# On Parnate. Wonderful but temporary remission. Questions.



## Gillman fan (Sep 24, 2016)

In this post I want to briefly share my experiences. I am on Parnate 50mg and right now it isn't doing much, if anything. BUT it was working and I have learned about the drug and about myself. I also have questions for the more experienced users here re: high dose Parnate, side effect management, and certain meds used with it.

For reference, I was taking 900mg lithium, 150mg lamictal, 150 mg Wellbutrin XL.
20 mg - feeling of things being interesting. Everything is more interesting and pleasureable. Unfortunately this does not motivate me in any way.
30 mg - Amazing things! I finally understand anhedonia and the impact it has had on my life. Most psychiatrists traffic in shoddy constructs of "mood" and "depression" as defined in the DSM. There have been times when my mood has been relatively good but the anhedonia has been pretty constant.

There where so many times where I struggled, but managed to do the right thing for myself. Making friends, doing well in school, getting a law degree. But at the end of the day I wasn't enjoying it. I had no feeling of positive reinforcement, of reward, when I succeeded in life.

Currently I do not think I have social anxiety per se, even without meds, although I did when I was younger. But social anhedonia has had a major impact. Even when I have the skills to socialize I just find it so unrewarding that I often will take any excuse to stop contact with people

I have experienced depression many times, and each time it felt inevitable, I felt I had so little to lose, there was so little I enjoyed anyway.

So with my remission, I felt so much more engaged with people and so much more motivated to do things. Little things. I cleaned up my house thoroughly, for the first time since moving in. I felt proud of my accomplishment in a way that I never did before. I felt ready to make plans for the future, move forward with life.

Side note: I am bipolar II. There is of course the risk of a medication precipitating a manic switch of some kind. I think this risk is overblown for Bipolar II specifically. Heinjen et al. did a metanalysis of Parnate studies performed on bipolar patients. During the time period studied, Parnate users suffered a 6% manic switch rate. Which may seem bad... until you realize the control group had an 18% switch rate. I felt very mentally centered and stable. Sleep deprivation normally affects my mood greatly, less since I started lamictal, but with Parnate it didn't affect my mood at all.

Side effects: Weakness/fatigue/faintness, need for afternoon nap, difficulty falling asleep, early waking.

Unfortunately this remission did not last. This was just like 3-4 days. I think I took my last dose of Ketamine ~2 weeks before hand and it may have been involved in my temporary response.
*
Questions:
*1. I am interested in high dose Parnate! I have read the published studies. My question: is there explanation or mechanism behind this? What I have read is that a lot of the side effects disappear. This seems like the most elegant solution to the side effect problem... instead of taking a NE drug, a wakefulness drug, and a sleep drug. Anyone experience side effects on a low dose and then no side effects at a higher dose?

2. Any SUCCESS stories people have to share about managing the side effects?

3. I am interested in Noritryptiline, and I even have a prescription, but my doctor wants me to titrate at a very slow rate, so right now 25mg or whatever isn't doing anything. My impression of this drug is that it does 4 things: NE reuptake inhibition, histamine antagonism, 5ht2a and 5ht2c antagonism. The first two seem at cross purposes - is this drug sedating or energizing? Does the whole serotonin receptor antagonism thing provide a noticeable benefit?

Thanks in advance!


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## rockyraccoon (Dec 13, 2010)

Gillman fan said:


> In this post I want to briefly share my experiences. I am on Parnate 50mg and right now it isn't doing much, if anything. BUT it was working and I have learned about the drug and about myself. I also have questions for the more experienced users here re: high dose Parnate, side effect management, and certain meds used with it.
> 
> For reference, I was taking 900mg lithium, 150mg lamictal, 150 mg Wellbutrin XL.
> 20 mg - feeling of things being interesting. Everything is more interesting and pleasureable. Unfortunately this does not motivate me in any way.
> ...


I found nortriptyline to be sedating, but no where near the sedation of trimipramine. You have to appreciate that nortriptyline is a tric-cyclic anti depressant, and this class of drugs are known for their sedation.


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## ChilledMonkeyBrains (Feb 4, 2013)

Gillman fan said:


> 1. I am interested in high dose Parnate...
> 
> 2. Any SUCCESS stories people have to share about managing the side effects?
> 
> ...


Hi,
Just my quick feedback regarding my 100mg Parnate dosage. I've been on this dose for about 4 months for Major depression and social anxiety issues that have disabled my life.

*1.* I still struggle to get to sleep, but never feel tired. Though I am probably more depressed on the days when I don't get enough sleep.

I still get depressed, anxiety is still there, but I feel slightly more motivated to do things (like socialising or talking to people).

I tweak my dosage every now and then. Currently going to try 80mg per day to see if that helps me sleep. If I ever take 5 pills at once I get a buzzy high that lasts for about an hour. I usually have 4 in the morning, 4 in the afternoon and 2 in the evening, I'm going to try dropping the the 2 in the evening to help me sleep. For me it's really bothersome to have to take these pills 3 times a day.

Notable side effects for me of a large dosage is temporary shrinkage of genitalia, which isn't fun. Parnate does affect libido regardless. Weight gain/loss negligible. Depression reduction slightly better than an SNRI (I previously took Pristiq 100mg which just didn't cut it, but its effects were similar to parnate).

*2.*By biggest issue is the insomnia effect and libido decline on parnate. Insomnia I take Melatonin which helps sometimes and libido i'll take supplements or tadalafil/cialis to help in that area. Any blood pressure abnormalities when increasing the dose usually subside after a week.

I don't think Parnate works that well for anxiety as I still get nervous dealing with people. Nardil, I assume, would be the the best alternative.

*3.*Noritryptiline and parnate can't be taken together according to drug interaction report. I'm not sure if that's what you meant. I've never tried it.


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## Gillman fan (Sep 24, 2016)

Sorry about your depression. You should know that there are PLENTY of safe ways to augment your medication if you are not getting a good enough response. Have you talked to your doctor?

On a related note, Noritryptiline and Parnate - just look up Dr. Ken Gillman, go to his website, you can download his paper on Serotonin Syndrome a/k/a serotonin toxicity, poisoning, etc. I do not expect you to take the word of a random, non MD forum poster here.

Basically most doctors that come out of med school get 10-15 minutes of education about MAOIs, because they are considered obsolete. This includes no education about serotonin poisoning because the safety risks of an obsolete drug are not considered relevant topics. Outside of med school, doctors will spend the rest of their lives being bombarded with information presented by friendly pharmaceutical company representatives. People who bring glossy pamphlets of exciting, new, up to date, and EXPENSIVE drugs. The money from new drugs greases the wheels of pharma companies. There is no one around to promote or advocate for old drugs in this way.

A more accurate source of information is scholarly journals. If you search PubMed you will find maybe 1/2 a dozen reviews written in the last decade that exclaim MAOIs are underutilized, not as dangerous as they are commonly regarded, and have superior efficacy. How often do you think these are read by Joe Schmoe, MD, your family doctor or even a practicing psychiatrist who does not specialize in MAOIs or treatment-resistant depression? NEVER! They are too busy.

Knowledge does not propagate itself for free. Check out Ken Gillman's website, and at least his summary of serotonin syndrome and the tyramine reaction, etc. 

I contacted Jay Amsterdam about high dose Parnate, and he responded rather vaguely by encouraging me to consult my doctor and sent me a bunch of PDFs. These were all of studies he performed and additionally Ken Gillman's MAOI review. Another online colloquium.I found included a number of psychiatrists who specialized in MAOIs discussing the risks. They all agreed upon what serotonergic agents were dangerous - the tricyclics other than Imipramime and Clomipramine are considered safe. In fact there wasn't even any discussion of this topic.


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## watertouch (Nov 4, 2013)

ChilledMonkeyBrains said:


> Notable side effects for me of a large dosage is temporary shrinkage of genitalia, which isn't fun. Parnate does affect libido regardless.
> 
> *3.*Noritryptiline and parnate can't be taken together according to drug interaction report. I'm not sure if that's what you meant. I've never tried it.


You could actually take them togeather, i could also suggest trying like a low dose Nortriptyline (25mg) or so towards night, both for it can help sleep, but also the A1 blocking effect and anticholinergic effect can help with the "shrinkage"...

I also get the "shrinkage" when taking higher doses Parnate or Stims like D-Amph...Strangely not Methylphenidate...
(my libido is also reduced on higher doses Parnate)...


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## SFC01 (Feb 10, 2016)

didn't know you had room for shrinkage watertouch, cutting it a bit fine haha

I took amitriptyline and nardil together for over 6 months, no issue at all.


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## watertouch (Nov 4, 2013)

SFC01 said:


> didn't know you had room for shrinkage watertouch, cutting it a bit fine haha


Neither did i, but apperently... And its not aesthetically appealing!:wink2:

For some reason the Seinfeld episode when George was in the pool, pops up...


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## ChilledMonkeyBrains (Feb 4, 2013)

^ Haha, classic.

Thanks again Water I'll look in to it.

Gillman fan, I'm due to see a doc soon so will discuss options. Thanks. I usually just get my basic drug interaction info from drugs.com

Conclusion: higher dose of Parnate is really the standard dose of Parnate as far as I'm concerned. Recommended dosage is a joke. Go for it if you can.


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## jaiho (Feb 14, 2015)

Are you following Gillman's guide on blood pressure & finding out if your MAO-A & B are inhibited enough?
One has to be careful to differentiate from a feeling of high vs normality.


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## Gillman fan (Sep 24, 2016)

Actually at this point both the positive and negative effects have basically worn off. I slept in until 8:30 two days in a row, where before I felt lucky if I woke up at 5 or 6. I have a normal appetite, low motivation. No postural hypotension. It has gone from being very potent in positive and negative ways to being a sugar pill.

I am not sure what the connection is between blood pressure and being high. The way I understand it, if your MAO is being inhibited you will exhibit postural hypotension, even if you don't "feel" the benefits yet. Not sure how normal vs high is related to this. In my opinion these are basically moral terms. I have depression that is chronic and of such a long duration I have no idea what "normal" feels like. So I look at things on a functional level... is my functioning improved? How do other people evaluate my behavior? I would have to say yes to both. Of course it felt pleasureable, any drug that boosts dopamine will give you a feeling of pleasure compared to the more "serene" feeling of serotonin.

Jaiho didn't you say you were on Noritriptilyn? What is your impression?


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## watertouch (Nov 4, 2013)

There are so to say 2effects from an MAOI, the inhibition of MAO, and the effect from the pill.

One could probably take Parnate everyother day if its just inhibition of MAO one is after...
For the other effects one probably needs to take it daily, and in varius doses till getting best effect.


