26 replies to this topic

[Mind_Paralysis]

Yeee-ee-eess!

 

I have in recent days come to the conclusion (after atomoxetine finally reached an effective dose-level and started bringing me out of the stupor it's put me in) that I simply cannot ignore any potential bipolar symptoms I may show: these must be acted upon and DEFEATED! I cannot close my eyes to them, if, the planned screening actually ends up diagnosing me with the disease.

 

As such, I was drawn to Lithium this evening, as it's considered the MOST EFFECTIVE compound there is, when it comes to the treatment of BD. However, it also, sadly, has some of the most severe and DEADLY side-effects of all of the treatments! This is some serious stuff, lads...

 

So, this got me thinking - do we know enough about Lithium's MOA to be able to create a specific Bipolar Disorder -stack? What compounds are bound to span all of the effects of Lithium but in a better, more selective, less side-effects prone manor?

 

With the help of this nifty little study I noted that we actually know a LOT more about Lithium's effects these days! So, now it might actually be possible to build a stack here...

 

Failing stacking, what else could one create, stacks-wise, to ERADICATE any and all side-effects of Lithium? And then there's the question of creating NEW lithium-compounds - Lithium-Orotate has long been noted to be more effective at lower dosages than the traditional formulations - but what about something like Lithium-L-THREONATE? Could not LiLT be far more effective even, since Threonate passes the blood-brain barrier??

 

Exciting stuff! : D

 

 

These are the reported and confirmed effects of Lithium, which may be needed to result from the stack as well:

 

 

1. Neurogenesis (preferrably in the prefrontal cortex, hippocampus and amygdala)

2. Reduce neuronal oxidative stress

3. Upregulation of BDNF

4. Anti-apoptotic effects (delay cell-death, in the brain, lithium does this through modulation of Bcl-2 and inhibition of GSK-3)

 

5. Reduce dopamine and glutamate activity

6. Increase GABA-activity

7. Downregulation of Adenyl Cyclase (this may be problematic, discuss and suggest)

8. Downregulation of protein kinase C (this may be problematic, discuss and suggest)

 

9. Uncompetitive inhibition of inositol monophosphatase

 

 

 

Anyways, here's my suggestion for a new Lithium-replacement-stack:

 

Omega-3 EPA (high dose - 3 grams perhaps?)
HIOC

https://en.wikipedia.org/wiki/HIOC

 

NAS (n-acetylserotoning, may be used instead, but is most likely only suggested if the subject has HIGH blood-pressure)

https://en.wikipedia...Acetylserotonin

 

Diosmetin (another TrkB-agonist - would need a HIGH dose! It's quite weak. Does our friend GamesGuru know more about this one?)
https://en.wikipedia.../wiki/Diosmetin

 

Dihydrokavain (regular Kavain is more studied, but dihydrokavain seems to be more responsible for GABA-A-upregulation. once again, our friend gamesguru is needed for consultation)

https://en.wikipedia...i/Dihydrokavain

http://www.longecity...r-upregulation/

 

NAC

Ibudilast

Montelukast (this may be overkill, combining all three, AND Omega-3 EPA...! But, we need multiple modes here)

 

Memantine (10 mg)

 

 

Phew! I'm still missing several MOA's, there's definitely more that needs to be added to get the FULL effects of Lithium, without taking lithium, but this might be a possible first start... What do you think, ladies and gentlemen? At what doses should some of these compounds be used? Which ones would interfere with each other? And which ones would give unacceptable side-effects?

Remember, folks, we want to create something which is equally effective as Lithium, but SAFER!

 

 

 

References:

------------------

Potential Mechanisms of Action of Lithium in Bipolar Disorder

http://link.springer...0263-013-0039-0

 

Molecular mechanisms in lithium-associated renal disease: a systematic review

http://link.springer...1255-016-1352-6

 

 

Pharmacologic implications of inflammatory comorbidity in bipolar disorder.

https://www.ncbi.nlm...pubmed/27400335

Edited by Stinkorninjor, 21 January 2017 - 05:32 PM.

[PeaceAndProsperity]

Why not use the bioavailable lithiums that are not toxic like the patented version is?

Also, neurogenesis of the prefrontal cortex - is that even possible? I thought only specific parts of the brain were capable of post-natal growth.

 

[Mind_Paralysis]

Why not use the bioavailable lithiums that are not toxic like the patented version is?

Also, neurogenesis of the prefrontal cortex - is that even possible? I thought only specific parts of the brain were capable of post-natal growth.

It should be noted that those versions are also toxic, it's just that they become toxic at much higher effective dosages - meaning that they might never become toxic at therapeutic effects, however one never knows if one is sensitive. (just a small note)

 

However, on the topic - what do you think about creating a NEW bio-available compound? By enhancing blood-brain-barrier penetration, the side-effects should be possible to diminish even further!

 

I wonder... can Lithium be bound to L-Threonate? In theory it should be a simple process...?

[jack black]

there is nothing wrong with Li in small doses (unless one has hypothyroidism). the typical dose used by psychiatrists is 600-1200mg Li2CO3 (requires blood levels monitoring). Many people report results in small doses many times lower that those.

Edited by jack black, 21 January 2017 - 11:03 PM.

[PeaceAndProsperity]

I took lithium orotate 5mg to 10mg for at least a whole month and I felt extremely awful, like the worst ocd and sleeping issues and such that you could imagine. I was stuck doing the same repetitious behaviors endlessly and I was seriously contemplating suicide because I felt so awful, plus my anhedonia/blunted affect got ten times worse. 

I too have sleeping issues with at least one month each year where I sleep too much and another month where I sleep too little, but mostly it's sleeping too little, and I too wanted to test whether I might be bipolar. 

