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Current Stack Update: Depression, Anhedonia, Cognitive Decline, GAD, Social Anxiety

depression anxiety escitalopram agomaletine buspirone nsi 189

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#1 VICREP

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Posted 27 January 2015 - 04:02 AM


I'm going to post up my current Pharmaceutical stack I'm taking hoping to reveres the damage of years of depression coupled with moderate drug abuse.

 

My main goal is to repair the significantly noticeable brain fog and cognitive decline I have faced after chronic stress and bouts of MDD. I have also had no sexual desire or libido for years either. Note I'm a 23 year old Male.

 

I was literally at rock bottom before starting this stack and am still having  some problems. See if you guys can help.

 

I'll also break down my stack with supporting studies. BTW, every pharmaceutical I take is prescribed legally in Aus.

 

Stack

5mg Escitalopram.(lexapro) - Daily

Busprione 5 mg - T.I.D

Agomelatine (Valdoxan) 50 mg - Nightly

NSI-189 20mg - B.I.D (just added)

 

occasionally

15-25mg Dextroamphetamine - Daily(5mg doses)

 

 

Stack Synopsis

 

Lexapro

  • I take lexapro for my depression/anxiety/OCD symptoms. It has been an enormous help so far in eliminating about 50% of my Depression/Anxiety. Looking to take it for 6-12 months since i sincerely believe I have been deficient in Serotonin function for quite some time and am hoping some long standing adaptive changes will take place in my brain and lifestyle. 
  • Hippocampal neurogenesis is a proposed benefit from chronic SSRI treatment (http://www.ncbi.nlm....pubmed/19623606)
  • My concerns are that my already suppressed libido will further become damaged by the serotonin flooding my mesolimbic system.

Busprione

  • Should help counter some some of the sexual sides from Lex whilst improving the efficacy, especially for anxiety (http://www.ncbi.nlm....pubmed/11465522, also http://www.ncbi.nlm.nih.gov/pubmed/8666569)
  • Additionally when paired with melatonin (Agomelatine) is linked to having neurgenesis properties of benefit to MDD (http://www.sciencedi...022395612002464)
  • A few queries I have about buspirone are does it need to be at stable blood levels (short half-life) to elicit it's pro-sexual effects with SSRI's? Even though it has DA antagonists properties that has preferential affinity for the presynaptic/auto-receptors, should I be concerned it may impact on the effects of amphetamine?

Agomelatine

 

NSI-189

 

Dextroamphetamine

  • I was diagnosed by my Psych as having Adult ADHD. I'm not hyperactive, more severe inattention. I struggle to watch a movie, TV show, or apply and sustained mental effort, even when the task is seemingly interesting. I really don't want to be using an amphetamine due to the potential risks to the brain, reward system, and also the hair thinning I seem to get, but it is the only thing working to keep me calm, directed and focused. Without it, I'm a disorganized, procrastinating, amotivational mess.
  • I wouldn't think that there would be any concerns using low-end therapeutic doses for short periods of time.

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#2 TheWorldAroundUs

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Posted 28 January 2015 - 09:40 PM

Would you be willing to try Non-pharmaceutical supplements as well? For one I would recommend supplementing with Antioxidants that can cross the BBB(N-acetylcysteine, Vitamin C, Vitamin E, Green Tea etc.) and Neurotransmitter Precursors(L-tyrosine and L-tryptophan) as well as Neurotransmitter synthesis cofactors(Magnesium, Folate, Vitamin B6 and B12, L-lysine and a few others) to prevent/reduce Dextroamphetamine Neurotoxicity and Neurotransmitter Depletion if you are going to keep using it. Additionally you might want to look into NMDA antagonists(Magnesium, Zinc, L-phenylalanine) to protect your brain from any Glutamate Excitotoxicity that the Amphetamine might cause.

 

Alternatively you could look for alternatives to Dextroamphetamine, especially if focus is the main reason why you are using it. I find high doses of L-tyrosine combined with a low dose of ephedrine or high dose of caffeine to work great for my ADHD. You could also look into acetylcholinergic supplements and substances for your focus(Choline, Racetams, CDP-Choline and a few others). They could potentially be much safer than amphetamine, but not always, always double check the studies done on them.

