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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 49 to 73 of 73. Go back in thread:
Posted by zeugma on October 26, 2006, at 13:17:17
In reply to Re: Ca2+ » zeugma, posted by SLS on October 26, 2006, at 8:34:46
it makes perfect sense that you would not want to repeat the experiment. Calcium is an intensely aversive stimulus for you.
As to underlying pathology, I don't know. Sigma-1 agonists are theorized by some to be antidepressant, and it appears that they slow K+ efflux and speed Ca2+ efflux from cells. Have you ever noticed an effect on your mood from any other mineral (potassium especially?).Looking on notes I took last summer, it seems AMPA receptor stimulation phosphorylates Na+ and K+ channels, and NMDA stimulation phosporylayes K+ and Ca2+ channels. That's why the Polish pharmacologists (who are the main source of interest in the "NMDA hypothesis" of depression) recommend amantadine and similar drugs for augmentation.
since my computer has lost its ability to cut and [paste, i will summarize a fragment. They hypothesize that amantadine and sigma ligands synerdize with AD's chiefly via D2/D3 receptors and alpha-1 adrenoceptors. D2 signalling is thought to be responsible for attentional flexibility, as well as being anti-anhedonic/motivational. What is your cognitive phenotype? (I've been reading these articles too long.) Excessive D2 is thought to create 'flexible but unstable' representations, while excessive D1 creates an inability to process novel information due to the excessive stabilty of the cognitive representations. D1 receptors physically interact (not just colocaloze) with NMDA receptors; it seems the D1 receptors randomly drift in the cellular space until 'trapped' by NMDA receptors. This probably explains why D1 receptors couple to so many second messenger systems.
in any case, if you google 'amantadine' and 'antidepressants', you will come with a lot of this stuff :-)
But I am just trying to think of what the pattern is to your AD (or dysphoric) responses. I have a close friend who had a severely dysphoric reaction to Wellbutrin, and some researchers at Lilly found that adding bupropion to clozapine potentiated NMDA function in the PFC. Do you have OCD-like symptoms, or is it closer to the cognitive chaos of ADHD?
Sorry of these questions are too personal; feel free not to answer them. You can clearly see the perseveration in my own thought process :-)
-z
Posted by ed_uk on October 26, 2006, at 13:54:32
In reply to Re: Ca2+ » zeugma, posted by SLS on October 26, 2006, at 8:34:46
>One time, I took 1000mg of calcium supplement. I felt horribly more depressed within 1/2 hour.
Have you ever taken a magnesium supplement? How did you react?
Ed
Posted by corafree on October 26, 2006, at 13:59:18
In reply to Re: Ca2+ » zeugma, posted by SLS on October 26, 2006, at 8:34:46
Z & S:
This is 'way over my head', but if U take 1000mg calcium, u might need take double dose(?) magnesium alongside it.
Posted by zeugma on October 26, 2006, at 13:59:51
In reply to Re: Ca2+ » SLS, posted by ed_uk on October 26, 2006, at 13:54:32
Ed, you read my mind!
Personally, I reacted badly to magnesium.
But the effect could just as easily been a GI disturbance as a psychotropic effect.
-z
Posted by corafree on October 26, 2006, at 14:11:27
In reply to Re: Lyrica left me feeling worse. » corafree, posted by SLS on October 26, 2006, at 8:46:06
S - I was attacked and thrown around. C2-3, 3-4, 4-5 were damaged. Most damage @ C4-5 w/ signal on MRIs.
It's hard 2 tell if have fibromyalgia or not, as the injury occurred same time proximity as it would have onset.
I'm also on levothroid and estrogen patch.
Yep ... just dump daily pill supply out on my bed in a.m. 2 gather up my morn' cocktail.
I am doing well. Having my coffee.
I haven't forgotten nortriptyline and have 'stored in memory bank as possibility in the future'. Yes; this I've not been on b4.
Someday let me know why steer clear of Eff-XR.
4now,tksS, cf
Posted by linkadge on October 26, 2006, at 17:01:06
In reply to Re: Lyrica left me feeling worse. » SLS, posted by corafree on October 26, 2006, at 14:11:27
SLS reacts well to NRI's (?). Isn't there a intricate relationship between noradrenaline and glutamatergic function?
Some studies linked positive response to TCA's with a dramatically increased affinitity of zinc to hippocampal neurons. I found zinc to be a better antidepressant than magnesium. Both are NMDA antagonists, but magnesium decreases BDNF while zinc upregulates it. Zinc also increases BCL-2 like lithium. BCL-2 increase supposedly has antidepressant effect. Valproate also increases BCL-2, but not other mood stabilizers.
