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.
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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.
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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.
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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,
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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.
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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.
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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)
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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.
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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.
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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.
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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.
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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).
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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
poster:Marty
thread:857746
URL: http://www.dr-bob.org/babble/20081016/msgs/859121.html