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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 2 to 26 of 26. Go back in thread:
Posted by SLS on January 24, 2023, at 14:41:52
In reply to Lithium biochemistry (low level mechanisms), posted by undopaminergic on January 24, 2023, at 11:50:25
> Here is an article on the low-level biochemistry of lithium. I'm mentioning it because it added something to my understanding. For example, most articles simply state that lithium inhibits GSK3 (an enzyme) -- this article elucidates *how* and *why*.
>
> "Free and Bound Therapeutic Lithium in Brain Signaling"
> https://pubmed.ncbi.nlm.nih.gov/31556294/
>
> Full article on Sci-Hub:
> https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/31556294/
>
> Note: no clinically applicable information.
>
> -undopaminergic
>This is a great article. I see you found Sci-Hub, too. It's a great resource.
This is just one more report of the plethora of biological activity that lithium exerts on the brain.
Aspirin for the brain?
- Scott
Posted by SLS on January 24, 2023, at 21:05:32
In reply to Lithium biochemistry (low level mechanisms), posted by undopaminergic on January 24, 2023, at 11:50:25
Hi, UD.
> Note: no clinically applicable information.
My concern with the posting behavior on PB isn't that all posts should be clinically applicable. My concern is that there aren't nearly enough. Pure neuroscience research is extraordinarily valuable, but more so for those who will come after us. Can someone use what they learn from research papers to design a treatment? Of, course they can. Unfortunately, this is uncommon.
Another thing that concerns me is that people obtain the right tools, but have no idea how to use them correctly.
This has been on my mind for awhile as a treatment for depression:
1. Wellbutrin
2. Nortriptyline (or another tricyclic)
3. Effexor (or Pristiq or Cymbalta)4. Low-Dosage Lithium ?
5. Lamictal? (Bipolar Depression) ?
This should be a killer combination according to my blackboard, but how does anyone know if it will work in real life? I don't know. I personally have never seen anyone use it, though. That's clinical. Clinical is more empirical than it is theoretical. Not only does a psychiatrist learn from his own track record, but he also learns from the track records of his buddies.Psychiatry is guess-work.
- Scott
Posted by Lamdage22 on January 25, 2023, at 2:15:42
In reply to Re: Lithium biochemistry (low level mechanisms) » undopaminergic, posted by SLS on January 24, 2023, at 21:05:32
Lithium is the new big thing on Psychobabble :)
Posted by undopaminergic on January 25, 2023, at 4:40:16
In reply to Re: Lithium biochemistry (low level mechanisms), posted by Lamdage22 on January 25, 2023, at 2:15:42
> Lithium is the new big thing on Psychobabble :)
I've been going through recent lithium review articles systematically.
-undopaminergic
Posted by undopaminergic on January 25, 2023, at 4:47:57
In reply to Re: Lithium biochemistry (low level mechanisms) » undopaminergic, posted by SLS on January 24, 2023, at 21:05:32
> Hi, UD.
Hi SLS.
> > Note: no clinically applicable information.
>
> My concern with the posting behavior on PB isn't that all posts should be clinically applicable. My concern is that there aren't nearly enough. Pure neuroscience research is extraordinarily valuable, but more so for those who will come after us. Can someone use what they learn from research papers to design a treatment? Of, course they can. Unfortunately, this is uncommon.
>I've always largely (perhaps excessively) allowed the theory to guide me, and that includes research articles. For example, I was interested in vortioxetine (which I'm on right now) because I had read it acts on serotonin 5-HT3 receptors, which was interesting to me because I had never tried anything else with an effect on those receptors.
> Not only does a psychiatrist learn from his own track record, but he also learns from the track records of his buddies.
>Yes.
> Psychiatry is guess-work.
Yes.
-undopaminergic
Posted by SLS on January 25, 2023, at 6:57:35
In reply to Re: Lithium biochemistry (low level mechanisms), posted by Lamdage22 on January 25, 2023, at 2:15:42
> Lithium is the new big thing on Psychobabble :)
Actually, that is sad. If I'm right about low-dosage lithium treatment, then thousands and thousands of opportunities have been wasted.30% of people with depression end up being treatment-resistant. That's huge. How many cases could have been successfully treated if low-dosage lithium had been added as an augmenter? I like to think that low-dosage lithium treatment will convert non-responders or inadequate-responders to responders. According to a paper I found, there is a bimodal dosage distribution between low-dosage versus high-dosage lithium. Low dosages of lithium increased the release of glutamate in the hippocampus, while high dosages decreased it. More recently,the hippocampus has been recognized as, not only the structure most associated with memory, but a it is also a contributor to the regulation of mood and emotions.