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## jaiho (Feb 14, 2015)

The high is the initial response to a drug. Until tolerance kicks in and then the anti depressant effect becomes evident later.

Personally i found relief from SSRI + Nortriptyline for a period of time and then the effect died off again. I didn't really feel comfortable pumping up doses on the SSRI.

I have also been on Parnate + Nortriptyline. Great combo for pleasure, but i found i was too absorbed in my activities to be social at all. I kind of lost my ability to be social, somehow. Verbal articulation was shot, same with my ability to be sexual. but i was sure having fun with video games. Better than the Anhedonic baseline thats for sure, though.

So now im trying my old friend combination of NSI-189 + Moclobemide, with the occasional MDMA/Shrooms/LSD.
Dabbling in these drugs seem to make me feel more alive & human than the pharma soups of MAOIs & SSRIs.


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## Gillman fan (Sep 24, 2016)

Watertouch I read the full text of a review of Parnate's mechanism of action. Aside from the MAO effect, it does like 6 things that may or may not be clinically relevant and are very, very poorly understood. Crazy stuff.

Jaiho - yeah I hope the combo of MDMA and Moclobemide works out for you. I did MDMA once, 13 years ago. I loved it but it was the Ketamine I took afterwards that had a bigger impact on my life. It offered temporary relief from dysthymia / anhedonia / prodromal symptoms that had not yet resolved into depression. This motivated me to seek treatment, and here I am today... after trialling many many ineffective drugs, and having had my head shrunk while I sat on different psychologist's couches.

Actually I will credit psychotherapy with helping my symptoms of anxiety / neuroses. But my core problem, which is getting worse after each depression, is anhedonia, and I don't think talking my feelings will help with anhedonia.

Jaiho can you offer any more detail on what Noritryptiline did for you?

Also if Caedmon reads this can you tell me what you think of Trazodone? I like the pharmacological profile... but then I read that it metabolizes into mCPP https://en.wikipedia.org/wiki/Meta-Chlorophenylpiperazine which seems to hit all the wrong receptors!


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## Caedmon (Dec 14, 2003)

Get your dose to at least .7 mg per kg body weight. Be aggressive, if you can. You doc may feel differently but I see no reason not to try doses up to 120 mg if needed!

Nortriptyline is an awesome augmentation. Lucky you, getting to try this!



Gillman fan said:


> Also if Caedmon reads this can you tell me what you think of Trazodone? I like the pharmacological profile... but then I read that it metabolizes into mCPP https://en.wikipedia.org/wiki/Meta-Chlorophenylpiperazine which seems to hit all the wrong receptors!


Yes I've read this too but on further research, IIRC, it doesn't metabolize into a quantity that is clinically significant. In other words not an issue.


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## Gillman fan (Sep 24, 2016)

Caedmon: Thank you for the info! I have read SO much literature and I must have read that .7 mg/kg ratio three different times but I forgot and never told my doctor. Yeah right now I do want to raise the dose more aggressively. I am 6' 2" and almost 120 kilos so ~84 mg. I have sat on 50 mg for about 3 weeks now.. time for more aggressive titration.

Re: Nortriptyline - right now I am at 50 mg, and as I said I am a 260 lb man who is also an ultra-rapid metabolizer of this drug. I am shocked but I am already experiencing positive effects, not what I expected!

The first thing I noticed as soon as I went to 50 mg was a "drip drip" of dopaminergic pleasure. It came on pretty quickly while I was in bed. Not sure how else to describe it. 
The second thing is a feeling of calmness, maybe a little sedation. I feel less... neurotic? My thoughts flow more naturally. 

The first one is pretty easy to label as 5-HT2C antagonism. I reviewed the literature recently and found that Noritryptiline is a pretty potent antagonist here, since it is at a close to 1:1 ratio with the main NE reuptake mechanism. 5-HT2C antagonism is supposed to disinhibit the release of dopamine and norepinephrine. It is funny that Agomelatine, marketed as a D+ NE disinhibitor, is significantly less potent at this receptor site.
The second one - I know it isn't histamine because I have tried that before, histamine feels like pure sedation for me. 
Is this 5-HT2A? Anyone care to speculate for me? I researched this receptor and I don't feel like I have a good understanding, except that the blockade is a good thing.
Also only extremely mild side effects with the 50 MG. 

Noritryptiline gets two thumbs up! Even at this low dose, the "calmness" effect is incredibly natural, it doesn't feel like a drug such as e.g. benzos, opiates, alcohol, etc. 

Right now I don't need a sleep aid... but I have discovered that antihistamines give me acid reflux. A lot of drugs like Remeron are basically antihistamines with a few other effects tacked on. Trazodone looks like one of the better hypnotics/sedatives that doesn't rely completely on antihistamine activity. How is it working for you Caedmon? Isn't it a 7 or 8 hour half life? Do you feel sedated the next day? Do you experience therapeutic benefits that last longer than the half-life, during the day time?


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## Gillman fan (Sep 24, 2016)

I wanted to repost Caedmon's source re: the .7 mg/kg number. I thought this was just lore but this was part of some rational study:

*Re: parnate question-dosage?*

Posted by Caedmon on May 27, 2006, at 16:25:01
In reply to Re: parnate question-dosage? » deuce224, posted by Crazy Horse on May 27, 2006, at 12:53:49Maybe you need to get to 80% MAO inhibition first. Take a look at this: 
[from CLINICAL PSYCHOPHARMACOLOGY SEMINAR: ANTIDEPRESSANT DOSING, Paul Perry, Ph.D, BCPP, Brian C. Lund, Pharm.D. 
http://www.tu.edu/user_files/10/17.html ]
>>Grasso et al (1991) studied five adult patients, 33 to 61 years old who received tranylcypromine (TCP) for management of their affective illness. Each patient was given TCP 20 mg/d for at least one week. Blood levels of TCP were drawn at 0, 14, 20 and 24 hours following the last dose of the drug. Each patient, except for one nonresponding patient who was switched to ECT, was then restarted at 30 mg/d or 40 mg/d for at least one week. Blood samples were drawn at times similar to those for the first set of samples. Platelet MAO activity was measured. From these data, a statistically significant correlation (r2 = 0.60) between % MAO inhibition and TCP dose was found. This relationship was described by equation 3 and presented in figure 2.
% MAOI = 118.8 (log TCP dose) + 98.7 (Eq. 3)
Even though no patient in this study achieved a % MAO inhibition greater than 64.8%, the resulting logarithmic relationship indicates that 80% MAO inhibition can be achieved with a tranylcypromine dose of 0.7 mg/kg/d (p < or = 0.05).>>

So, you might try a dose that corresponds to .7 mg/kg. If that doesn't work, there is evidence of antidepressant efficacy increasing up to 130 mg/day for tranylcypromine, as I recall. Good luck!
- Chris

So full credit to Caedmon for this 10 year old post! I mainly wanted people to see the study part.
Here is the source: http://aop.sagepub.com/content/25/1/99.2.extract​


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## Gillman fan (Sep 24, 2016)

So I met with my psychiatrist. He is a character. I think our meeting lasted around an hour and a half, he showed me his pile of work he needed to do but I think he enjoys the challenge of working with me and working with a drug that is outside of his ordinary practice.

Raising the dose of Parnate totally doesn't faze him. I am authorized to titrate up 10 mg every 5 days, up to 100 mg, up to and including euthymia. Great!

He wants me to... lower the dose once it starts working, to try to mess around and see how much of it is placebo. I am not sure I understand his rationale here but whatever, I can spend a few days messing with my dose.

I discussed my problem with antihistamine sleep meds and he was happy to write an Rx for Trazodone. He also understands the problem of the "afternoon nod" but I actually don't want an Rx for that, yet.

We had a wide-ranging discussion of MBTI stuff (I am INTJ), the placebo effect, hope, etc. and it was great. We are on the same page in a lot of areas. I mostly write about med stuff here, but in addition to my normal mental fog I have been feeling gratitude for all the people willing to help me on this.

I didn't intend for this to be a diary originally... but it is just too important for me not to. I was a little afraid he wouldn't want to push the dose. I feel very relieved and I think I am going to get the best chance possible to give Parnate a trial. I feel sorry for all the posters I see who get a Parnate Rx... and then their psychiatrist won't give them a dose above 20 or 40 mg.


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## Gillman fan (Sep 24, 2016)

This is my 2nd day on 80 mg and I am starting to notice some side effects. Feel significantly dizzy when I stand up after I have been sitting down a while. Also, I tried taking 80mg of Parnate at once - IT PUT ME TO SLEEP! So I will start dividing the doses again.

Trazodone is even better than I anticipated! Just such a great feeling before I drift off to sleep. Feel well rested in the morning. I also did some research and some scientists think it helps with slow wave sleep, which sounds pretty kewl. I want to be well-rested even on Parnate. Also mCPP sucks and I think it is responsible for some of the side effects people experience, but for me it isn't a problem in practical experience. In theory, my CYP metabolizer status(es) would work together to minimize my blood levels of mCPP relative to Trazodone.

I hope Parnate will be activating for me... at least now I am experiencing some side effects, spending so much time with no effects whatsoever was irksome.
So here are my two paradoxical reactions so far:
1. 80mg of Parnate taken at once makes me want to sleep;
2. I am immune to caffeine. 400 mg is less stimulating than a small coffee was before I started Parnate.


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## Gillman fan (Sep 24, 2016)

So, it turns out that taking 80mg at once isn't what made me sleepy, the drug is working now, a little bit.

Basically it is like Opium. I feel good, mild pleasure feeling, and I just want to lie down all day long! It had the same effect when I was at 20 mg. 

Wellbutrin SR isn't cutting it in terms of keeping me awake and counteracting the fatigue. I will try a higher dose tomorrow.

The options I am considering for staying awake are:
1. Raise Noritryptiline dose;
2. (ar)modafinil; or
3. Amphetamines. 

Probably just gonna do nothing in the short run, maybe raise Wellbutrin dose. I have a full 30 pills of Wellbutrin XL too.


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## watertouch (Nov 4, 2013)

Interesting the whole MBTI test i also was INTJ... Had to google it to see what that test was, and found an online test. I was questioning it abit, but the varius types one could get, it seems abit legit... as do MADRS or HAM-D, BAI..

Ohh BTW, girls write diarys, men write Journals! :grin2: hehe, But anyway i like it! Im actually following your thread, so Keep it going!


Best wishes! Alex


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## Gillman fan (Sep 24, 2016)

WOOHOO! Yesterday I noticed 25 point drop in blood pressure upon standing, significant dizziness, so I knew something was going to happen.