 

Honestly I can not recommend taking anything other than vitamins and minerals alongside pharmaceuticals because of potential interactions. But if you were to say, dump all the pharms and start from scratch: I would recommend looking into Kava, its a sedative herb that acts on the brain similar to alcohol/benzos, yet is basically non-addictive and actually improves the function of GABA receptors in the long term, instead of damaging and desensitizing them like alcohol and benzos. It also has other goodies like a dopamine reuptake inhibitor, a norepinephrine reuptake inhibitor, an maoi inhibitor and a cannabinoid receptor agonists so it could prove very useful for your anxiety disorders(because of Gaba enhancing actions) your anhedonia and depression(because of its dopamine and norepinephrine reuptake inhibition as well as its mao-b inhibition) and cognitive decline(Because of its actions on dopamine, norepi and mao-b). Other stuff to look at for that is L-tyrosine(Dopamine precursor) and perhaps even low doses of Mucuna pruriens(Contains L-dopa, a dopamine precursor that is more potent than L-tyrosine).

 

Also take a look at Gaba and serotonin enhancing supplements like L-tryptophan(Serotonin precursor), 5-htp(Serotonin precursor that is more potent than L-tryptophan, use very sparingly due to heart risks), L-theanine(Enhances Gaba activity), Kava(Stated above) and a few others for your anxiety issues.

 

Additionally, in the long term you might look into supplements that modulate(help regulate) the neurotransmitter systems in your brain, Uridine is a good one for Dopamine, i'm not sure about other ones, take a quick look around the forums and you're sure to find a few great ones.

 

If I were you and I dumped all my pharms and started from scratch, I would start off with each recommended supplement ALONE and then slowly introduce them in combination in very low doses just to see how they interact. Make sure to talk to your psych about dumping the meds because withdrawal symptoms may be present, especially with the SSRIs

 

Best of luck and keep me posted.


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#3 the_apollo

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Posted 28 January 2015 - 11:39 PM

Buspirone isnt that great,

 

 

Live cell assays also revealed that buspirone, and its metabolites, function as antagonists at both D3 and D4 receptors.

http://www.fasebj.or...Abstracts/661.4

 

 

Our results indicate that buspirone at 1.25, 2.5, 5 mg/kg blocks only presynaptic nigrostriatal D2 DA autoreceptors while at 10, 20, 40 mg/kg, it blocks postsynaptic striatal D2 and D1 DA receptors. Furthermore,

buspirone at 1.25, 2.5, 5 mg/kg by selectively blocking presynaptic nigrostriatal D2 DA autoreceptors

http://www.ncbi.nlm....pubmed/18476392

 

The last one could explain why so many who try buspirone says they experience negative changes on mood, anxiety and motivation.

The dosages is the said study would be high in human, but im guessing that it's rat dosage, which is much higher than human dosage in comparison.



#4 VICREP

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Posted 29 January 2015 - 02:42 AM

Thanks for your replies guys

 

Would you be willing to try Non-pharmaceutical supplements as well? For one I would recommend supplementing with Antioxidants that can cross the BBB(N-acetylcysteine, Vitamin C, Vitamin E, Green Tea etc.) and Neurotransmitter Precursors(L-tyrosine and L-tryptophan) as well as Neurotransmitter synthesis cofactors(Magnesium, Folate, Vitamin B6 and B12, L-lysine and a few others) to prevent/reduce Dextroamphetamine Neurotoxicity and Neurotransmitter Depletion if you are going to keep using it. Additionally you might want to look into NMDA antagonists(Magnesium, Zinc, L-phenylalanine) to protect your brain from any Glutamate Excitotoxicity that the Amphetamine might cause.

 

Alternatively you could look for alternatives to Dextroamphetamine, especially if focus is the main reason why you are using it. I find high doses of L-tyrosine combined with a low dose of ephedrine or high dose of caffeine to work great for my ADHD. You could also look into acetylcholinergic supplements and substances for your focus(Choline, Racetams, CDP-Choline and a few others). They could potentially be much safer than amphetamine, but not always, always double check the studies done on them.

 

Honestly I can not recommend taking anything other than vitamins and minerals alongside pharmaceuticals because of potential interactions. But if you were to say, dump all the pharms and start from scratch: I would recommend looking into Kava, its a sedative herb that acts on the brain similar to alcohol/benzos, yet is basically non-addictive and actually improves the function of GABA receptors in the long term, instead of damaging and desensitizing them like alcohol and benzos. It also has other goodies like a dopamine reuptake inhibitor, a norepinephrine reuptake inhibitor, an maoi inhibitor and a cannabinoid receptor agonists so it could prove very useful for your anxiety disorders(because of Gaba enhancing actions) your anhedonia and depression(because of its dopamine and norepinephrine reuptake inhibition as well as its mao-b inhibition) and cognitive decline(Because of its actions on dopamine, norepi and mao-b). Other stuff to look at for that is L-tyrosine(Dopamine precursor) and perhaps even low doses of Mucuna pruriens(Contains L-dopa, a dopamine precursor that is more potent than L-tyrosine).