I have to say that the lithium does work really well for mood stabilization even at those dosages because I was completely careless about pretty much everything in life and insults didn't do a thing to me at all. 

[Mind_Paralysis]

there is nothing wrong with Li in small doses (unless one has hypothyroidism). the typical dose used by psychiatrists is 600-1200mg Li2CO3 (requires blood levels monitoring). Many people report results in small doses many times lower than those.

 

I've heard about this as well - but isn't the current dosages of Lithium-compounds rigorously tested, through placebo and such? Surely there must to be a reason that they use more often up to a GRAM worth of Lithium...!

 

Has this phenomenon with the efficacy of lower dosages of Lithium actually been properly studied? I've always figured they were simply therapeutic outliers, special cases whom are extra sensitive to the effects of Lithium.

 

 

I know Lithium Orotate -users generally report results from low dosages, but in that case there's a clear reason for it - Li-Orotate has in theory up to 30 times better bioavailability (some would say it's only 8 times higher, but still...!) - enabling efficacy from lower dosages.

 

Here in Scandinavia they use Lithium Sulphate in general, seemingly slowly phasing out Lithium Carbonate, Benzoate, Chloride and even Citrate.

Not sure why they're doing this...

 

Lithium Citrate seems like the logical compound to keep - since other metal chelations with citrate in general have better bio-availability than the other, inorganic compounds.

 

 

Btw, your note got me checking out comparisons between Lithium compounds, and in so doing, I found something unexpected... EBSELEN! A complex form of selenium-chelate, an entire molecule which uses Selenium as part of its structure - it's rather interesting, seems to be in trial for the treatment of Bipolar Disorder at the moment - and the results are promising so far... The side-effects-profile is completely superior to Lithium as well! : D

 

https://en.wikipedia.org/wiki/Ebselen

 

Human trials suggest ‘rescued’ drug could be safer treatment for bipolar disorder

http://www.ox.ac.uk/...ipolar-disorder

 

 

It's probably hard to get a hold of though, and I need to find more info on it - is the efficacy really there?

 

I also just noticed a very, very serious side-effect of Ebselen (well, for ME!) - it decreases Slow-Wave Sleep... : [

 

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans

http://www.nature.co...pp2015343a.html

[jack black]

Could someone tell why one can't quote the original post here (quote button missing)?

 

anyhow, RE:

 

 

9. Uncompetitive inhibition of inositol monophosphatase

 

this part always gave me a pause, as a lot of people find inositol helpful (i did, but only short term).

i tried low dose Li orotate (5-10mg elemental Li) a few times, and was not sure if any effects. i actually have access to Li carbonate, so i may try medium doses (150-300 mg, 25-50mg elemental Li) and see what happens.

 

Stinkorninjor, if you find a source of that EBSELEN, let us know. Selenium should be beneficial for thyroid, so this could be a great solution for people not able to take Li due to thyroid problems.

Edited by jack black, 22 January 2017 - 03:16 PM.

[PeaceAndProsperity]

Interesting. If lithium decreases inositol, and inositol reduces function of the 5HT2A receptor, that may perfectly well explain why I had so insanely bad ocd, irritability and so on and so forth, when using lithium orotate, while inositol does the opposite to me.

[pecanpie]

I love Lithium. I take 900mg of the carbonate and it's great. I want to take more. It potentiates other drugs and turns up the volume on antidepressants IME.

Very common to give a TRD patient low dose lithium 300-600mg.

Thyroid is shot anyway, Hashimoto's plus a couple tumors. I'm on T3/T4 already so that's not an issue.


What might be an issue is sublingual daily low dose ketamine with Lithium long term. High dose lithium in the long term wreaks havoc on your kidneys and ketamine is not nephrofriendly either. Just thinking out loud here I need to find a good kidney and UT flush
Cranberry juice?

Edited by pecanpie, 24 January 2017 - 01:01 AM.

[Lia-chan]

I'm also suspicious that I might have BP, but it seems, that my terrible mood swings have a more common with BPD (Because they are VERY severe and suicidal), rather than BP, I've tried lamotrigine several times and it greatly helped me to control myself, but it seems that, as the time pass by I become more lazier while taking 150 mg of Lamotrigine. After a while I've started to think that the only option is to try ketamine and it worked wonderfull, but I still have severe troubles with relationships as usual for someone with BPD. Also, it toke almost a month for ATX to stabilize in my case, it's also helps me a lot to stay on track, while I do any kind of work. So let's return to the main problem... Can lithium cause severe cognition problems or blunt emotions so severly as lamotrigine? I'm very anticipated to try it!

[Finn]

Why not use the bioavailable lithiums that are not toxic like the patented version is?

Also, neurogenesis of the prefrontal cortex - is that even possible? I thought only specific parts of the brain were capable of post-natal growth.

 

https://www.ncbi.nlm...les/PMC2693231/

 

Prefrontal Gray Matter Increases in Healthy Individuals after Lithium Treatment: a Voxel-Based Morphometry Study

 

Healthy right handed volunteers. Left and right DLPFC and left ACC gray matter volumes increased significantly following 4-week lithium administration.

 

Interestingly, in inattentive ADHD it is theorized that that  DLPFC issues are responsible for" sustainable attention, problem solving" issues and dorsal ACC issues are responsible for "selective attention" issues. 

 

https://www.research...man_grey_matter

 

This one was also 4 week trial, though on bipolar patients

 

Lithium-induced increase in human brain grey matter

 

Drevets and colleagues have shown that a specific region in the frontal lobe grey-matter identified as the subgenual prefrontal cortex (region sg24) was significantly smaller (about 40%) in patients with bipolar disorder than in matched controls. In view of the effects of lithium and  valproate on bcl-2 concentrations in the frontal cortex, the investigators reanalysed the imaging data. Patients treated with lithium or valproate had significantly higher subgenual prefrontal cortex volumes than non-treated patients, but volumes were not significantly different from controls.