BCL-2 transgenic mice (with dramatically increased BCL-2), seem to have low anxiety. BCL-2 may be a target for anxiety disorders. The ratio of certain members of the BCL-2 antiapoptotic/apoptotic family has a big influence on apoptosis and anxonal regeneration.
Linkadge
Posted by SLS on October 26, 2006, at 23:35:04
In reply to Re: Ca2+ » SLS, posted by zeugma on October 26, 2006, at 13:17:17
> Sigma-1 agonists are theorized by some to be antidepressant, and it appears that they slow K+ efflux and speed Ca2+ efflux from cells.
I am not that familiar with sigma receptors. Where are they located and what are their function?
> Have you ever noticed an effect on your mood from any other mineral (potassium especially?).
I find magnesium calming.
> Looking on notes I took last summer, it seems AMPA receptor stimulation phosphorylates Na+ and K+ channels, and NMDA stimulation phosporylayes K+ and Ca2+ channels. That's why the Polish pharmacologists (who are the main source of interest in the "NMDA hypothesis" of depression) recommend amantadine and similar drugs for augmentation.
I responded briefly to memantine. I wish I had thought to augment it with magnesium. It would have been an interesting experiment.
> since my computer has lost its ability to cut and [paste, i will summarize a fragment. They hypothesize that amantadine and sigma ligands synerdize with AD's chiefly via D2/D3 receptors and alpha-1 adrenoceptors. D2 signalling is thought to be responsible for attentional flexibility, as well as being anti-anhedonic/motivational. What is your cognitive phenotype?
Dumb and dumber.
> (I've been reading these articles too long.) Excessive D2 is thought to create 'flexible but unstable' representations, while excessive D1 creates an inability to process novel information due to the excessive stabilty of the cognitive representations.
I would be excessive D1, then.
> in any case, if you google 'amantadine' and 'antidepressants', you will come with a lot of this stuff :-)
I still have some amantadine lying around. Maybe I'll try adding it to an MAOI. What is the "latest" as to what amantadine does physiologically?
> But I am just trying to think of what the pattern is to your AD (or dysphoric) responses. I have a close friend who had a severely dysphoric reaction to Wellbutrin,
I would characterize my reaction to Wellbutrin as being moderately dysphoric.
> and some researchers at Lilly found that adding bupropion to clozapine potentiated NMDA function in the PFC. Do you have OCD-like symptoms, or is it closer to the cognitive chaos of ADHD?
I would say the OCD.
Thanks for "perservering".
:-)
- Scott
Posted by SLS on October 26, 2006, at 23:49:30
In reply to Re: Lyrica left me feeling worse., posted by deniseuk190466 on October 26, 2006, at 12:13:32
Hi Denise.
> Just want to say, I'm really sorry that the Lyrica didn't work for you, I'm waiting for the day when you post on this board saying how great you feel.
Yeah. Won't that be cool.
> I hope you feel better than you do now soon, at least you know it's the lyrica that's caused this set back so hopefully in a couple of weeks you will feel a bit better.
Today was a little lighter than yesterday. Maybe tomorrow will be a little lighter still.
> I know what you mean about the VNS, I would seriously think about it myself but the statistics on it don't look that great. However, there are some people it really seems to have helped.
Statistics are disappointing but testimonials are compelling.
> I'm not sure how bad you were feeling before trying out the Lyrica or what risks you would consider taking in order to feel really truly well. But would you consider something like Deep Brain Stimulation?
I think I would wait a few years before going with that. From what I understand, they are starting to receive reports of adverse cognitive side effects with DBS including decreased verbal fluency, decline in executive functions, verbal learning, and memory. A friend of mine received a Biological Therapies in Psychiatry newsletter describing this.
> I know the samples have been small so far but the results seem to be really promising.
For some types of depression, I think Brodman Area 25 is the right target. I hope that they will soon find some way of testing a prospect for hyperexcitability in that area before committing them to the procedure.
> Anyway, if you don't answer that's fine just wanted to say something as you've always been so encouraging and reassuring with me and I only seem to post on this board to whinge and moan (refer to my next post for more whinging :-))
Thanks, Denise.
I look forward to your venting.
Take care.
- Scott
Posted by SLS on October 26, 2006, at 23:53:21
In reply to Re: Ca2+ » SLS, posted by ed_uk on October 26, 2006, at 13:54:32
> >One time, I took 1000mg of calcium supplement. I felt horribly more depressed within 1/2 hour.