Parnate is working for me, and I am pretty sure it is real! This feels much more sustainable than my previous euphoria/euthymia. I feel constant pleasure... just a little bit, general emotional improvement. I am quite calm and reflective.

Unfortunately, Parnate is also putting me to sleep. I slept for 16 hours yesterday. I am getting over a cold. It feels sooooo good to lie down, I have a slight smile on my face when I do. No other side effects.

I want to get going cause I have a lot of **** I need to get done. Just took an extra 200mg wellbutrin making it 500 mg total, and a caffeine pill although that does nothing. 

There are a lot of technical details to consider. My doctor and I both want to dick around with the dose to see if this is an optimal dose for me. I need a stimulant until this sleepiness side effect goes away. I feel like I do NOT need any more dopamine, something like adderall would just be excessive. Other things to consider... right now I am just going to enjoy the feeling. I think I have ****ing earned it, spent so much time researching drugs, trying **** out, blah blah I am just going to enjoy the feeling for a little bit.

Watertouch - I think MBTI is very interesting for INTJs because we are... different. I have talked with a number of my psychiatrists and they will be like "You could be Aspergers... not quite" or you "you are different" without being able to explain why. Most villains in movies are INTJ, they come up with elaborate schemes, are often brilliant, and are anti social. If you want we can continue a conversation on this topic via Skype.

Oh and Dr. Gillman is 100% INTJ, I could go on but he loves skewering the conventional wisdom. 

I think there are a couple of people wavering in their devotion to Nardil. Come to the DARK SIDE! Experience the low side effects, powerful lift, and rapid action of Parnate!


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## Gillman fan (Sep 24, 2016)

I think a lot of what I experienced yesterday might have been placebo, or my brain is just wicked good at stamping on dopaminergic activity. I am still feeling *mood* benefits, like I feel good, but also apathy, which is kind of the opposite of what I need. 

Up to 90 mg. My psychiatrist wants to try some augmentation now. We agreed that it is time to kick the Nortriptyline into a higher dose and see how it helps. 

I also learned that he is prepared to wage chemical warfare inside the confines of my skull. Next steps to try include Ketamine, Amphetamines and he is open to Modafinil but he mentioned it would be an insurance hassle. It is like he is getting up to speed with these old drugs he has some experience using. He liked to prescribe Desipramine / Nardil in the past which seems like a pretty legit combo. 

Having a conversation with him is hilarious sometimes. He needs someone to keep him on track sometimes. He will start to recommend some herbal therapy that he can't remember the name of... or he will recommend ballroom dancing, or he could Rx amphetatmines.

Ultimately I am bored waiting for this to happen, and my current state of mind feels like I am medicated on SSRIs, which is a cruel irony considering I am shooting in the opposite direction. So be it. By hook or by crook, I will have my response.


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## jaiho (Feb 14, 2015)

How long have you been on the combo now? What dose of Nortriptyline?
Your Parnate dose might be too high, The serotonin part is pushing hard so maybe thats why you're getting apathy.
Though apathy is normal when you're adjusting to a new dose.

Ketamine gave me great relief for about a month. It's not sustainable as a treatment unfortunately, unless it was far cheaper.


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## Gillman fan (Sep 24, 2016)

Jaiho - you are right, my doctor and I agreed to try to get Noritryptiline to a more therapeutic dose before other changes.
This is my 2nd day on 90mg of Parnate.
I have been on Nortriptyline from the start, but only 50 mg, tonight is my first 75 mg dose. I am 260 lbs and an ultra-rapid metabolizer of CYP2D6, so Nort. dosage is tricky. I had my blood levels done and with 50 mg I was at 46 ug/mL, therapeutic range is 50-150. So the plan is go to 100mg Nort. and hopefully end up in the middle of the therapeutic range.

The 260 lb ultra rapid part also applies to Parnate. Parnate apparently has 3 metabolic pathways, 2D6 is only one, but just adjusting for body weight and 2D6 I may not be in a good therapeutic range. My weight is 120 kilos, at the .7mg / kg dose I would need 84 mg.

Here is the thing about Ketamine Jaiho - if you can find a doc who is open minded (the same type that would prescribe MAOI) then you can get a prescription for *sublingual *Ketamine that you can fill at any compounding pharmacist. This was costing me $80 a month for ~400 mg of Ketamine. Insurance will never cover it. I read a book on this topic, _Ketamine and Depression_ by Hyde. I went into some detail about sublingual K on this tread: http://www.socialanxietysupport.com/forum/f30/hope-to-go-on-parnate-soon-1881497/. If you have any questions about it I can try to answer.

The idea is that Ketamine will potentiate / reduce tolerance to Parnate just the same as Memantine works with stimulants/opiods. Except Ketamine is much more powerful and so are MAOIs lol.


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## Gillman fan (Sep 24, 2016)

I am at 100mg Nort now and I like it. For a while there I was feeling apathetic, experiencing sexual side effects, diarrhea, and "positive" feelings, free from worry. 100mg Nort has helped me with everything but the sexual side effects.

We were talking about Trazodone and priapism in the other thread... the funny thing is that this is not much of a concern for me right now! 

Any ideas on the sexual side effects? Nort is doing good work on most of the serotonergic side effects... maybe a little more would help. 

Wellbutrin isn't doing much, I think it conflicts with Nort (Thanks watertouch for pointing this out). I am going to try to go off of it.

My doctor already said Ketamine is on the menu for our next visit. If I had infinite patience I would probably try to bump up Parnate to around 150mg to see if I get more of a response... but I am not so impatient, and I think I can get Ketamine to work for me right away. I have done a bit more research on the topic. This isn't an additive effect, not just adding two different antidepressants with different mechanisms of action. Although it will do that. Ketamine should also reduce tolerance to... all of my meds. This works off the NMDAR antagonism of Ketamine, which is probably separate from its antidepressant effect. Ketamine is the most potent NMDAR antagonist available. I consider Parnate to be the most potent dopaminergic antidepressant available. And if this doesn't work, I have the option of adding amphetamines too, which would also be effectively multiplied in potency by Parnate and Ket.


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## jaiho (Feb 14, 2015)

When i was on parnate + nort, there wasn't anything that could help with the sexual sides except cannabis.
They seem more manageable on the ssri + nort combination, since you can reduce binding to SERT with 5ht1a agonists.


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## Gillman fan (Sep 24, 2016)

Thank you Jaiho!


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## Gillman fan (Sep 24, 2016)

Been on 100mg Nort for a while and it is doing a real stand-up job. No more serotonergic side effects, except delayed orgasm. This is actually the best I have felt, med-wise in a while, but I am greedy and want more motivation.


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## jaiho (Feb 14, 2015)

Its a good combo isn't it.
I felt too anti social on it though. Heaps of dopamine transmission, i was so focused & enjoying my hobbies i had no desire to talk to anyone haha

Is the delayed orgasm as bad as SSRIs?
The main reason i quit the combo is because of the anti social factor, and inability to have an erection.


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## Gillman fan (Sep 24, 2016)

Well Parnate hasn't really kicked in for me yet. It is just doing SSRIish stuff right now. Delayed orgasm - yes as bad as SSRI, and libido is somewhat reduced, but I can get an erection just fine.

I have been doing some sniffing about ketamine + Parnate. There is one journal case report saying it is safe, but not much else, in fact, not much about combining antidepressants with NMDAR antagonists.

This guy tries to come up with an explanation for how NMDAR affect tolerance: http://www.addforums.com/forums/showthread.php?t=102335
This guy has links to a bunch of studies on the topic: http://www.longecity.org/forum/topic/41080-nmda-antagonists-for-drug-tolerance-does-it-work/
This is the only study with an antidepressant, Imipramine, and an NMDAR Ant., Amantadine. Very promising results. http://www.if-pan.krakow.pl/pjp/pdf/2004/6_735.pdf
Interestingly enough, the same treatment protocol showed elevated dopamine receptors on rats:

Ketamine did fine at .25, .5 mg/kg, and 1 mg/kg this was the only dose finding study I saw, but unfortunately this was done on rats so I do not know how well it translates. .06 and .12 mg/kg did not succeed in any of the trials. I was really glad to see this because Ketamine saw the most use by anaesthesiologists, and they use very high doses.

I still haven't decided I want to do this for sure, but it certainly is very interesting.


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## Gillman fan (Sep 24, 2016)

I just wanted to post some of my research here, because I haven't found any similar info gathering on the web.
Ketamine burst method:100 / day for 3-5 days
Another method: 100, 200, 300 etc. in short period of time.
Imipramine / Amantadine. Sensitizes dopamine receptors. Coadministered for 6 weeks, AM dose: 100-150 2x day.
Ketamine equivalent: 72-300
Dose equivalent chart, burst methodology: https://www.uspharmacist.com/article/the-emerging-role-of-nmda-antagonists-in-pain-management
Ketamine review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933765/
Another review of dosage: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933765/


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## SFC01 (Feb 10, 2016)

doesn't ketamine increase dopamine as well ?

I have unwittingly tried it in the past in what was sold to me a E, apparently it contained ketamine, phenelzine and ephedrine - me and the mates were all over the place. Remember being trapped in a hallway at a party with about 6 doors trying to find the living room one but kept on picking the cupboard ones instead - was stuck in there for a about 20 mins trying to find a way out.


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## Gillman fan (Sep 24, 2016)

My first and only ketamine experience was 13 years ago, when I was 19, before my first major depressive episode. I did enough to go into a K hole which wasn't terribly interesting to me, no ill effects. This was at a big electronic music festival in Canada that wasn't policed at all, the drugs were high quality.

Anyway the next one or two weeks I experienced an improvement in agency, volition, and motivation. I felt more centered. I didn't know this was due to Ketamine so you can consider this a "blinded" experiment, I think Ketamine's properties as an anti-depressant were not even known at that time. I know I researched on Erowid and found nothing like that back then.

This positive memory - not the K hole but the one or two weeks after - was enough to motivate me to seek help during my first depressive episode. Of course it didn't do me a lot of good!

Dopamine: yes, and this is why Ketamine raises blood pressure. But the effect is quite small compared to the other effects. This rise in blood pressure is the most dangerous property of K *at therapeutic doses*. Recreational abuse involves doses 100x higher, and includes a significant risk of bladder damage.

SFC your experience does not sound like fun! I am kind of indifferent to the hallucinogenic properties of K, I am sure they won't bother me.

So Ketamine does a number of different things but two are important: its action as an NMDAR antagonist and its action on AMPA receptors. Ketamine is the most potent NMDAR available on the market. Some people, including me, assumed that its anti-depressant action was due to NMDAR but current theory is that property comes from AMPA.

