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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 9 to 33 of 36. Go back in thread:
Posted by Ritch on May 7, 2002, at 8:29:33
In reply to Mitch, update here! » Ritch, posted by Janelle on May 7, 2002, at 2:38:36
> I should have done the search BEFORE I posted just above to you - sorry.
>
> I did a search on GABA which confirmed that I am RIGHT - it IS a calming thing - it's a non-essential amino acid that has a calming effect.
>
> Thus, my question to you regarding Klonopin and benzos still stands:
>
> Are you saying that because a GABA receptor-specific med like Klonopin (and other benzos) kind of "fools" the synapses/receptors into "thinking" there is plenty of GABA around, that being fooled like this, the brain would then lower/stop GABA production?
>
> Since GABA acts to calm a person, I would think that Klonopin and other benzos somehow create more GABA in the brain, but not according to what you said! Which leads me to also wonder/ask just how do Klonopin and other benzos manage to calm anxiety if they do not increase GABA?
>
> Hmmmmmmm ...!
Janelle,Since GABA is an inhibitory ("calming") neurotransmitter, and Klonopin/benzos act at the GABA receptors, I think that it makes the GABA receptor more "sensitive" to what GABA happens to be present thus inhibiting neuron firing more so than it would do otherwise without the receptors being "sensitized". Just a hunch-going on memory-no coffee yet :-)
Mitch
Posted by Ritch on May 7, 2002, at 8:51:46
In reply to Re: Mitch, update here! » Janelle, posted by Ritch on May 7, 2002, at 8:29:33
Janelle
Check out SusanC's post below if you haven't already. The article is very interesting about Depakote.
http://www.dr-bob.org/babble/20020503/msgs/105320.html
Posted by katekite on May 7, 2002, at 13:15:57
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
Hi Janelle,
Ok so here's how it works, read thru to the end for new information:
GABA is a neurotransmitter. GABA is the key, it fits into the GABA receptor (lock). GABA receptors are present on the surface of GABA based neurons.
Most GABA based neurons are inhibitory to other neurons. This means when they are activated by GABA, brain activity is slightly inhibited.
This leads to the results of less anxiety, sleepiness, or decrease in seizure (which is extreme overactivity in some part of the brain).
Benzodiazepines such as klonopin are chemicals that bind to a site on the GABA receptor that is NOT the site where GABA binds. (think of it as a big lock) The sites where GABA and benzodiazepines bind are very close to eachother. It is thought that the benzodiazepine binding changes the conformation of the GABA receptor, and this change in shape actually allows GABA to bind more easily.... ie it changes the shape of the lock to fit the key better.
The analogy is instead of jiggling the key in the lock before it turns, it turns smoothly the first time. So basically benzodiazepines are like oil, they lube up the slot where GABA fits.
So with a benzodiazepine like klonopin attached, GABA binds easier and may stay there longer, all of this makes the GABA neuron more likely to be able to send its inhibitory signal.
Hope that helps.
Not sure how depakote works.
kate
Posted by Janelle on May 7, 2002, at 17:34:44
In reply to Janelle! Update here! :-0 » Ritch, posted by Ritch on May 7, 2002, at 8:51:46
Posted by Janelle on May 7, 2002, at 17:36:39
In reply to benzodiazepine mechanism, posted by katekite on May 7, 2002, at 13:15:57
Posted by Janelle on May 7, 2002, at 17:44:12
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
I did a quick search and found the following about Depakote and Gaba:
"Although the mechanism of action is not established, its [Depakote's) activity may be related to increased brain levels of gamma aminobutyric acid (GABA). This may also account for its prolactin lowering effects.
Depakote (valproic acid) may also inhibit an enzyme responsible for the catabolism of GABA, potentiate postsynaptic GABA responses, affect the potassium channel or have a direct membrane stabilizing effect."
Based on this, somehow (not sure just how) Depakote does something to enhance the presence of GABA in the brain!
Posted by Janelle on May 7, 2002, at 17:50:40
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
Check this out - it actually compares benzos like Klonopin directly to Depakote in their action on GABA! I think I've answered my question! (can you tell I'm just a wee bit excited?!)