There isn't very much written about this. However, I remember an investigation performed 20 years ago by Harvard looking into the combination of fluoxetine and lithium wherein the dosage of lithium used was 300-600 mg/day. If I remember correctly, 450 mg/day was much more effective than 600 mg/day. I don't recall the relative effectiveness of 300 mg/day, but it was higher than placebo. For me, lithium 300 mg/day plays an integral role with my other three medications. When I increase the dosage from 300 mg/day to 450 mg/day, I relapse (big time). It only took three days after the discontinuation of lithium for me to deteriorate.
I am but n=1.
I represent only one clinical anecdote. However, considering the bimodal results of one neuroscientific study and the dosages used by Harvard in their clinical study, I am *somewhat* optimistic that a significant percentage of people with TRD will find that low-dosage lithium augmentation converts TRD to remission. That's what it did for me.
It's kind of a no-brainer to use low-dosage lithium. Lithium exerts an incredible number of actions in the brain. I consider low-dosage lithium to be sort of like aspirin for the brain. The danger of having thyroid and kidney damage at these low dosages is very, very small. These two side effects are dosage-dependent. The second argument for this no-brainer is that low dosages of lithium seems to reduce the risk of contracting Alzheimer's Disease. It might have utility in other neurodegerative brain diseases like Parkinson's Disease. That's why I decided to continue taking 300 mg/day of lithium for life. It is integral to the treatment that produced my remission. It was completely unexpected - and fortuitous. If a great number of people who have MDD or BD respond this way, it argues in favor of leaving lithium onboard in the background as one progresses through their drug trials.
- Scott
Posted by SLS on January 25, 2023, at 7:09:30
In reply to Re: Lithium biochemistry (low level mechanisms) » SLS, posted by undopaminergic on January 25, 2023, at 4:47:57
> > Hi, UD.
>
> Hi SLS.
>
> > > Note: no clinically applicable information.
> >
> > My concern with the posting behavior on PB isn't that all posts should be clinically applicable. My concern is that there aren't nearly enough. Pure neuroscience research is extraordinarily valuable, but more so for those who will come after us. Can someone use what they learn from research papers to design a treatment? Of, course they can. Unfortunately, this is uncommon.> I've always largely (perhaps excessively) allowed the theory to guide me, and that includes research articles. For example, I was interested in vortioxetine (which I'm on right now) because I had read it acts on serotonin 5-HT3 receptors, which was interesting to me because I had never tried anything else with an effect on those receptors.
Are you still taking vortioxetine?I think scientists had been focusing on the ability of vortioxetine to antagonize 5-HT7 receptors. However, the drug does so many different things, that it is sort of like throwing as much crap at the the serotoninergic wall (serotonergic receptors and SERT), that some of it is bound to stick.
> > Not only does a psychiatrist learn from his own track record, but he also learns from the track records of his buddies.> Yes.
> > Psychiatry is guess-work.
> Yes.
>
> -undopaminergicI hope that your incorporation of pure research to your treatment strategies yields a robust response. The combining of MAOI with TCA was also based to a great degree on the basic research performed in the late 1970s and 1980s.
Whatever works.
- Scott
Posted by SLS on January 25, 2023, at 7:28:27
In reply to Re: Lithium biochemistry (low level mechanisms) » undopaminergic, posted by SLS on January 25, 2023, at 7:09:30
Incorporating pure research into treatment design is especially valuable when nothing tried previously was effective. It can increase one's probability to succeed.
If the first drug you tried worked, how would you have spent your spare time over the years? Had you been studying adenylate cyclase and second messenger cascades, would it have helped you choose the right treatment? I wouldn't have. I would have preferred to be ignorant of neur1oscience rather than having a need to study it.
For me, remission was essential to my survival financially and satisfaction with the rewards life has offered me.
Obviously, the key to success in treatment-resistant affective disorders is to strike a balance between the empirical and the theoretical. There just aren't enough posts devoted to clinical (empirical) research - What works without giving much consideration to how it works.
