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Best nootropic antidepressant?

ssris snris dnris antidepressant nsi-189

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#1 Heinsbeans

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Posted 03 February 2016 - 03:47 PM


Hi, I'm 25 y/o and I've been issues with attention, motivation, mental energy, learning, memory and problem solving for as long as I can remember which has always been negatively affecting my ability to work/find work and get decent grades. I was never an academic person and I didn't get good marks in high school so I had to give up higher education and my life became much harder after high school since I had to find a job. TL;DR

 

I went to the the doctor about my mental struggles and he told me I was "depressed" which was the cause of all of my cognitive problems(which I didn't/still don't believe) and put me on 10mg Escitalopram. Although Lexapro/Escitalopram has helped with my frequent low mood, it worsened my memory and made me even more demotivated and not care about anything in life.

 

So I then made an appointment with an psychiatrist and she told me that I have a generalised anxiety disorder and depression which is what's causing my cognitive issues(which I don't believe either). She initially said that I should try a higher dose of Escitalopram but then she changed her mind and told me I should try Cymbalta. She eventually bumped me up to 120mg and I've been on 120mg for over 3 months now. To my surprise, Cymbalta has increased my motivation, attention and mental energy but it also made me anti-social and harder laugh, smile, empathise and socialise with people. I still feel like there's room for improvement. Should I consider switching to other antidepressants? Which antidepressants are considered to have the most 'nootropic' effect? 

 

I've been using this website to figure out which antidepressant I should try next: http://www.drugs.com...depression.html but my doctor told me that I shouldn't rely on which drugs has more positive reviews since every drug affects people differently.

 

My current depression/brain fog stack is Cymbalta 120mg, Souvenaid, Coffee, ALCAR, Alpha GPC, Magnesium L-Threonate, Fish oil, occasional High-strength Krill oil, Phosphatidylserine, Longvida curcumin and Beetroot juice. Thus far, I'm feeling the most cognitive benefit from Cymbalta, Coffee and Souvenaid/Uridine. I feel like my memory recall has improved since I've started taking Uridine. 

 

From the limited research I've done, I'm considering trying Centrophenoxine, Lions Mane, Bacopa, Myo-Inositol, Sulbutiamine, Cerebrolysin, Memantine as well as other antidepressants such as NSI-189 or Wellbutrin. But I'm still in the middle of researching about them to figure out if they're safe, worth experimenting with and appropriate for my condition.


Edited by Heinsbeans, 03 February 2016 - 04:17 PM.

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#2 medievil

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Posted 25 February 2016 - 10:09 AM

I would start with either coluracetam or nsi



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#3 Ovi

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Posted 04 March 2016 - 07:19 PM

The most used antidepressant with nootropic properties is probably tianeptine. Works just as well as a SSRI and lacks the cognitive side effects. A reversible MAO-A inhibitor such as moclobemide might also be a better choice than SSRIs since it's less likely to have cognitive side effects, although it's not nootropic. Typical nootropics such as selank and semax also have anxiolytic and antidepressant effects, but these effects are less significant than that of say tianeptine. Antidepressant experimental drugs that seem to be very effective and are nootropic include NSI-189 and NMDA partial agonists such as GLYX-13 and NRX-1074.


Edited by Ovi, 04 March 2016 - 07:22 PM.

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#4 medievil

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Posted 04 March 2016 - 08:55 PM

Cafeine has been shown to enhance the nootropic effect of cymbalta as an aside, that said dont change your antidepressant if you notice beneficial effects, if you find something that works stick with it, some ppl think treatment resistance is no issue and you can just change anything that has any issues to a plethoria of differened options, haha if that was true.If cymbalta makes you antisocial then you need to look into dopaminergic augmentation.

 

Low dose amisulpiride, amphetamine, ritalin etc



#5 medievil

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Posted 04 March 2016 - 09:01 PM

The most used antidepressant with nootropic properties is probably tianeptine. Works just as well as a SSRI and lacks the cognitive side effects. A reversible MAO-A inhibitor such as moclobemide might also be a better choice than SSRIs since it's less likely to have cognitive side effects, although it's not nootropic. Typical nootropics such as selank and semax also have anxiolytic and antidepressant effects, but these effects are less significant than that of say tianeptine. Antidepressant experimental drugs that seem to be very effective and are nootropic include NSI-189 and NMDA partial agonists such as GLYX-13 and NRX-1074.

I dont really see the point is those ketamine based antidepressants, what makes them better, and what is less significant then tianeptine? imo they are far superior nootropics, not really sure how strong of antidepressants they are, but if they are antidepressants and not as strong as tianeptine thats diappointing imo, as tianeptine is only as strong as prozac and simular antidepressants... eg really weak



#6 Autumn Knight

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Posted 28 March 2016 - 04:27 AM

Is it possible to get Tianeptine without a prescription?



