40 replies to this topic

[Heinsbeans]

My depression symptoms: https://docs.google....dit?usp=sharing

 

A little background:

 

I've been on 20mg Trintellix for the past 7 months and it's my favourite antidepressant so far since it has slightly improved my cognitive function and memory. And most importantly, it's not causing as much emotional blunting as Lexapro/Cymbalta which I was previously on. But the only problem is, I feel very lethargic and unmotivated on Trintellix which is how I similarly felt on Lexapro. I was significantly more self motivated, energetic, socially engaged and my mood was a lot better when I was on 120mg Cymbalta. I came off Cymbalta because the emotional blunting became too much to deal with.

 

So in conclusion, I'm trying to create the most pro-cognitive antidepressant combo for my abnormally low drive and energy mediated depression.

 

The following meds are available in my country which I'm thinking of using:

• Remeron (Mirtazapine), Valdoxan (Agomelatine), Zoloft (Sertraline), Trintellix (Vortioxetine), Effexor (Venlafaxine), Pritiq (Desvenlafaxine), Cymbalta (Duloxetine), Edronax (Reboxetine), Wellbutrin (Bupropion).

The following meds are also available in my country but I'm less inclined towards using: 

• Seroquel (Quetiapine), Risperdal (Risperidone), Zyprexa (Olanzapine), Solian (Amisulpride), Latuda (Lurasidone), Abilify (Aripiprazole), Mirapex (Pramipexole), Lamictal (Lamotrigine), Emsam (Selegiline).

The following meds are not yet unavailable in my country or still under development: 

• Viibryd (Vilazodone), Fetzima (Levomilnacipran), Rexulti (Brexpiprazole), Vraylar (Cariprazine), Addyi (Flibanserin), S32212, Roxindole, Pimavenserin.

Criteria:

• Must be safe to take long-term (e.g. doesn't pose a risk to health taking it long-term like with SGAs causing extrapyramidal side effects, increased risk of diabetes, galactorrhea, gynecomastia, tardive dyskinesia etc).
• Must be pro-cognitive and not detrimental to one's cognitive functioning long-term.
• Must have the largest motivation, attention, memory, mood, vigilance, energy improvement.
• Must be effective in reaching remission and not easily poop out.
• Must have the least cognitive side effects (e.g. emotional blunting, loss of interest/drive (apathy), loss of feeling pleasure (anhedonia), sexual dysfunction, drowsiness/sedation, anticholinergic effects, cognition/memory impairments).

#1) Trintellix + Edronax

• I'm leaning towards this the most since I responded really well to Cymbalta (bar its emotional blunting). Bear in mind though, Edronax is a very weak AD on its own so it must be combined with serotonergic antidepressants.

#2) Trintellix + Valdoxan

• 5-HT1A full agonism and a blockade of 5-HT3/2C/7 without the histamine, dopamine or muscarinic antagonism. 

#3) Trintellix + Remeron

• 5-HT1A full agonism with blockade of 5-HT2A/2C/3/7 and Alpha 2A/2C adrenergic receptors which seems like a great combination in theory. But I'm slightly hesitant to try it because it's a potent H^1 antagonist (1.6nM). The drowsiness/sedation is supposed to subside/become more tolerable over time but some say it never goes away and having to stop taking it. There's also some discussion about antihistamines possibly disrupting dopamine signalling. It also has a mAChrs antagonism of 670nM (on rats) which isn't significant but still fairly anticholinergic and concerning. But overall, Remeron seems to have a  much better pharmacological profile over SGAs as an adjunctive medication to SSRI.

#4) Trintellix + DA agonist/partial agonist (e.g. Abilify, Rexulti, Vraylar etc.)

• I'm still researching about the efficacy of DA agonists/partial agonists in the treatment of depression. AFAIK, there hasn't been enough concluding evidence showing that DA agonists/partial agonists are safe and effective for treating depression. Some possible side effects include addiction and compulsive behaviour. But it's probably more preferable over DA antagonists which reduces DA transmission in the striatum/mesolimbic pathway and have extrapyramidal side effects. From my limited research, it sounds like it's not a good long-term solution.
• Have anyone taken DA agonists/partial agonists(e.g. Rexulti/Vraylar) with SSRI for depression and have they been worth it? 

#5) Cymbalta + Remeron, Valdoxan, Latuda, Abilify, Mirapex.

• If I still feel lethargic and unmotivated on Trintellix + any combination, I could consider using Cymbalta as a backbone since it's noradrenergic.

#6) Wellbutrin by itself or with a low dose SSRI

• Wellbutrin seems to be the best antidepressant for increasing motivation and energy while not having the side effects that comes with SSRI like emotional blunting, fatigue, loss of interest/motivation (apathy), loss of feeling pleasure (anhedonia) and sexual dysfunction. I'm slightly hesitant to try it since it's a potent nAChrs antagonist and fair number of people have complained of it causing impaired cognition and memory loss. I've also heard it poops out rather quickly.

Which combination of antidepressants do you think will be the most pro-cognitive and motivating long-term? Thanks a bunch.

 

Other places I've been getting help from:

https://www.reddit.c...chotics_for_my/

 

 

 

Edited by Heinsbeans, 30 January 2017 - 03:41 PM.

[Lia-chan]

I suggest that you should try MAOI, Aurorix for example or even something like Tranylcipromine and Phenelzine.

I'm also interested in making of perfect cocktail for my depression and I want the same as you do.

Yesterday I've made a post about how diffrent antidepressants afffect the brain.

 

Neurochem Res. 2009 Mar;34(3):542-55. doi: 10.1007/s11064-008-9818-2. Epub 2008 Aug 27.

Brain region-specific effects of short-term treatment with duloxetine, venlafaxine, milnacipran and sertraline on monoamine metabolism in rats.

Muneoka K1, Shirayama Y, Takigawa M, Shioda S.