 

 

Edited by Finn, 25 January 2017 - 08:11 AM.

[Mind_Paralysis]

 

Why not use the bioavailable lithiums that are not toxic like the patented version is?

Also, neurogenesis of the prefrontal cortex - is that even possible? I thought only specific parts of the brain were capable of post-natal growth.

 

https://www.ncbi.nlm...les/PMC2693231/

 

Prefrontal Gray Matter Increases in Healthy Individuals after Lithium Treatment: a Voxel-Based Morphometry Study

 

Healthy right handed volunteers. Left and right DLPFC and left ACC gray matter volumes increased significantly following 4-week lithium administration.

 

Interestingly, in inattentive ADHD it is theorized that that  DLPFC issues are responsible for" sustainable attention, problem solving" issues and dorsal ACC issues are responsible for "selective attention" issues. 

 

https://www.research...man_grey_matter

 

This one was also 4 week trial, though on bipolar patients

 

Lithium-induced increase in human brain grey matter

 

Drevets and colleagues have shown that a specific region in the frontal lobe grey-matter identified as the subgenual prefrontal cortex (region sg24) was significantly smaller (about 40%) in patients with bipolar disorder than in matched controls. In view of the effects of lithium and  valproate on bcl-2 concentrations in the frontal cortex, the investigators reanalysed the imaging data. Patients treated with lithium or valproate had significantly higher subgenual prefrontal cortex volumes than non-treated patients, but volumes were not significantly different from controls.

 

 

You bring up an interesting point here! Namely, that of the bio-markers of Bipolar Disorder - is there somewhere wherein one can actually find the known and accepted neural imaging bio-marker parameters for Bipolar Disorder?

 

That could seriously be useful info, for those of us whom are being examined for the disease - that would be some legitimate PROOF of neurological abnormalities that need a plausible explanation - and, if the symptoms are similar, then that explanation is of course going to be Bipolar Disorder.

 

 

Btw, I had a Dr.'s appointment yesterday, I presented my recent BSDS and MDQ results to her and she came to a different conclusion than my previous Dr, namely that I probably don't have the disease - the evidence are more or less inconclusive, so she wants to hold off on any diagnosis until she has seen my reactions to antidepressants and stimulating compounds.

 

She was also actually familiar with Tianeptine! She has a background practising in another European country, where the drug is approved, and finds it to be a GREAT antidepressant! Needless to say, I was rather excited when she said she would try and get it prescribed through import-prescription for me.

 

She's also transferring me to the ADHD-department once more, and I might be getting back on Atomoxetine (legitimately) soon.
 

 

Small note on the abnormalities in ADHD-PI btw, even though that may be correct, you have to remember that the data may not be relevant to SCT, seeing as the newest data points towards the posterior networks, and in particular the Right Superior Parietal Lobe being the source of many of the symptoms - this is in line with the disease being one of norepinephrine, and not of Dopamine.

 

I think I recall some believing the ACC in ADHD isn't involved with attention btw, but rather, it's involved with the faulty emotional control whom some with the disease suffer from? I.E the patients with ADHD whom also qualify, or almost qualify, for a diagnosis of BORDERLINE PERSONALITY DISORDER as well. Professor Pedrag Petrovic has written some about this, and I believe Russell Barklay as well - Petrovic is the one specializing in it though, and who wants to create a new sub-group of ADHD: ADHD-PE -  of Predominantly Emotional Dysfunction.

 

The ACC -abnormalities may be one of the reasons why some of the more dysphoric and emotional patients with ADHD gravitate towards Cannabis-abuse btw - since THC works as a blunter of emotional pain by overloading the cannabinoid-receptors in the ACC, causing a flattening of affect.

 

And finally, neurogenesis in sections of the ADHD-brain showing atrophy may not actually amount to much of an effect on the core symptoms, since the general accepted view is that ADHD isn't a neuro-degenerative disease like Depression, but more one of already faulty neural circuits - more of the same broken machinery won't actually be able to work any better.

 

Still, it might improve some other areas of cognition.

[Mind_Paralysis]

I'm also suspicious that I might have BP, but it seems, that my terrible mood swings have a more common with BPD (Because they are VERY severe and suicidal), rather than BP, I've tried lamotrigine several times and it greatly helped me to control myself, but it seems that, as the time pass by I become more lazier while taking 150 mg of Lamotrigine. After a while I've started to think that the only option is to try ketamine and it worked wonderfull, but I still have severe troubles with relationships as usual for someone with BPD. Also, it toke almost a month for ATX to stabilize in my case, it's also helps me a lot to stay on track, while I do any kind of work. So let's return to the main problem... Can lithium cause severe cognition problems or blunt emotions so severly as lamotrigine? I'm very anticipated to try it!

 

Ketamine holds promise here, but I'm sad to say that regular ketamine cannot stabilize emotional tone as much as some of the metabolites.

 

The king of emotional control should be DeHydroNorKetamine - DHNK, which acts as a potent, selective Nicotinic Alpha-7-receptor antagonist.

 

https://en.wikipedia...ydronorketamine

 

 

If you can find some HydroxyNorKetamine - HNK, then that may work as well, since that has Alpha-7-dampening effects too. (it's of course also known as the most antidepressantly potent of all ketamine-variants, as well)

 

HNK was recently, supposedly, synthesized in a GROUP BUY, so it might actually finally be available through some channels.

 

Check out this thread and see if you can get a hold of some of the participants:

 

 

http://www.longecity...for-depression/

 

 

They might be interested in selling you some of their left-over stash.

[PeaceAndProsperity]

I have this theory and observation that female psychiatrists are more likely to diagnose their patients irregardless of their gender as female-typical diseases like borderline, bipolar, histrionic, etc. If I were you I'd be careful about their conclusions when it comes to these affective diseases.