Whatever works.
- Scott
Posted by undopaminergic on January 25, 2023, at 8:26:49
In reply to Re: Lithium biochemistry (low level mechanisms) » undopaminergic, posted by SLS on January 25, 2023, at 7:09:30
>
> > I've always largely (perhaps excessively) allowed the theory to guide me, and that includes research articles. For example, I was interested in vortioxetine (which I'm on right now) because I had read it acts on serotonin 5-HT3 receptors, which was interesting to me because I had never tried anything else with an effect on those receptors.
>
>
> Are you still taking vortioxetine?Yes (I mentioned above that I'm on it right now).
> I think scientists had been focusing on the ability of vortioxetine to antagonize 5-HT7 receptors.
>I was excited about that receptor, until I tried lurasidone, which turned out not to do much, if anything.
> However, the drug does so many different things, that it is sort of like throwing as much crap at the the serotoninergic wall (serotonergic receptors and SERT), that some of it is bound to stick.
>Yes. The agonism at serotonin 5-HT1A is interesting too. It's my understanding that vortioxetine has a more "full" agonism than most other agents active at this receptor.
Apparently, the actions at all these receptors allows vortioxetine to work at lower levels of serotonin transporter (SERT) occupancy than other SERT inhibitors.
-undopaminergic
Posted by Lamdage22 on January 25, 2023, at 9:09:52
In reply to Re: Lithium biochemistry (low level mechanisms) » SLS, posted by undopaminergic on January 25, 2023, at 8:26:49
'Lithium in drinking water' is an interesting google search. My main motivation was decreasing suicidal thoughts and it did. It didn't evaporate them but tuned them down I'd say 70%. The remaining percentiles went away through other means. My suicidality is almost nonexistant these days. I have better coping skills than that.
Posted by SLS on January 25, 2023, at 9:51:36
In reply to Re: Lithium biochemistry (low level mechanisms), posted by Lamdage22 on January 25, 2023, at 9:09:52
> 'Lithium in drinking water' is an interesting google search. My main motivation was decreasing suicidal thoughts and it did. It didn't evaporate them but tuned them down I'd say 70%. The remaining percentiles went away through other means.
> My suicidality is almost nonexistant these days. I have better coping skills than that.
Excellent.
- Scott
Posted by undopaminergic on January 25, 2023, at 10:40:38
In reply to Re: Lithium biochemistry (low level mechanisms) » Lamdage22, posted by SLS on January 25, 2023, at 6:57:35
>
> According to a paper I found, there is a bimodal dosage distribution between low-dosage versus high-dosage lithium. Low dosages of lithium increased the release of glutamate in the hippocampus, while high dosages decreased it.
>Sounds a lot like the article I posted about at:
https://www.dr-bob.org/babble/20220917/msgs/1121444.htmlAccording to that, the reverse is true about hippocampal glutamate levels. In other words, lower lithium doses are associated with a reduction, and higher doses with an increase.
-undopaminergic
Posted by SLS on January 25, 2023, at 11:30:23
In reply to Re: Lithium biochemistry (low level mechanisms) » SLS, posted by undopaminergic on January 25, 2023, at 10:40:38
> >
> > According to a paper I found, there is a bimodal dosage distribution between low-dosage versus high-dosage lithium. Low dosages of lithium increased the release of glutamate in the hippocampus, while high dosages decreased it.
> >
>
> Sounds a lot like the article I posted about at:
> https://www.dr-bob.org/babble/20220917/msgs/1121444.html
>
> According to that, the reverse is true about hippocampal glutamate levels. In other words, lower lithium doses are associated with a reduction, and higher doses with an increase.
>
> -undopaminergic
>This certainly needs more investigation. Obviously, it is important to know the relationship between glutamate levels and mood.
- Scott
Posted by undopaminergic on January 25, 2023, at 12:24:00
In reply to Re: Lithium biochemistry (low level mechanisms) » undopaminergic, posted by SLS on January 25, 2023, at 11:30:23
> > >
> > > According to a paper I found, there is a bimodal dosage distribution between low-dosage versus high-dosage lithium. Low dosages of lithium increased the release of glutamate in the hippocampus, while high dosages decreased it.