>
> Have you ever taken a magnesium supplement? How did you react?
I found it calming and pleasant. I didn't receive an antidepressant effect from it. But then again, I didn't take it for more than a week. Maybe I should try again?
- Scott
Posted by SLS on October 27, 2006, at 0:05:08
In reply to Re: Lyrica left me feeling worse., posted by linkadge on October 26, 2006, at 17:01:06
Hi Linkadge.
> SLS reacts well to NRI's (?).
Actually, I reacted adversely to reboxetine. It exacerbated my depression severely and made me suicidal. Also, I find imipramine and nortriptyline better for me than desipramine. It seems that a mixture of 5-HT and NE reuptake inhibition produces a better effect for me than a selective NE reuptake inhibition.
> Isn't there a intricate relationship between noradrenaline and glutamatergic function?
I don't know how that works other than to characterize NE as being generally excitatory upon GLU pathways.
> Some studies linked positive response to TCA's with a dramatically increased affinitity of zinc to hippocampal neurons. I found zinc to be a better antidepressant than magnesium.
What dosage of zinc did you find helpful?
> Both are NMDA antagonists, but magnesium decreases BDNF while zinc upregulates it. Zinc also increases BCL-2 like lithium. BCL-2 increase supposedly has antidepressant effect. Valproate also increases BCL-2, but not other mood stabilizers.
Thanks for this information.
- Scott
Posted by zeugma on October 27, 2006, at 5:00:16
In reply to Re: Ca2+, posted by SLS on October 26, 2006, at 23:35:04
I had been wondering how SSRI's work on OCD when it seemed (following Robbins and Cools) that the OCD cognitive phenotype was insufficient D2 striatal stimulation. Fluvoxamine, which is also a sigma-1 agonist (Ki=36 nM) apparently leads to to a 7-10% upregulation of raclopride binding in the D2 receptors of the striatum in OCD patients.
This is very simplistic of course. But it was found that while 6-OH-dopamine lesions had no effect on the behavioral effects of NRI's, they blocked the effects of SSRI's in animal models.
I will post on the location and function of sigma-1 receptors later. The truth is that they are myststerious- sigma-knockout mice exhibited no evident abnormalities, and apparently these receptors share no homology with any other known type of receptor. Sigma-1 ligands are also famous for narrow, bell-shaped dose curves, which has probably made it difficult for these ligands to have their functions clarified.
-z
Posted by zeugma on October 27, 2006, at 17:26:05
In reply to brief note on OCD » SLS, posted by zeugma on October 27, 2006, at 5:00:16
believed to be implicated in AD effects: in the hippocampus.
-z
Posted by Phillipa on October 27, 2006, at 18:35:44
In reply to Re: brief note on sigma-1 receptors, posted by zeugma on October 27, 2006, at 17:26:05
Gee I never realized vitamins especially Calcium and Magnesium could be detrimental too. So then why do they tell people to take Calcium and magnesium in a l:2 ratio of bone health? I'm confused here. Love Phillipa
Posted by linkadge on October 28, 2006, at 7:15:12
In reply to brief note on OCD » SLS, posted by zeugma on October 27, 2006, at 5:00:16
I was under the impression that sigma-1 receptors were involved in certain forms of neurite outgrowth. Supposedly, that in the presence of NGF, sigma receptors have some neurotrophic action. Sigma agonists are "smart drugs" are they not.
Linkadge
Posted by SLS on October 28, 2006, at 7:45:33
In reply to Re: brief note on OCD, posted by linkadge on October 28, 2006, at 7:15:12
> Sigma agonists are "smart drugs" are they not.
I could use as much as I can get my hands on right now. I'm as dumb as dirt.
On a somewhat related note, my doctor decided it was time to give Emsam a try. I don't expect much from it other than a lot of irritated skin.
- Scott
Posted by corafree on October 28, 2006, at 13:26:01
In reply to Re: Ca2+ » ed_uk, posted by SLS on October 26, 2006, at 23:53:21
And, maybe 'add in' zinc too.(?)
cf
Posted by zeugma on October 28, 2006, at 13:26:19
In reply to Re: brief note on OCD, posted by linkadge on October 28, 2006, at 7:15:12
> I was under the impression that sigma-1 receptors were involved in certain forms of neurite outgrowth. Supposedly, that in the presence of NGF, sigma receptors have some neurotrophic action. Sigma agonists are "smart drugs" are they not.