[Mind_Paralysis]

I have this theory and observation that female psychiatrists are more likely to diagnose their patients irregardless of their gender as female-typical diseases like borderline, bipolar, histrionic, etc. If I were you I'd be careful about their conclusions when it comes to these affective diseases.

I don't know about that, I'm guessing I might have been more emotionally unstable because of my previous use of NSI-189 and Tianeptine earlier, hence why they started thinking about some kind of atypical Bipolar.

 

I was actually diagnosed as ADHD-PI by a female psychologist you see - we had a fairly good understanding that this was the correct diagnosis for my particular issues.

[Finn]

 

there is nothing wrong with Li in small doses (unless one has hypothyroidism). the typical dose used by psychiatrists is 600-1200mg Li2CO3 (requires blood levels monitoring). Many people report results in small doses many times lower than those.

 

I've heard about this as well - but isn't the current dosages of Lithium-compounds rigorously tested, through placebo and such? Surely there must to be a reason that they use more often up to a GRAM worth of Lithium...!

 

Has this phenomenon with the efficacy of lower dosages of Lithium actually been properly studied? I've always figured they were simply therapeutic outliers, special cases whom are extra sensitive to the effects of Lithium.

 

 

I'd say it is rigorously tested mostly just for BP-I and most severe forms of BP-II. Since it is so old drug, patents pretty much expired before rise of "milder" forms of BP, so there hasn't been much of an incentive to do further studies.  For example, one might think people suffering of cyclothymic disorder/cyclothymia might benefit from some little extra mood stability, yet I couldn't find a single paper of using lithium on that. Those few hits on google scholar looking promising, were citation translation titles of really old, originally German or French articles, which probably were of bipolar disorder anyway, not cyclothymia or cyclothymic disorder, since at one point cyclothymia was commonly used as a synonym for bipolar disorder in some countries. 

 

You're not classic BP-I. SSRI+methylphenidate, which apparently is the ultimate combo to send a BP-II or BP NOS with "great" cycling potential on Tour de France, didn't screw you up.

 

While thesis "people with "milder" bipolar spectrum disorders can get enough mood stabilization from smaller doses of lithium" hasn't been scientifically proven, it hasn't been scientifically disproved either. I think it would be logical to test this first, before trying to get "normal lithium dose"-like effects from some new, untested combination of drugs.

 

There has been some studies of even smaller lithium doses on some other conditions. 

 

 

https://www.research...eimer's_Disease

 

Microdose Lithium Treatment Stabilized Cognitive Impairment in  Patients with Alzheimer’s Disease 

 

The dose was 300 μg = 0.3 mg of elemental lithium, given as lithium carbonate (1.6 mg of lithium carbonate) or gluconate. The usual 300 mg lithium carbonate tablet contains 56 mg of elemental lithium, and bipolar I patients typically take 2-6 of those tablets.

 

 

 

This study used 0.4 mg elemental dose.

 

http://link.springer...2916824?LI=true

 

 

Effects of nutritional lithium supplementation on mood

 

Group A received 400 μg/d of lithium orally, in tablets composed of a naturally lithium-rich brewer's yeast, for 4 wk.  Group B was given normal, lithium-free brewer's yeast as a placebo.  

 

In Group A, the scores increased consistently for all subcategories until wk 4 and remained essentially the same in wk 5. In Group B, the combined mood test scores showed no consistent changes during the same period. 

 

 

So  mega doses are not always needed for therapeutic effects, it might be needed for BP type 1 monotherapy in most cases, but maybe not for other conditions. 

 

 

http://www.psychiatr...ium-and-thyroid

 

It is widely known that patients receiving lithium therapy commonly develop hypothyroidism. Johnston and Eagles (1999) found hypothyroidism in 10.4% of 718 patients treated with lithium. Women suffered a higher risk of developing hypothyroidism within two years of therapy, compared to the general population of the geographical area studied. Hypothyroidism occurred in 14% of women, significantly more frequently than in men (4.5%),

 

 

 So with men, even at classic dosages the hypothyroidism is that low when compared to women, with non-classic, smaller doses it should be much lower.

 

Edited by Finn, 28 January 2017 - 10:04 PM.

[Mind_Paralysis]

 

 

there is nothing wrong with Li in small doses (unless one has hypothyroidism). the typical dose used by psychiatrists is 600-1200mg Li2CO3 (requires blood levels monitoring). Many people report results in small doses many times lower than those.

 

I've heard about this as well - but isn't the current dosages of Lithium-compounds rigorously tested, through placebo and such? Surely there must to be a reason that they use more often up to a GRAM worth of Lithium...!

 

Has this phenomenon with the efficacy of lower dosages of Lithium actually been properly studied? I've always figured they were simply therapeutic outliers, special cases whom are extra sensitive to the effects of Lithium.

 

 

I'd say it is rigorously tested mostly just for BP-I and most severe forms of BP-II. Since it is so old drug, patents pretty much expired before rise of "milder" forms of BP, so there hasn't been much of an incentive to do further studies.  For example, one might think people suffering of cyclothymic disorder/cyclothymia might benefit from some little extra mood stability, yet I couldn't find a single paper of using lithium on that. Those few hits on google scholar looking promising, were citation translation titles of really old, originally German or French articles, which probably were of bipolar disorder anyway, not cyclothymia or cyclothymic disorder, since at one point cyclothymia was commonly used as a synonym for bipolar disorder in some countries. 

 

You're not classic BP-I. SSRI+methylphenidate, which apparently is the ultimate combo to send a BP-II or BP NOS with "great" cycling potential on Tour de France, didn't screw you up.