 

Also take a look at Gaba and serotonin enhancing supplements like L-tryptophan(Serotonin precursor), 5-htp(Serotonin precursor that is more potent than L-tryptophan, use very sparingly due to heart risks), L-theanine(Enhances Gaba activity), Kava(Stated above) and a few others for your anxiety issues.

 

Additionally, in the long term you might look into supplements that modulate(help regulate) the neurotransmitter systems in your brain, Uridine is a good one for Dopamine, i'm not sure about other ones, take a quick look around the forums and you're sure to find a few great ones.

 

If I were you and I dumped all my pharms and started from scratch, I would start off with each recommended supplement ALONE and then slowly introduce them in combination in very low doses just to see how they interact. Make sure to talk to your psych about dumping the meds because withdrawal symptoms may be present, especially with the SSRIs

 

Best of luck and keep me posted.

 

Trust me the pharmaceutical route was not even on my radar a couple years ago when I first started try to treat my symptoms. It was only after I had exhausted all non-pharmaceutical treatment that I started exploring medical intervention.

 

I have tried racetams, deprenyl, various vitamins & minerals, SJW, L-Dopa, choline sources, Dopamine agonists, Bupropion, hormonal agents (Arimidex, test boosters), etc, etc. I think I'm starting to make some progress in my treatment using a combination of AD's, and other pharms.

 

 

Buspirone isnt that great,

 

 

Live cell assays also revealed that buspirone, and its metabolites, function as antagonists at both D3 and D4 receptors.

http://www.fasebj.or...Abstracts/661.4

 

 

Our results indicate that buspirone at 1.25, 2.5, 5 mg/kg blocks only presynaptic nigrostriatal D2 DA autoreceptors while at 10, 20, 40 mg/kg, it blocks postsynaptic striatal D2 and D1 DA receptors. Furthermore,

buspirone at 1.25, 2.5, 5 mg/kg by selectively blocking presynaptic nigrostriatal D2 DA autoreceptors

http://www.ncbi.nlm....pubmed/18476392

 

The last one could explain why so many who try buspirone says they experience negative changes on mood, anxiety and motivation.

The dosages is the said study would be high in human, but im guessing that it's rat dosage, which is much higher than human dosage in comparison.

 

Busprione is a tricky one. I was hopeful using Buspirone would help mitigate the sexual side effects of Lexapro, however I think  have noticed that it negatively impacts mood, motivation, etc, without a significant impact on libido.

 

I was under the impression adding it wouldn't hurt since it's DA anatgonism at low doses (I'm on 5mg TID) was preferentially presynaptic, leadin to an increase in DA neurtransmission, possibly being synergistic with stimulants.

 

I wouldn't take Dex or any other stimulant unless I think I really needed it. Before starting the SSRI I had pretty severe inattention difficulties, but they were often secondary to my concerns in relation to my depressed mood and anxiety. Of course since Lexapro has been working so well on these issues, i'm now left with a flat, apathetic, inattentive state, which is hard to differentiate between whthere it has been worsened by the SSRI, or more evident in the absence of mood/anxiety issues.

 

I'm not too concerned even if I don't have true ADHD and am using a stimulant whilst I'm on the SSRI, as long as the dose doesn't escalate beyond therapeutic range, an I think it helps me beyond the initial euphoria stimulats tend to induce.

 

 



#5 the_apollo

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Posted 29 January 2015 - 07:34 PM

Busprione is a tricky one. I was hopeful using Buspirone would help mitigate the sexual side effects of Lexapro, however I think  have noticed that it negatively impacts mood, motivation, etc, without a significant impact on libido.

 

I was under the impression adding it wouldn't hurt since it's DA anatgonism at low doses (I'm on 5mg TID) was preferentially presynaptic, leadin to an increase in DA neurtransmission, possibly being synergistic with stimulants.

 

As was i when i tried buspirone, but within a day or two i became very lethargic, with almost only my anxiety keeping me mentally active,

not a very good combination or experience for me.


Edited by the_apollo, 29 January 2015 - 07:37 PM.