"VPA affects the action of GABA (gamma amino butyric acid), similar to agents such as phenobarbital and benzodiazepines. While these sedative hypnotics appear to enhance the postsynaptic action of GABA, VPA appears to increase the amount of GABA available to the CNS. Valproate has been shown (in vitro) to increase GABA levels by increasing the activity of glutamic acid decarboxylase and inhibition of GABA transaminase."
Posted by djmmm on May 7, 2002, at 18:42:05
In reply to Here's something right on Klono vs. Depa and GABA!, posted by Janelle on May 7, 2002, at 17:50:40
Most anticonvulsants manipulate both GABA and sertonin...depakote increases *and* decreases monoamine levels in various specific parts of the brain, also, levels of tyrosine are increased.
The increase in Dopamine is mediated by the activation of 5-ht1a receptors, decreased levels are connected to the GABA-A receptors.
Klonopin mechanism of action (from cp-online):
"Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS, and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and coma. The action of these drugs is mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Central benzodiazepine receptors interact allosterically with GABA receptors, potentiating the effects of GABA and thereby increasing the inhibition of the ascending reticular activating system. Benzodiazepines block the cortical and limbic arousal that occurs following stimulation of the reticular pathways."
Posted by Janelle on May 7, 2002, at 19:30:49
In reply to Re: Here's something right on Klono vs. Depa and GABA!, posted by djmmm on May 7, 2002, at 18:42:05
Posted by JohnX2 on May 8, 2002, at 1:00:17
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
> I have read that Klonopin and Depakote both work on GABA, but apparently in different ways. I don't understand how each of these meds works on GABA and would very much appreciate it if anyone who knows how they each affect GABA could explain it briefly and as simply as possible. Thank you!
Here's a paper I dug up on Gaba:
http://www.vcu-cme.org/gaba/gaba2_22.pdf
One should note that there are various types of
Gaba receptors; namely Gaba-A and Gaba-B.Klonopin and most benzos work at the Gaba-A receptors.
Depakote from what I understand has some affinity for the
Gaba-B receptor.John
Posted by Ron Hill on May 8, 2002, at 15:23:43
In reply to Re: What about Klonopin, Depakote and GABA... » Janelle, posted by JohnX2 on May 8, 2002, at 1:00:17
Posted by SLS on May 8, 2002, at 17:08:07
In reply to Hey folks: Look what I found re Depakote/GABA!!, posted by Janelle on May 7, 2002, at 17:44:12
Hi Janelle.
> Based on this, somehow (not sure just how) Depakote does something to enhance the presence of GABA in the brain!
Depakote (valproate) increases the amount of GABA available by inhibiting an enzyme known as GABA transaminase. This mechanism is analogous to how MAO-inhibitors work to increase the levels of the monoamines (DA, NE, 5-HT). Two other drugs I know of inhibit GABA transaminase: the MAOI Nardil (phenelzine) and the anticonvulsant Sabril (vigabatrin).
Depakote also acts to stabilize nerve cell membranes by slowing-down the movement of ions (electrically charged molecules) through sodium channels.
- Scott
Posted by SLS on May 8, 2002, at 17:20:47
In reply to Re: Hey folks: Look what I found re Depakote/GABA!! » Janelle, posted by SLS on May 8, 2002, at 17:08:07
I filled in some more of my chart. Please let me know if you find any errors of misinformation.
http://sl.schofield3.home.att.net/medicine/psychiatric_drugs_chart.html
- Scott
Posted by Ritch on May 8, 2002, at 23:12:33
In reply to Re: Hey folks: Look what I found re Depakote/GABA!!, posted by SLS on May 8, 2002, at 17:20:47
Posted by Ron Hill on May 9, 2002, at 0:04:41
In reply to Re: Hey folks: Look what I found re Depakote/GABA!!, posted by SLS on May 8, 2002, at 17:20:47
Scott,
Nice table. Do you store your web page(s) on your own server or do you rent server space?