Author information

 

Abstract

We examined brain region-specific changes in monoamines and metabolites, and their ratios, after short-term administration of antidepressants to rats. Serotonin noradrenaline reuptake inhibitors (SNRIs; duloxetine, venlafaxine, milnacipran) and a serotonin-selective reuptake inhibitor (SSRI; sertraline) elevated serotonin (5-HT) levels in the midbrain (MB). Duloxetine and venlafaxine increased 5-HT levels in the brainstem and 5-HT terminal areas, whereas milnacipran and sertraline increased levels in the brainstem only. Significant reductions in 5-HT turnover were observed in various forebrain regions, including the hippocampus and hypothalamus, after treatment with all of the tested drugs except for milnacipran. In addition, there was reduced 5-HT turnover in the dorsolateral frontal cortex (dlFC), the medial prefrontal cortex (mPFC), and both the dlFC and the mPFC after treatment with duloxetine, sertraline, and venlafaxine, respectively. Venlafaxine significantly increased dopamine (DA) levels in the nucleus accumbens (NAc) and the substantia nigra and decreased DA turnover in the NAc. Similar changes were observed after treatment with duloxetine and sertraline in the NAc, whereas milnacipran increased DA levels in the mPFC. Limited increases in noradrenaline levels were detected after treatment with duloxetine, venlafaxine, or sertraline, but not after treatment with milnacipran. These results show that SNRIs and SSRIs induced region-specific monoaminergic changes after short-term treatment.

 

[prunk]

Vortioxetine completely wrecked my sleep and made me pretty lethargic and unmotivated, but it clearly improved some aspects of my cognition. However it did worsen my episodic memory to a disturbing degree, probably due to 5HT1a agonism, I guess.

[jack black]

My vote is for polygala tenuifolia extract. The examine.com has extensive info how it works as antidepressant and procognitive. I tried it on days I was depressed and the effect was immediate. IMHO this is the real deal and one of the best supplements I tried. I use it only as needed because I'm afraid tolerance may develop.

[Autumn Knight]

I really think you should consider Selegiline more. It is supposed to have neuro-anti-aging and neuro-protective properties so much that it is used to treat Parkinson's, but aside from that, it's supposed to be good for your brain in many other ways. Some use it just for its cognitive benefits. Probably you knew all of that though

[Lia-chan]

I really think you should consider Selegiline more. It is supposed to have neuro-anti-aging and neuro-protective properties so much that it is used to treat Parkinson's, but aside from that, it's supposed to be good for your brain in many other ways. Some use it just for its cognitive benefits. Probably you knew all of that though

Maybe it's neuro anti-aging and neuroprotective properties are only thanks to similarity with levomethamphetamine? I've started to use it recently it it feels really great! But this summer I want to start taking classes in uni, so I still have thoughts, what would be really better for me, moclobemide + selegiline or tranylcipromine with strattera. AFAIK it's safe to use Strattera with MAOI. I also find INI very useful thing.

[Duchykins]

Bupropion was the only one to not make me retarded, apathetic or sleepy.  To me, SSRIs  and tricyclics are the devil, partly because they increase the rate of the migraines I get.  I am a biology student with a 4.0 and an unhealthy perfectionist streak so I try to keep on track of stuff like this.  

 

However, bupropion made me more anger-prone (probably the NRI part) and so I swapped it out for some good ole fashioned methylphenidate and fleshed it out with high doses of theanine.  Say no to the amphetamines though.  Just no.  I also take 10mg  memantine every single day, and have been taking it for more than a year now with no intention of ever stopping, but that's for migraine prophylaxis.  And ginger + lion's mane seems to cap it altogether nicely.

 

Ritalin has been demonstrated to be neuroprotective against adderall's adverse effects on the dopaminergic system, isn't that cute?  They're simply not equivalent drugs.  It's also been demonstrated to prevent abnormal brain development in kids with ADHD (unmedicated, they grow up with abnormally-shaped basal ganglia and some atrophy in certain regions).

 

But all of this is beside the point - if you have a specific chemical imbalance that's related to your depression, then trying to go for the most "pro-cognitive" is not really going to help you since they all work differently.  So for example if you really do have a chronic problem with low serotonin, then something like bupropion is just going to make your depression worse.

 

I have to be very honest here: no prescription antidepressants have helped me in the long run.  Only getting into supplements that support mitochondrial functioning have ever helped me in a well-rounded way, with few side effects.  It's a much more expensive way because I cannot get them covered by insurance, but they work.

Edited by Duchykins, 06 February 2017 - 06:52 AM.

[Dolph]

The most pro-cognitive antidepressant is the one that relieves your depression best!

For me it was trimipramine, and even though(!) it's anticholinergic it helped me getting rid of cognitive issues that were just a symptom of depression as such.

[jack black]

I have to be very honest here: no prescription antidepressants have helped me in the long run. Only getting into supplements that support mitochondrial functioning have ever helped me in a well-rounded way, with few side effects. It's a much more expensive way because I cannot get them covered by insurance, but they work.

Could you tell us more about this?

[normalizing]

he probably means nicotinamide riboside. ive tried it for depression but that crap makes me even more tired even tho its suppose to boost your mitochondria energy pft

[Mind_Paralysis]

Bupropion was the only one to not make me retarded, apathetic or sleepy.  To me, SSRIs  and tricyclics are the devil, partly because they increase the rate of the migraines I get.  I am a biology student with a 4.0 and an unhealthy perfectionist streak so I try to keep on track of stuff like this.  

 

However, bupropion made me more anger-prone (probably the NRI part) and so I swapped it out for some good ole fashioned methylphenidate and fleshed it out with high doses of theanine.  Say no to the amphetamines though.  Just no.  I also take 10mg  memantine every single day, and have been taking it for more than a year now with no intention of ever stopping, but that's for migraine prophylaxis.  And ginger + lion's mane seems to cap it altogether nicely.

 

Ritalin has been demonstrated to be neuroprotective against adderall's adverse effects on the dopaminergic system, isn't that cute?  They're simply not equivalent drugs.  It's also been demonstrated to prevent abnormal brain development in kids with ADHD (unmedicated, they grow up with abnormally-shaped basal ganglia and some atrophy in certain regions).