Which means I could potentially experience both a conventional, additive antidepressant effect (via AMPA) and a tolerance reducing effect, or as I like to think of it a receptor re-virginizer.

:nerd:Sorry for long posts but after a length research sesh I feel the need to unwind, sort of like a runner who goes down to jogging before they relax.


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## SFC01 (Feb 10, 2016)

it wasn't a bad experience just very messy - remember clinging onto a door staring intently at the sofa readying myself to make an attempt to get to the sofa - the room was full of sober people as well so must have looked weird to them. Also remember the same pills at a club and wading through a circle of people only to stumble on two blokes fighting, I just stood right over them rolling on the floor watching them, they both stopped and walked off haha.

It certainly does sound interesting as an antidepressant though.


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## Gillman fan (Sep 24, 2016)

I was expecting Parnate to hit me like a thunderbolt, and it did at 30mg giving me two days of heaven (and uber functionality). 

Right now, the Nortriptyline is helping me for sure. It is more like a little spark. I am doing a better job taking care of myself and accomplishing basic household chores. I am enjoying certain things more - playing with my one year old and two year old, or snuggling with them, sometimes feels like heaven, bliss without my normal degree of dissociation.

Not sure what Parnate is doing but I noticed these effects after titrating up to 100mg Nort. I am sure that Parnate is not inert in my system but I am 100% tolerant to whatever it is doing.


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## Gillman fan (Sep 24, 2016)

I got the Rx for 150 mg Parnate, amphetamines and ketamine are still on the menu, I haven't mentioned Pramipexole yet but I feel like it is a backup plan.

I am not too concerned about my blood pressure, my doc is more concerned, willing to prescribe meds to help. https://en.wikipedia.org/wiki/Guanfacine and https://en.wikipedia.org/wiki/Clonidine, both look pretty interesting.

Nortriptyline 100mg / night is causing almost no side effects, just some daytime sedation and I think it is increasing my appetite. Interestingly the difference I have felt the most is an increase in love. I feel it towards my children and LDR GF more in general, and then quite intensely at certain appropriate moments. I did not anticipate this, but it is pretty cool.

Parnate is already having some effects at 90mg so I am pretty excited, I have a good feeling about the med working in this dosage range.


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## jaiho (Feb 14, 2015)

If you're starting to feel emotions & pleasure i'd say you're on a good enough combo, maybe wait it out abit. Ketamine, amphetamines & pramipexole might be going overboard. You don't want to hit psychosis.
I found Parnate + Nort was already on the border of excess dopamine, i tried smoking weed on the combo and starting hearing weird voices that ive never experienced before. so i'd be careful there.


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## Gillman fan (Sep 24, 2016)

Went up to 120 mg yesterday, woke up early this morning. Feel energized.

Jaiho I respect your opinion this is one of the few places on the web where I can find experiences of other MAOI users. I just find I am more functional when Parnate kicks in after increasing dose. 

All the other stuff I mentioned, ketamine, amph, etc. I hope I don't need it, I just like being able to plan ahead! 

Alex also brought up the topic of lithium in a PM so I thought I would write about it here. There are other posters here Dx with bipolar so maybe this will help. 

This is a topic I feel I have to discuss very carefully because many who want to go "off meds" so they can experience mania. This does not interest me. I have talked about lithium with my doctor many times and went from 1200 mg / day to 900 mg / day. Right now my blood level is .2 ug/ml and therapeutic level is generally higher, more like .5 ug/ml +. That said, it is hard to know what effect lithium is having on me.

First, I have only had one positive mood episode. I went on lithium in the first place, bit of an overreaction I think in retrospect, but I was scared by my 3 days of not sleeping, an apparent hypomania. 8 depressions and constant chronic depression indicate depression is more my problem, hard to know for sure though because it might be lithium helping.

Lithium is bad for your kidneys and causes diahrrea. This alone is reason enough to try to determine if it is working.

Third it may be lowering my energy, causing fatigue, lowering my response to MAOI. However lithium can also be used as an augment for antidepressants, not sure what it is doing here.

I have discussed this with my doctor on numerous occasions. He does want to lower my lithium in order to test if it is necessary, we both suspect it isn't. I think I have bipolar II at most, lithium is not ordinarily used here, especially when depression is 99% of the problem. However there are also consequences to changing lithium. Changing the level abruptly may reduce its efficacy. You can't just stop taking it for a week and then start again. If I were to stop abruptly it may cause a mood change, also my doctor believes that stopping abruptly may reduce its efficacy... if I need it I can't go back on.

Finally, my doctor wants to wait for any lithium changes. Wait until I am on my peak of antidepressant efficacy. It doesn't make sense to go off of Li, then raise my antidepressant dose and find out that I needed Li. It is easier to tweak the other meds first and then worry about lithium.

Lithium's ability to act as an antidepressant augment is kind of a dark horse. Not sure if it is doing that for me.

Anyway this is something my doctor and I have given thought to and I believe it is the best course of action. We discuss this sort of thing in depth.

Feeling hopeful. 120 mg is the first big boost in drive and motivation I have experienced since 30 mg. I also feel very prepared to deal with side effects thanks to my med cocktail and experience.


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## 546617 (Oct 8, 2014)

is parnate good for ur social anxiety?


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## Gillman fan (Sep 24, 2016)

Sorry for not responding Kurdish - I read your question and I responded in Cassoulet's thread. Not sure why.

As I said in that thread SA isn't a big problem for me. Parnate hasn't been doing much yet... but Nortriptyline is been fantastic for generalized anxiety.

I went up to 150 mg today and I am sure it is kicking in, it is a little different in the past. I took my standard 60 in the morning and around noon, then another 30 around 3 pm. 

I am glad I pushed the dosage this high. I am 270 lbs 6' 3" and an ultra rapid metabolizer of CYP2D6. 

So what does it feel like? More like amphetamines for sure, but a lot smoother. 

I am happy it is working now... going to wait before I celebrate. I have almost always developed tolerance within 24 hours.


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## Gillman fan (Sep 24, 2016)

Parnate is still working quite smoothly at 150 mg. It is great. I feel energized, I don't feel as neurotic, I want to get stuff done, AND I am more normal emotionally. I feel more emotionally labile - I was emotionally constipated before. I mean I don't have mood swings on a day to day basis but I can feel situationally appropriate emotions where I couldn't before.

I had a week of confusing sleep issues that really got me down. I would sleep for 12 hours, not be sleepy at a normal bedtime, go to bed later, sleep for 12 hours, rinse repeat. I would wake up feeling barely functional, tired but also kind of sedated and anergic. I thought this was my sleeping pill causing problems. Turns out this is Parnate WITHDRAWAL! So moving part of my dose later in the day is fine. I have to go up to 150 mg Trazodone but that is fine, I like the feeling it gives me as I drift off to sleep  and this is still a low dose.

At this point I am prepared to declare that Parnate is working for real and isn't a placebo effect. 2 1/2 weeks.

My psychiatrist is happy for me, also suggests parts of me may still be "missing" after so many years of depression. His recommendation? Psilocybin (magic mushrooms). After researching this, many people suggest Parnate will potentiate it and a lower dose is needed. Two people on Parnate claimed it didn't work for them. My gut reaction is that, like other psychedelics, Psilocybin will not work.

His rationale is actually quite convincing, but I am afraid it won't work.


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## SFC01 (Feb 10, 2016)

he is very open your psychiatrist mate !!

did he say how the process would work for psilocybin ? Go into a nice room, relax etc or can you be let loose !!


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## Gillman fan (Sep 24, 2016)

No the idea is I meet with him. It makes you more suggestible. That is a very, very good thing for me because I have iron emotional barriers towards most people. He would facilitate and guide my trip.

Psychadelics and MDMA were actually used in therapy for years without incident. I don't think MDMA would help me, better for people who have traumas they can't access.

Even with Parnate, I have deficits in my sense of self, "who am I," "what do I believe in?," "what do I want for myself?." I think he is right and this is one of my biggest problems. He really looks at things in a way most psychiatrists never would. He runs the psych ward of a hospital and also has his private practice. We meet for an hour. He has a lot of ideas and not all of them are good but I filter out the ones I don't like. 

Also I am effectively a "special" patient. He never prescribed Ketamine before and hasn't prescribed an MAOI in decades, but I am very persuasive, have a good working relationship with him, and best of all I inform him of *all* risks after thorough research. Doctors love this.

Also he is open to experimenting. This is the most normal I have been since... adolescence? But I have decades of bad habits and missing life skills to overcome too.

What was Nardil like for you, psychologically SFC?


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> No the idea is I meet with him. It makes you more suggestible. That is a very, very good thing for me because I have iron emotional barriers towards most people. He would facilitate and guide my trip.
> 
> Psychadelics and MDMA were actually used in therapy for years without incident. I don't think MDMA would help me, better for people who have traumas they can't access.
> 
> ...


He sounds great !!

You may have to clarify your question a little if I misunderstand - but nardil gives me a lot of self confidence, which I`ve had at times in my life in certain situations, and although I`ve never suffered SA, I did suffer from shyness particular with people who I felt were superior to me whether intellectually or "cooler"  and this became a particular issue in my job as I got promoted and had to start flying up and down the country and holding meetings with executives etc where I was expected to lead the meetings and important stuff like that and it caused a great deal of anxiety to the point where it was all I was thinking about *all *the time. Nardil got rid of that quite spectacularly and I can breeze those situations, hold my nerve, joke with them, be assertive and build relationships rather than me assuming they thought i was weirdo !!

I can make small talk all day now, initiate conversations with strangers, be jokey with them, flirt a bit with the ladies - one of the best things with nardil is how it slows down my thought process - i can think and take my time during conversations about how to respond and at the same time having the confidence to be spontaneous. If i make a fool of myself, I can quickly recover the situation by making a joke, correcting myself etc. I don't dwell on things anymore for example if I do make a fool of myself, or if something went badly or something nerve wracking or troubling is happening in the future.

Plenty of other stuff as well, and of course, 100% remission of depression and anxiety - its almost impossible to feel down for any longer than a few mins.

Nardil also got me over the separation from my long term partner and having to move out of the house from my kids - it did this within 2 weeks of starting taking it, where as in the previous 9 months it was just getting worse.


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## Gillman fan (Sep 24, 2016)

Actually the most important thing re: my doctor may be that he is willing to listen to me on the med stuff and doesn't have a *big ego. *I hadone other psychiatrist/psychologist (dual therapist) who was awesome like this and let me try Memantine because of my positive reaction to Ketamine, but for the most part I was trying to make do with psychotherapy when I saw her. SFC, thank you for answering. I guess for me it isn't about talking to people or things like confidence etc. These are ultimately feelings that can come or go quickly.