-- Ron
Posted by SLS on May 9, 2002, at 0:30:56
In reply to Re: Nice table Scott » SLS, posted by Ron Hill on May 9, 2002, at 0:04:41
> Scott,
>
> Nice table. Do you store your web page(s) on your own server or do you rent server space?
>
> -- Ron
Hi Ron.I use AT&T Worldnet as my ISP. They give you 60 Mb of server space to use for e-mail or webpages.
I am probably going to try S-AMe before the end of the week. I'm not sure I want to go above 400mg, though. Hopefully, I'll respond to it similarly to you. We'll see.
I gave low-dosage lithium (300mg) a try, but it worsened my depression. Lithium has always treated me this way, but I had doubted that it would affect me negatively at such a low dosage. I was hoping to have it on-board permanently - if for nothing else, to take advantage of its reported neuroprotective and neurotrophic effects. Of course, it might also have acted as an augmentor of whatever antidepressants I might try in the future. If Manji and others are right, it might make sense for some sufferers of neurodegenerative diseases (bipolar disorder, schizophrenia, Parkinson's, Alzheimer's, Huntington's) to begin taking lithium continuously at dosages between 300-600mg. As is often the case with me, I got screwed once again. Sh_t.
I want to thank you again for your support and encouragement.
- Scott
Posted by petters on May 9, 2002, at 8:57:51
In reply to Re: Nice table Scott » Ron Hill, posted by SLS on May 9, 2002, at 0:30:56
Dear Scott...
Very glad to hear from you again. I have been thinking about you, and your condition. Very sorry for the bad side effect from Litium. I´m sure that you know , that giving it a fair chans taks up to severel month. Do you think there is a chans that the side effect possible wean off after some month? I am quite sure that you also considered that. What about Topamax + Lamictal ( I know you use Lamictal, 300 mg, if my memory is not wrong ) There seems to be many positive result from this combo in treating affective syndrom.
I did follow your advise to raise Lamictal from 100 mg to 200 mg, and it was really positive. More energi, and more stable mood. I also raised my Effexor dosage from 150 mg to 300 mg. 300 mg seems to be an optimal dose for me; I have tried to reduced the dosage to 150 mg severel times but the depression symptom occured. So I must say I´m quite satisfied with my states, except partial sexual dysfunktion. Remeron was the best in this respect in combo with Effexor. But Remeron gave me side effect that I couldn´t tolerated.
So my combo today:
Lamictal 200 mg
Effexor 300 mg
Litium (0.6 mmol/)
Nefadar 400 mgI hesitate to believe that this meds combo will hold, and be sufficient in the future, because I and I know you have experienced so many cruel games with this dam... poop out
Anyway I will think about you and your trial on SA-Me, and pray for your. You have suffer more than enough.
Stay well and be well.
Sincerely
/// Petters
Posted by lizzyg on May 9, 2002, at 11:40:41
In reply to Re: Hey folks: Look what I found re Depakote/GABA!!, posted by SLS on May 8, 2002, at 17:20:47
Many thanks for updating this table, Scott; it's looking really good and I've printed it as a crib sheet. Would it be possible to jump the alphabetical order and just fill in a few of the remaining blanks that pertain to the 'sexy' medications that are talked about on this board all the time? Nefazodone is an obvious culprit. All the European names look pretty much there, too, just a few random benzos that are different as far as I can make out.
I haven't been on this board much recently (depression seems to have lifted...), but you wrote an excellent piece a couple of weeks ago in the nature versus nurture debate and I wanted to query something with you. From what I (and various psychiatrists and psychotherapists) can tell, my depressive episodes are endogenous. You said:
"For some people, the biological system can begin to function abnormally in the absence of concurrent depressive pressure. A variety of genetic and environmental factors can play a role in the evolution of system dysfunction... ...Treatment with antidepressants alone are necessary and often sufficient... ...Indefinite treatment with antidepressants is often necessary, especially if recurrent episodes have occurred. Each successive collapse of the system produces an increasing deformity of the structure of the biological system, such that it becomes less amenable to repair and treatment-resistant."
