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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by linkadge on June 23, 2004, at 16:44:53
I don't know of one person who has not experienced a decline in effectivness in their medications.
Sure, everyone at the beginning gets that rush, as if they will never be unhappy again but it always fades. It either moves to a complete relapse or just to a steady apathy.
You see the problem is that neurotransmitters are only half the battle. You can jolt them with as much neurotransmitter as you want, but eventually the circutry itself gets tired. Glutamate is the final destination excitory neuotransmitter and if you push that one too hard it gets angry and kills off the neuron (glutamate toxicity).
Sorry to seem like such a downer, but its true, even our best antidepressant ECT is notorious for pooping.
Linkadge
Posted by SLS on June 23, 2004, at 17:22:36
In reply to only one rule - *evenually everything poops*, posted by linkadge on June 23, 2004, at 16:44:53
> Sorry to seem like such a downer, but its true, even our best antidepressant ECT is notorious for pooping.
I wonder if the probability of pooping is reduced when pychotherapy is employed. Could reducing psychosocial stress lead to a decrease of glutamatergic overload?
Just a thought.
BTW, your comments on 5-HT2c receptors in another thread were very helpful. Thanks.
- Scott
Posted by linkadge on June 23, 2004, at 17:35:14
In reply to Re: only one rule - *evenually everything poops*, posted by SLS on June 23, 2004, at 17:22:36
About the 2c receptor
It has been noted that some patients swiched to novel compounds such as mirtazapine, or nefazedone, which potently block the 2c recptor suffer a prompt relapse in OCD symptoms.
It was speculated that the 2c receptor was involved because of its controll of inosotide signalling ,and the unexpected efficacy of inositol in treating symptoms of OCD.
I believe that reduction of overall glutamate activity would be beneficial to neuroprotection, and perhaps to the sustaining of antidepressant effect. Agencts that controll the firing of glutamate neurons act as mood stabalizers, they can help prevent lows at the cost of the highs.
Linkadge
Posted by Sebastian on June 23, 2004, at 21:10:50
In reply to only one rule - *evenually everything poops*, posted by linkadge on June 23, 2004, at 16:44:53
if the nuron is dead, does that mean you are curred????
Posted by Pfinstegg on June 23, 2004, at 21:30:19
In reply to Re: only one rule - *evenually everything poops*, posted by linkadge on June 23, 2004, at 17:35:14
What agents can lower glutamate?
Posted by Questionmark on June 24, 2004, at 2:50:18
In reply to only one rule - *evenually everything poops*, posted by linkadge on June 23, 2004, at 16:44:53
> I don't know of one person who has not experienced a decline in effectivness in their medications.
>
> Sure, everyone at the beginning gets that rush, as if they will never be unhappy again but it always fades. It either moves to a complete relapse or just to a steady apathy.
>i think you are probably right (unfortunately). But...
> You see the problem is that neurotransmitters are only half the battle. You can jolt them with as much neurotransmitter as you want, but eventually the circutry itself gets tired. Glutamate is the final destination excitory neuotransmitter and if you push that one too hard it gets angry and kills off the neuron (glutamate toxicity).
...i don't agree that glutamate, or glutamate-induced excitotoxicity is the primary factor in medication poop-out. The main reasons, i believe, are almost certainly receptor adaptation, adaptation of neurotransmitter release (and of reuptake and of degrading enzymes such as MAO and COMT), and-- probably even more so, and involving all of the aforementioned factors-- changes in neuronal gene... [i don't know what the correct word is--] (structure? transcription?) (something or rather)... genetic changes in the neurons. i think the only real way to absolutely prevent poop-out would by through genetic engineering or manipulation or something (genetics is way over my head-- obviously). i hope i'm wrong but i don't think so.
> Sorry to seem like such a downer, but its true, even our best antidepressant ECT is notorious for pooping.
>
> Linkadgei know, me too.
It's true (about ECT).
Posted by linkadge on June 24, 2004, at 9:10:25
In reply to Re: only one rule - *evenually everything poops* » linkadge, posted by Questionmark on June 24, 2004, at 2:50:18
There are many agents that can prevent glutamate toxicity. b12,c,creatine, lithium,magnesium, and many more.
You are probably entirely right, Question mark. Basically what I am trying to say, is that glutamate, is the final destination for nerve firing, and regardless of neurotransmitter function, the nerve can only fir so often before resting. It *may* not be responsable for poop out, but it is *a* limiting factor in how good your can feel for a certain amount of time.