#7 tintinet

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Posted 09 April 2016 - 10:17 PM

Is it possible to get Tianeptine without a prescription?


Yes

#8 FunkOdyssey

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Posted 09 April 2016 - 11:37 PM

Heins: before you embark on further trials of psychiatric medication, I humbly suggest you read Kelly Brogan's new book, A Mind of Her Own.  Despite its feminist theme and exclusive focus on women, it should be essential reading for anyone suffering from psychiatric disorders.  The approach it prescribes is far more promising than drug treatment which, as almost anyone who has tried it long enough and extensively enough will tell you, rarely causes a permanent / sustained remission of symptoms and more often ensures the continued decline of your mental health.  Hopefully, the book saves you the 10 years of failed experimentation with drugs that it took me to reach the conclusion that they are not a legitimate solution.


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#9 OneScrewLoose

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Posted 10 April 2016 - 06:43 AM

I find Cymbalta to be an unusual medication for only a 2nd antidepressant, but I'm glad it's working for you. I think you should stay on it and mitigate the side effects.

Stop adding things to your stack. I see large stacks on here, and when the variables get to high, it becomes hard to say what does what. If you truly want to add something, take away something else first.

 

When you're next appointment with your doc? Buspar might be worth a short to combat the side-effects. It activates the 5HT1a receptor, which releases oxytocin and might make you more sociable again.


Edited by OneScrewLoose, 10 April 2016 - 06:44 AM.


#10 Heinsbeans

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Posted 16 May 2016 - 02:08 AM

Although Cymbalta didn't negatively affect my memory as much as Escitalopram did and it even increased my alertness and motivation(from norepinphrine inhibition), I felt like it was hindering my creative thoughts and ability to learn/retain information(long-term memory). What's the point of being motivated if I have trouble learning and forming long-term memories? So I decided to get off of it in February this year and I've been feeling much better without it. I was on it for 7 months.

 

I've heard the recent news about a lot of antidepressants having anticholinergic effects and they're supposedly permanent: https://www.reddit.c..._damage/d2af7mo

 

I was considering trying Wellbutrin but not anymore since this guy said he never felt the same again ever since he took Bupropion: https://www.reddit.c..._damage/d2aeynf

 

I'm worried now, I've read that Duloxetine isn't very anticholinergic but it can be at high dosage according to this study: http://www.ncbi.nlm....pubmed/18510583

 

And my psychiatrist put me on the highest possible dosage @ 120mg and she wanted me to stay on it for at least a year...

 

I was considering NSI-189 but since we don't know its MoA, for all we know, it could be extremely anticholinergic so I'm not sure if I should even try it. Besides, NSI-189, I'm considering trying Zoloft since Esctialopram and Sertraline has been shown to be the most effective antidepressant according to this 2009 meta-analysis study( http://www.ncbi.nlm....pubmed/19185342 ) and I've already tried Escitalopram which just worsened my memory and lowered my motivation. And also because I've read that Zoloft in particular have been shown to restore hippocampal volume in depressed people which tends to be shrunken from chronic depression(assuming that my cognitive deficits are causes by depression):  http://www.psychiatr...article/437481/

 

But then again, SSRIs antidepressants are based on 30 years of outdated theory so I'm not sure if it's even worth taking it and risking the side effects...I probably should just stick with nootropics with antidepressant effects instead.

 

I've recently begun taking 30mg Noopept and it's beginning to help my mood and short-term memory so I might just stick with it for now and see how long the benefit lasts.


Edited by Heinsbeans, 16 May 2016 - 03:01 AM.


#11 Heinsbeans

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Posted 16 May 2016 - 03:20 AM

Here are my experience with other nootropics: https://www.reddit.c...ith_nootropics/

 


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#12 cat-nips

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Posted 23 May 2016 - 01:01 PM

I've been looking at brintellix for its pro-cognitive effects. Unfortunately it's not covered by insurance and I have no experience with it to give an anecdotal.

That being said, any SSRI after a couple of days will start to induce apathy and demotivation for me so I generally avoid them or only take a minute dose for 2 or 3 days when I start to feel too edgy and irritable. Currently I'm using celexa or lexapro at 5mg for this but at the lowest amount possible because while anxiety does diminish, the motivation trade off isn't worth it.

I'm not sure about mixing so many race tams with your cymbalta. I would never expect anything ssri related to help with cognition. Maybe if you take the ssri in the evening and then modafinil in the morning, it could be helpful and help alleviate your cognitive issues. Perhaps ask your psych to try it or switch to brintellix, although I remain cynical until more is known.

