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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 18 of 18. This is the beginning of the thread.
Posted by badhaircut on September 14, 2004, at 8:19:03
Just ranting.
If psych meds impact specific brain dysfunctions, where are the tests that identify which patients will respond to which meds? We've got DNA, EEG, MRI, PET, CSF, etc etc, *and* paper-&-pencil tests galore. Why doesn't the medical world have an idea which antidepressant will benefit which patient?
It's still guesswork guesswork guesswork. (You may have guessed I've been nonresponsive to ADs.)
Posted by Bill LL on September 14, 2004, at 8:36:54
In reply to where are the diagnostic tests?!!, posted by badhaircut on September 14, 2004, at 8:19:03
Your ranting is very true unfortunately. It's all trial and error at the present time.
> Just ranting.
>
> If psych meds impact specific brain dysfunctions, where are the tests that identify which patients will respond to which meds? We've got DNA, EEG, MRI, PET, CSF, etc etc, *and* paper-&-pencil tests galore. Why doesn't the medical world have an idea which antidepressant will benefit which patient?
>
> It's still guesswork guesswork guesswork. (You may have guessed I've been nonresponsive to ADs.)
Posted by Denise1904 on September 14, 2004, at 9:52:41
In reply to where are the diagnostic tests?!!, posted by badhaircut on September 14, 2004, at 8:19:03
I think the only way you're going to get some of these tests is to try and get on as many trials for depression or other mental ilnesses as possible where they actually use them. At least that's what I'm trying to do.
The thing is I'm not sure if any of these things actually are a really good indicator is, I mean 8 years ago I responded really well to 20mg of Seroxat, now I respond partially to 40mg (after two years of trying different things)of Seroxat, I'm just wondering if any diagnostic tools would have showed this up.
I really hope they start making some breakthroughs with this illness, because at the moment I feel as though I'm gonna have to wait another ten years or so (maybe more) just to feel normal again and by that time I'll probably have Emphysema from smoking so much.
Denise
Posted by SLS on September 14, 2004, at 9:56:33
In reply to Re: where are the diagnostic tests?!!, posted by Denise1904 on September 14, 2004, at 9:52:41
Hi Denise.
> The thing is I'm not sure if any of these things actually are a really good indicator is, I mean 8 years ago I responded really well to 20mg of Seroxat, now I respond partially to 40mg
Have you ever tried adding lithium to the Seroxat? It can be a miracle for some people who only respond partially to it. If you are unipolar, you might not need more than 300-600mg.
- Scott
Posted by SLS on September 14, 2004, at 10:01:47
In reply to where are the diagnostic tests?!!, posted by badhaircut on September 14, 2004, at 8:19:03
> Just ranting.
>
> If psych meds impact specific brain dysfunctions, where are the tests that identify which patients will respond to which meds? We've got DNA, EEG, MRI, PET, CSF, etc etc, *and* paper-&-pencil tests galore. Why doesn't the medical world have an idea which antidepressant will benefit which patient?
That's a great question that is continually asked of the medical community. I think there might already be enough information available to take advantage of these tests, but I don't see that an effort is being made to focus on compiling this data to ferret out associations between test results and treatment modality.
- Scott
Posted by badhaircut on September 14, 2004, at 11:31:43
In reply to Re: where are the diagnostic tests?!!, posted by SLS on September 14, 2004, at 10:01:47
If I lived by one of Daniel Amen's clinics, or if I had tons of disposable income, I'd get all possible tests done on myself as a public service. Then, if anything actually ever cured my depression, I'd post the results. "Got a hyperactive lobe X with genotype Y? Try treatment Z!"
Posted by zeugma on September 14, 2004, at 11:32:39
In reply to Re: where are the diagnostic tests?!!, posted by SLS on September 14, 2004, at 10:01:47
> > Just ranting.