 

While thesis "people with "milder" bipolar spectrum disorders can get enough mood stabilization from smaller doses of lithium" hasn't been scientifically proven, it hasn't been scientifically disproved either. I think it would be logical to test this first, before trying to get "normal lithium dose"-like effects from some new, untested combination of drugs.

 

There has been some studies of even smaller lithium doses on some other conditions. 

 

 

https://www.research...eimer's_Disease

 

Microdose Lithium Treatment Stabilized Cognitive Impairment in  Patients with Alzheimer’s Disease 

 

The dose was 300 μg = 0.3 mg of elemental lithium, given as lithium carbonate (1.6 mg of lithium carbonate) or gluconate. The usual 300 mg lithium carbonate tablet contains 56 mg of elemental lithium, and bipolar I patients typically take 2-6 of those tablets.

 

 

 

This study used 0.4 mg elemental dose.

 

http://link.springer...2916824?LI=true

 

 

Effects of nutritional lithium supplementation on mood

 

Group A received 400 μg/d of lithium orally, in tablets composed of a naturally lithium-rich brewer's yeast, for 4 wk.  Group B was given normal, lithium-free brewer's yeast as a placebo.  

 

In Group A, the scores increased consistently for all subcategories until wk 4 and remained essentially the same in wk 5. In Group B, the combined mood test scores showed no consistent changes during the same period. 

 

 

So  mega doses are not always needed for therapeutic effects, it might be needed for BP type 1 monotherapy in most cases, but maybe not for other conditions. 

 

 

http://www.psychiatr...ium-and-thyroid

 

It is widely known that patients receiving lithium therapy commonly develop hypothyroidism. Johnston and Eagles (1999) found hypothyroidism in 10.4% of 718 patients treated with lithium. Women suffered a higher risk of developing hypothyroidism within two years of therapy, compared to the general population of the geographical area studied. Hypothyroidism occurred in 14% of women, significantly more frequently than in men (4.5%),

 

 

 So with men, even at classic dosages the hypothyroidism is that low when compared to women, with non-classic, smaller doses it should be much lower.

 

 

Thank you for the references, they have certainly helped me to de-dramatize the narrative regarding Lithium.

 

I'm not entirely convinced of trying Lithium just yet though, mainly because the Bipolar NOS evaluation is more or less off, the new Chief Doctor at my unit reviewed my BSDS and MDQ -screening results and found the evidence to be at most, inconclusive.

 

I'm being transferred once more to the ADHD-unit and am up for a drug-screen to start receiving stimulant-treatment.

 

 

I have however told them that I don't want stimulants, rather I want Atomoxetine and Modafinil - preferrably in combo.

 

 

If they do not drop the issue of Bipolar, I will suggest a trial of low-dose Lithium instead of the antipsychotics they wish to test me on at the moment. (quetiapine and aripiprazole, the latter was my suggestion)

 

However, do you know if there is any data on Lithium and EPILEPSY? And Restless Legs Syndrome? And even better - PLMD - Periodic Limb Movement Disorder?

 

I have recently figured out, from interviews with my bed-mates and family, that there is ample evidence of me convulsing and flailing about in my sleep - this then explains my issues with non-restful sleep which has plagued me for most of my life.

 

I'm vary of trying Lithium until I know it won't worsen my PLMD - do you know if it's been confirmed safe for use in people with RLS, PLMD and EPILEPSY? (all disorders seem related to some extent, and are treated with somewhat similar drugs - gabapentin, which improves my sleep dramatically, is the unifying element here)

 

 

I've used Promethazine in the past, and that gave me severe day-time somnolence and fatigue, and sometimes induced slight RLS.

 

I've also used Propiomazine which DEFINITELY induced a great amount of RLS in me (I don't usually suffer from RLS), it also induced the similar somnolence and fatigue which Promethazine did.

 

Mirtazapine also induces similar symptoms... the pattern is fairly clear now.

 

 

With this in mind, is Lithium safe to use when you have these issues?

 

 

(in contrast, low-dose Modafinil enhances my sleep-structure to an unparallelled degree...! Not even when using mirtazapine in conjunction with it, did I have the same issues of nocturnal awakenings and day-time fatigue.)

[Lia-chan]

 

 

there is nothing wrong with Li in small doses (unless one has hypothyroidism). the typical dose used by psychiatrists is 600-1200mg Li2CO3 (requires blood levels monitoring). Many people report results in small doses many times lower than those.

 

I've heard about this as well - but isn't the current dosages of Lithium-compounds rigorously tested, through placebo and such? Surely there must to be a reason that they use more often up to a GRAM worth of Lithium...!

 

Has this phenomenon with the efficacy of lower dosages of Lithium actually been properly studied? I've always figured they were simply therapeutic outliers, special cases whom are extra sensitive to the effects of Lithium.

 

 

I'd say it is rigorously tested mostly just for BP-I and most severe forms of BP-II. Since it is so old drug, patents pretty much expired before rise of "milder" forms of BP, so there hasn't been much of an incentive to do further studies.  For example, one might think people suffering of cyclothymic disorder/cyclothymia might benefit from some little extra mood stability, yet I couldn't find a single paper of using lithium on that. Those few hits on google scholar looking promising, were citation translation titles of really old, originally German or French articles, which probably were of bipolar disorder anyway, not cyclothymia or cyclothymic disorder, since at one point cyclothymia was commonly used as a synonym for bipolar disorder in some countries. 

 

You're not classic BP-I. SSRI+methylphenidate, which apparently is the ultimate combo to send a BP-II or BP NOS with "great" cycling potential on Tour de France, didn't screw you up.

 

While thesis "people with "milder" bipolar spectrum disorders can get enough mood stabilization from smaller doses of lithium" hasn't been scientifically proven, it hasn't been scientifically disproved either. I think it would be logical to test this first, before trying to get "normal lithium dose"-like effects from some new, untested combination of drugs.