 

But all of this is beside the point - if you have a specific chemical imbalance that's related to your depression, then trying to go for the most "pro-cognitive" is not really going to help you since they all work differently.  So for example if you really do have a chronic problem with low serotonin, then something like bupropion is just going to make your depression worse.

 

I have to be very honest here: no prescription antidepressants have helped me in the long run.  Only getting into supplements that support mitochondrial functioning have ever helped me in a well-rounded way, with few side effects.  It's a much more expensive way because I cannot get them covered by insurance, but they work.

 

Curious! How different one brain can be from another, even though genetic differences are, apparently, according to geneticists, FRIGHTENINGLY BADLY SMALL between even completely non-related humans! Two gorillas from the same tribe can apparently have better genetic diversity then two humans from different continents.

 

To me, SSRI's and SNRI's work just fine - meanwhile, Bupropion turns me into:

 

a) A rage-monster!! Seriously, the stories of HYPER-sexuality and violent behaviour from Bupropion are NOT fairy-tales - they're real.

 

b) An IMBECILL! I get some sort of speech-impediment, it's like my verbal memory takes a BIG hit, and I keep forgetting words - I'll go like this: "Oh yeah, it's one of those... uh... like a... uh... a bear... sort of... uh... that's... uh... what's your name again?"
 

So yeah, I guess everyone is different - hence the BIG market there is for AD's - all of them simply don't work for everyone.

 

 

Seems like I'm very, very sensitive to anticholinergic effects btw, which is worrisome, since it could imply a vulnerability to dementia.

[Heinsbeans]

Vortioxetine completely wrecked my sleep and made me pretty lethargic and unmotivated, but it clearly improved some aspects of my cognition. However it did worsen my episodic memory to a disturbing degree, probably due to 5HT1a agonism, I guess.

 

I agree, vortioxetine has improved certain aspect of my cognition but I can’t grasp exactly where. I have also noticed a mild improvement in my memory.  I agree with the lethargy and decline in motivation from vortioxetine which is one of the biggest downside with it. In fact, I’m finding vortioxetine more lethargy-inducing than the 10mg Lexapro that I was on for 7 months.

 

Although to be fair, I was only on 10mg Lexapro so if I had increased the dose to 20mg, I might have experienced a similar effect on fatigue.

 

This is why I’m considering adding reboxetine to help with my energy and motivation.

 

 

I suggest that you should try MAOI, Aurorix for example or even something like Tranylcipromine and Phenelzine.

I'm also interested in making of perfect cocktail for my depression and I want the same as you do.

Yesterday I've made a post about how diffrent antidepressants afffect the brain.

 

 

 

I’ve heard that MAOIs are one of the most effective antidepressant for treatment resistant depression. I should probably consider MAOIs but I don’t feel comfortable with having restricted diet. 

 

I really think you should consider Selegiline more. It is supposed to have neuro-anti-aging and neuro-protective properties so much that it is used to treat Parkinson's, but aside from that, it's supposed to be good for your brain in many other ways. Some use it just for its cognitive benefits. Probably you knew all of that though

 

I haven’t really looked into Selegiline. But I do know that it’s one of the few antidepressants that are considered pro-cognitive. On the upside, it doesn’t cause any sexual dysfunction but it’s not very frequently prescribed. And I’ve heard that it can make people prone to getting angry. It’s hard enough as it is getting prescribed anything else besides SSRI in an uptight country like Australia no matter how severe or treatment resistant your depression is. So it’s going to be very difficult to even get my hands on it.

 

Here's some research I've been doing on antidepressant medications:

 



> It’s believed that the side effects from SSRI/SNRI are coming from SRI perpetually activating the inhibitory or 'problematic' 5-HT receptors that regulate the release of other neurotransmitters, even after bulk of the down-regulation has been achieved.


 


> Anhedonia/apathy/emotional blunting from SSRI is thought to be mediated by a reduction of DA neurotransmission in the 'reward' pathway(mesolimbic pathway). Consistent with this, is the known fact that SSRIs do in-fact blunt/reduce DA release in these areas.
 


https://www.ncbi.nlm...les/PMC2674976/

https://www.ncbi.nlm...pubmed/19721109

https://www.depressi...comment-923186


 


> SSRIs are indiscriminate so it increases synaptic serotonin and post synaptic binding across the board. With reference to their anhedonia/apathy/emotional blunting side effects, this could be linked to their perpetual activation of inhibitory receptors such as 5-HT2A/2C/3/7, inherent in regulating dopamine release in the striatum/mesolimbic pathway.


 


> So in general, SRI, NRI, 5-HT1A agonism/partial agonism, 5-HT2A/2C/3/7 antagonism and Alpha-2 adrenergic receptor antagonism are believed to be the core target for antidepressant purposes.



https://www.ncbi.nlm...cles/PMC446220/


http://www.sciencedi...006295215001562

 


 
> There's currently only a limited evidence for dopamine agonism, partial agonism and antagonism in the treatment of non-schizophrenia/bipolar mediated depression.
 


 

> I assume my psychiatrist chose risperidone as an adjunctive therapy to vortioxetine since it preferentially targets 5-HT2A and Alpha-2C adrenergic receptor at a low dose over dopamine/histamine. In theory, this should have been helpful for my depression but unfortunately it only caused side effects on me.

 

From my recent research on pro-cognitive antidepressants:

• Selegiline because it's a MAO-B which increases DA neurotransmission. But I've heard it can make people prone to becoming angry.
• Edronax because the NRI indirectly increases DA neurotransmission in PFC and NET inhibition has positive effect on motivation and energy. But too much NRI may make some people feel robotic and cause social avoidant behaviour.
• Wellbutrin, same reason as Edronax because of NRI. But the nAChRs antagonism can cause memory impairments in some people. Ironically, the nAChRs antagonism is what's thought to be contributing to the antidepressant effect.
• Perhaps DA agonists that specifically targets D3 receptor which is known to have pro-cognitive effects and increase motivation. But DA agonists are known to cause fatigue, irritability and severe dependence. There's also a risk of developing gambling and addictive behaviour on it.
• Perhaps multimodal 5-HT antagonists. Some 5-HT receptors modulate the acetylcholine/glutamate/dopamine/norepinephrine release in PFC or mesolimbic pathway. E.g. Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission Quote "These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission."
• NSI-189 (neurogenic antidepressant) has been shown to increase hippocampal volume.
• Rapastinel (glutamatergic antidepressant) has been shown to have pro-cognitive effects.

