there are a lot of ways to counter the increased anxiety that comes with taking nsi. natural ones i've had some success with: Relora (involves the 5ht1a receptor), L-Tyrosine (increases Noradrenaline) or L-Theanine.
a lot of people in this thread reported successfully using pregabalin or tianeptine to mitigate nsi-induced anxiety.
It should be noted, that there is recent proof that one of the effects of Pregabalin, much like closely related compound Gabapentin, is that they IMPEDE NEUROGENESIS, as part of their general impairment of neural signalling and activity.
As such, it's probably not the best anxiolytic to combine with NSI-189, for DAILY use - using during the night might be more beneficial, at least it was to me.
There's of course also the quite bothersome side-effect that Pregabalin turns you into an absolute IMBECILE! : O Gabapentin isn't lovably called "MORONtin" for nothing, friend! Some whom are using NSI-189 for the effects of cognition, would obviously be unable to use Pregabalin in that case.
I'd more recommend an SSRI actually, or Memantine, that seems to be two good options which dampen anxiety very, very powerfully, without impeding the positives of NSI-189.
It's true though that some experience relief from the anxiety with Tianeptine or Noopept - I personally did not experience much of a relief though... NMDA-antagonism from high-dose Magnesium-L-Threonate did far more than either of those two. Tianeptine was fairly synergistic for the antidepressant effects though, should be noted.
Stinkorninjor! :D you're one of my favorite Longecity posters lol
Anyways; thank you for the elaborate information on combinations with NSI-189.
Since I've got your attention here in the thread already: Do you have any recommendations on how I could best taper off and completely quit Nardil without losing my mind at work in the process?
From my research, it seems that Nardil's primary effects are actually through 1) Catecholamine increase & 2) re-sensitization of glucocorticoid system/receptors... I'm wondering what else out there nootropics-wise or supplementally would work in similar fashion? I've read that Atypical depression sufferers in particular like me are the ones who benefit the most from increased levels of glucocorticoids and/or increased receptor sensitivity for some reason. I think there must be some relevance to positively increasing dopaminergic activity...? :P
Lol! Well, here's the sign that I've been posting too much...! xD I've turned into one of the regulars! Cheers that you find my posts informative though. = )
Quick question - is Phenelzine (nardil) working? If so, I wouldn't change anything.
Otherwise, I had a look at some of the more recent data on atypical depression, let's have a look here...
They mention how the inflammatory markers are different, and how IL-6 seems to be a big difference between melancholic and atypical depression - they also mention how metabolic dysfunction is more common in Atypical, and less with HPA-axis dysfunction... Hmm... Do you have any problems with weight-gain? Prior to starting Phenelzine (nardil), that is. That would imply more accurately that it is truly Atypical Depression which ails you.
I'd go with some combination of anti-inflammatories and IL-6 lowering compounds - also, drugs which help with obesity might be helpful as well, and I think I have some idea as to why... The Hypothalamus is involved in functions regarding obesity, because of the hormones it regulates, Leptin and such.
A drug which effects Dopaminergic function to some degree, but also binds quite a bit to the Hypothalamus, is BUPROPION! I'd try a combination of Bupropion and Naltrexone, somethnig like MySimba.
As such:
Omega-3 high-dose
Pramlintide (amylin analogue, a drug for diabetes, but it should help with obesity as well)
Bupropion
Naltrexone (it might also be beneficial to skip Nalt and instead use CERC-501, which is a selective Kappa-antagonist - these drugs increase dopaminergic activity as well, and are being researched for the treatment of addiction and anhedonia)
Sertraline (the most stimulating SSRI, since they're the modern AD's with the most evidence backing lowering IL-6)
BTW, there's evidence that people whom are treated with a nitro rocket-fuel combo of Venlafaxine and Bupropion, which have Atypical Depression, actually appear to have Bipolar Type 2, and then they become UTTERLY manic... might be a good idea to taper the drugs if you become manic and then put in some Aripiprazole or BREXpiprazole to take care of the problem while you increase some parts of dopaminergic activity. Just an idea, if you turn out to be Bipolar as well...
Of course, all of my ideas are based on the idea that you're having some weight-gain as well, if you DON'T...! Then f*** if I know what to do... : O
References:
-------------------
Atypical depression Puzzled? How to piece together symptoms and treatments
http://www.mdedge.co...mptoms/page/0/2
Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression
https://search.proqu...holar&cbl=44096
Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression☆
http://www.sciencedi...006322315009518
Elevated IL-6 levels in patients with atypical depression but not in patients with typical depression
http://www.sciencedi...165178114001346
Effects of Ketamine on Atypical and Typical Symptoms of Depression
http://www.biologica...(17)31247-7/pdf
There is some evidence towards the idea that it's more the TYpical and not ATypical forms of of depression which are helped by Ketamine btw - this has relevance regarding NSI-189 and Atyp Dep, because Ketamine causes very robust neurogenesis thanks to its AMPA-agonism which induces BDNF-production - this implies that Atypical Depression may not be one of the forms of depression that has all that much to do with loss of brain-mass.
Neuropsychological changes in melancholic and atypical depression: A systematic review
http://www.sciencedi...149763416301890
The idea that Atypical Depression isn't linked to impaired neurogenesis is backed up by the study above, which implies that cognition is greatly more diminished in Typical Depression than in Atypical Depression - this is fully in line with the idea that neurogenesis is impaired in Typical Depression.
Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues
https://www.ncbi.nlm...les/PMC4010969/
A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor
https://www.ncbi.nlm...cles/PMC514842/
The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: A Meta-Analysis
https://www.ncbi.nlm...les/PMC3194072/
Impact of Antidepressants on Cytokine Production of Depressed Patients in Vitro
https://www.ncbi.nlm...les/PMC3847723/
Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial
https://www.ncbi.nlm...les/PMC4081040/
(the above study actually shows that Sertraline does indeed lower IL-6 levels ever, ever so slightly... although it also comes to the conclusion that cytokine-levels weren't too relevant to depression - HOWever...! The study is not designed to take into account the differences between typical and atypical depression, and as such, it may be irrelevant the conclusions they come to, because they were ALL using regular depressed patients, and not patients with Atypical depression,)