> > >
> >
> > Sounds a lot like the article I posted about at:
> > https://www.dr-bob.org/babble/20220917/msgs/1121444.html
> >
> > According to that, the reverse is true about hippocampal glutamate levels. In other words, lower lithium doses are associated with a reduction, and higher doses with an increase.
> >
> > -undopaminergic
> >
>
> This certainly needs more investigation. Obviously, it is important to know the relationship between glutamate levels and mood.
>
>
> - ScottThe article did not find a correlation between the glutamate levels and depressive status. I think some people benefit from a reduction and others from an increase. Or, (rarely?) the current level may be ideal.
-undopaminergic
Posted by Lamdage22 on January 25, 2023, at 22:10:46
In reply to Re: Lithium biochemistry (low level mechanisms) » Lamdage22, posted by SLS on January 25, 2023, at 6:57:35
> > Lithium is the new big thing on Psychobabble :)
>
>
> Actually, that is sad. If I'm right about low-dosage lithium treatment, then thousands and thousands of opportunities have been wasted.An awful lot of peoples lives are wasted. Living in totalitarian states, human trafficking for sex or slave labor, abuse, neglect. Extreme poverty. Billions.
Posted by Lamdage22 on January 25, 2023, at 22:14:08
In reply to Re: Lithium biochemistry (low level mechanisms), posted by Lamdage22 on January 25, 2023, at 22:10:46
> > > Lithium is the new big thing on Psychobabble :)
> >
> >
> > Actually, that is sad. If I'm right about low-dosage lithium treatment, then thousands and thousands of opportunities have been wasted.
>
> An awful lot of peoples lives are wasted. Living in totalitarian states, human trafficking for sex or slave labor, abuse, neglect. Extreme poverty. Billions.And war of course.
Posted by SLS on January 26, 2023, at 8:58:54
In reply to Re: Lithium biochemistry (low level mechanisms) » SLS, posted by undopaminergic on January 25, 2023, at 12:24:00
Hi, UD.
> The article did not find a correlation between the glutamate levels and depressive status. I think some people benefit from a reduction and others from an increase.
I think you mentioned this once before.
I hate when that happens. With the brain, there are many seemingly contrary or paradoxical observations, interpretations, and theories.
Are there any data indicating what low vs high glutamate levels indicate with respect to mood?
- Scott
Posted by SLS on January 26, 2023, at 9:03:16
In reply to Re: Lithium biochemistry (low level mechanisms), posted by Lamdage22 on January 25, 2023, at 22:10:46
> > > Lithium is the new big thing on Psychobabble :)
> >
> >
> > Actually, that is sad. If I'm right about low-dosage lithium treatment, then thousands and thousands of opportunities have been wasted.
>
> An awful lot of peoples lives are wasted. Living in totalitarian states, human trafficking for sex or slave labor, abuse, neglect. Extreme poverty. Billions.
>That's heavy duty - and you are right. I don't hesitate for milisecond acknowledging my being fortunate and blessed to live in the United States of America.
- Scott
Posted by undopaminergic on January 26, 2023, at 9:09:50
In reply to Re: Lithium biochemistry (low level mechanisms) » undopaminergic, posted by SLS on January 26, 2023, at 8:58:54
> Hi, UD.
Hi SLS.
>
> Are there any data indicating what low vs high glutamate levels indicate with respect to mood?
>Glutamate where? Hippocampus? Nucleus accumbens? Glutamate is the brain's predominant excitatory neurotransmitter, with many receptor subtypes. Global elevations or reductions will probably improve some functions and worsen others. But blocking NMDA-subtype receptors seems to ameliorate depression, at least judging from the effects of ketamine.
-undopaminergic
Posted by SLS on January 28, 2023, at 19:11:10
In reply to Re: Lithium biochemistry (low level mechanisms) » Lamdage22, posted by SLS on January 25, 2023, at 9:51:36
> > 'Lithium in drinking water' is an interesting google search. My main motivation was decreasing suicidal thoughts and it did. It didn't evaporate them but tuned them down I'd say 70%. The remaining percentiles went away through other means.
>
> > My suicidality is almost nonexistant these days. I have better coping skills than that.
>
> Excellent.
>
>
> - Scott
I forgot to mention that the idea that the tiny amount of lithium found in the drinking water of certain cities prevents Alzheimer's Disease was debunked, even though medicinal lithium does.