Edited by Heinsbeans, 20 February 2017 - 06:48 AM.

[Lia-chan]

> But too much NRI may make some people feel robotic and cause social avoidant behaviour

Do you have any proof of that?

And what about the potency of Edronax in compare to Strattera?

>I should probably consider MAOIs but I don’t feel comfortable with having restricted diet. 

I consider people, who are still have any preferences in food and can't sustain a proper diet don't need any antidepressants, because I can't imagine how a human being WITH DEPRESSION can reject all the things that MAOIs can offer.

> Selegiline because it's a MAO-B which increases DA neurotransmission. But I've heard it can make people prone to becoming angry

You can just something like Lamictal to Selegiline, so this side-effect would simply go away.

 

If you really interested in what antidepressants I've found so far that improve my cognition, you can text me in skype, I'm free to share you my experience with ton of different antidepressant meds, dopamine agonists and et cetera. I'm sure, that I've tried more antidepressants than 99% of people with depression. I think, both of us have almost the same troubles and we both search for an ultimate silver bullet, so I think it would be really useful for us to cooperate. My skype nickname is liamia-chan

 

[Mind_Paralysis]

How is it that NO-ONE has as of yet not suggested Tianeptine? And how is it that the OP hasn't as well? It improves cognition in a subset of people, and it has a tremendously good side-effects profile.

 

It's probably not available in Australia, but it can be obtained through the internet and is reasonably cheap, well-documented and safe.

 

 

I can't recall as well, but Heinsbeans, looking at your response to Duloxetine (cymbalta) and your issues with low motivation and fatigue - have you ever considered that you may not have JUST depression, but SCT as well?

 

Logically, a combo of Reboxetine and Tianeptine could do wonders, since I recall there's actually a small study which found that Tianeptine increased activity in the SPL - the section of the brain implicated in SCT, and Reboxetine is an NRI, affecting the neurotransmitter hypothesized to be implicated in SCT.

 

I myself identify with SCT and can vouch for Noradrenergics and Tianeptine - it's good stuff!

[jack black]

How is it that NO-ONE has as of yet not suggested Tianeptine?

 

simple, i discovered a better thing for depression. BTW, have you noticed you had double negatives in that sentence?

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

[normalizing]

stink, tineptine also has effect on the opiod receptors which is not a good idea long term use. personal experience, the depression in withdrawal feels similar to opiate withdrawal and i think this should be a pretty reasonable reason for people not to try this one as first time treatment

 

on the other hand, i tried to participate in rapastinel trial but couldnt qualify, but a buddy of mine was involved in one of their many trials and claims its one of the best antidepressants there is. the biggest problem right now, its not available and it wont be available for years and when it is, it will be super expensive. now, THATS ONE people should try ill say. if i can find it online, ill go for it but good luck!

[Mind_Paralysis]

 

How is it that NO-ONE has as of yet not suggested Tianeptine?

 

simple, i discovered a better thing for depression. BTW, have you noticed you had double negatives in that sentence?

 

 

Oh? What's that then? I must have missed it earlier in the thread.

 

I hope you're taking into account that Autistic depression may not necessarily be depression in the same way we know it traditionally - a bit like SCT-depression or ADHD-depression - the moment the symptoms of the Neurodevelopmental disease is alleviated, the patient all of a sudden feel tons and tons better - hence the patients low mood is caused by ultra-intense perpetual environmental stressors. (i.e ones symptoms, from ones neurodevelopmental disease)

 

And no, I missed that double negative, haha!

 

stink, Tianeptine also has effect on the opiod receptors which is not a good idea long term use. personal experience, the depression in withdrawal feels similar to opiate withdrawal and i think this should be a pretty reasonable reason for people not to try this one as first time treatment

 

on the other hand, i tried to participate in rapastinel trial but couldnt qualify, but a buddy of mine was involved in one of their many trials and claims its one of the best antidepressants there is. the biggest problem right now, its not available and it wont be available for years and when it is, it will be super expensive. now, THATS ONE people should try ill say. if i can find it online, ill go for it but good luck!

 

But that is generally considered to be a rare side-effect - we have a whole thread debating it, even. It would seem as if there's a certain percentage of the people getting withdrawal which have been using too high of a dose as well - more than the standard, only allowed dosage of 3 x 12,5 mg per day.

 

Rapastinel... well there is the problem of availability, otherwise I would have suggested something like JDtic or CERC-501 as well!

[jack black]

How is it that NO-ONE has as of yet not suggested Tianeptine?

simple, i discovered a better thing for depression. BTW, have you noticed you had double negatives in that sentence?

Oh? What's that then? I must have missed it earlier in the thread.

I hope you're taking into account that Autistic depression may not necessarily be depression in the same way we know it traditionally - a bit like SCT-depression or ADHD-depression - the moment the symptoms of the Neurodevelopmental disease is alleviated, the patient all of a sudden feel tons and tons better - hence the patients low mood is caused by ultra-intense perpetual environmental stressors. (i.e ones symptoms, from ones neurodevelopmental disease)

And no, I missed that double negative, haha!

I mentioned this in one of my above posts: polygala tenuifolia extract.

Your point about autistic depression is excellent. It could be applies to oranges indeed.

As a matter of fact, every case of depression could be unique.

Edited by jack black, 22 February 2017 - 01:32 PM.

[Duchykins]

 

I have to be very honest here: no prescription antidepressants have helped me in the long run. Only getting into supplements that support mitochondrial functioning have ever helped me in a well-rounded way, with few side effects. It's a much more expensive way because I cannot get them covered by insurance, but they work.

Could you tell us more about this?

