I suffer from depression very badly since it got worse month by month. I went to a few psychiatrists with little to no benefits. With them I tried escitalopram, which helped a bit, but dropped for prolactine increase (which lead to sexyual dysfunction), and then tried paroxetine, which helped a lot for a little anxiety I had, but not for depression, and then sertraline which did very little since I can't figure out what exactly. So I went to research more aggressive antidepressant options with the knowledge I started building up and this is what is helping me very much (even though I will post updates). I do not take fancy nootropics that only help with cognition, oxidative stress etc... because at the moment I have just a goal and I don't want to mess up things since they are already complicated enough.
I don't say the dosages because it varies from person to person and you can find a guide by reading the package leaflet.
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Pirlindole: SNRI and RIMA, its antidepressive effect starts from day one because of the MAO-A inhibition, contrary to a normal SNRI where symptoms get worse. Best antidepressive in SSRIs/MAOI class IMHO. Still maintaining the neurotrophic effects of SSRIs. Compared to 300mg of methylene blue which is the only other RIMA I have tried feels it is extremely more potent (as it should being also an SNRI), especially in regards to norepinephrine, I am very impulsive or "explosive" when for example I recognize someone on the street etc... At first this could also become excessive for me since for example I started to raise my voice so much in excitement. For anxiety I would not know what to tell you regarding my personal experience, as I have never been extremely anxious except years ago where I had a social anxiety on a level that I was afraid even to go out the front door, however it went waning as soon as I started taking psychiatric drugs. However even before starting the stack I have always been depressed and not anxious in social settings, I can tell you that now I am much more active and empathetic. But beyond my experience it is very suitable for anxiety.
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Selegiline: selective irreversible inhibitor for MAO-B, it increases dopamine concentration, probably I'll drop it because there isn't really a need for it. Depression is not because of low dopamine, low dopamine is because of depression. All those people who are trying the most dopaminergic ways are just curing the symptomps of depression and some day they will feel worse. (take a look at something called dopamine (or amphetamine) withdrawal, it is something that acts on nmdar pathways and is cured by ketamine which is an antidepressant... so yeah you are worsening your depression directly by acting in the same pathways).
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Ketamine: It is very fun and it reverses the epigenetic changes caused by stress that lead to depression. You get an instant antidepressive effect that lasts for a lot of days, continuous treatment ideally increase the duration of a single administration. Just do not abuse it because of bladder issues and also because of that do not use it as only treatment (it is approved as an adjiuvant).
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Cerebrolsyn: It is a concentration of neurotrophic factors used in a lot of neurodegenerative diseases, so it helps a lot here for potentiating the (already happening because of other pharma) neuronal changes that recover you from depression in the long term.
One day pirlindole will be substituted by serotonin releaser agent, I also find that psychedelics helps with depression, so it might have some psychedelics proprieties.
I will replace it when I find or come out an SRA (with RIMA proprieties) that will suit me, at the moment a lot of SRAs have also been discovered for antidepressant purposes (such as MDAI), however they have not been investigated that much and eventually approved, so I need time to eventually find someone with better effects than pirlindole (I've always preferred them in general), then I also talk about psychedelic effects because there are some like 6-APB that actually has them, but they have many side effects that make them unsustainable in the long run like cardiotoxicity.
One last thing. As you can see from this stack and the latest research on depression, efforts are now not only on increasing neurotransmitters to have an immediate effect, but also on neural circuits, neuroplasticity etc ... This is because atypical depression is a function of our body to adapt to stress, as well as genetic causes. So I realized that I can't expect to have big improvements if I don't remove the causes of my stress from my life, because at the same time as the depression that is gradually being treated by the drugs, the brain is gradually giving me more because of the stress; by uncontrollable stress I mean for example being subject to abusers. It is clear that this is not the case for everyone since often the causes of stress were present only in the past and now there is only depression left, or maybe your depression is purely genetic. But I think it is good to specify it.
Edited by Frank Walter, 05 April 2022 - 07:21 PM.