But my own experience has been the exact opposite to your final two sentences - each successive episode has been easier to manage, and the time lapse between episodes has increased. The first time I experienced depression and anxiety I couldn't function at all (luckily I was at university so it didn't matter too much!). I didn't understand the symptoms (was the anxiety presaging psychosis/schizophrenia?), didn't know which treatments might work (and had to contend with uninformed doctors), and didn't have a sense of how long the episode would last (would I ever recover?). During successive attacks, I've experienced more treatments options, have learnt that the episodes are self-limiting, and have discovered lifestyle changes that act as prophylactics to a certain extent (for me, exercise is the best form of therapy; in fact, indolence seems to be a trigger factor for depression). I was lucky to have had well over six years between my last depression and the most recent earlier this year.
To your knowledge, is my pattern unusual, or are there any studies with similar findings? Historically, I've always dropped the ADs after four or five months, and been subsequently symptom free for anything from a year to six years. At the moment, I'm just using SAM-e and fish oils, so I guess it wouldn't be a great hardship to keep this going for longer... Any views?
Thanks for your input.
Lizzy
Posted by SLS on May 9, 2002, at 18:46:04
In reply to Re: Nice table Scott, posted by petters on May 9, 2002, at 8:57:51
Hi Petters.
> Very glad to hear from you again. I have been thinking about you, and your condition. Very sorry for the bad side effect from Litium. I´m sure that you know , that giving it a fair chans taks up to severel month. Do you think there is a chans that the side effect possible wean off after some month?
Maybe. However, lithium has consistently worsened my depression at dosages of 600mg and higher. This worsening does not subside after 9 months. I really didn't think lithium would affect me negatively at dosages as low as 100mg. I wanted to take 300mg lithium indefinitely because of the recent reports describing it as having neuroprotective and neurotrophic properties. I'm pretty pissed.
> What about Topamax + Lamictal ( I know you use Lamictal, 300 mg, if my memory is not wrong ) There seems to be many positive result from this combo in treating affective syndrom.
Really? My doctor mentioned Topomax a while ago. I am afraid of the cognitive disturbances it can produce.
I am becoming more interested in trying the anticonvulsant Gabitril (tiagabine). Gabitril increases GABAergic neurotransmission by inhibiting the reuptake of GABA. Some people have described Gabitril as being activating. However, others have reacted very badly to it, suffering severe cognitive disturbances. For me, the following drugs have produced transient antidepressant effects:
1. Nardil (phenelzine): GABA increase
- GABA aminotransferase inhibition (reduces GABA elimination)2. Depakote (valproate): GABA increase
- GABA transaminase inhibition (reduces GABA elimination)
- SSAD dehydrogenase inhibition (increases GABA synthesis by reducing end-product inhibition)3. Neurontin (gabapentin): GABA increase
- increased synthesis?Is Gabitril available in Sweden?
> I did follow your advise to raise Lamictal from 100 mg to 200 mg, and it was really positive. More energi, and more stable mood. I also raised my Effexor dosage from 150 mg to 300 mg. 300 mg seems to be an optimal dose for me;
I am very glad to hear that. Effexor 300mg seems to be the optimal dosage for most people with TRD.
> I have tried to reduced the dosage to 150 mg severel times but the depression symptom occured. So I must say I´m quite satisfied with my states, except partial sexual dysfunktion. Remeron was the best in this respect in combo with Effexor. But Remeron gave me side effect that I couldn´t tolerated.
Has anyone else described an increased number of infections with Remeron?
> So my combo today:
>
> Lamictal 200 mg
> Effexor 300 mg
> Litium (0.6 mmol/)
> Nefadar 400 mg> I hesitate to believe that this meds combo will hold, and be sufficient in the future, because I and I know you have experienced so many cruel games with this dam... poop out
Cruel indeed. However, I think you will have good luck with this combination. It seems to me that very few people experience poop-out with Effexor or Lamictal once optimal dosages are established.
> Anyway I will think about you and your trial on SA-Me, and pray for your. You have suffer more than enough.
Thanks. I'll be praying for you too.
:-)
Take care.