Poop out is really a humbling concept. Makes you really consider what well is. Is the poop out really the AD effect pooping out, or is it the *better than well* feeling pooping.
Linkadge
Posted by zeugma on June 24, 2004, at 15:59:13
In reply to Re: only one rule - *evenually everything poops*, posted by linkadge on June 24, 2004, at 9:10:25
i have never felt better than well. in fact, i have never felt 'well', except possibibly some time before the age of five.
i think 'poop out' has a lot to do with the fact that antidepressants essentially treat one imbalance with another imbalance. Delgado's studies of amine depletion showed that if you deplete an ordinary person of amines, depression is not induced, but if you deplete someone on fluoxetine of 5HT, they will suffer a relapse, and if you deplete someone on desipramine of NE, they will also suffer a relapse. If you deplete someone on fluoxetine of NE, they will not suffer a relapse. This shows that drugs act on the amine system in a way that elevates mood, but it is the antidepressant creating an effect unrelated to whatever caused the depression in the first place. There might be two imbalances created (one from the depression and one from the AD) and two imbalances does not necessarily equal balance.
This is the pitfall of treatment that is merely symptomatic.
Posted by linkadge on June 24, 2004, at 17:01:49
In reply to Re: only one rule - *evenually everything poops*, posted by zeugma on June 24, 2004, at 15:59:13
I have a few problems with tryptophan depleation
with SSRI relapse. People that have the illness are significantly more prone to fall into depression than people who do not. Their whole brain is more fraile and sensitive. Also what causes depression on one person may not in another person.Mental health is really a continuom. You can have extremely mentally healty people that may take a lot more than simple tryptophan depleation to get them down. They probably have stores of endorphens and PEA, and who knows what to keep them going.
I think the chemical imballence theory is fairly sound. Remember the days back in the 50's when people were treated for high blood pressure with reserpine. This depleates all three monoamines, and has a very high propensity to cause depression even in the most mentally healthy.
Posted by zeugma on June 24, 2004, at 19:29:25
In reply to Re: only one rule - *evenually everything poops*, posted by linkadge on June 24, 2004, at 17:01:49
> I have a few problems with tryptophan depleation
> with SSRI relapse. People that have the illness are significantly more prone to fall into depression than people who do not. Their whole brain is more fraile and sensitive. Also what causes depression on one person may not in another person.> Mental health is really a continuom. You can have extremely mentally healty people that may take a lot more than simple tryptophan depleation to get them down. They probably have stores of endorphens and PEA, and who knows what to keep them going.
>
> I think the chemical imballence theory is fairly sound. Remember the days back in the 50's when people were treated for high blood pressure with reserpine. This depleates all three monoamines, and has a very high propensity to cause depression even in the most mentally healthy.Reserpine did cause some suicides among people taking it for nonpsychiatric reasons, and this combined with the fact that antidepressants were either MAOI's or amine reuptake inhibitors led to the formulation of the amine theory of depression. So amines have a powerful effect on mood.
Simply taking an amine reuptake inhibitor, however, hasn't made me feel mentally well. Maybe my endorphins or what ever are abnormally low, and I remain subject to depressive moods even though I don't suffer from the full effects of melancholic depression. I think there are people who have episodes of depression and the antidepressant clears it up and they are fine again. The amine theory would be an adequate one if that were the case for all of us. I think that what happens in those subject to chronic depression is a tendency to dysregulate that is reflected in many systems, including the amine systems, and manipulations of the amine systems only succeed partially, because many other systems (many of which are in balance with the amine systems) interfere with these manipulations.
People who don't have depression often assume that because you're on an AD, you're fine, because it 'controls' the symptoms. I feel like my symptoms are 'controlled' to some extent, but that doesn't mean that I'm not depressed. In fact I feel that my treatment has made me better able to function but has left me in an emotional limbo where I almost feel worse than I did before, because aminergic manipulation gets me out of bed in the morning but doesn't make me feel like a healthy person at all. (maybe, after I'm done with the Provigil titration, I need to persuade my dr. to let me try Anafranil.)
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Posted by linkadge on June 24, 2004, at 19:42:11
In reply to Re: only one rule - *evenually everything poops*, posted by zeugma on June 24, 2004, at 19:29:25
I know exactly where you are. The antidepressants helped in the past but they don't seem to be doing so anymore. I am only 21 years old, but have been on every antidepressant except for the tricylics. I exercsie every day (which helps), but I would kill myself at the drop of a hat.
No doctor seems to get that point.Linkadge
This is the end of the thread.
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