 

 

My daily stack is ridiculous partly because I take everything separately and stagger the larger doses through the day, but here's just the ones I take that focus on different aspects of mitochondrial function:

 

riboflavin (400 mg)

 

thiamine (400 mg)

 

adenosylcobalamin / hydroxocobalamin  50%/50% (2 mg)  (methylcobalamin is excessively popular but is not a substitute for the adenosylcobalamin - you need both and your body can make methylcobalamin from adenosylcobalamin but not vice versa)

 

pantethine (300 mg)

 

niacin-bound chromium (200 mcg)

 

(this is in addition to an all-active B complex from Swanson's, because that complex doesn't have enough of certain things and I really need the 400 mg riboflavin for migraine prophylaxis)

___

 

benfotiamine  (25 mg)

riboflavin 5'-phosphate (25 mg)

inositol hexanicotinate (50 mg)

pyridoxal 5'-phosphate  (25 mg)

methylfolate (400 mcg)

methylcobalamin (250 mcg)

pantethine (25 mg)

biotin (25 mcg)

___

 

 

ubidecarenone (200 mg, sometimes 300 mg)

 

creatine, micronized (1 g)

 

l-carnitine (not ALCAR - they are not the same molecule) (1 g)

 

l-carnosine (1 g)

 

taurine (500 mg)

 

citrulline malate (1 g)

 

l-lysine (500 mg)

 

All the usual electrolytes, including low-dose lithium.  The magnesium supp I take comes with extra 12.5 mg benfotiamine and 2.5 mg P5P, which is fine.

 

A very low-dose, low-copper, iron-free Albion multimineral.

 

I take a 1g high-DPA, high-DHA, low-EPA fish oil capsule once every third day.  The fatty acid supplements should not be taken daily, and it's a waste of money to do it.

 

I also take a 5 mg biotin capsule every third day, but that's just because the brand I was usually getting 1 mg caps from stopped making them, which pissed me off.  5 mg biotin is too much to take daily for an extended period of time.

 

 

 

The explanations for all of these are very long-winded, took hours and weeks of poring over medical literature (probably forgot half of it by now), and I can't be bothered with the time right now.  But the information for all of these in relation to general mitochondrial function (cell energy production, energy transport, etc) is easily found in medical literature and databases.

 

I've not tried nicotinamide riboside.  Sounds like hype, but I've not tried anything new in a long time since I seemed to have hit a sweet spot with my supps and don't want to mess with a good thing.  Being a migraineur makes everything more complicated since a lot of things that work well for most people will trigger migraines in me.  It's also why I take nearly everything separately, most blends and multis contain at least one thing that I should not have.

Edited by Duchykins, 24 February 2017 - 05:58 AM.

[Duchykins]

stink, tineptine also has effect on the opiod receptors which is not a good idea long term use. personal experience, the depression in withdrawal feels similar to opiate withdrawal and i think this should be a pretty reasonable reason for people not to try this one as first time treatment

 

on the other hand, i tried to participate in rapastinel trial but couldnt qualify, but a buddy of mine was involved in one of their many trials and claims its one of the best antidepressants there is. the biggest problem right now, its not available and it wont be available for years and when it is, it will be super expensive. now, THATS ONE people should try ill say. if i can find it online, ill go for it but good luck!

 

I buy Ceretopic's tianeptine and agree with your assessment of it.  It definitely has a warm narcotic feel to it, not unlike hydrocodone, and should be for periodic use only.

 

What originally interested me in the drug is its apparent modulation of NMDA; I wanted to try this for migraine prophylaxis.  I do get a calm happy on it but it seems clear to me that it is too much like an opioid high that would not prove to be therapeutic in the long run.

 

I get an uncomfortable side effect from it if I take small morning doses more than three days in a row - palpitation attacks at nighttime.  This is either the tianeptine itself or it might be an interaction with memantine but I cannot be sure since I stay on memantine all the time.  I've done this three-day thing four times over the past six months just to be sure the pattern existed and was not a one-time thing.   Each time I stopped on the third day, for two days afterward I experienced phantom body aches, moodiness and lethargy that are exactly the same symptoms I would get withdrawing from low-dose tramadol, something I used to take on and off for a back injury.

 

In any case, extended use of tianeptine seems to be ineffective and does more harm than good, much like phenibut, it should be held on reserve.  It sits in the back of my cabinet and I pull it out just every once in a while, maybe two or three times a month, usually when I feel really stiff and unproductive (that lower back injury triggered arthritis there).  I probably won't buy anymore once this last bottle is gone.

Edited by Duchykins, 24 February 2017 - 06:44 AM.

[Duchykins]

 

 

 

Curious! How different one brain can be from another, even though genetic differences are, apparently, according to geneticists, FRIGHTENINGLY BADLY SMALL between even completely non-related humans! Two gorillas from the same tribe can apparently have better genetic diversity then two humans from different continents.

 

To me, SSRI's and SNRI's work just fine - meanwhile, Bupropion turns me into:

 

a) A rage-monster!! Seriously, the stories of HYPER-sexuality and violent behaviour from Bupropion are NOT fairy-tales - they're real.

 

b) An IMBECILL! I get some sort of speech-impediment, it's like my verbal memory takes a BIG hit, and I keep forgetting words - I'll go like this: "Oh yeah, it's one of those... uh... like a... uh... a bear... sort of... uh... that's... uh... what's your name again?"
 

So yeah, I guess everyone is different - hence the BIG market there is for AD's - all of them simply don't work for everyone.

 

 

Seems like I'm very, very sensitive to anticholinergic effects btw, which is worrisome, since it could imply a vulnerability to dementia.

 

 

It is crazy how subtly unique our biochemistries makes us.  

 

I'm not sure about bupropion's effect on my cognitive function, aside from making me angry as fuck which makes you stupid all by itself.  But honestly I was already having problems with episodic memory due to having untreated PTSD, depression and probable autism for years before I got medical insurance in my 30s.  Verbal skills is a different story - my language capabilities have always been fairly strong, to the point where I have occasionally (and shamefully) sold my skills writing papers for other students, and sometimes I get a little verbose when on a favorite topic, but you wouldn't know this if we only spoke face-to-face.  I sound like a moron when I try to talk (to me, at least) and I don't talk much if I can get away with it.  I often have difficulty finding ordinary words, much like you described.  It's humiliating sometimes.  