Sincerely,
Scott
Posted by geno on May 9, 2002, at 19:47:01
In reply to Re: Here's something right on Klono vs. Depa and GABA!, posted by djmmm on May 7, 2002, at 18:42:05
GHB and GABA:
When Dr Henry Laborit in 1952 was trying to figure a way to pass gaba through the BBB, he discovered a chemical called GHB which Inhibits GABA B. Can anyone explain this.
Also ghb suppresses dopamine (unknown what receptor site, thus causing a build up of dopamine, then releases such.
GHB also increases seratonin levels.
GHB also increases oxytocin level.
GHB also increases REM sleep
WOW how such an interesting substance, which is already present in the body and does multiple manipulation to brain chemicals is now a schedule 1 drug. This drug needs to be more researched and possibly used in psyciatry.geno
Posted by SLS on May 10, 2002, at 7:54:53
In reply to Looking good, Scott » SLS, posted by lizzyg on May 9, 2002, at 11:40:41
Hi Lizzy.
The "depressive pressure" conceptualization is my own, and should not be construed as fact. However, it has helped me to explain depressive disorders to people.> From what I (and various psychiatrists and psychotherapists) can tell, my depressive episodes are endogenous. You said:
> > "Each successive collapse of the system produces an increasing deformity of the structure of the biological system, such that it becomes less amenable to repair and treatment-resistant."
> But my own experience has been the exact opposite to your final two sentences - each successive episode has been easier to manage, and the time lapse between episodes has increased.
It's nice to be wrong sometimes. :-)
(only sometimes)
> The first time I experienced depression and anxiety I couldn't function at all
Depression comes in many flavors (none of them being a gustatory delight). Not only does depression manifest differently between individuals, but it can also vary its expression within any one individual over time. During the first 3-5 years of my depression, the most prominent features were depressed mood and paralyzing social anxiety, rumination, and occasional suicidal ideation. Although my memory and concentration were moderately impaired, I was able to read, learn, and remember enough to do well during my first two years at college. However, as the years passed, both depressed mood and anxiety diminished while anergia and cognitive impairment worsened. Now, I can't read more than two complete sentences consecutively. I've had to rely upon skimming, targeting key words to focus upon.
I think this scenario represents the majority. As one ages, depression drifts away from depressed mood and towards cognitive impairement. In the elderly, depression is often misdiagnosed as dementia. In fact, the term "pseudodementia" is used to describe this.
Regarding the reduction of my experience of depressed mood and anxiety, I can't exclude the contribution of the psychological improvements that I have worked (and continue to work) toward. One issue that I have resolved significantly is perfectionism. One of my former doctors told me that even if I were to respond well to a particular treatment, continued chronic obsessive perfectionism might lead to medication break-through and relapse. His words have stayed with me. I have thus broadened the scope of "depressive pressures" to remove or mitigate so as to include just about anything that produces psychosocial stress.
> During successive attacks, I've experienced more treatments options, have learnt that the episodes are self-limiting, and have discovered lifestyle changes that act as prophylactics to a certain extent (for me, exercise is the best form of therapy; in fact, indolence seems to be a trigger factor for depression). I was lucky to have had well over six years between my last depression and the most recent earlier this year.
By far, the single most significant reduction of psychosocial stress (depressive pressure) for me has been the understanding that my depressive thinking and vegetative state was being caused by a self-perpetuating abnormal brain function that was beyond my cognitive control. Perhaps you have experienced something similar with what you have learned and now understand about the nature of your illness. I guess a didactic argument can be made that the reduction in the frequency and severity of your depressive episodes is due to a reduction of depressive pressure facilitated the changes you have made in your lifestyle and your psychological relationship with the depression once it is triggered.
> To your knowledge, is my pattern unusual, or are there any studies with similar findings? Historically, I've always dropped the ADs after four or five months, and been subsequently symptom free for anything from a year to six years. At the moment, I'm just using SAM-e and fish oils, so I guess it wouldn't be a great hardship to keep this going for longer... Any views?
If I were you, I would not consider Scott's views to be reliable. :-)
Don't fix it if it ain't broke? I guess you are doing the right thing for yourself. As you describe your life-chart, it seems that the trend has been toward reduced frequency and severity, and increased treatability. The key for you seems to be prophylaxis.