> >
> > If psych meds impact specific brain dysfunctions, where are the tests that identify which patients will respond to which meds? We've got DNA, EEG, MRI, PET, CSF, etc etc, *and* paper-&-pencil tests galore. Why doesn't the medical world have an idea which antidepressant will benefit which patient?
>
>
> That's a great question that is continually asked of the medical community. I think there might already be enough information available to take advantage of these tests, but I don't see that an effort is being made to focus on compiling this data to ferret out associations between test results and treatment modality.
>
>
> - ScottPart of the reason there is little effort is, paradoxically, that AD's have become such big business. Each pharmaceutical company wants their new drug to treat *all* depression, not just one possibly rare subtype of it. There was more incentive for pharmaceutical companies to look for a niche for their product when the market was seen as relatively small to begin with. Greed is the driving force behind a great deal of research and it is not leading to better treatments IMO, especially for depression, which has always been a heterogeneous disorder in presentation.
-z
Posted by badhaircut on September 14, 2004, at 11:39:34
In reply to Re: where are the diagnostic tests?!! » SLS, posted by zeugma on September 14, 2004, at 11:32:39
Posted by Denise1904 on September 14, 2004, at 14:30:50
In reply to Re: where are the diagnostic tests?!!, posted by SLS on September 14, 2004, at 10:01:47
Hi Scott,
How are you, feeling any better? if not hope you're not feeling too low. What's happening with the Cymbalta now?
You've probably guessed by now that I have a rather large bumble bee in my bonnet about the fact that the paroxetine (Seroxat) doestn't work like it used to, I manage to squeeze that fact into any thread I can :-)
Yes, I have tried Lithium with the Seroxat, I went up to about 500mg and nothing, no side effects or anything, which suprised me because I thought that Lithium was supposed to be a strong drug. I had my blood levels checked out at 300mg I think and it was about 0.5, although can't be sure. Have you tried lithium, how did it make you feel and at what dose?
I've managed to find another study that's going on for a drug similiar to mefipristone in the UK so am going to try and get on that. Sometimes I wonder though what the hell I'm doing.
Denise
Posted by Denise1904 on September 14, 2004, at 14:34:06
In reply to Re: where are the diagnostic tests? - SLS, posted by Denise1904 on September 14, 2004, at 14:30:50
Scott,
Sorry just seen another thread of yours and it sounds like you're not up to talking about how the drugs are affecting right now, I thought you were taking Cymbalta though??
Anyway, please let me know when you're feeling a bit better.
Denise
Posted by Denise1904 on September 14, 2004, at 14:35:20
In reply to If I could test myself, I would, posted by badhaircut on September 14, 2004, at 11:31:43
.
Posted by SLS on September 14, 2004, at 15:42:20
In reply to Re: where are the diagnostic tests?!! » SLS, posted by zeugma on September 14, 2004, at 11:32:39
> Part of the reason there is little effort is, paradoxically, that AD's have become such big business. Each pharmaceutical company wants their new drug to treat *all* depression, not just one possibly rare subtype of it. There was more incentive for pharmaceutical companies to look for a niche for their product when the market was seen as relatively small to begin with. Greed is the driving force behind a great deal of research and it is not leading to better treatments IMO, especially for depression, which has always been a heterogeneous disorder in presentation.
Definitely.The silly drug companies should realize that their drugs will be no less effective because tests are developed to match individuals to specific drugs. The nature of the illness isn't such that a drug is matched to an illness subtype, but that a drug is matched to an individual's unique circuitry. The drug companies are lucky in that their products will always match a sizeable percentage of varying phenotypes, despite attempts to categorize them.
- Scott
Posted by zeugma on September 14, 2004, at 17:28:19
In reply to Re: where are the diagnostic tests?!!, posted by SLS on September 14, 2004, at 15:42:20
>
> > Part of the reason there is little effort is, paradoxically, that AD's have become such big business. Each pharmaceutical company wants their new drug to treat *all* depression, not just one possibly rare subtype of it. There was more incentive for pharmaceutical companies to look for a niche for their product when the market was seen as relatively small to begin with. Greed is the driving force behind a great deal of research and it is not leading to better treatments IMO, especially for depression, which has always been a heterogeneous disorder in presentation.