 

Memantine did make me quite retarded during the first few months, but not so much that it affected my grades.  I recall going back and re-reading a few posts I wrote during my first month on memantine and being really embarrassed by my bizarre sentence structure and stupid use of grammar.  I believe that since I am taking it all the time, there must be some lasting negative effect on either my learning or cognition; I am quicker to forget things that I've read, of that much I am certain... but the benefits still tip the scales toward continued use.  I'm willing to trade the IQ points in favor of generally-improved quality of life.

 

Anticholingerics ... I'm the opposite of you.  I'm horribly sensitive to anything that boosts ACh, in any manner, whether directly or indirectly.  ALCAR, alpha-GPC, citicoline, lecithin, DHEA, bacopa, even whole foods like eggs and quinoa bother me because of their naturally high choline content.  Symptoms ranged from brain fog to irritability to TMJ pain, chest tightness, palpitations, shallow breathing and sleep apnea (the scariest by far, and it happened with low doses of bacopa all by itself - and that's when I stopped playing with cholingerics, by that point the pattern was too obvious).  Wasted lots of money playing with nootropics acclaimed for their ACh activity.  Never got headaches playing with piracetam by itself either.

Edited by Duchykins, 24 February 2017 - 07:46 AM.

[Mind_Paralysis]

 

 

 

 

Curious! How different one brain can be from another, even though genetic differences are, apparently, according to geneticists, FRIGHTENINGLY BADLY SMALL between even completely non-related humans! Two gorillas from the same tribe can apparently have better genetic diversity then two humans from different continents.

 

To me, SSRI's and SNRI's work just fine - meanwhile, Bupropion turns me into:

 

a) A rage-monster!! Seriously, the stories of HYPER-sexuality and violent behaviour from Bupropion are NOT fairy-tales - they're real.

 

b) An IMBECILL! I get some sort of speech-impediment, it's like my verbal memory takes a BIG hit, and I keep forgetting words - I'll go like this: "Oh yeah, it's one of those... uh... like a... uh... a bear... sort of... uh... that's... uh... what's your name again?"
 

So yeah, I guess everyone is different - hence the BIG market there is for AD's - all of them simply don't work for everyone.

 

 

Seems like I'm very, very sensitive to anticholinergic effects btw, which is worrisome, since it could imply a vulnerability to dementia.

 

 

It is crazy how subtly unique our biochemistries makes us.  

 

I'm not sure about bupropion's effect on my cognitive function, aside from making me angry as fuck which makes you stupid all by itself.  But honestly I was already having problems with episodic memory due to having untreated PTSD, depression and probable autism for years before I got medical insurance in my 30s.  Verbal skills is a different story - my language capabilities have always been fairly strong, to the point where I have occasionally (and shamefully) sold my skills writing papers for other students, and sometimes I get a little verbose when on a favorite topic, but you wouldn't know this if we only spoke face-to-face.  I sound like a moron when I try to talk (to me, at least) and I don't talk much if I can get away with it.  I often have difficulty finding ordinary words, much like you described.  It's humiliating sometimes.  

 

Memantine did make me quite retarded during the first few months, but not so much that it affected my grades.  I recall going back and re-reading a few posts I wrote during my first month on memantine and being really embarrassed by my bizarre sentence structure and stupid use of grammar.  I believe that since I am taking it all the time, there must be some lasting negative effect on either my learning or cognition; I am quicker to forget things that I've read, of that much I am certain... but the benefits still tip the scales toward continued use.  I'm willing to trade the IQ points in favor of generally-improved quality of life.

 

Anticholingerics ... I'm the opposite of you.  I'm horribly sensitive to anything that boosts ACh, in any manner, whether directly or indirectly.  ALCAR, alpha-GPC, citicoline, lecithin, DHEA, bacopa, even whole foods like eggs and quinoa bother me because of their naturally high choline content.  Symptoms ranged from brain fog to irritability to TMJ pain, chest tightness, palpitations, shallow breathing and sleep apnea (the scariest by far, and it happened with low doses of bacopa all by itself - and that's when I stopped playing with cholingerics, by that point the pattern was too obvious).  Wasted lots of money playing with nootropics acclaimed for their ACh activity.  Never got headaches playing with piracetam by itself either.

 

 

Interesting.

 

You know, if it wasn't for your other problems, then because of the fact that you don't get headaches from Piracetam without filling up with choline, I would almost peg you as suffering from Borderline Personality Disorder...

 

Reason being that the disorder seems to have a clear connection to the cholinergic system - people with BPD produce many, many times more choline than regular people - a recent genetic study found this out, which then jumpstarted my many posts on the subject (wrote a prototype mini-article on it and everything) - Acetylcholine you see, is selective for certain aCh-receptors than others - notably, it's selective for the Nicotinic Alpha-7-receptor!

 

The NaCh-7-receptor controls much of the activity out of the Amygdala, much like the alpha-2-receptors control activity out of the Superior Parietal Lobe - hence, if you have problems with excessive aCh, emotional control is going to be very, VERY difficult...!

 

 

An interesting note btw - in the thread we also discussed how the diagnostic criteria for Autism is mainly geared towards men, and how the symptoms are actually DIFFERENT between the two sexes - autistic women often get slapped with an incorrect diagnosis, such as Borderline Personality Disorder - which then accounts for a great deal of the gender-discrepancy in that disorder - the amount of women afflicted have been inching closer to the amount of men afflicted for close to 15 years now - used to be 5% vs 95%, then it was 10%, but now it's friggin' 15%!

 

All because of new data, and fMRI and PET-scans, which show that these women do NOT have Bipolar or BPD, but are in fact autistic.

 

IMHO, this data will continue this trend - of altering diagnostic criteria according to new data, shrinking the gender-discrepancy.

