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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 29 to 53 of 53. Go back in thread:
Posted by West on October 23, 2008, at 7:14:18
In reply to Re: Beauty and sadness » West, posted by Marty on October 22, 2008, at 21:52:04
>
> I sense that the beauty being more accessible in sadness could be called 'morbid beauty' .. where into depression the death of the ego allows to feel more of the beauty in the world.. where the contrast between the ugly and the beautiful is increased because everything ordinary is looking dark and ugly... then only beautiful got our attention as the rest is dirt, including our innerself.. our ego.The sadness is melancholy (one of the four temperaments or 'tempers' in old parlance where the other four are phlegmatic, sanguine & choleric). Duhrer's famous etching (http://en.wikipedia.org/wiki/Melancholia) provides some kind of idea of the common perceptions of this. It probably represents a middle stage in the depressive spectrum where sadness exists but without rumination. This allows for the expansion or reflection.
major depression is like an absence of air or adequate cushioning between you and the world. Each noise grates, every motion assults stillness + the mind turns in on itself.
Posted by linkadge on October 23, 2008, at 7:16:33
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 22, 2008, at 21:19:18
>Don't want to hammer my points in my other post >to you about Prozac.. but you surely sounds like >someone having too much 5-HT2c >stimulation! ..maybe just coincidence.. but is >your 'affect' different since starting Prozac ?
I don't know why this should be seeing as prozac is a 5-ht2c *antagonist*.
Linkadge
Posted by linkadge on October 23, 2008, at 7:22:20
In reply to Re: Beauty and sadness » West, posted by Marty on October 22, 2008, at 21:52:04
All I know is that I don't feel right on meds and I don't feel right off of them.
Antidepressanst don't make me happy they just numb the pain and every other emotion allong with it. I don't want to live my life like that. When they tell me I need to make a choice (meds or no meds) what kind of choice is that?
You can feel sh*tty, or sh*tty in a different way, you choose!
I like many parts of myself that the medicatons completely wipe out.
How about inventing something that actually does something?
Linkadge
Posted by Marty on October 23, 2008, at 9:55:15
In reply to Re: Beauty and sadness » Marty, posted by linkadge on October 23, 2008, at 7:16:33
> I don't know why this should be seeing as prozac is a 5-ht2c *antagonist*.
---
Read my post on your other thread "I feel worst on Prozac" and you'll understand why I'm talking about endogenous agonism rather than antagonism by Prozac. In summary, your 5-HT2c upregulation caused by Prozac antagonism may be exaggerated to a point where you end up having more 5-HT2c endogenous stimulation than before you start taking Prozac. That shouldn't be a typical reaction but our neurology aren't exactly typical when compared to normal responders out there.One important point that I'm not 100% sure: do you feel worst on Prozac than on the other typical SSRIs ?
/\/\arty
Posted by Marty on October 23, 2008, at 10:19:09
In reply to Re: Beauty and sadness, posted by linkadge on October 23, 2008, at 7:22:20
> How about inventing something that actually does something?
---
Not all antidepressant numbs your emotions. I don't remember you medication trial history but from what your saying the antidepressant which doesn't numbs you doesn't work at all with you ?What about Bupropion, Tianeptine, Amineptine, Chromium and Agomelatine ? They don't numb you and the side effects are very tolerable. Or low dose Ziprasidone (5-HT2c antagonism only) ?
Remind me your Dx please Linkadge,
/\/\arty
Posted by linkadge on October 23, 2008, at 11:19:31
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 23, 2008, at 9:55:15
>Read my post on your other thread "I feel worst >on Prozac" and you'll understand why I'm talking >about endogenous agonism rather than antagonism >by Prozac. In summary, your 5-HT2c upregulation >caused by Prozac antagonism may be exaggerated >to a point where you end up having more 5-HT2c >endogenous stimulation than before you start >taking Prozac.