Guanfacine also helps with memory considerably but has some trade offs like sedation or hypotension or even depression. In this case, less is more. You have to take it beyond the 3-4 day period at the same time and yes it will cause extreme sedation at first but it will usually level out and go away after that. Dosing schedule is important here and I found that the higher doses made me feel worse and more tired/cold/depressed, probably from the lowered blood pressure. But lower doses at 1 mg or less were effective for memory and even anxiety a bit, but it had to generally be taken at the same time. I have not tried Tenex, the ER version.

I would think modafinil in the ams and a low dose ssri in the evening may be helpful. Clearly the dopamine/serotonin balance is important here as you don't want to have extremely high serotonin levels effecting learning and motivation.

#13 tintinet

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Posted 28 May 2016 - 12:13 PM

I've tried many things. The only ones I've found effective for me are uridine, modafinil, and caffeine.

#14 medievil

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Posted 28 May 2016 - 07:01 PM

Heins: before you embark on further trials of psychiatric medication, I humbly suggest you read Kelly Brogan's new book, A Mind of Her Own.  Despite its feminist theme and exclusive focus on women, it should be essential reading for anyone suffering from psychiatric disorders.  The approach it prescribes is far more promising than drug treatment which, as almost anyone who has tried it long enough and extensively enough will tell you, rarely causes a permanent / sustained remission of symptoms and more often ensures the continued decline of your mental health.  Hopefully, the book saves you the 10 years of failed experimentation with drugs that it took me to reach the conclusion that they are not a legitimate solution.

As i allways say, you have to stay open to all potential options, but saying that drugs wont work long term and that that is the way to go is the sam idiocy as ppl saying natural sups are the way to go, or ppl just saying go for meds etc, evertyone has their own individual solution which you can you only find by staying open to alloptions.


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#15 sativa

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Posted 01 June 2016 - 07:14 PM

But then again, SSRIs antidepressants are based on 30 years of outdated theory so I'm not sure if it's even worth taking it and risking the side effects...I probably should just stick with nootropics with antidepressant effects instead.


Yes, IMHO pharmaceutical SSRI's are an abysmal yet widely used method of "patching up" depression. The SSRI mode of action has detrimental long term undesirable side effects all stemming from serotonin receptor down regulation and dysfunction.

I recently acquired some Tianeptine which, when dosed at 12-25mg (usually once a day) has pleasant antidepressant effects with an added cognitive enhancing boost.

#16 normalizing

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Posted 01 June 2016 - 11:31 PM

did you get in original box or some of those powders? i have hard time dealing with the powders not sure how much to take as unike the pills, they do not as well in the accepted range of mgs



#17 Autumn Knight

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Posted 02 June 2016 - 04:15 AM

How would a person go about getting NSI-189?



#18 sativa

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Posted 02 June 2016 - 09:29 PM

did you get in original box or some of those powders? i have hard time dealing with the powders not sure how much to take as unike the pills, they do not as well in the accepted range of mgs


I got a gram of Tianeptine powder, which I dissolved in some vodka so that each milliliter equates to ~22.5mg.

One ~22.5mg dose is good for me for a day and I feel positive after effects for at least the next day.

Note that i'm not treating any underlying condition and don't regularly take any drug (except adaptogens most days).

I avoid redosing Tianeptine due to Mu (mainly) and Delta opioid receptor agonism which, in high doses, can cause uncomfortable opioid withdrawal (due to receptor down regulation).

Which reminds me, I had 3 drops of iboga tincture last night so potentially, iboga could offset the receptor down regulation from high dose Tianeptine.

There seems to be no need for high doses of Tianeptine anyway, from what I've read, 12-25mg seems adequate for most people.

This also reminds me to make a solution of my memantine powder!

I was also considering combinations with Tianeptine and uridine/theanine/agmatine/memantine.

What about memantine and uridine?

Perhaps memantine and other antagonists taken first to unregulate various important receptors, eg +a small dose of scopolamine (from datura stramonium seeds) for full acetylcholine receptor upregulation - followed by uridine or Tianeptine or another agonist to make full use of the newly upregulated receptors.

Perhaps some BDNF/GDNF/NGF substances too (whuch would also affected by memantines alpha 7 activity).

Take antagonists before bed then take the agonists or positive modulators upon waking...

I digress!!

Edited by sativa, 02 June 2016 - 09:40 PM.


#19 jaiho

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Posted 04 June 2016 - 12:21 AM

The reason SSRI/SNRIs cause cognitive & emotional deficits is due to free reign on the 5HT2A/C system.

Block these receptors with an augmenting agent like Nortriptyline, and you reduce sexual side effects, and get increased dopamine transmission.

All SSRIs need 5HT2C potently blocked, otherwise dopamine transmission is reduced (Anhedonia, lack of motivation blahness)

 


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#20 sativa

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Posted 04 June 2016 - 12:35 PM

What about down regulation of serotonin receptors! Doesn't the play a role in the side effects/emotional blunting etc?