 

 

However... this data is also interesting in the OTHER direction! Borderline Personality Disorder is a disease much more commonly diagnosed in WOMEN than in men, but, once again... there is new data implying that the previously HUGE gender-discrepancy among those afflicted, is as a matter of fact the results of incorrect diagnosing - many men are misdiagnosed as ADHD or Antisocial Personality Disorder, when in reality, they have BPD!

 

Now, coupled with all of the new data implying that BPD is NOT a "personality disorder", but rather it is a form of Neurodevelopmental Disorder - similar in some ways to both ADHD and Autism - then, you can see how this becomes intriguing, when it comes to you...
 

 

...Have you considered that you could have BPD as a matter of fact, and NOT autism? Not all BPD-ers are social and outgoing, quite a lot of them are also the quiet, introverted types - suffering more in silence from uncontrollable emotion, than the extroverted types.

 

 

If you do have problems with hyper-emotionality, then I figure something like HydroxyNorKetamine and AM-404 should do the trick.

Both are compounds I hope to administer to BPD-ers in the future, to study the effects - could they be the magic bullets that reign the emotionality in...?

[Duchykins]

 

 

 

 

 

Interesting.

 

You know, if it wasn't for your other problems, then because of the fact that you don't get headaches from Piracetam without filling up with choline, I would almost peg you as suffering from Borderline Personality Disorder...

 

Reason being that the disorder seems to have a clear connection to the cholinergic system - people with BPD produce many, many times more choline than regular people - a recent genetic study found this out, which then jumpstarted my many posts on the subject (wrote a prototype mini-article on it and everything) - Acetylcholine you see, is selective for certain aCh-receptors than others - notably, it's selective for the Nicotinic Alpha-7-receptor!

 

The NaCh-7-receptor controls much of the activity out of the Amygdala, much like the alpha-2-receptors control activity out of the Superior Parietal Lobe - hence, if you have problems with excessive aCh, emotional control is going to be very, VERY difficult...!

 

 

An interesting note btw - in the thread we also discussed how the diagnostic criteria for Autism is mainly geared towards men, and how the symptoms are actually DIFFERENT between the two sexes - autistic women often get slapped with an incorrect diagnosis, such as Borderline Personality Disorder - which then accounts for a great deal of the gender-discrepancy in that disorder - the amount of women afflicted have been inching closer to the amount of men afflicted for close to 15 years now - used to be 5% vs 95%, then it was 10%, but now it's friggin' 15%!

 

All because of new data, and fMRI and PET-scans, which show that these women do NOT have Bipolar or BPD, but are in fact autistic.

 

IMHO, this data will continue this trend - of altering diagnostic criteria according to new data, shrinking the gender-discrepancy.

 

 

However... this data is also interesting in the OTHER direction! Borderline Personality Disorder is a disease much more commonly diagnosed in WOMEN than in men, but, once again... there is new data implying that the previously HUGE gender-discrepancy among those afflicted, is as a matter of fact the results of incorrect diagnosing - many men are misdiagnosed as ADHD or Antisocial Personality Disorder, when in reality, they have BPD!

 

Now, coupled with all of the new data implying that BPD is NOT a "personality disorder", but rather it is a form of Neurodevelopmental Disorder - similar in some ways to both ADHD and Autism - then, you can see how this becomes intriguing, when it comes to you...
 

 

...Have you considered that you could have BPD as a matter of fact, and NOT autism? Not all BPD-ers are social and outgoing, quite a lot of them are also the quiet, introverted types - suffering more in silence from uncontrollable emotion, than the extroverted types.

 

 

If you do have problems with hyper-emotionality, then I figure something like HydroxyNorKetamine and AM-404 should do the trick.

Both are compounds I hope to administer to BPD-ers in the future, to study the effects - could they be the magic bullets that reign the emotionality in...?

 

 

 

I don't have any of the key symptoms of BPD.   If I have a PD, it's schizoid.  I'm not hyperemotional like my mom is, whom we believe has BPD.    My docs are still having trouble deciding if I'm an aspie, or schizoid.  I have several of the key symptoms of SPD except for the conduct problems and narcissism (I have a pathological sense of underentitlement, which we think was caused by my mom's sense of overentitlement and her repeated attempts to sabotage my developing independence), and I have huge trouble making eye contact and need to carry headphones everywhere I go since I have sensory processing problems and a desperate need for routine and periods of solitude to recover from ordinary things, which peg me for autism ... but everything is compounded by the very clear presence of PTSD via hypervigilance and hyperarousal and likelihood of ADHD since it runs in my family and my younger brother has it.  I have long-standing sleep-onset insomnia.  My daughter is autistic.   At this point, my docs don't seem to be intent on pinpointing a diagnosis and want to focus on treating symptoms, which I don't object to.

[Lia-chan]

I don't have any of the key symptoms of BPD.   If I have a PD, it's schizoid.  I'm not hyperemotional like my mom is, whom we believe has BPD.    My docs are still having trouble deciding if I'm an aspie, or schizoid.  I have several of the key symptoms of SPD except for the conduct problems and narcissism (I have a pathological sense of underentitlement, which we think was caused by my mom's sense of overentitlement and her repeated attempts to sabotage my developing independence), and I have huge trouble making eye contact and need to carry headphones everywhere I go since I have sensory processing problems and a desperate need for routine and periods of solitude to recover from ordinary things, which peg me for autism ... but everything is compounded by the very clear presence of PTSD via hypervigilance and hyperarousal and likelihood of ADHD since it runs in my family and my younger brother has it.  I have long-standing sleep-onset insomnia.  My daughter is autistic.   At this point, my docs don't seem to be intent on pinpointing a diagnosis and want to focus on treating symptoms, which I don't object to.

 

I have almost the same symptoms and I fully agree, that the only thing you have - is just to treat your symptoms. Hang in there good guy, I hope you'll get better.