I don't think it works that way. The reason the receptors upregulate is becuae they aren't being stumulated enough. They woudnl't upregulate to the point that they're being overstimulated, cause if they were being overstimulated, they'd downregulate.
>One important point that I'm not 100% sure: do >you feel worst on Prozac than on the other >typical SSRIs ?I hate all SSRI's. I don't need neurotoxic, endocrine disrupting mind controllers.
Linkadge
Posted by Marty on October 23, 2008, at 12:40:26
In reply to Re: Beauty and sadness, posted by linkadge on October 23, 2008, at 11:19:31
> don't think it works that way. The reason the receptors upregulate is becuae they aren't being stumulated enough. They woudnl't upregulate to the point that they're being overstimulated, cause if they were being overstimulated, they'd downregulate.
---
It doesn't work that way in normal peoples brain or maybe even "normal depressive/responder" people, but in non-responder or atypical responder there's something that may doesn't work the same 'normal' way .. so those homeostatis/adaptation mechanism may be out of balance.. that's the whole point Linkadge.That said, if you don't feel worst on Prozac than on any other SSRIs, the hypothesis is worthless. Otherwise, I for one, would pursue it if I was in your position.
Have a nice day,
/\/\arty
Posted by West on October 23, 2008, at 15:00:58
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 23, 2008, at 12:40:26
the ssris have almost always saved me from certain death but i continually experience the flat effect which i eventually take to be insodious and then try to come off them. That and insomnia, anti-social tendancies, low ambition desire/taste etc. The numbing is not a consequence of the SSRIs themselves but a combination of the raised serotonin levels and the subsequent lowering of responsiveness at DA regulating parts of the brain that implies. Other undesirable side effects such as poor arousal + retarded orgasm, muscular jerks, tremor and diarrhea are all consistent with raised serotonin levels. The drugs really do their job perfectly they're just totally unsuitable for long-term existence.
Tianeptine could help, some feel a bit clouded over or detatched on it. I did. Agomelatine i imagine everyone here will jump on as soon as they get the chance, who knows what advantages it will offer. As for me i'm taking the last of my duloxetine at 10mg/day and 5-HTP 2-3 times a day. I'll probably start the perika brand of st.john's wort in a week. I'm really irritable atm but thankful for the increased emotional range and un-chemicalised state.
Posted by linkadge on October 23, 2008, at 16:40:28
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 23, 2008, at 12:40:26
>It doesn't work that way in normal peoples brain >or maybe even "normal depressive/responder" >people, but in non-responder or atypical >responder there's something that may doesn't >work the same 'normal' way .. so those >homeostatis/adaptation mechanism may be out of >balance.. that's the whole point Linkadge.
Un, not ncessarily. The receptor adaption hypothesis is just a hypothesis (and a very old and weak on IMHO).
Just because an SSRI isn't working doesn't necessarily mean the receptors are not downregulating/upregulating. It could also mean you are messing with a particular brain system which is not even involved in your disease. I.e. if your disorder involves endorphin, gaba, PEA, dopamine, norepinephrine, substance P, galanin, oxytocin, vasopressin, NGF, BDNF, histamine, or any one of the other dozens of brain chemicals that might be implicated in depression then of course your brain is not going to respond to an SSRI like other patients.
So it doesn't really make sense in my mind to suggest that because somebody doesn't respond to an SSRI then there brain is not respondiing "as it should". Thats like saying that because aspirin doesn't kill childbirth pain that there is something wrong with the way a mother's inflamation system is repsonding to the aspirin.
Linkadge
I've been on all the SSRI's a million times. I don't know why I let a doctor convince me into trying a worthless (for me) drug again.
Posted by linkadge on October 23, 2008, at 16:43:45
In reply to Re: Beauty and sadness, posted by West on October 23, 2008, at 15:00:58
>The numbing is not a consequence of the SSRIs >themselves but a combination of the raised >serotonin levels and the subsequent lowering of >responsiveness at DA regulating parts of the >brain that implies.