>
> Linkadgethey do stimulate neurite outgrowth.
sigma-1 agonists can compensenate for deficiencies in spatial navigation tasks induced in rats exposed to prenatal cocaine.
apparently they also are promising interventions for other prenatal insults, such as exposure to alcohol or nicotine.
-z
Posted by corafree on October 28, 2006, at 13:28:11
In reply to Re: Lyrica left me feeling worse. » linkadge, posted by SLS on October 27, 2006, at 0:05:08
Just wanted to say, I think zinc would be pretty safe to go 'high' in amount.
cf
Posted by linkadge on October 28, 2006, at 18:39:57
In reply to Re: brief note on OCD » linkadge, posted by zeugma on October 28, 2006, at 13:26:19
Which is interesting since cocaine is a sigma-1 agonist.
Linkadge
Posted by linkadge on October 28, 2006, at 18:44:13
In reply to Re: Lyrica left me feeling worse. » SLS, posted by corafree on October 28, 2006, at 13:28:11
I find a benifit from lower dose range. Ususally between 10-20mg.
In animal studies too, zinc generally lowers the effective dose necessary of antidepressants to reduce depression related behaviors.Linkadge
Posted by linkadge on October 28, 2006, at 18:47:40
In reply to Re: Lyrica left me feeling worse. » SLS, posted by corafree on October 28, 2006, at 13:28:11
Combining smart drugs:
AMPA receptor active drug
Sig-1r receptor active drug.
BCL-2 active drug.
GAP-43, BDNF, GDNF active drugs.How about...
Imipramine, Ginkgo, Zinc, and melatonin.
In some paradigms, smart drugs work as antidepressants.
Linkadge
Posted by Phillipa on October 28, 2006, at 20:10:38
In reply to Re: Lyrica left me feeling worse., posted by linkadge on October 28, 2006, at 18:47:40
I thought that you could only take one ad if you were on EMSAM and that is the one. And low levels of zinc boost ad results? Love Phillipa
Posted by linkadge on October 29, 2006, at 10:23:02
In reply to Re: Lyrica left me feeling worse., posted by linkadge on October 28, 2006, at 18:47:40
Zinc in general, augments antidepressants. Just as folic acid, and omega-3 can. I don't know the best dose of zinc for augmentation.
Linkadge
Posted by Dr. Bob on October 29, 2006, at 18:27:25
In reply to Re: Lyrica left me feeling worse., posted by linkadge on October 29, 2006, at 10:23:02
> Zinc in general, augments antidepressants.
Sorry to interrupt, but I'd like to redirect follow-ups regarding Zinc to Psycho-Babble Alternative. Here's a link:
http://www.dr-bob.org/babble/alter/20061013/msgs/698818.html
Thanks,
Bob
Posted by Cairo on November 2, 2006, at 20:52:51
In reply to Lyrica left me feeling worse., posted by SLS on October 21, 2006, at 17:06:31
I, too, feel worse after discontinuing Lyrica. I was only taking 50-100mg HS and tapered off VERY slowly. My new pdoc said that it might take 6-8 weeks or more before some of my symptoms abate, IF they are due to discontinuation of the Lyrica. I've been on so many different meds over the years that he says my receptors don't know which end is up. I'm having PVCs, headaches, irritability, panic attacks, my blood pressure is up and more.
He now has me on super low dose doxepin, which he says should help with anxiety, panic, sleep, pain if we can get my dose right. I'm only at 4mg at night, but he's ordering a blood level as I suspect I'm either a very slow metabolizer or have pharmacodynamic problems. He's into the vasoactive intestinal protein theory for FMS and doxepin should help with that. We'll see.
I'm taking 100mg of magnesium taurate at night to augment the doxepin for sleep. Seems to help. I remember reading that you shouldn't take magnesium within a couple of hours of taking Neurontin as it competes for receptor sites or something.
As for zinc, whenever my trigger points act up, white spots appear on my fingernails, a sign of zinc deficiency. I've been taking Krebs cycle chelates for a month now and my trigger points are better and no new white spots are appearing.
Interesting site- http://www.ctds.info/
Hope you feel better soon.
Cairo
> Lyrica did something to leave me feeling worse. I discontinued it over a week ago. Neurontin affected me the same way. The exacerbation of my condition does not become apparant until it is unmasked by the discontinuation the drug.
>
> I have no idea how long I will be feeling worse for.
>
> I have not been in a very healthy state of mind.
>
> My outlook is bleak. I feel that I have run out of options.
>
>
> - Scott
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