, 2018, at 18:10:01
> > > How the f*ck is Vilazodone totally different?
> > > It's an SSRI with some 5HT partial agonism...
> > In what ways were you disappointed by vilazodone?> I am not disappointed in it, because I haven't tried it
Would the world be a better place without vilazodone? I don't know.
> but it's nothing "new".
Perhaps it is new enough for some people.
Again, I would like to express the sentiments of research clinicians that for each new antidepressant that becomes available, a certain percentage of people who were previously TRD will respond to it. Why not just get rid of all SSRIs other than Prozac? That would be a bad idea, of course. A bunch of people who failed to respond to Prozac went on to respond to Zoloft when it came out.
Perhaps vilazodone is cleaner than SSRI + buspirone with respect to side effects (mental and physical). I wouldn't know, but it is conceivable. I found vilazodone to be cleaner than any SSRI I tried. Unfortunately, my response to it was short-lived. Still, it "felt" different than Lexapro.
> Take an old SSRI and add Buspirone and you get Vilazodone.
In my experience, things are not always so tidy, but I understand your logic. Buspirone is a full antagonist at dopamine D2 receptors last I heard. I don't think I would want that. It depends on dosage, I guess. The lower the dosage of buspirone, the more likely it is to produce an increase in DA activity (presynaptic biased). At higher dosages, it lowers activity. The question is, at what dosage does 5-HT1a partial agonism become potent enough to have a therapeutic antidepressant effect? Will it be so high that you get antipsychotic effects?
I would be interested to see an investigation: SSRI + buspirone (low-dose) versus SSRI + buspirone (high-dose) versus vilazodone.
I understand people's frustrations with old and new drugs alike.
What do you think of vortioxetine?
If I get stuck, I think I'll ask my doctor to experiment with low-dosage buspirone in combination with Effexor.
- Scott
Posted by Lamdage22 on April 14, 2018, at 10:29:54
In reply to Re: pharmaceutical industry and their 'reinventions'. » Hordak, posted by SLS on April 14, 2018, at 0:41:12
How do you come up with the energy to try all these drugs?
Posted by SLS on April 14, 2018, at 13:22:25
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by Lamdage22 on April 14, 2018, at 10:29:54
> How do you come up with the energy to try all these drugs?
For me, depression is a life or death condition - a walking death. I have no choice.
Actually, I have been on the same drugs, albeit at varying dosages, for over a year. Parnate has been the core around which my treatment has been built. However, it has become obvious to me that Parnate is a dead end. So I'm going to attempt to find a replacement. In my mind, I have three choices that make sense to me. I would try them in the following order if necessary:
1. Vortioxetine (Trintellix)
2. Venlafaxiine (Effexor) - High dosage > 300 mg/day; possibly with buspirone (Buspar) at low dosages
3. Phenelzine (Nardil)Currently:
Parnate 80 mg/day
nortriptyline 100 mg/day
Lamictal 300 mg/day
lithium 300 mg/day
Abilify 15 mg/day
prazosin 6 mg/dayThis regime has brought me to a place of moderate-to-severe depression. Without it, I suffer from very severe depression. I don't know how bad I'll feel when I come off the Parnate. Hopefully, the other drugs will keep me out of the basement.
Hamilton Rating Scale for Depression:
http://tools.farmacologiaclinica.info/index.php?sid=43496
* Answer the security question (simple math) and click on "Continue" NOT on "Start Now".
- Scott
Posted by Hordak on April 14, 2018, at 13:42:11
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by SLS on April 14, 2018, at 13:22:25
> > How do you come up with the energy to try all these drugs?
>
> For me, depression is a life or death condition - a walking death. I have no choice.
>
> Actually, I have been on the same drugs, albeit at varying dosages, for over a year. Parnate has been the core around which my treatment has been built. However, it has become obvious to me that Parnate is a dead end. So I'm going to attempt to find a replacement. In my mind, I have three choices that make sense to me. I would try them in the following order if necessary:
>
> 1. Vortioxetine (Trintellix)
> 2. Venlafaxiine (Effexor) - High dosage > 300 mg/day; possibly with buspirone (Buspar) at low dosages
> 3. Phenelzine (Nardil)
>
> Currently:
>
> Parnate 80 mg/day
> nortriptyline 100 mg/day
> Lamictal 300 mg/day
> lithium 300 mg/day
> Abilify 15 mg/day
> prazosin 6 mg/day
>
> This regime has brought me to a place of moderate-to-severe depression. Without it, I suffer from very severe depression. I don't know how bad I'll feel when I come off the Parnate. Hopefully, the other drugs will keep me out of the basement.
>
> Hamilton Rating Scale for Depression:
>
> http://tools.farmacologiaclinica.info/index.php?sid=43496
>
> * Answer the security question (simple math) and click on "Continue" NOT on "Start Now".
>
>
> - ScottThat drug-regimen sounds familiar...
You are not by any chance Gillman-Fan from Socialanxietysupport?
Posted by SLS on April 14, 2018, at 19:17:50
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by Hordak on April 14, 2018, at 13:42:11
> You are not by any chance Gillman-Fan from Socialanxietysupport?
Different people.
:-)
- Scott
Posted by linkadge on April 16, 2018, at 16:48:05
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by SLS on April 14, 2018, at 19:17:50
For me, the mirtazapine / venlafaxine combination is a bit superior to say amitriptyline in the sense that I can adjust the individual doses.
I also seem to get fewer cardiac side effects.
Linkadge
Posted by Hordak on April 16, 2018, at 16:51:31
In reply to Re: pharmaceutical industry and their 'reinventions'. » Hordak, posted by SLS on April 14, 2018, at 0:41:12
> > > > How the f*ck is Vilazodone totally different?
> > > > It's an SSRI with some 5HT partial agonism...
>
> > > In what ways were you disappointed by vilazodone?
>
> > I am not disappointed in it, because I haven't tried it
>
> Would the world be a better place without vilazodone? I don't know.
>
> > but it's nothing "new".
>
> Perhaps it is new enough for some people.#==> Yes, but there is a certain dogma among psychiatrists to push SSRIs on everybody... for different types of depression there are different fitting antidepressant-classes, but many doctors try the "one size fits all" route...
If someone suffers from psychomotor retardation, hypersomnia, weight gain, then Sertraline, Duloxetine or Bupropion might indeed be the fitting med. But pushing the same med on someone with converse symptoms might be fatal.
> I found vilazodone to be cleaner than any SSRI I tried. Unfortunately, my response to it was short-lived. Still, it "felt" different than Lexapro.
> What do you think of vortioxetine?#==> From what I have read the 5ht1a agonism of Vortioxetine is awesome, for a few weeks. This receptor develops tolerance rapidly - more rapidly than other receptors. No stable way to achieve response here. Apparently it does all the wonderful things that MDMA does for empathy & pro social feeling (in a smaller proportion), but this effect will not last.
There are better more long lasting ways to achieve an anxiolytic effect. If it was practical to antagonize 5ht1a directly in a long lasting manner, that would be a great anxiolytic, but the drugs that work here develop tolerance VERY rapidly...
Posted by Hordak on April 16, 2018, at 16:54:27
In reply to Re: pharmaceutical industry and their 'reinventions'., posted by linkadge on April 16, 2018, at 16:48:05
> For me, the mirtazapine / venlafaxine combination is a bit superior to say amitriptyline in the sense that I can adjust the individual doses.
>
> I also seem to get fewer cardiac side effects.
>
> LinkadgeYes, indeed.
Using two separate drugs makes it easier to titrate and adjust the pharmacology :=)
This is the end of the thread.
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