Thats one theory. And besides, I would still consider it to be an effect of the "drugs themselves"
>The drugs really do their job perfectly they're >just totally unsuitable for long-term existence.Then, they're not really doing their job. I don't think people intended for these drugs to suck as much as they do.
Linkadge
Posted by linkadge on October 23, 2008, at 16:44:37
In reply to Re: Beauty and sadness, posted by West on October 23, 2008, at 15:00:58
B.T.W. I personally don't think they do their job. I feel worse on most of them.
Linkadge
Posted by Marty on October 23, 2008, at 19:33:33
In reply to Re: Beauty and sadness, posted by linkadge on October 23, 2008, at 16:40:28
Link,
There's something interesting in this discussion ONLY if your response is worst on Prozac than on the other (more typical) SSRIs. Is it the case or not ?
If you already answered me about it when I asked the other times than I'm sorry; I've missed it.
You said: " Thats like saying that because aspirin doesn't kill childbirth pain that there is something wrong with the way a mother's inflammation system is repsonding to the aspirin."
It's not. What I'm saying is more like if aspirin induce migraine each time Joe the plumber is taking one then Joe may have something biologically different that's causing this atypical response... something different from the people who benefit from the typical response.
IF you feel way worst on Prozac than on other SSRIs, it COULD be because of the 5-HT2c antagonistic properties of Prozac since it's about the only -relevant- difference between Prozac and others. It matters because 5-HT2c antagonism very typically makes people feels better.. and so, while it doesn't tell you more about the precise etiology of your disorder, it gives you the opportunity to tweak something that may end up improving your condition.
Things I would think about/try based on this atypical response to 5-HT2c antagonism:
1. More/different 5-HT2c antagonism with no SRI action: Agomelatine (already out there) or low dose Geodon (pre-DA antagonistic dose = 5-HT2c antagonism)2. Light (Not LSD strong) 5-HT2c agonism: low dose mCPP could do the trick. One of Trazodone metabolite happen to be mCPP. SRIs properties of Trazo is pretty weak and it's 5-HT2a antagonistic properties are good for emotions. To see how 5-HT2c agonism makes you feel only 1 or 2 days of Trazo would be enough to see.. you take it before bed and a couple hours after you wake up you'll feel it. No need for clinically active dose.
Anyway... Wish you well,
/\/\arty
Posted by linkadge on October 24, 2008, at 6:29:15
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 23, 2008, at 19:33:33
>There's something interesting in this discussion >ONLY if your response is worst on Prozac than on >the other (more typical) SSRIs. Is it the case >or not ?
Like I said, they all suck for me. I can't really tell much of a difference.
>It's not. What I'm saying is more like if >aspirin induce migraine each time Joe the >plumber is taking one then Joe may have >something biologically different that's causing >this atypical response...I don't know if I'd call my responce to prozac atypical. The drug is known to cause all shades of akathesia and dysphoria upon start up. It is known to cause early symptomatic worsening and suiciadiality in many pepople. I stopped blaming myself for not responding to a particular drug a long time ago.
The aspirin example was a bad one because SSRI response rates are much poorer than what common belief dictates. They are much more poorly tolerated than aspirin.
If you are saying that the neurobiology of responders is different than the neurobiology of nonresponders then yes, of course. But, I certainly wouldn't lable this difference as something that makes the individual more sick, (unless you measure the degree of sickness by the degree to which something can be treated)
Basically, I refuse to think that there is something "wrong" with me for not responding to SSRI's. I think the drugs are garbage, and it is ultimately their fault for not targetting what is wrong with unresponsive patients.
(Some studies suggest that no more than 50% of patients takin SSRI's actually get a meaningful improvement)
>IF you feel way worst on Prozac than on other >SSRIs, it COULD be because of the 5-HT2c >antagonistic properties of Prozac since it's >about the only -relevant- difference between >Prozac and others.
There are differences to prozac than just 5-ht2c antagonism. Prozac has effects on MAO-a and b. It also has a longer halflife which may pose more problems for neuroendocine regulation, sleep wake cycle etc.