I am looking more at the course of my illness has affected me psychologically other than my mood. I had chronic depression as an adult from age 19, not "I can't get out of bed" but a lack of energy and desire to participate in life. I had eight more severe depressive episodes, and the worst part is that I would never recover. I have not experienced "normal" before.

So in most ways I _feel _normal now, but like my doctor said I have problems with "who am I," "what do I believe in?," "what do I want for myself?" This is something most people build psychologically, layer by layer, over the course of a lifetime. When I was depressed it was painful to ask myself these questions, I avoided this pain for years. Now the pain has gone away, but I think my sense of myself needs to develop. It is an opportunity but it helps to know what to focus on.


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## SFC01 (Feb 10, 2016)

Well the main reason I asked for nardil was because I became badly depressed after the break up, and things were just gettiing worse and worse for me so getting out of that was the main goal, the rest was just an unexpected bonus.

I know what you mean about those questions though - my future disappeared in a breath and hit me hard - so "who am i" "where am i going" etc were also running through my mind and it is so painful - my past just made me too sad, I didn't really know if I had a future and the present was tortuous and filled with doom - it was like not being part of the world and makes me shudder to think about sometimes.

Luckily nardil got rid of that very quickly.


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## Gillman fan (Sep 24, 2016)

That is great actually. I mean depression isn't great but you really nipped it in the bud. Some people go years and years without effective treatment. I am one such person.

I think feeling sad and depressed are different things. Sadness can be healthy and appropriate. Ironically, I couldn't really feel sad when I was depressed. I could not experience the catharsis and release of crying. Now I can. It is very liberating.


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## Gillman fan (Sep 24, 2016)

Parnate is almost completely side effect free at this point. The sexual stuff is getting better my libido is probably 70% of normal, which is OK because I had libido to spare. 

I did my reading and high dose Parnate only has small trials, but consistently excellent results, like 70% remission + response. Even for a bipolar patient population. It is almost a different drug at the high dosage.


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## jaiho (Feb 14, 2015)

I wish i could dose Parnate that high, that would set me back $10 a day almost.
I suppose it's better than being depressed though.

How different is parnate at high dose? I never went above 50mg.


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## watertouch (Nov 4, 2013)

jaiho said:


> I wish i could dose Parnate that high, that would set me back $10 a day almost.
> I suppose it's better than being depressed though.
> 
> How different is parnate at high dose? I never went above 50mg.


I would compare it to Parnate + Amph... But like less "jittery" or stimulating.


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## Gillman fan (Sep 24, 2016)

Basically 30 mg I had three days of super elevated mood.
At 80ish mg I experienced serotonin related side effects and some degree of calmness. I went up to 100 mg Nortriptyline and it helped with the side effects and feels tremendously calming to me (the 2A blockade).

At 120 I had a burst of energy that lasted... a few hours in the morning.
Since 150 I have had better energy, motivation, drive etc. 

I was on Adderall a few years. Best comparison I can make. I took a low dose, 7.5 mg in the am and 5 mg around noon. I do not have ADD, this was offlabel Rx for depression. It also felt energizing, and it improved my focus significantly. Increased confidence. Increased ability to perform boring tasks. It numbed me to a lot of negative emotions, which made it easier to be around people generally.

BUT
At this stage in my life I do not want to feel numbed. High dose Parnate is a much "smoother" and more natural feeling. I am better able to access my emotions (compared to Adderall). I can focus on a task when I want to but it isn't automatic as it was on Adderall. It doesn't wear off so it doesn't cause any kind of a crash. I dunno. Unfortunately Parnate is not as effective as Adderall for boring tasks! I hate tidying up. 

Parnate has all the other benefits as Adderall but it is just so much "smoother." 
As for anxiety etc. I can't say because I have felt completely calm since I added Nortriptyline.


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## Cassoulet94 (Apr 3, 2014)

Gillman fan said:


> Basically 30 mg I had three days of super elevated mood.
> At 80ish mg I experienced serotonin related side effects and some degree of calmness. I went up to 100 mg Nortriptyline and it helped with the side effects and feels tremendously calming to me (the 2A blockade).
> 
> At 120 I had a burst of energy that lasted... a few hours in the morning.
> ...


I know a lot of people who hate tyding up.

Your doc must be really open to prescribe you such doses ! (I know some studies show it can be effective but most doc would still not do it).


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## Gillman fan (Sep 24, 2016)

I feel like a bit of a fraud. As I was typing my previous post, I felt it was questionable that I was feeling the benefits of Parnate 150mg, but maybe it was just some placebo effect/ excitement wearing off.

At this point the benefits of 150 mg Parnate have gone away. They did last two or three weeks, which is an awful long time. I realized this yesterday (after the post) when I was very hungry at 6PM even though I ate a huge amount at lunch. It made me realize when I started 150 mg that I had significant anorexia and could just "forget to eat." for most of the day. Now my ravenous appetite is back.

My doctor wants me to lower the dose of Parnate, wait a few days, then go back up to 150 mg. I understand the logic of his decision here, this is sniffing out the placebo effect. And I still do have contingency plans. Just frustrated because I was so sure 150 mg would work... I think I developed a tolerance to the effects quite rapidly.


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## jaiho (Feb 14, 2015)

Sounds like you were high on the dopamine releasing portion of Parnate. Appetite suppression.
Im surprised you arent in remission considering the punchy combination you're on.


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## Gillman fan (Sep 24, 2016)

Jaiho I think you are right, full inhibition of MAOI occurs for most people at a lower dose, going to a higher dose is mainly relying on releasing effect of Parnate. 

First of all my goal is to treat chronic symptoms. I had had 8 depressive episodes before, so simply being "good enough" is going to lead to another relapse. I experienced a more severe depression while seeing my current psychiatrist but I remitted to my "normal" after life changes - my wife moving out. 

Chronic depression is hard to define, but it does exist. See my example re: Ketamine above, that was age 19. I think it is actually harder to treat and gets worse responses then more acute depressions. Acute depressions are an alteration of homeostasis in the brain and most remit naturally, without any invervention, given enough time. Chronic depression IS homeostasis, so it is logical that it takes more pharmaceutical firepower to change it.


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## jaiho (Feb 14, 2015)

Same for me, i have never returned to a full remission like i had achieved before. Each episode is getting harder to nail down.
Eventually i'll have to do DBS.
Might be an option for you looking at the cocktail you're on.


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## Gillman fan (Sep 24, 2016)

I am open-minded about DBS, but I would have to research it. I wonder how much of a tolerance people can build to the effects over the years.

I think medications have been improving very very slowly or not at all in terms treatment-resistant depression. The only "new" drugs that I think might be useful are Ketamine and Pramipexole. 

On the other hand I think they are getting better and better at DBS, combining it with brain scans to see which areas achieve the best results, etc. If I could make it a few more years I bet DBS will be much improved.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> I am open-minded about DBS, but I would have to research it. I wonder how much of a tolerance people can build to the effects over the years.
> 
> I think medications have been improving very very slowly or not at all in terms treatment-resistant depression. The only "new" drugs that I think might be useful are Ketamine and Pramipexole.
> 
> On the other hand I think they are getting better and better at DBS, combining it with brain scans to see which areas achieve the best results, etc. If I could make it a few more years I bet DBS will be much improved.


Can't remember if you said whether you have tried nardil or not Gf ?

Also, all the other meds you take, could they possibly counter some parnate effect ? As I mentioned a while back, when I took traz for example, it seemed to make my mood a bit wobbly, and I know I felt better on nardil after I dropped lyrica.


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## Gillman fan (Sep 24, 2016)

I have not tried Nardil. I don't feel I need the anti-anxiety aspect, or the side effects. If I had to try another I would do Marplan first lol. Still on the market in the US.

You may be right re: meds working against each other. Watertouch has suggested the same possibility. I will talk about it with my Dr. According to my theoretical understanding of my cocktail they shouldn't, but what the hell do I know. Lithium is a med that is still very poorly understood.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> Watertouch has suggested the same possibility.


 @*watertouch* , I`m your brother from another mother - I got the looks and you got the erm...


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## SFC01 (Feb 10, 2016)

.....the belly


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## watertouch (Nov 4, 2013)

SFC01 said:


> @*watertouch* , I`m your brother from another mother - I got the looks and you got the erm...


Yeah, i know its like the movie "Twins" with Arnold and Danny Devito....:grin2:


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## SFC01 (Feb 10, 2016)

watertouch said:


> Yeah, i know its like the movie "Twins" with Arnold and Danny Devito....:grin2:


:grin2:


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## Gillman fan (Sep 24, 2016)

Haven't written an update in a while. Having 150 mg Parnate lose effectiveness was a huge bummer. So I lowered dosage to 110 mg for two or three days, sleeping 12+ hours a day, then went back up to 150 mg. And I am getting **** done!

I just met with my doctor and it was a heartening experience. The result:
1. Test 180 mg Parnate
2. Test Vyvanse dissolved in water in order to increase dose slowly
3. Ketamine / Memantine for tolerance stuff

Lowering my dose a few days and then bumping back up is not optimal, but as a worst case scenario I am ok with it.

I wanted to note two things:
These massive doses and adding in stimulants on top may make it seem like I am sky high, but my Dr. sees the effect on me and we both agree I am quite tolerant. 
I do feel more positive emotion but at this high dose of Parnate I feel so much less emotionally flat. I can feel joy or happiness or contentment in a new way, but I can also feel pain, sadness and loss too. I probably only cried (for emotions, not pain) once every 5 years before this, now I have it in me to visit that pain and hold on to it without being numb.


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## Gillman fan (Sep 24, 2016)

Finished my third day of 180 mg Parnate, I am taking 60 upon waking, 60 upon noon, and 60 around 5 pm. 

The good: Extremely pro-social. I don't feel the need to isolate that I normally do. This is more extreme introversion than social anxiety per se. This doesn't mean that I want to become the "life of the party" but I can relate to people better, be more direct with my thoughts and feelings etc. I had a great long chat on the first night with my LDR GF. She immediately noticed the change I am describing here. This effect didn't kick in at 180 mg out of nowhere, but it is quite apparent now.

Small increase in motivation / energy.

The mixed: Increased feelings of pleasure in general, can be good or bad, need to utilize discipline here.

The bad: I don't daydream about sex as much, but I find the idea very pleasurable. Able to get erection, unable to orgasm. This usually happens at the start of a dosage bump and goes away in time.