- Scott
Posted by Lamdage22 on January 29, 2023, at 13:10:12
In reply to Re: Lithium biochemistry (low level mechanisms), posted by SLS on January 28, 2023, at 19:11:10
> > > 'Lithium in drinking water' is an interesting google search. My main motivation was decreasing suicidal thoughts and it did. It didn't evaporate them but tuned them down I'd say 70%. The remaining percentiles went away through other means.
> >
> > > My suicidality is almost nonexistant these days. I have better coping skills than that.
> >
> > Excellent.
> >
> >
> > - Scott
>
>
> I forgot to mention that the idea that the tiny amount of lithium found in the drinking water of certain cities prevents Alzheimer's Disease was debunked, even though medicinal lithium does.
>
>
> - ScottWhat about alleviating harmful tendencies to self and/or others?
Posted by SLS on January 29, 2023, at 13:34:09
In reply to Re: Lithium biochemistry (low level mechanisms), posted by Lamdage22 on January 29, 2023, at 13:10:12
> > > > 'Lithium in drinking water' is an interesting google search. My main motivation was decreasing suicidal thoughts and it did. It didn't evaporate them but tuned them down I'd say 70%. The remaining percentiles went away through other means.
> > >
> > > > My suicidality is almost nonexistant these days. I have better coping skills than that.
> > >
> > > Excellent.
> > >
> > >
> > > - Scott
> >
> >
> > I forgot to mention that the idea that the tiny amount of lithium found in the drinking water of certain cities prevents Alzheimer's Disease was debunked, even though medicinal lithium does.
> >
> >
> > - Scott
>
> What about alleviating harmful tendencies to self and/or others?
I don't think the anti-suicide property of lithium occurs at the low concentrations found in drinking water. However, I never looked for such a study.
- Scott
Posted by undopaminergic on January 30, 2023, at 7:06:48
In reply to Re: Lithium biochemistry (low level mechanisms) » Lamdage22, posted by SLS on January 29, 2023, at 13:34:09
> > >
> > > I forgot to mention that the idea that the tiny amount of lithium found in the drinking water of certain cities prevents Alzheimer's Disease was debunked, even though medicinal lithium does.
> > >
> > >
> > > - Scott
> >
> > What about alleviating harmful tendencies to self and/or others?
>
>
> I don't think the anti-suicide property of lithium occurs at the low concentrations found in drinking water. However, I never looked for such a study.
>I've heard a lot about the studies that found that higher levels of lithium in the drinking water correlated with fewer suicides and homicides.
-undopaminergic
Posted by SLS on January 30, 2023, at 16:05:07
In reply to Re: Lithium biochemistry (low level mechanisms), posted by undopaminergic on January 30, 2023, at 7:06:48
> > > >
> > > > I forgot to mention that the idea that the tiny amount of lithium found in the drinking water of certain cities prevents Alzheimer's Disease was debunked, even though medicinal lithium does.
> > > >
> > > >
> > > > - Scott
> > >
> > > What about alleviating harmful tendencies to self and/or others?
> >
> >
> > I don't think the anti-suicide property of lithium occurs at the low concentrations found in drinking water. However, I never looked for such a study.
> >
>
> I've heard a lot about the studies that found that higher levels of lithium in the drinking water correlated with fewer suicides and homicides.
>
> -undopaminergic
>
Those reports are bogus according to follow-up investigations.
- Scott
Posted by Lamdage22 on February 4, 2023, at 4:32:08
In reply to Re: Lithium biochemistry (low level mechanisms), posted by SLS on January 30, 2023, at 16:05:07
> > > > >
> > > > > I forgot to mention that the idea that the tiny amount of lithium found in the drinking water of certain cities prevents Alzheimer's Disease was debunked, even though medicinal lithium does.
> > > > >
> > > > >
> > > > > - Scott
> > > >
> > > > What about alleviating harmful tendencies to self and/or others?
> > >
> > >
> > > I don't think the anti-suicide property of lithium occurs at the low concentrations found in drinking water. However, I never looked for such a study.
> > >
> >
> > I've heard a lot about the studies that found that higher levels of lithium in the drinking water correlated with fewer suicides and homicides.
> >
> > -undopaminergic
> >
>
>
> Those reports are bogus according to follow-up investigations.
>
>
> - ScottOr the follow up investigations are bogus.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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