>It matters because 5-HT2c antagonism very >typically makes people feels better.
Thats very hard to say because we have no clinically avaiable seletive 5-ht2c antagonsts.
>and so, while it doesn't tell you more about the >precise etiology of your disorder, it gives you >the opportunity to tweak something that may end >up improving your condition.
I've tweaked everything. Now I am a little tweaked.
>1. More/different 5-HT2c antagonism with no SRI >action: Agomelatine (already out there) or low >dose Geodon (pre-DA antagonistic dose = 5-HT2c >antagonism)
>2. Light (Not LSD strong) 5-HT2c agonism: low >dose mCPP could do the trick. One of Trazodone >metabolite happen to be mCPP. SRIs properties of >Trazo is pretty weak and it's 5-HT2a >antagonistic properties are good for emotions. >To see how 5-HT2c agonism makes you feel only 1 >or 2 days of Trazo would be enough to see.. you >take it before bed and a couple hours after you >wake up you'll feel it. No need for clinically >active dose.
I fail to see the strength in your logic. Just because drug x doesn't work, doesn't mean anti-x will. I.e. just because 5-ht2c antagonism makes me feel worse, doesn't mean that 5-ht2c agonism will make me feel better.(If there is nothing wrong with that particualr system to begin with, then any chemical modulation of it could have the propensity to make me feel worse).
Linkadge
Posted by Marty on October 24, 2008, at 14:49:23
In reply to Re: Beauty and sadness, posted by linkadge on October 24, 2008, at 6:29:15
> Like I said, they all suck for me. I can't really tell much of a difference.
---
Then there's no 'hint' at all in your Prozac experience and this whole discussion is pointless.>I stopped blaming myself for not responding to a particular drug a long time ago.
---
Blaming? It's not about blaming anything. It's about learning more about your unique neurology/biology each time you try a new medication. After many trial, you MAY got some hints that can influence the course of your next trials. It's not about determining NOTHING else that "What could make me react that way to this medication versus the other in the same class ? and how I can use those hypothesis."
> The aspirin example was a bad one because SSRI response rates are much poorer than what common belief dictates. They are much more poorly tolerated than aspirin.
---
That has nothing to do with response rates. It's about paradoxal response which can the hypothesized upon for the sake of getting new ideas on what could be tried to make you feel better.> If you are saying that the neurobiology of responders is different than the neurobiology of nonresponders then yes, of course. But, I certainly wouldn't lable this difference as something that makes the individual more sick,
---
Who's sicker than who is as irrelevant than if antidepressant works or not.. or who's to blame for this or that. Totally irrelevant regarding getting a clue about your neurology in order to plan some new psychopharmacology strategy which would have -slightly- more chances of helping than any other randomly chosen by your pdoc. (We're not at our 3 or 4 'in the box' strategies .. we may as well think out of the box now that there's nothing more in the box for us to try. What's the other options ? more of the same ? abandon ?)> Basically, I refuse to think that there is something "wrong" with me for not responding to SSRI's.
---
Wrong ? first "blaming" than "Wrong" ? It's about differences .. you respond differently because of a difference which is in the antidepressant way of doing a descent job OR that renders the etiology of your disorder different to a point where those SRIs are as appropriate for you as insulin is to treat athritis ....
> I think the drugs are garbage, and it is ultimately their fault for not targetting what is wrong with unresponsive patients.
---
The drugs are good for people for who it works. What's garbage is the simplistic view pushed by an immature field of medicine (psychiatry) that depression is ONE disease/disorder and that one or two mechanisms of action is enough to relieve that disorder! .. Depression is only a losely coupled bunch of symtoms which, without doubt, arise from a multitudes of different disorder/disease which all possess their own different ethiology... IMPOSSIBLE that the current arsenal of antidepressant can relieve all of those ethiolgy AND bypass all the different biological barriers that are on their road (individual genetic varriants at many level which reduce, nullify or even inverse the effect of a drug. Ex: Enzyme variants, subunits variants etc)> (Some studies suggest that no more than 50% of patients takin SSRI's actually get a meaningful improvement)
---
No doubt in my mind that's the case.