The ugly: Muscle weakness/fatigue/pain. I am motivated to do more but it is exhausting. Doing regular household tasks feels like running a marathon and results in muscle pain.

Honestly I never expected Parnate to be so pro-social. It is nice. What I really want is more drive/motivation though. 180 mg is an improvement but a small one.


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## Gillman fan (Sep 24, 2016)

Testing Vyvanse 70 mg dissolved in water, just starting with 10 mg today.

Worried that it will just poop out like amphetamines, but this is a time-honored med combo and my doctor is an expert in ADD and stimulants.


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## watertouch (Nov 4, 2013)

Gillman fan said:


> The ugly: Muscle weakness/fatigue/pain. I am motivated to do more but it is exhausting. Doing regular household tasks feels like running a marathon and results in muscle pain.


Is it the "lactic acid" feelin, the "burn", weakness?...

Ive noticed that type of feeling while on Parnate, it gave me the energy to load the washing machine, but when it came to hanging it, specially bed sheets, my arms felt really fast like "spagetti"

Somewhat high doses you use!:wink2:,
But still you do seems to need higher doses... 
Nice "touch" using the "waterbottle technique" for Vyvanse...

Any update on how that works for you?

I found Parnate+ vyvanse to be verry "pro-social"

Best wishes! Alex


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## Gillman fan (Sep 24, 2016)

Ok I feel like I lost a week of my life to Vyvanse.

The good: Little need to eat or sleep. Felt "good" in a way. Physical energy to get stuff done.
The bad : total inability to focus (or rather, control what I am focused on). Tremendous emotional flattening. Each dose lasted *more* than 24 hours. Significant tremors when attempting to grip something. Memory impairment.

Went much worse than I thought. For anyone who wants to add a stimulant to an MAOI, I do not recommend Vyvanse. It lasts WAY too long. Start with something like dexamphetamine or adderall.

I have a horrible, depressing feeling after discontinuing vyvanse. Very vivid dreams. Things are just starting to go back to normal now.

I am quite amazed at how different vyvanse is compared to my uber high dose Parnate.


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## Cassoulet94 (Apr 3, 2014)

Gillman fan said:


> So, it turns out that taking 80mg at once isn't what made me sleepy, the drug is working now, a little bit.
> 
> Basically it is like Opium. I feel good, mild pleasure feeling, and I just want to lie down all day long! It had the same effect when I was at 20 mg.
> 
> ...


You are really resistant to this drug I can't go higher than 60mg ! With 60mg I already have light carpal tunnel syndrome.

Yesterday I took 70mg and I had to put a splint to give my wrists some relief.

Although I guess that taking 80mg at once must be nice, with 40mg I have a slight buzz. You want to lie down ? I just get speedy ! Maybe I will try 60mg at once, should be fun, I think I will be a bit hyper.

But after it wear off I just wanna sleep.

Looking forward to hear what you experience with your augmentation strategies


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## jackbeam (Nov 17, 2016)

Gillman fan said:


> Start with something like dexamphetamine or adderall.


How what size dose have you taken with parnate before out of curiosity?


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## Gillman fan (Sep 24, 2016)

Max trial was 180 mg.


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## jackbeam (Nov 17, 2016)

Gillman fan said:


> Max trial was 180 mg.


Sorry, I meant what's been your largest dose of adderall while taking parnate?


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## watertouch (Nov 4, 2013)

jackbeam said:


> Sorry, I meant what's been your largest dose of adderall while taking parnate?


I don't mean really to "but" in, but i think that he means that Vyvanse is to "long acting", while Adderall IR (instant release), or DexA IR is, much shorter acting.

For me i actually found the "comedown" with Vyvanse being rather "ok" when combined with MAOI-Parnate, (better then just using Vyvanse)

Here is an PDF from Stahl about MAOI, and combinations with stimulants, page 3,and 11 if im not mistaken
http://www.psy-world.com/1008CNS_Stahl.pdf


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## Gillman fan (Sep 24, 2016)

Oh my largest dose of Vyvance was 70 mg. I didn't bother with my blood pressure (I should) but I was monitoring stuff like my heart rate, etc. I have a very sluggish temperament. It didn't affect me physically in any negative way except the tremors.

Watertouch I missed your earlier question re: fatigue - yes it feels exactly like that, lactic acid, the burn. 180 mg does provide motivation but the fatigue is pretty bad, not like anything I experienced on lower doses. I found any form of physical exertion difficult.

And yes Jackbeam the doses are not really equivalent. Vyvanse is "supposed" to be about 12 hours vs 4 hours of Adderall. So a simple way of looking at it would be to cut the dose into a third. But it is really more complicated when you consider how long it takes Vyvanse to reach maximum therapeutic effect in your blood stream... it is like uhm pot brownies vs. smoking pot. Not a good analogy.

SO I met with my doctor. Topics included me getting more exercise, eating some red super herb/berry mix that he uses, review of Vyvanse and talking about the next step.

The bad news is I have to spend two or three weeks doing a trial I am not super enthusiastic about - more Wellbutrin. I have to check my notes but I think he OKed me to go up to 600 MG+. I do like the "get **** done" effect but it just seems like a weird combo with Parnate. My doctor is kind of obsessed with Wellbutrin.

The GOOD news is he is ok with Ketamine after this, SPECIFICALLY we are looking at the tolerance-reducing effects of Ketamine. Actually we spent half of the time talking about Ketamine + Parnate. I have a lot of research but it can be difficult to directly translate it into recommendations for him, because there is alot of "translation" needed from what people are doing currently. 

Anaesthesiologists are totally comfortable with Ketamine. They have been using it for decades. Psychiatrists are bizarrely squeamish about the drug, indeed, to use a word that Dr. Gillman quizzed me on, they are pusillanimous. Anyway as I mentioned before the use of ketamine to reduce tolerance which has been PUBLISHED in multiple papers since 2004 is very exciting. Throw in a lot of anecdotal information on the use of stimulants + memantine and I certainly hope this works. Also anecdotal information from doctors that run Ketamine clinics, who have noticed that patients typically need to lower the doses of other medications after starting K.

If you asked me months ago when I was starting Parnate, I would be shocked if I was this tolerant to 150 mg. My drug cocktail is already pretty ridiculous. BUT I am still hopeful, and once things start working I can worry about paring down unnecessary parts of my drug cocktail.


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## Gillman fan (Sep 24, 2016)

Finally... Ketamine prescription called in. I am ready for this.

My brain is like "come at me bro" and I do, I hit it as hard as it can, but it never seems to lose balance (homeostasis) for more than a few seconds. It isn't some agile featherweight boxer, it is a huge SUMO *****ING WRESTLER.

It is time for unrestricted chemical warfare!

I will be taking a dose of Ketamine high enough (higher actually) for it to have an independent effect as an anti-depressant in its own right, but I am pretty good at "tasting" which parts of my med cocktail are hitting me. Should be interesting. 

FYI as far as safety, I read Dr. Gillman's 90 page thingy and spoke to him about this well, a few months ago. I wonder what impression someone who does not know me might get from reading posts like this!


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## jaiho (Feb 14, 2015)

That's some serious treatment resistance if you're still not in remission after ketamine on top of that cocktail.
I had a taste of remission from ketamine, it's beautiful. But never lasts longer than a couple weeks.


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## Gillman fan (Sep 24, 2016)

So I started out being frustrated and upset that 200 mg sublingual ketamine didn't work. I took it yesterday around the middle of the day, it produced a not unpleasant dissociative effect, maybe the equivalent of 4-5 drinks. Oddly enough I immediately started doing housework. But after 24 hours it is pretty clear that it hasn't provided a boost to Parnate's effectiveness. 

I thought 200 mg would be enough, I read everything I could on the dosage and it is clear that the anaethesiologists using Ketamine to combat opiate tolerance were using sub-anaesthetic / sub-dissociative doses. But then again it difficult to translate IV into sublingual, also many of the dosage routines called for an IV drip... which I cannot do.

So my original plan that I thought was very likely to work is a dud. Frustrating, but after thinking I can come up with a few alterations on the same theme:
Lower Parnate dose for a few days, *then* dose with K, then go up on Parnate.
Increase K dose to maximum Dr. will allow. I have 750 mg remaining in tiny bottle... it is so cute it is like a few drops, super heavily concentrated.

Also I re-read my experience at 180 mg. I lost most, but not all, of the positive effects after a day. But strangely enough the side effects are encouraging. 

If none of this works... Pramipexole is worth a shot. Alex didn't you try this? It is kind of exotic, I don't know many who have. I did some reading on Parkinsons recently and the similarities with my symptoms are intriguing. What I read (I haven't read much) is that Parkinsons is reflected in movement, people who have it move very slowly or very little. They can move faster, but they have a strong disinclination to doing so. Treatment (with various dopamine boosters) just changes the equilibrium so that it is easier for them to move. I have a massive amount of dopamine in my system already... but it is possible a targeted approach may yield a benefit that carpet bombing cannot.


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## jaiho (Feb 14, 2015)

Can you take the Ketamine intranasally? 

I got remission after 7 days using this protocol. Intranasal requires far less dosing.

0.1mg/kg x 5, 10 min intervals between dose. 

Idea of this is to keep Ketamine active in your system as long as possible to get the neurogenesis happening.

Ketamine doesn't always give full relief until you've used it daily for about a week, some people required 12 infusions for remission.


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## Gillman fan (Sep 24, 2016)

To answer your question Jaiho - yes I could, however I have read far less about that protocol. I have read a number of case reports online in places like Bluelight where people do the whole microdosing thing - one guy did intramuscular injections... lots and lots, owch. The theory makes sense but I am just copying what I have read.

Also - the mechanism of action is different. Ketamine is a dirty drug, and I don't think its "antidepressant" action synergizes too well with Parnate. Last I read, the "scientists" decided that Ketamine's antidepressant activity is not due to NMDAR antagonism but AMPA. But I am quite sure that the tolerance is related to NMDAR based on other, cleaner agents producing similar results.

ALSO - success! I am truly baffled, it took *THIRTY HOURS* to kick in. I might have been slightly more optimistic earlier today, but an hour or two ago I laid down in bed, started smiling, and realized I am getting the Parnate "body buzz" that I experienced at 20 mg. Mental energy is slightly improved. I am making different choices. I prepare healthy meals for my two boys (almost 2 and 3) that require the minimum effort, but when it comes to my own eating I often don't prepare food that requires 2 minutes of microwaving until I ate all the easier choices. Now I stride into the kitchen and decide I want strudel that takes 1 hour to prepare. Now I know that this does not reflect well upon me... but it is an improvement.