>
>
> Definitely.
>
> The silly drug companies should realize that their drugs will be no less effective because tests are developed to match individuals to specific drugs. The nature of the illness isn't such that a drug is matched to an illness subtype, but that a drug is matched to an individual's unique circuitry. The drug companies are lucky in that their products will always match a sizeable percentage of varying phenotypes, despite attempts to categorize them.
>
>
> - ScottScott,
You don't think that the concepts of melancholia and atypical depression are valid subtypes? There's an interesting paper written by Quitkin which attempts to identify the specific presentations (I suppose that's a colloquial word for phenotype, I'm feeling dazed right now!) of MAOI-responsive depression, as opposed to the 'classic' or 'TCA-responsive' depression subtype. http://www.psychiatrist.com/pcc/pccpdf/v04n03/v04n0302.pdf
it's remarkable that after 50 years, these theoretical constructs are still being played around with.
in any case understanding the individual's unique circuitry would appear to be a staggering task, given that our understanding of human brain circuitry in general is sketchy at best (and much of it is gleaned from the study of what existing psychotropics do in there). I'm also feeling a little frustrated that nortriptyline appears to be the only psychotropic that doesn't damage my circuitry somewhere, although it does not treat all my symptoms and so is acquiring quite a stable of fellow passengers in my bloodstream. I would like a neuroscientist to explain to me why this agent is so benign in contrast to the legion of other pharmaceuticals I have tried.
-z
Posted by SLS on September 14, 2004, at 17:53:25
In reply to Re: where are the diagnostic tests?!!, posted by zeugma on September 14, 2004, at 17:28:19
Hi Z.
> You don't think that the concepts of melancholia and atypical depression are valid subtypes?
I definitely do.
> There's an interesting paper written by Quitkin
I was one of Quitkin's early subjects when he began to study this issue in the early 1980s.
> it's remarkable that after 50 years, these theoretical constructs are still being played around with.
Quitkin has been resting on the laurels of his work by repeating it over and over.
> in any case understanding the individual's unique circuitry would appear to be a staggering task,
Maybe not so much. I don't know. I think it is a question of choosing the right biological probes or drugs to challenge the system with, and then seeing which areas of the brain, if any, light up in a PET scan or fMRI. It would be more empirical than deductive. This might be further improved perhaps by having the subject perform certain tasks while being exposed to the probe to better resolve regional or circuit activities.
> I'm also feeling a little frustrated that nortriptyline appears to be the only psychotropic that doesn't damage my circuitry somewhere,Damage in what way? How can you tell?
> although it does not treat all my symptoms and so is acquiring quite a stable of fellow passengers in my bloodstream.
What are your thoughts about trying Cymbalta? I can't think of any reason why you couldn't combine it with nortriptyline.
- Scott
Posted by zeugma on September 14, 2004, at 18:45:40
In reply to Re: where are the diagnostic tests?!! » zeugma, posted by SLS on September 14, 2004, at 17:53:25
> Hi Z.
Hi Scott.
> Quitkin has been resting on the laurels of his work by repeating it over and over.That is the fate of many academics, I'm afraid. Are there any researchers you are aware of who are especially worth looking at?
>
> > in any case understanding the individual's unique circuitry would appear to be a staggering task,
>
> Maybe not so much. I don't know. I think it is a question of choosing the right biological probes or drugs to challenge the system with, and then seeing which areas of the brain, if any, light up in a PET scan or fMRI. It would be more empirical than deductive. This might be further improved perhaps by having the subject perform certain tasks while being exposed to the probe to better resolve regional or circuit activities.I agree that empiricism would be the way to go. These procedures have been extensively used in ADHD research, which have confirmed that methylphenidate and other stimulants improve specific performances on tasks, and that there is a differential response to methylphenidate in ADHD individuals as opposed to neurocognitive normals. there are some abstracts I've looked at that contrast AD classes in this way, but the (to me) interesting stuff, such as the observation that differential performance on tasks that required activation of hemisphere-specific abilities responded preferentially to TCA's and that the reverse was true of MAOI's, was done long ago, as evidenced by the drugs used in the studies. Most of what I've seen of more recent studies contrast the damaging effects of muscarinic antagonism on memory with the lack of such effects by newer AD's, which is hardly a surprise...