> There are differences to prozac than just 5-ht2c antagonism. Prozac has effects on MAO-a and b. It also has a longer halflife which may pose more problems for neuroendocine regulation, sleep wake cycle etc.
---
Yes and those differences could also be relevant, contrary to what I've said in my past posts. The point is that there's not much clue/pratical hypothesis you can work on about the those other differences. The more complex/multilayered the hypothesis and the less value. But any way, like you said you don't feel worst of differently worst on Prozac than any other SSRIs.. so ...
>> >It matters because 5-HT2c antagonism very >>typically makes people feels better.
> Thats very hard to say because we have no clinically avaiable seletive 5-ht2c antagonsts.
---
Pure 5-ht2c antagonist ? not marketed for humans, but some are good enough(pure, selecive and potent) that they allowed the scientific community to arrive at a consensus (based on animal model with antagonist/agonism/inverse agonism and 5-ht2c knockout subject) that 5-HT2c antagonism was --typically-- good for mood and some cognitive/memory functions. For human, Agomelatine is the one with the best ratio 5-HT2c Antagonist VS else. After that you have LOW dose Geodon which doesn't have much antadopaminergic effect at low dose. And the other with SRIs properties like Prozac and (yes) Citalopram.
> I've tweaked everything. Now I am a little tweaked.
---
I feel you. Tried alot myself.
> I fail to see the strength in your logic. Just because drug x doesn't work, doesn't mean anti-x will. I.e. just because 5-ht2c antagonism makes me feel worse, doesn't mean that 5-ht2c agonism will make me feel better.
---
Then you must fail to see strenght in most neuroreseachers logic since the advent of the mental disorder chemotherapy. It's common approach in this field to study some drugs mechanism of action that induce the symptoms of a disorder they want to develop a drug for. For exemple LSD and PCP has been studied in order to design better antipsychotic drugs.. and that was by enginering drugs with some mechanism of action that was acting in the inverse ways of those studied. So my logic isn't that weak: whatever your individual complex etiology, you may be sensible to 5-HT2c transmission modulation and well brushed you could benefit from this neurologic feature of yours. But to find out, you need to play around with it.. more, less, differently localized etc. Again, since you don't react differently on Prozac than on the other more typical SSRIs.. this isn't something worth pursuing.
> (If there is nothing wrong with that particualr system to begin with, then any chemical modulation of it could have the propensity to make me feel worse).
---
Or better. This goes in both senses and so is irrelevant. And again, it's not about something wrong or not. There would be nothing wrong about your 5-HT2c "system".. we would only have learned something about it that you could have investigate in order to see if that 'feature' of yours could be used to your advantage.I'll babblemail you in the next minute about something, you'll be glad to know, is unrelated to this discussion.
/\/\arty
Posted by Marty on October 24, 2008, at 14:52:44
In reply to Re: Beauty and sadness, posted by linkadge on October 24, 2008, at 6:29:15
Forget about my babblemail. I didn't know yours was desactivated.
Can't tell you what I want here.
It could have interested you..
Any way I can send you something in private ?/\/\arty
Posted by linkadge on October 26, 2008, at 10:03:17
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 24, 2008, at 14:52:44
Yeah, I was going to babble mail you my email adress but I can't even remember how to babble mail.
How do I acess babblemail?
Linkadge
Posted by Marty on October 26, 2008, at 15:31:19
In reply to Re: Beauty and sadness, posted by linkadge on October 26, 2008, at 10:03:17
> Yeah, I was going to babble mail you my email adress but I can't even remember how to babble mail.