Thanks for following my notes Jaiho. I write a lot for my own benefit as much as anything, but I am glad you are around. What about your meds? I get the impression your current regimen is not working, and you have tried a lot yourself. Still getting some help from Nortriptyline?


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## watertouch (Nov 4, 2013)

Gillman fan said:


> If none of this works... Pramipexole is worth a shot. Alex didn't you try this?
> I have a massive amount of dopamine in my system already... but it is possible a targeted approach may yield a benefit that *carpet bombing *cannot.


Yes i messaged you, but hmm just came across this article about combing dexamph with pramipexole (so maybe the Vyvanse didn't effect the trial of Pramipexole

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033120/
Jan Fawcett is one of the authors,

But you went on with Ketamine, nice to hear it seems to work, keep us updated!

Has it effected your BP/pulse?

If i recall right one of the concerns about MAOI+Ketamine combo was that it could raise the BP.


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## jaiho (Feb 14, 2015)

> Thanks for following my notes Jaiho. I write a lot for my own benefit as much as anything, but I am glad you are around. What about your meds? I get the impression your current regimen is not working, and you have tried a lot yourself. Still getting some help from Nortriptyline?


I'm also a Gillman fan so your posts are interesting to me 
Nortriptyline is one of my favorites, i think ill be using it for quite some time.

I'm on the SRI + Nort combo at the moment, still tapering up doses. I would love to be on the Parnate + NTP combination but it causes severe sexual dysfunction for me.


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## Gillman fan (Sep 24, 2016)

That sucks Jaiho. Sorry I don't have much more to add... usual cause of sexual dysfunction is serotonin hitting 2C, but I think too much dopamine alone can do it, e.g. people using crystal meth. Might be worth researching.

So my first 200 mg Ketamine trial was like.. a week ago? Maybe a little more. I thought I experienced just a day of benefits, but there seems to be an ebb and flow. Today I woke up around 9, ran some errands, did some cleanup and then just felt exhausted and went back to having a nap. The combination of motivation + fatigue is very Parnate-esque, and although this is rather minor it is certainly more than I have experienced for some time, certainly I don't experience something even this small without titration.

500 mg Ketamine trial tomorrow. Given all that I have read on both topics, I am not too concerned. Blood pressure + very dangerous to drive is main area of concern. Lowering dose to 30 mg @noon today and tomorrow.

Also response to Alex's earlier posts - sometimes I re-read them and see more I want to respond to.
Stahl is right on many things, but then I read something like this and I just LOL:


> Any drugs that block NE reuptake, including
> not only the stimulants but also antidepressants,
> attention-deficity/hyperactivity drugs (such as
> atomoxetine), appetite suppressants (such as
> ...


Yes so he devotes two pages to describing the tyramine reaction and other NE pressor effects, which is well and good because a doctor or patient should be aware of these risks. But then, in one paragraph, he claims medications that simultaneously combat fatigue and block the pressor effect are dangerous!

Jan Fawcett - I read one of his powerpoints and this is what really got me interested in Pramipexole. He isn't just an academic, his practice includes a specialization in treatment-resistant depression. His powerpoints showed the very rational treatment of ~5 individuals with serious treatment resistance, he pulled out the big guns including Parnate. Some of the patients responded to Pramipexole who didn't respond to Parnate.

That said, I have a very strong bias towards making Parnate work. I feel it does just the right thing for me, motivation, mental energy, and even more emotional responsiveness to the world around me plus a better emotional range. Not really something you see as a criterion for academics or doctors, but as a patient it is super important.


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## watertouch (Nov 4, 2013)

Aa yes the whole TYR30 pressor thing.
I started to read Gillmans TCA-review, but ehh to mentally fatiuged... 
From giving it a glance it seems to be a question of how much it blocks the NAT/NET (transporter).


I'll PM you.


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## Gillman fan (Sep 24, 2016)

In the last few days I have been noticing more and more benefits of Parnate kick in due to my initial 200mg Ketamine trial a week ago. Without any major side effects, yet (fingers crossed). I thought that two fast acting drugs would interact in a fast way, but instead the synergy seemed to get stronger and stronger over the course of a week. So I had a 500 mg Ketamine trial planned last night, but I went down to 400 mg instead since the 200 mg went so well.

The 400 mg trial was pretty uneventful. I spent the night with my father and his boyfriend so that they could respond if anything went wrong. The Ketamine was actually quite a pleasant experience, the dissociation of alcohol without the stupidity, inebriation and sleepiness. I have also clearly reached the limit of what I can do with a 100 mg/ mL solution... I couldn't fit 4 mL under my tongue in order to get the direct absorbtion into my bloodstream, so 400 mg Ket was not that much stronger than 200 mg Ket.

Aside from the details I feel like I can breathe easy now. I have been on Parnate with my mood going up several times and then back to baseline, each time my mood went up it was like I was holding my breath, waiting to see if the benefits last. Now I feel confident that I can stay at the same dose and experience more and more benefits. . . maybe even lower my dose eventually.

I also find myself a bit saddened and angry too. The level of care that I have received is so much higher than what the average depressed patient gets... I can give myself credit because a lot of this is due to my own research and advocacy for myself, that I only began after years and years of failed treatments and passivity on my part. I was able to do this but I think many depressives are not in any place to advocate for themselves and are reliant on their doctors. Yet the psychiatric profession as a whole delivers such terrible results here....

Why is it that a layman with no medical education can come up with such an effective solution when the thousands and thousands of psychiatrists in the U.S. usually put patients on the SSRI merry-go-round? I did not arrive at this cocktail by serendipity, I performed careful research using only the most authoritative sources (although I was inspired by the Memantine + amphetamine craze). The information on MAOI efficacy and Ketamine tolerance busting is already out there.

I hope my posts are able to help at least one other person achieve remission even in the face of profound treatment resistance. If my treatment is effective after a few months I will make a separate forum post, maybe in the future someone does a search and is able to read about my experiences and advocate for themselves successfully with their doctor.

Edit: @*jaiho* Nort has several rare effects in one med, it is uniquely well-suited for treating SSRI side effects, but what is astounding to me is the lack of side effects. I can't think of another psychiatric med with such a good therapeutic index (i.e. benefit / risk).

@ *Alex *- the TCA review is an example of excellent scholarship on Dr. Gillman's part, he draws upon a lot of information and his own analysis includes physiological _in vivo_ test results, such as using the tyramine pressor effect to measure NE reuptake. His writing is also deeply conservative and he doesn't touch upon any new-fangled theories related to TCAs. All and all it is a boring read, but effective scholarship is often boring. It is a writing very worthy of publication in the BMJ but I doubt you will find anything new or interesting in it.

Edit2 : Jaiho re: your sexual SE, I also sometimes got them when I titrated up, even with Nort, but they faded over time. But I experienced profound sexual dysfunction when I tried adding Vyvanse. I haven't researched this - but maybe your sides are the result of too much dopamine hitting a specific receptor? This is very common with people abusing cocaine and methamphetamine. I haven't researched this at all... but this may be a clue that can help you deal with your SE. You may be able to block whatever receptor is responsible.


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## jaiho (Feb 14, 2015)

Good to hear things are improving 



> Why is it that a layman with no medical education can come up with such an effective solution when the thousands and thousands of psychiatrists in the U.S. usually put patients on the SSRI merry-go-round?


I suspect because of liability. Doctors want a drug that they can throw at lots of patients and wash their hands of it.
TCAs & MAOIs require more careful monitoring, generally, and doctors don't want that responsibility. For example, if a patient decides to goto a rave and take MDMA on Parnate, or get into an accident and the paramedics miss their MAOI tag or whatnot.
I think alot of people out there wouldn't have the care some of us do about our own mental health, and that would scare many doctors off using them.

I must admit i didn't stay on Parnate + NTP for too long after those kind of SEs.. I probably should have given it a longer trial.
Seems to be harder to sort out MAOI based sexual dysfunction. SSRIs can kind of be managed with 5ht1a agonists & 5ht2c antagonists.


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## Gillman fan (Sep 24, 2016)

**** this forum man. I lose so many posts and I never learn to copy the posts before I click "quick reply."

This has been an emotional roller coaster because I have so invested in getting this cocktail to work. I had sleeping problems on Sunday and I thought it was due to depression coming back, but now I feel the "body buzz" and I realize my sleep problems fit the Parnate pattern of mid-day "nap time" and early waking. Now that I know what I am dealing with, I have the tools to adjust my sleep cycle - Trazodone, bright light therapy, and a wee bit of Vyvanse to stop nap time. Oh and the "body buzz" isn't the same as Parnate working, rather it always seems to precede the big benefits in motivation and mental energy for me.

I "know more" than my doctor in the sense that I am doing the research so I read stuff first hand, but I tell him EVERYTHING I read including the risks, unknowns, etc. I am very lucky that I have the time to do this during our meetings. He is a fantastic listener and asks many questions but gives me time to present my data. I am an attorney (haven't renewed license due to depression) but what I love about that field is the research and writing, just like I am doing now! Anyway knowledge is not the same thing as judgment, I trust his judgment and I am very lucky that we have the time to discuss all of this together. He trusts my research, I am completely honest about risks, uncertainty etc. but this hasn't happened overnight, we have been working together for some time.

Jaiho I think that is a big part of it, that is a completely rational reason for MDs not to prescribe MAOIs, lots of patients use drugs / are suicidal etc., but I think there are other factors:
1. Hard (and expensive) to measure mental symptoms. Nothing as simple as taking blood pressure or blood sugar. Expensive studies required.
2. No big, placebo controlled studies showing MAOI efficacy. STAR * D seems to show Parnate is only as effective as "California Rocket Fuel!" Measurement tools are inexact and do not capture the difference between SSRI apathy and remission. 
3. Big pharma money plays a disproportionate role compared to other fields of medicine because of #1. Doctors rely more on what "key opinion leaders" are doing because it is so hard to accurately measure effect of meds. Just look at all the misinformation claiming that Moclobemide or Emsam is the "new, just as effective" version of a real MAOI. 
4. Most of what doctors know about MAOIs is obsolete. Information from Dr. Gillman isn't widely propagated because it hasn't been backed by expensive studies & key opinion leaders. I think psychiatrists don't immediately realize how reliable toxicology data is, they don't normally work with it. Hopefully, Dr. Stahl enlists Dr. Gillman for some good continuing medical education... but even then MAOIs are not a "hot topic."