- Scott
--------------------------------
Major depression:"Very often, a combination of genetic, psychological, and environmental factors is involved in the onset of a depressive disorder. Later episodes of illness typically are precipitated by only mild stresses, or none at all."
http://www.nimh.nih.gov/publicat/depression.cfm#ptdep4
"Untreated depression often has an accelerating course, in which episodes become more frequent and severe over time. Researchers are now considering whether early intervention with medications and maintenance treatment during well periods will prevent recurrence of episodes. To date, there is no evidence of any adverse effects of long-term antidepressant use."http://www.nimh.nih.gov/publicat/depresfact.cfm
--------------------------------
Bipolar disorder:"Over time a person may suffer more frequent (more rapid-cycling) and more severe manic and depressive episodes than those experienced when the illness first appeared."
http://www.nimh.nih.gov/publicat/bipolar.cfm#bp3
--------------------------------
Posted by lizzyg on May 17, 2002, at 11:31:29
In reply to Re: Looking good, Scott » lizzyg, posted by SLS on May 10, 2002, at 7:54:53
Dear Scott
Many thanks for a thoughtful and well-written note. If this is you with cognitive impairment, seeing you fully functioning must be almost scary!
> You said: I guess a didactic argument can be made that the reduction in the frequency and severity of your depressive episodes is due to a reduction of depressive pressure facilitated by the changes you have made in your lifestyle and your psychological relationship with the depression once it is triggered.
Your hypothesis is logical but, coming back to the nature versus nurture discussion that sparked this off, might I propose a simpler (simplistic?) argument? Viz: The reduction in the frequency and severity of my depressive episodes is due to an increase in neurotransmitters, brought about initially by antidepressant therapy, then perpetuated by physical/lifestyle adjustments (lots of exercise, eating well, sleeping the right amount, continuing with pleasurable activities and avoiding alcoholic excess [although the last point is more difficult in Europe when it's such a way of life!]).
> Concerning your own symptoms you said: Regarding the reduction of my experience of depressed mood and anxiety, I can't exclude the contribution of the psychological improvements that I have worked (and continue to work) toward. One issue that I have resolved significantly is perfectionism... ...I have thus broadened the scope of "depressive pressures" to remove or mitigate so as to include just about anything that produces psychosocial stress.
The psychological improvements you've made are obviously extremely useful, but from what I've read it seems your depression has a large biological component, so do you feel you've done all you can on the physical/behavioural side? I think somatic and sensory stimulation is very important, which is why those old cures for melancholy - cold baths, beating with birch twigs etc - might have had some validity! ('Be not solitary, be not idle' - Robert Burton, 1621) For example, in my younger days, after going to a nightclub or or anywhere with loud music, I'd feel the depression had lifted for a while. It's been my personal experience that inactivity can trigger or worsen depression, and maybe removing too many psychosocial stressors is a bad thing. I certainly feel much better if I go to work and interact with people when depressed. Although it's often difficult to get the motivation to do these things, I've always found them beneficial. Agree or disagree?
I think you're spot on when you say that, for me, prophylaxis is the key. And also recognising the prodromal symptoms so medication can be started straight away to nip the depression in the bud. Hope you continue to find ways of lessening the burden, too. Thanks again for your wise words, Scott.
Best wishes
Lizzy
Posted by SLS on May 26, 2002, at 22:39:33
In reply to Re: Looking good, Scott » SLS, posted by lizzyg on May 17, 2002, at 11:31:29
Done for now...
I'm sure it needs tweaking.
http://sl.schofield3.home.att.net/medicine/psychiatric_drugs_chart.html
- Scott
Posted by Seamus2 on May 27, 2002, at 9:43:50
In reply to Re: Looking good, Scott, posted by SLS on May 26, 2002, at 22:39:33
Posted by Chloe on May 27, 2002, at 18:41:50
In reply to Re: Looking good, Scott, posted by SLS on May 26, 2002, at 22:39:33
Go forward in thread:
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Dr. Bob is Robert Hsiung, MD,
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Script revised: February 4, 2008
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