---Someone told me my babblemail was desactivated. Weird. You are supposed to be able to babblemail someone by clicking on their name at the top of a message. Ex: "Posted by linkadge on October 26".. If you babblemail was activated (go in your account options) I would be able to click on "linkadge" at on that line and wrote you a private message.
I'll take a look at my own option and see why my babblemail is desactivated. I suggest you do the same since it looks like yours is too.
/\/\arty
Posted by linkadge on October 26, 2008, at 18:53:26
In reply to Re: Beauty and sadness » linkadge, posted by Marty on October 26, 2008, at 15:31:19
Hey, I turned my babblemail back on. I still can't babblemail you it says yours has been deactivated.
Linkadge
Posted by Phillipa on October 26, 2008, at 19:04:29
In reply to Re: Beauty and sadness, posted by linkadge on October 26, 2008, at 18:53:26
Marty tried yours again says deactivated. Love Phillipa
Posted by Phillipa on October 26, 2008, at 19:37:21
In reply to Re: Beauty and sadness, posted by linkadge on October 26, 2008, at 18:53:26
Link your's works and your name is blue like mine Marty's is red what does that mean? Phillipa
Posted by Marty on October 26, 2008, at 19:48:08
In reply to Re: Beauty and sadness, posted by linkadge on October 26, 2008, at 18:53:26
> Hey, I turned my babblemail back on. I still can't babblemail you it says yours has been deactivated.
---
You're right. My babblemail has been disabled a couple weeks ago because I was talking about something forbidden here. I wrote Dr.Bob a couple hours ago and ask him to enable my babblemail.When fixed I'll wrote you.
/\/\arty
Posted by Marty on October 26, 2008, at 20:07:16
In reply to Re: Beauty and sadness » linkadge, posted by Phillipa on October 26, 2008, at 19:37:21
> Link your's works and your name is blue like mine Marty's is red what does that mean? Phillipa
---
Red ? I can only guess that it means I'm passionate....oh wait...
Maybe not. Maybe it's to show how ashamed I am to be punished publicly like this, ashamed of being pointed as a persona nongrata by the system. :S
Later ;)
/\/\arty
Posted by Phillipa on October 26, 2008, at 20:29:59
In reply to Re: Beauty and sadness » Phillipa, posted by Marty on October 26, 2008, at 20:07:16
Marty remember the book the Scarlet Letter? Love Phillipa
Posted by Marty on October 27, 2008, at 10:40:20
In reply to Re: Beauty and sadness » Marty, posted by Phillipa on October 26, 2008, at 20:29:59
> Marty remember the book the Scarlet Letter? Love Phillipa
---
Only the title/\/\arty
Posted by JadeKelly on October 31, 2008, at 9:40:26
In reply to Re: Beauty and sadness » Phillipa, posted by Marty on October 27, 2008, at 10:40:20
Linkage and Marty, are you 2 brothers? Hilarious.
On a serious note, I think depressives in general, not all, do feel and see more than non-depressives. I do. Thats why I've been in a hating life depression for 2 years. Too many bad things over and over to my loved ones and my brain finally shut down. I'm sure someone else would have moved on by now. I couldn't.
I'm on Parnate now, the world has color again. If this med fails, there won't be anything beautiful about it. I will scratch and claw my way out of this depression, and it won't be pretty or romantic until I do. Prazac made me feel crazy by the way, as do all ssri's. Thats just me tho.
The 2 artists in my family (quite talented, and quite depressed), obviously see beauty all around them. I do at times.
I just think you'd be robbing yourself to romanticize major depression, if thats what you have. It sounds more like you're tired of the fight and just want to jump off the rat wheel and enjoy the scenery for awhile. Nothing wrong with that.
I hope you'll get back in there and "defend that island" when your done!
I have no idea what your med history is but would be happy to swap info if you'd like. Mine's rather atypical in meds and response I'd say.
Good luck Linkage, sorry for the long post, I blame it on Parnate.
Best to you, Jade
PS-If Marty's "idea" turns out to be a winner, you'll share with the rest of the class right?
This is the end of the thread.
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