 

There has been some studies of even smaller lithium doses on some other conditions. 

 

 

https://www.research...eimer's_Disease

 

Microdose Lithium Treatment Stabilized Cognitive Impairment in  Patients with Alzheimer’s Disease 

 

The dose was 300 μg = 0.3 mg of elemental lithium, given as lithium carbonate (1.6 mg of lithium carbonate) or gluconate. The usual 300 mg lithium carbonate tablet contains 56 mg of elemental lithium, and bipolar I patients typically take 2-6 of those tablets.

 

 

 

This study used 0.4 mg elemental dose.

 

http://link.springer...2916824?LI=true

 

 

Effects of nutritional lithium supplementation on mood

 

Group A received 400 μg/d of lithium orally, in tablets composed of a naturally lithium-rich brewer's yeast, for 4 wk.  Group B was given normal, lithium-free brewer's yeast as a placebo.  

 

In Group A, the scores increased consistently for all subcategories until wk 4 and remained essentially the same in wk 5. In Group B, the combined mood test scores showed no consistent changes during the same period. 

 

 

So  mega doses are not always needed for therapeutic effects, it might be needed for BP type 1 monotherapy in most cases, but maybe not for other conditions. 

 

 

http://www.psychiatr...ium-and-thyroid

 

It is widely known that patients receiving lithium therapy commonly develop hypothyroidism. Johnston and Eagles (1999) found hypothyroidism in 10.4% of 718 patients treated with lithium. Women suffered a higher risk of developing hypothyroidism within two years of therapy, compared to the general population of the geographical area studied. Hypothyroidism occurred in 14% of women, significantly more frequently than in men (4.5%),

 

 

 So with men, even at classic dosages the hypothyroidism is that low when compared to women, with non-classic, smaller doses it should be much lower.

 

It seems that's what exactly what kind of "Tour de France" I've got after I've started the treatment with antidepressants. I'm still not sure if I really have BP-II or BPD, but when I've tried to switch antidepressants the effects becomes more pronounced each time, currently I have a bunch of new scars on my hand thanks to my last attempts of suicide, last year I had 3 admissions to the hospital with suicide attempts, they are always exaggerated by someone else's reminds me while talking about a specific field or skill in wich I would love to succed and just couldn't focus on it, even that I've made numerous numbers of attempts, that kills me so much. My "Hypomanic" episoded are not that pronounced, but there was a time, when I haven't slept for 24 hours and after that I've slept for like 12-14 hours... Sometimes, they are very mild, like I'm motivated as fuck and everything seems perfect in my life and then something awful start to happen and I'm kinda stimulated for a while, after *any* accident, but that energy lasts for a... maybe a couple of days, thats it. My circadian rythms are also kinda fucked up, because I always forget that I need to sleep. 

[Mind_Paralysis]

 

 

 

there is nothing wrong with Li in small doses (unless one has hypothyroidism). the typical dose used by psychiatrists is 600-1200mg Li2CO3 (requires blood levels monitoring). Many people report results in small doses many times lower than those.

 

I've heard about this as well - but isn't the current dosages of Lithium-compounds rigorously tested, through placebo and such? Surely there must to be a reason that they use more often up to a GRAM worth of Lithium...!

 

Has this phenomenon with the efficacy of lower dosages of Lithium actually been properly studied? I've always figured they were simply therapeutic outliers, special cases whom are extra sensitive to the effects of Lithium.

 

 

I'd say it is rigorously tested mostly just for BP-I and most severe forms of BP-II. Since it is so old drug, patents pretty much expired before rise of "milder" forms of BP, so there hasn't been much of an incentive to do further studies.  For example, one might think people suffering of cyclothymic disorder/cyclothymia might benefit from some little extra mood stability, yet I couldn't find a single paper of using lithium on that. Those few hits on google scholar looking promising, were citation translation titles of really old, originally German or French articles, which probably were of bipolar disorder anyway, not cyclothymia or cyclothymic disorder, since at one point cyclothymia was commonly used as a synonym for bipolar disorder in some countries. 

 

You're not classic BP-I. SSRI+methylphenidate, which apparently is the ultimate combo to send a BP-II or BP NOS with "great" cycling potential on Tour de France, didn't screw you up.

 

While thesis "people with "milder" bipolar spectrum disorders can get enough mood stabilization from smaller doses of lithium" hasn't been scientifically proven, it hasn't been scientifically disproved either. I think it would be logical to test this first, before trying to get "normal lithium dose"-like effects from some new, untested combination of drugs.

 

There has been some studies of even smaller lithium doses on some other conditions. 

 

 

https://www.research...eimer's_Disease

 

Microdose Lithium Treatment Stabilized Cognitive Impairment in  Patients with Alzheimer’s Disease 

 

The dose was 300 μg = 0.3 mg of elemental lithium, given as lithium carbonate (1.6 mg of lithium carbonate) or gluconate. The usual 300 mg lithium carbonate tablet contains 56 mg of elemental lithium, and bipolar I patients typically take 2-6 of those tablets.

 

 

 

This study used 0.4 mg elemental dose.

 

http://link.springer...2916824?LI=true

 

 

Effects of nutritional lithium supplementation on mood

 

Group A received 400 μg/d of lithium orally, in tablets composed of a naturally lithium-rich brewer's yeast, for 4 wk.  Group B was given normal, lithium-free brewer's yeast as a placebo.  

 

In Group A, the scores increased consistently for all subcategories until wk 4 and remained essentially the same in wk 5. In Group B, the combined mood test scores showed no consistent changes during the same period. 

 

 

So  mega doses are not always needed for therapeutic effects, it might be needed for BP type 1 monotherapy in most cases, but maybe not for other conditions. 