[Duchykins]

 

I don't have any of the key symptoms of BPD.   If I have a PD, it's schizoid.  I'm not hyperemotional like my mom is, whom we believe has BPD.    My docs are still having trouble deciding if I'm an aspie, or schizoid.  I have several of the key symptoms of SPD except for the conduct problems and narcissism (I have a pathological sense of underentitlement, which we think was caused by my mom's sense of overentitlement and her repeated attempts to sabotage my developing independence), and I have huge trouble making eye contact and need to carry headphones everywhere I go since I have sensory processing problems and a desperate need for routine and periods of solitude to recover from ordinary things, which peg me for autism ... but everything is compounded by the very clear presence of PTSD via hypervigilance and hyperarousal and likelihood of ADHD since it runs in my family and my younger brother has it.  I have long-standing sleep-onset insomnia.  My daughter is autistic.   At this point, my docs don't seem to be intent on pinpointing a diagnosis and want to focus on treating symptoms, which I don't object to.

 

I have almost the same symptoms and I fully agree, that the only thing you have - is just to treat your symptoms. Hang in there good guy, I hope you'll get better.

 

 

Thanks, it feels nice to know some out there is like me and understands.

[jack black]

My vote is for polygala tenuifolia extract. The examine.com has extensive info how it works as antidepressant and procognitive. I tried it on days I was depressed and the effect was immediate. IMHO this is the real deal and one of the best supplements I tried. I use it only as needed because I'm afraid tolerance may develop.

Sadly, I spoke too soon. Polygala does nothing after several days. One of the reviewers on Amazon mentioned that too.

But, I discovered something new. Piracetam is antidepressant for me. I thought I felt some stimulation from it before, but was not depressed at that time. Recently got depressed due to stress/personal/work/setbacks. I'm super sensitive to that. After suffering for over a week, I started using some of my old supplements. It was not until I took piracetam, the depression magically lifted within a couple of hours. It could be the entire combo, but I found a publication on it being helpful in anxiety and depression.

Enjoy: https://www.ncbi.nlm...pubmed/20166767

[normalizing]

i also want to mention polygala being useless as antidepressant. after reading so many good positive results i had to try it and from the very first 2 times i used it, i felt confused and sedated kind of, but not in a comfortable antidepressive way at all, it made me more depressed in fact. first time i took it i wasn't even depressed mostly curious, but it definately made me depressed and made me feel crappy, for sure.

Edited by hazy, 10 March 2017 - 09:18 PM.

[jaiho]

It took me far too long to learn that self treating depression with random nootropics & supplements doesn't work out so well.

Especially if it's very severe (Anhedonia, blank mind, emptyness)

 

You're on the right path OP.

I agree with others that the most pro cognitive is the one your brain is compatible with. Your brain makeup decides what receptors are occupied by certain drug actions.

Hence why some people get no sexual side effects, others do. And same with anti cholinergic side effects, and emotional numbness.

[SimplyHuman]

But all of this is beside the point - if you have a specific chemical imbalance that's related to your depression, then trying to go for the most "pro-cognitive" is not really going to help you since they all work differently. So for example if you really do have a chronic problem with low serotonin, then something like bupropion is just going to make your depression worse.

I have to be very honest here: no prescription antidepressants have helped me in the long run. Only getting into supplements that support mitochondrial functioning have ever helped me in a well-rounded way, with few side effects. It's a much more expensive way because I cannot get them covered by insurance, but they work.

Care to elaborate about what supplements support mitochondrial function? And does this relate to receptor health?

[SimplyHuman]

I have to be very honest here: no prescription antidepressants have helped me in the long run. Only getting into supplements that support mitochondrial functioning have ever helped me in a well-rounded way, with few side effects. It's a much more expensive way because I cannot get them covered by insurance, but they work.

Could you tell us more about this?

My daily stack is ridiculous partly because I take everything separately and stagger the larger doses through the day, but here's just the ones I take that focus on different aspects of mitochondrial function:

riboflavin (400 mg)

thiamine (400 mg)

adenosylcobalamin / hydroxocobalamin 50%/50% (2 mg) (methylcobalamin is excessively popular but is not a substitute for the adenosylcobalamin - you need both and your body can make methylcobalamin from adenosylcobalamin but not vice versa)

pantethine (300 mg)

niacin-bound chromium (200 mcg)

(this is in addition to an all-active B complex from Swanson's, because that complex doesn't have enough of certain things and I really need the 400 mg riboflavin for migraine prophylaxis)
___

benfotiamine (25 mg)
riboflavin 5'-phosphate (25 mg)
inositol hexanicotinate (50 mg)
pyridoxal 5'-phosphate (25 mg)
methylfolate (400 mcg)
methylcobalamin (250 mcg)
pantethine (25 mg)
biotin (25 mcg)
___


ubidecarenone (200 mg, sometimes 300 mg)

creatine, micronized (1 g)

l-carnitine (not ALCAR - they are not the same molecule) (1 g)

l-carnosine (1 g)

taurine (500 mg)

citrulline malate (1 g)

l-lysine (500 mg)

All the usual electrolytes, including low-dose lithium. The magnesium supp I take comes with extra 12.5 mg benfotiamine and 2.5 mg P5P, which is fine.

A very low-dose, low-copper, iron-free Albion multimineral.

I take a 1g high-DPA, high-DHA, low-EPA fish oil capsule once every third day. The fatty acid supplements should not be taken daily, and it's a waste of money to do it.

I also take a 5 mg biotin capsule every third day, but that's just because the brand I was usually getting 1 mg caps from stopped making them, which pissed me off. 5 mg biotin is too much to take daily for an extended period of time.



The explanations for all of these are very long-winded, took hours and weeks of poring over medical literature (probably forgot half of it by now), and I can't be bothered with the time right now. But the information for all of these in relation to general mitochondrial function (cell energy production, energy transport, etc) is easily found in medical literature and databases.

I've not tried nicotinamide riboside. Sounds like hype, but I've not tried anything new in a long time since I seemed to have hit a sweet spot with my supps and don't want to mess with a good thing. Being a migraineur makes everything more complicated since a lot of things that work well for most people will trigger migraines in me. It's also why I take nearly everything separately, most blends and multis contain at least one thing that I should not have.

I just saw this. Interesting absence of L-Glutamate. Any specific reason? PS - you're awesome