#21 normalizing

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Posted 04 June 2016 - 01:51 PM

jaiho, not sure what makes you recommend specifically Nortriptyline, you have prior experience with this? its one of those nasty tricyclic antidepressants and i cannot ever think it might effect dopamine in any positive way



#22 thedevinroy

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Posted 05 June 2016 - 02:17 AM

As far as Cymbalta causing you to be more withdrawn, I too noticed a similar effect with Strattera. When reading that article about stress causing neuronal shrinkage and ALCAR reducing its effect, I would say it wouldn't be to out of line to assume that increased norepinephrine levels, which can put your thoughts into more stressful territory, could have an impact on the amygdala's function and consequently reduce socialization.

Good news is that ALCAR already is in your stack. Also, I would take the advice of others who have recommended certain adaptogens like Bacopa, for instance. Ashwagandha is my particular favorite. The theory behind adaptogens is that they help reduce stress in stressful situations. You would think that Cymbalta's serotonergic effects would help with that, but maybe you need more boost in that direction or maybe a GABAergic boost or even an endorphin boost to help reach your potential.

Edited by devinthayer, 05 June 2016 - 02:19 AM.


#23 Junk Master

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Posted 08 June 2016 - 04:33 AM

As an aside, I was on Cymbalta for a couple years and heard so many horror stories about brain zaps etc...upon cessation, but when after a few years of CBT and intense aerobic exercise, plus finding this site and Tianeptine, NSI-189, even Piracetam for starters, I decided to quit, I had very mild withdrawal symptoms for less than three weeks.



#24 NG_F

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Posted 27 August 2017 - 08:53 PM

The reason SSRI/SNRIs cause cognitive & emotional deficits is due to free reign on the 5HT2A/C system.

Block these receptors with an augmenting agent like Nortriptyline, and you reduce sexual side effects, and get increased dopamine transmission.

All SSRIs need 5HT2C potently blocked, otherwise dopamine transmission is reduced (Anhedonia, lack of motivation blahness)

 

Wouldn't Nortriptyline's anti-cholinergic effect negate the potential 2A/2C antagonistical properties?

 What about prozac, do the 5HT2C anatagonist properties diminish if high dosages of 20-60 mgs are neeeded? 

 

Others I can think of are Remeron and Agomelatine. 



#25 Heinsbeans

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Posted 28 August 2017 - 07:42 AM

It shouldn't. If I'm understanding correctly, anticholinergics mainly affect acetylcholine production/transmission. Prozac's 5-HT2C antagonism is not that potent, but it might become more pronounced if you combine it with Valdoxan. There aren't any favourable 5-HT2A/2C antagonists right now besides Remeron and Agomelatine. Flibanserin has a unique way of acting as NDDIs via 5-HT1A full agonism + partial agonism. The other's are either antipsychotics or TCAs which are anticholinergic and has lower toxicity ceiling. We'd have to wait until S32212 is released into the market.


Edited by Heinsbeans, 28 August 2017 - 07:46 AM.


#26 CWF1986

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Posted 04 October 2017 - 08:37 AM

There's some misunderstandings about nortriptyline.  It is a vast improvement over the earlier TCAs like amitryptyline or imipramine.  It isn't any more toxic than SSRI's and arguably just as tolerable.  

 

I take 150mg of nortriptyline and it's far less sedating than just 25mg of amitriptyline.  

 

The antihistamine effects are great for me because they help me sleep and where off by the time I need to wake up.  The anticholinergic effects are minimal to none after a month or so.  Arguably, the anticholinergic effects are part of the therapeutic effect.  I know taking even weaker cholinergics like lecithin can cause depression and anxiety for me and huperzine causes me straight up despair and suicidal thoughts (but not intent).  There's some good evidence and theory that acetycholine has an important role in depression.  It gave me a lot of relief from anxiety, depression, nervous stomach syndrome, adhd, and even fixed my mild to moderate allergies.  I also took it with adderall for adhd, granted it also helps with depression.  

 

There's two theoretical ways nortriptyline can increase dopamine.  First is the anticholinergic effects.  Decrease acetylcholine activity and you increase dopamine activity.  The second is 5ht2a/c antagonism.  This is most likely why prozac is generally the most activating SSRI.  

 

It was the first antidepressant for me.  Lexapro was then added many months later and the trio has given me complete relief from my anxiety and depression disorders.  Yes I get sad and nervous at times, but like normal people and not for long periods of time.  I have not experienced emotional numbing, amotivation, or sexual side effects.  I imagine this is at least in part due to the nortrip, but having never taken it on its own I can't say for certain for myself.  



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#27 Kinesis

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Posted 04 October 2017 - 10:30 PM

Here’s one advantage of amitriptyline:

https://www.ncbi.nlm...les/PMC2844702/

“... potent neurotrophic activity ...”





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