 

 

http://www.psychiatr...ium-and-thyroid

 

It is widely known that patients receiving lithium therapy commonly develop hypothyroidism. Johnston and Eagles (1999) found hypothyroidism in 10.4% of 718 patients treated with lithium. Women suffered a higher risk of developing hypothyroidism within two years of therapy, compared to the general population of the geographical area studied. Hypothyroidism occurred in 14% of women, significantly more frequently than in men (4.5%),

 

 

 So with men, even at classic dosages the hypothyroidism is that low when compared to women, with non-classic, smaller doses it should be much lower.

 

It seems that's what exactly what kind of "Tour de France" I've got after I've started the treatment with antidepressants. I'm still not sure if I really have BP-II or BPD, but when I've tried to switch antidepressants the effects becomes more pronounced each time, currently I have a bunch of new scars on my hand thanks to my last attempts of suicide, last year I had 3 admissions to the hospital with suicide attempts, they are always exaggerated by someone else's reminds me while talking about a specific field or skill in wich I would love to succed and just couldn't focus on it, even that I've made numerous numbers of attempts, that kills me so much. My "Hypomanic" episoded are not that pronounced, but there was a time, when I haven't slept for 24 hours and after that I've slept for like 12-14 hours... Sometimes, they are very mild, like I'm motivated as fuck and everything seems perfect in my life and then something awful start to happen and I'm kinda stimulated for a while, after *any* accident, but that energy lasts for a... maybe a couple of days, thats it. My circadian rythms are also kinda fucked up, because I always forget that I need to sleep. 

 

 

"Forgetting" the need for sleep does sound rather Bipolar - however, the suicidality and repeated attempts - ESPECIALLY via a sharp, sharp razor-blade, is more in line with Borderline.

 

Have you considered that perhaps you simply... have both?
 

If your symptoms cannot be explained by only one disease, then yes, occams razor suggests that the easiest explanation is that you really have more than one disease.

[Lia-chan]

It's all started after an incident -- I've been a completely diffrent person before my 1st hospitalization that happened after when I've tried to commit a suicide after I managed to stop taking Venlafaxine. My peresonality severly changed in all aspects of my life. Just try to imagine how psyward looks like with 40+ patients in each room and doctors do nothing about you, except for medicating you with russian benzo phenazepam. Not to mention how I've felt WAITING and doing nothing, except for staring into the wall/ That week inside of this hospital was a pure hell on earth, at least they gave me prescription for Venlafaxine, Lamotrigine and Strattera. Only after this happened to me, I've started to cut myself and couldn't get a proper sleep for MANY months. And the main problem, it seems that I have lesions in mPFC, because after been hospitilized I no longer enjoy watching movies and playing vidya games as I did before the accident. I'm also not able to make a copy of my patient history, thanks to russian laws. After everything that happened to me, the only thing they did, was to say "We're sorry that medicated you in a wrong way, because we didn't now you as we do now". That's. It.

Officially I have ADHD and a large page with other depressive spectrum illnesses, like OCD, GID, GAD, PD, AD and et cetera. Everything fits perfectly in this diagnosis. Yes, I also have severe autistic treats like sorting, categorizing and etc, I always prefered IT and hardware over chit-chatting, but still, sometimes I can really enjoy talking with someone who also shares my hobbies and I find very hard to fit into the society, because everything that I love to talk about is too weird and thanks to my hyperfocus on a particular interest that exaggerate something "special" about my personality. And this is how it was always been.

 

[jack black]

Yup, sounds like autism spectrum alright. It could be easily confused with other mental disorders. I went through a similar journey myself (I mean self discovery, not hospitalization). Recently, I'm functioning a bit better after adding medium dose Li to my stack: 2x75mg of carbonate. The first week was worse and I feelt depressed and now there is a steady improvement. My impulsive trait mellowed some. Not sure how long I'll tolerate Li. If that doesn't work, lamictal at medium dose (100mg) should be a good alternative.

[Lia-chan]

Yup, sounds like autism spectrum alright. It could be easily confused with other mental disorders. I went through a similar journey myself (I mean self discovery, not hospitalization). Recently, I'm functioning a bit better after adding medium dose Li to my stack: 2x75mg of carbonate. The first week was worse and I feelt depressed and now there is a steady improvement. My impulsive trait mellowed some. Not sure how long I'll tolerate Li. If that doesn't work, lamictal at medium dose (100mg) should be a good alternative.

I've heard that lithium is even more sedating than lamictal and can cause irreversible brain damage, but it's just an anecdotal report from reddit.

[Mind_Paralysis]

 

Yup, sounds like autism spectrum alright. It could be easily confused with other mental disorders. I went through a similar journey myself (I mean self discovery, not hospitalization). Recently, I'm functioning a bit better after adding medium dose Li to my stack: 2x75mg of carbonate. The first week was worse and I feelt depressed and now there is a steady improvement. My impulsive trait mellowed some. Not sure how long I'll tolerate Li. If that doesn't work, lamictal at medium dose (100mg) should be a good alternative.

I've heard that lithium is even more sedating than lamictal and can cause irreversible brain damage, but it's just an anecdotal report from reddit.

 

 

Unless you go SUPER-HEROIC(!) with the dosing, then Lithium will cause no such thing.

 

In fact, as our good friend Finn has shown us, Lithium is quite possibly the most neurogenic compound there is - triggering neurogenesis in multiple parts of the brain when used chronically.

 

That anecdotal note on Reddit honestly means nothing - was it supervised with a Dr.? Was it a traditional Lithium-compound? Was he taking a lot of other things as well, at the same time? (most likely...)
 

And so on and so forth.

 

So unless you have ambitions to become St. Petersburg's very own Supergirl, then you have nothing to worry about.