#6 VICREP

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Posted 30 January 2015 - 02:12 AM

 

Busprione is a tricky one. I was hopeful using Buspirone would help mitigate the sexual side effects of Lexapro, however I think  have noticed that it negatively impacts mood, motivation, etc, without a significant impact on libido.

 

I was under the impression adding it wouldn't hurt since it's DA anatgonism at low doses (I'm on 5mg TID) was preferentially presynaptic, leadin to an increase in DA neurtransmission, possibly being synergistic with stimulants.

 

As was i when i tried buspirone, but within a day or two i became very lethargic, with almost only my anxiety keeping me mentally active,

not a very good combination or experience for me.

 

 

I think I might drop the buspirone for now. 

 

I also want to get myself off dex for at least a few weeks, to see if my ADHD symptoms may be treated indirectly by the SSRI lowering my depression and anxiety.

 

NSI-189 I'm not sure about. I feel it's effects but its not really improving my mood. Maybe even this I should take a break from and let the SSRI and agomelatine take full effect.

 

I just know if I take the SSRI, and agomelatine by without anything to help with concentration and motivation, I'll be hopeless at getting anything done.



#7 owtsgmi

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Posted 31 January 2015 - 05:21 PM

Give NSI-189 a couple of weeks. If it works like it did for me, you will begin re-experiencing negative autobiographical memories and re-wiring your brain to resolve the embedded conflicts. A type of fear extinction. NSI-189 didn't do a lot of mood brightening but did it do repair work. I took it a few times for about a month each and no longer require it.

#8 VICREP

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Posted 17 February 2015 - 10:33 PM

Update:

 

Ok so I ended up adjusting things a bit based on my own subjective experience, and from digging a bit deeper with research.

 

I settled on 5mg escitalopram, 50mg Agomelatine, and 15-25mg Dextroamphetamine a day.

 

After a few weeks on 5mg escitalopram, I decided to bump it up to 10mg and have been on that for a couple of weeks now. This is where problems have begun. I believe what I thought was my own residual anxiety was infact probably the initial adjustment anxiety of the lexapro, and as such the 10mg dose has hit me way too hard leaving me feeling apathetic, sluggish, amotivational, as well as significantly impairing any effect of the D-amp, even when taking 1-2 days off and increasing the dose.

 

So now I'm going to drop the escitalopram back to 5mg, keep the Agomelatine at 50mg, and increase the D-amp to 25-35mg per day. I'm hoping to swap the Agomelatine for Trazodone in coming weeks. I'll post updates


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#9 AlmostEasy

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Posted 14 April 2015 - 04:32 AM

Hey man just wondering how things are progressing? I'm in a similar situation you can search my posts for details. They could make all the difference.

Anyway, I went the "try every obscure underwhelming nootropic/supplement under the sun" route. Estimation Russian roulette if you will. I wasted years and lots of money. I think for people coming from places of real cognitive damage they aren't truly what we're looking for. They're marginal benefits for already functioning people except in specific dysfunctional cases like schizophrenia and sarcosine. Parkinson's L Dopa.

Mainly I wasted time because of ignorance and lack of knowledge. It took all that to get here and I understand that.

To get to my point, we need to bust out the big guns. We're not looking for marginal benefits, we're looking for true repair, real results.

I suggest looking at Cerebrolysin/P21, Semax, Selank, NSI 189. If these aren't going to do it, along with rest, exercise, diet, abstaining from problem substances, not much may help. I wish I would've started there. I've received a lot of help from Semax and if I would've started here my life may have been significantly different. I cannot wait to try P21. Ritalin has also been huge for me. I have NSI 189 on the way.

Just my 2 cents that I wish someone would've suggested to me at the beginning of my journey. I may have had a doctorates degree and continued on the track I was meant to, for me every moment wasted was a huge deal.

Also did you abuse or even use benzos for any amount of time? How about alcohol? Specifics might help.

#10 Irishdude

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Posted 25 June 2015 - 03:31 PM

Any updates friend?



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#11 VICREP

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Posted 25 June 2015 - 10:12 PM

I'm along way from where I was when I made this thread.

I'm the most confident and emotionally stable I have ever been in my life. Self-esteem is though the roof.

How?

Supplements:
NSI -189
Psilocybin (Micro dosing and high dose trips)

Reading:
Scattered Minds by Gabor Maté
Six Pillars of Self Esteem by Nathaniel Branden
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