it appears also that progress in identfying genotypes for ADHD has been a lot more extensive than such work for depression. This is surprising in that adult ADHD is a more recent addition to the DSM than MDD.
> > I'm also feeling a little frustrated that nortriptyline appears to be the only psychotropic that doesn't damage my circuitry somewhere,
>
> Damage in what way? How can you tell?Strattera precipitated an anhedonic depression. provigil gave me headaches, GI disturbances, and eyelid twitches, which continue on Ritalin. Clonazepam precipitates hypnagogic hallucinations if I allow myself to fall asleep under its influence. Buspirone caused profound muscle weakness when I attempted, following my pdoc's instructions, to raise the dosage to the level where some efficacy in social phobia has been reported (I suppose he was trying at all costs to avoid prescribing me a benzo). Fluoxetine and other SSRI's produced nausea and worsened insomnia, which did not resolve after eight weeks in the case of fluoxetine (the others, which felt similar, produced much shorter trials as my tolerance for sleeplessness has declined over the years). I have never tried Effexor or an MAOI. Nortriptyline just feels 'right' to me. I can't explain it.
>
> > although it does not treat all my symptoms and so is acquiring quite a stable of fellow passengers in my bloodstream.
>
> What are your thoughts about trying Cymbalta? I can't think of any reason why you couldn't combine it with nortriptyline.
>
> The symptoms I am specifically concerned about are fatigue and ADHD related. Provigil helped both but was not clean at all and my pdoc did not like the sound of the s/e I reported to him. I have increased the methylphenidate to 20 mg and again, it is certainly working for the targeted symptoms, but also makes me feel that my CNS is under an unnatural stress. i suppose I'll either get used to it or drop it like I did the Provigil.by the way, what are your thoughts on therapy? I hold out hope for it because medications have their limits, and i don't feel like my CNS can handle more of them at the moment. The way I am thinking currently is that my medication regimen is forcing adaptations, and that one adaptation I am trying to make involves therapy. I.e. the degree i open up to her. The stims definitely make me more awake, and it's a lot easier to talk to a therapist when more of your brain would light up on a PET scan.
-z
>
> - Scott
>
Posted by Emme on September 14, 2004, at 18:56:06
In reply to Re: where are the diagnostic tests?!! » SLS, posted by zeugma on September 14, 2004, at 18:45:40
Hi All,
I'm too tired to write an actual post that makes any sense. But do a google search on
"pharmacogenetics psychiatry" and see what you think. Looks like some are trying to use genetic information to make a better guess at whether someone will have a good response to a drug or an adverse response.Emme
Posted by badhaircut on September 14, 2004, at 19:06:54
In reply to Pharmacogenetics, posted by Emme on September 14, 2004, at 18:56:06
Posted by zeugma on September 14, 2004, at 19:07:02
In reply to Re: where are the diagnostic tests?!! » SLS, posted by zeugma on September 14, 2004, at 18:45:40
Since stimulants are tightly controlled products, it seems that more energy is going into precise determination of just what the existing products are doing in the brain, and less on rushing to produce patentable molecules that will separate from placebo on an RCT. For example there is a huge amount of information on which areas of the brain are targeted by specific stims, but it has proved almost impossible to dig up fruitful information on which regions are targeted by specific AD's. Could it be that since the players (ie., methylphenidate, amphetamine, modafinil) are not going to change anytime soon due to government restrictions, more work is being done out of scientific curiousity rather than corporate greed?
-z
This is the end of the thread.
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