[Lia-chan]

Yup, sounds like autism spectrum alright. It could be easily confused with other mental disorders. I went through a similar journey myself (I mean self discovery, not hospitalization). Recently, I'm functioning a bit better after adding medium dose Li to my stack: 2x75mg of carbonate. The first week was worse and I feelt depressed and now there is a steady improvement. My impulsive trait mellowed some. Not sure how long I'll tolerate Li. If that doesn't work, lamictal at medium dose (100mg) should be a good alternative.

I also found bee pollen very useful for my usual depressed mood, thanks to it, I was able to reverse engineer a code inside a pretty big project and after that I've started to take it on regular basis, now I have a really big order on 3 kg of all-natural bee pollen.

I also have a lot of allergies, even for a simple thing like wheat. I don't know, but maybe autism spectrum disorder really explains, what my problem is? Yeah, I also have a strict routine that I love to follow every day and thanks to Strattera, at least I'm able to procrastinate a little bit less before I have to do sports, taking shower and that sort of things, that are very hard to do for me for as a typical person with ADHD and other part of my usual days consists of reading longecity a little chit-chat with half real life friends and do everything to calm damn my suicidal OCD, that is very distressing, thanks to my traumatized life and my own stimuli for perfection and symmetry in everything I do, that I'm hardly able to, of course thanks to my concentration troubles, so that's why I can simply compromise everything I've tried to plan to do, just by spending my entire day reading and analyzing new information for what I have VERY SEVERE cravings. And I've lived my entire life only in this way and I was able to make my relationships with people, only who have similar problems as I do. Atomoxetine, memantine, amantadine, venlafaxine and mirtazapine (Hello 5-HT2A!) were the only things that helped me so far. Lamictal didn't stabilize my mood even for a bit, I still cry for almost everyday and I already for serious have tried to commit suicide, because I know for sure that I'm completely diffrent than the society and the only thing I'm able to do so far is just to mimic, like I have other interests in life, except for knowledge, IT and video games for every. single. day. in. my. life. And was always a quiet person and used to spend all my childhood by playing videogames and I didn't know what people are need for, except for coop play in vidya and maybe trying to spend their time by doing so, at least, thanks to video games, I have some basic knowledge of english language, lol,

And I'm very passionate about knowledge part of my personality, or hyperfocus or whatever and psychopharmacology is my passion for now and I hope for my entire life. I've tried illegally dextroamphetamine for a several times and it was the only thing that helped me to stay on a task (lol, complete walkthrough of another tossed away videogame). And it's my 5th week of ATX so far, but maybe I still don't have a full effect of it, because first 2-3 weeks I was still coming off Wellbutrin, that did terrible things with my memory. So far, I have only 3 official legal prescription for 4 drugs, Effexor XR, Strattera and Lamictal. Andddd... that's it. 

[jack black]

Lia-chan (cool name, it's not your real name, is it?), You are very similar to myself and I have no doubt you have Asperger's syndrome/ASD, although I'm a milder case. I manage it without prescriptions and my trials and errors showed me the most helpful things are high doses of vitamin B complex (including inositol), carnosine, lithium, and polygala. I also took DMAE, tianeptine, memantine, and amantadine in the past and found them useful, but not taking it at the moment.

You are right about 5ht2a receptors. I used to have prescription for serzone long time ago and fund it helpful at very low dose, but unfortunately the drug was discontinued in my country. Inositol works a bit like that. Here is some more info on connection between 5HT and ASD: http://www.pnas.org/...4/5469.full.pdf

IMHO, anti-NMDA activity is also the key. You have it covered by lamictal. Li is a bit similar.

Edited by jack black, 02 February 2017 - 02:44 AM.

[gamesguru]

the thread should not be about finding an alternative to lithium but rather about how convince your neighbor to start taking it.  lithium is one of the few mGluR5 antagonists.  it's GSK-3 and choline uptake inhibitor, a GABAB, D2 & TPH2 inducer.  it targets the mitochondria.  as finn points out, less than a milligram for day can be effective.  it can be got from mineral water (notably, Gerolsteiner) or OTC orotate.

 

the closest you can come i suppose is magnesium (NMDA antagonist), theanine (GABA, dopamine and serotonin releaser), bacopa (TPH2 inducer, serotonin releaser), and Stephania intermedia (native to the Australian bush, a D2 antagonist, apparently so is yohimbine and homocysteine).  stuff like amisulpride and other antipsychs might be a piece to the puzzle too

[Mind_Paralysis]

Right, so let's move away from trying to replace Lithium, and instead look upon how we can IMPROVE it! : )

Orotate is a compound which seems to improve bio-availability substantially, and in general it seems to give comparable effects to much higher dosages of other lithium-compounds.

 

 

But, that's not really enough... we need to take it to the next level! Blood-brain barrier penetration - how do we achieve this? Magnesium finally cracked the code when it came to combining it with L-Threonate, which finally produced a Mag-compound which actually crosses the blood-brain barrier and causes non-competitive NMDA-antagonism. But would L-Threonate have the same effect on another metal, i.e Lithium? Or is it logical to assume that the effect wherein it pushes Magnesium into the brain is exclusive to Magnesium?

 

What do you say, fellas? Would it be worth it to create Lithium-L-Threonate?

 

 

 

Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration.

https://www.ncbi.nlm...pubmed/27178134

 

 

We discovered that threonate is naturally present in cerebrospinal fluid (CSF) and oral treatment with L-TAMS elevated CSF threonate...

...Mechanistically, threonate's effects were specifically mediated through glucose transporters (GLUTs).

 

 

Hmm... so Threonate is a naturally occuring component of spinal fluid... hmmm... This does imply that it could have some effect! However it also specifically mentions how Threonate seems to push naturally occuring magnesium from diet and such, into the brain, even without binding it to Magnesium in the first place!

 

Hmm...

 

...What do you think, fellas?