My doctor practiced at the tail end of the MAOI / TCA era and he knows that he got the best remissions, he loved the Nardil + Desipramine combo. But he told me about this and felt glad he didn't kill anyone! There was so much confusion about pressor effects vs. serotonin toxicity that MAOIs seemed much more dangerous. The last recorded MAOI death was in 2007 due to Imipramine in Europe, doctors didn't understand that Imipramine was causing ST, they thought it was just pressor effects / statistical noise. 

Anyway a lot of this post is just blowing off steam  I experienced sleep disruptions and I thought it was due to depression creeping back in, I tend not to post when I am depressed. Now the exact same side effects put a big smile on my face. 

Also quick note re: Ketamine - sublingual absorption is key, I went up to 400 mg but at 100 mg/ mL I had too much liquid for my sublingual tissues to absorb. If you can even convince your doctor to Rx 100 mg Ketamine at 100 mg/ mL I think it may be just as effective.


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## SFC01 (Feb 10, 2016)

nice post @Gilman fan,

with the early awakening, do you feel like you want to get up and get on with things, highly motivated ?

Thats what happens for me on nardil, I kind of like getting up so keep waking thinking lets get up and do stuff. It happened last night and I was about to get dressed and I realised it was only 1.30AM.

Had to take some quetiapine to get back to sleep, woke up at 4AM and decided thats an ok time to be up and about !! It seems to happen in spells of a week or so and then my sleep goes back to normal.


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## porkpiehat (Feb 13, 2017)

Gillman fan said:


> Watertouch I read the full text of a review of Parnate's mechanism of action. Aside from the MAO effect, it does like 6 things that may or may not be clinically relevant and are very, very poorly understood. Crazy stuff.
> 
> Jaiho - yeah I hope the combo of MDMA and Moclobemide works out for you. I did MDMA once, 13 years ago. I loved it but it was the Ketamine I took afterwards that had a bigger impact on my life. It offered temporary relief from dysthymia / anhedonia / prodromal symptoms that had not yet resolved into depression. This motivated me to seek treatment, and here I am today... after trialling many many ineffective drugs, and having had my head shrunk while I sat on different psychologist's couches.
> 
> ...


Can you detail what kind of phsychotherapy was helpful for you? I've been in talk therapy for two decades and I feel like I've been sold a bill of goods. Also now I can't tell the difference between regular mood variations, mood disorder, and drug effects/SEs


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## Gillman fan (Sep 24, 2016)

SFC - exactly. I do try to go back to sleep if it is before 4 or 5. My motivation often seems like it is best early in the day. As far as your symptoms - I thought you had no side effects? How often does this happen? If I can get great results like you I can deal with some sides no problemo.

I did end up adding 25 mg Vyvanse in order to avoid "nap time" and it worked. Past few days I have crashed so hard around noon-2 pm. Light therapy helped me the last time - use it *before* you go to bed. MAOIs mess with circadian rhythms, if you can fix that you won't have to use such high dosages of sleepers and stims. Of course, I was too lazy today to bother tonight...
@porkpie - therapy has done jack diddly squat for my anergia, anhedonia, and avolition. These symptoms get worse with every depression. 
I am not sure that therapy helped with social anxiety - but I do know it has gotten better over time. To me there are two kinds of people. People I enjoy talking with, I care what they think but if I am enjoying myself I don't feel neurotic. And people I don't enjoy talking with. I couldn't care what they think - I just try to be polite. I just don't care as much as I used to. So many people are boring - why should I care what they think?

As far as type - psychoanalysis was a load of crap, but I did remember and take to heart one phrase - "people always compare their bathrooms to others' living rooms." CBT I enjoyed more because I got to talk about the here and now, mainly had the same effect. Over time I have learned to accept that I am "different." People who are INTJ on the Meyers Briggs scale are different, that much is for sure.

Porkpie as far as bipolar there is one cardinal rule. One of my psychiatrists asked me how I can distinguish between mood variations and a mood episode. There is only one answer - sleep. A regular sleep schedule is incompatible with a hypomania. Your judgment will be sufficiently impaired that you cannot objectively consider your symptoms and diagnose yourself, but your sleep schedule doesn't lie.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> SFC - exactly. I do try to go back to sleep if it is before 4 or 5. My motivation often seems like it is best early in the day. As far as your symptoms - I thought you had no side effects? How often does this happen? If I can get great results like you I can deal with some sides no problemo.
> 
> I did end up adding 25 mg Vyvanse in order to avoid "nap time" and it worked. Past few days I have crashed so hard around noon-2 pm. Light therapy helped me the last time - use it *before* you go to bed. MAOIs mess with circadian rhythms, if you can fix that you won't have to use such high dosages of sleepers and stims. Of course, I was too lazy today to bother tonight...


Yes my motivation is sky high in the morning and I use light therapy around 7PM to 8PM in the evening now as opposed to the AM usually.

Its hard to say if its a side effect of nardil or not as I never had it the first 2 years on nardil at all, its just since last year when I decided to stop using so many sleeping meds that its kicked in. I had issues with sleep, mainly trying to get off to sleep long before I started to take nardil but mindfulness has seemed to have taken care of that. I would say that since being on nardil, when I do go thru any sleep disturbances, i dont get the tiredness the next day.

It happens sporadically I guess, last night I slept like a dream until a 15 mins ago, my alarm time.

Certainly had no side effects that you can definitely say these have only ever occured since starting nardil.


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## ikealand88 (Mar 13, 2017)

None of those drugs had many positive effects on me, but had lots of negative side effects, Had anyone Tried XANAX instead ?


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## Gillman fan (Sep 24, 2016)

SFC did I mention Sonata (Zaleplon)? It is one of the new "Z" drugs such as Ambien, generally I think they are just benzos with a fresh coat of paint. Sonata has one very specific property that makes it interesting though - its half life is like one or two hours. Meaning you can take it at 4 a.m. to get back to sleep and it will be almost completely out of your system to wake up. I wouldn't recommend it as a main sleep med, but this can help when you really need those few hours of extra sleep.

Nothing too exciting happening on my end. The first week was all improvement with no sides, this week it seems to be the reverse. Well at least my cocktail is doing... SOMETHING. I had thought that I would respond more dramatically to reduced tolerance, given my large dose of Parnate. 

I just finished my nap time :/ feel like I run a marathon every time I do some mild physical tasks. Still, better than experiencing nothing.


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## Gillman fan (Sep 24, 2016)

Met with doctor, I am happy with new plan. Actually I had no recommendations for our meeting lol. He wants to lower lithium, this is a topic I leave 100% to his judgment because I can't objectively observe my moods. Lithium may be putting a "cap" on my mood that won't let it go any higher.

2nd change is to double down on the Ketamine, 200mg / 2x / week. This may cause tolerance issue, actually I have read tons of Ketamine research and I can't really make heads or tails out of all the different dosage techniques. Surprisingly, most of them seem to work. His recommendation of 2x / week is quite logical, because it has generally taken 3-4 days for the Ketamine to "do its thing." 

Plan: KEEP ON TRUCKING. I have no idea how all of this is going to pan out lol.


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## Gillman fan (Sep 24, 2016)

It is funny, so much is going ****ty. I have a bad cold, which on top of Parnate side effects gives me: a bad cough, constant headache, fatigue, muscle pain, etc. Moreover, I have good reason to be pissed at my doctor because he waited a week to give me a refill. 

In spite of all of this, I feel more engaged with the world than usual. When I was just taking Parnate the benefits would kick in IMMEDIATELY and then fade pretty quickly. So they were quite obvious. The K/P combo creeps up on you slowly. I have skipped K for 8 days but I think the improvement is durable and noticeable. 

Still a long way to go. I am a bit concerned that the K will "freeze" my side effects in place, but really no way to know for sure yet. Unlike many doctors who prescribe an MAOI, my doc is quite willing to Rx something to help me deal with side effects, as needed. 

If this works I am going to try to find some Dr. to work with and publish a case study.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> SFC did I mention Sonata (Zaleplon)? It is one of the new "Z" drugs such as Ambien, generally I think they are just benzos with a fresh coat of paint. Sonata has one very specific property that makes it interesting though - its half life is like one or two hours. Meaning you can take it at 4 a.m. to get back to sleep and it will be almost completely out of your system to wake up. I wouldn't recommend it as a main sleep med, but this can help when you really need those few hours of extra sleep.


Only just saw this GF - have tried zopiclone many times, not a big fan but Sonata sounds interesting, seems perfect for the times I have my awakenings - will check it out and mention it to the GP.


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## Gillman fan (Sep 24, 2016)

After reading these forums and some other forums re: NMDA antagonist tolerance, I have bit the bullet and bought some vitamins. B6, B12 and Magnesium Citrate. It is possible my issue isn't tolerance but a bottleneck in neurotransmitter production... in any event, the risk is so tiny it can't hurt to try.


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## Gillman fan (Sep 24, 2016)

I still have intermittant boosts of motivation and energy from the Parnate, but it is time to move on to the next major trial. Going to try Pramipexole next week. At this point I have a bit of "enthusiasm fatigue" since my last two trials haven't really done anything for me. Nonetheless, I think this med is well indicated for my symptoms and it has done quite well in the limited clinical trials it has had for depression.


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## Gillman fan (Sep 24, 2016)

I was having my second thoughts about Nortriptyline. I am sure it is the culprit for my weight gain... I went from 260 to 280 lbs. And my doctor isn't so keen either. I went down to 75 mg, and I just feel like life is kicking me in the nuts, repeatedly. Lots of bad emotion that Nort took the edge off of. I almost forgot what it was like. Nort made a dramatic difference and it is the #1 most helpful med in my cocktail right now... it isn't helping with anhedonia and motivation issues. Maybe at one point I will not need such a security blanket. But for now I am going to ask to go back to 100 mg.


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## jaiho (Feb 14, 2015)

Interesting you find NTP more effective than Parnate.
Any reason you need to be on Bupropion at the same time?

Perhaps try adding Agmatine sulfate. It's a medication amplifier. Check this study out:
http://www.sciencedirect.com/science/article/pii/S0091305714003475


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## Gillman fan (Sep 24, 2016)

Parnate's positive effects come and go. NTP is more reliable. 
Buproprion: my doctor INSISTS. He has a tremendous hardon for wellbutrin. This is basically give and take. He has let me do what I want in terms of last several med choices... so I am giving wellbutrin a try. Doesn't do anything noticeable at this dose. Unlike Vyvanse, which ****s up my emotional processing big time.

Agmatine - fascinating. Extra effective on MK-801 and I have a prescription for Ketamine. This is something I will want to give a 1 week trial, if it works that is great, if not no big loss. The study you linked uses ludicrously small dosages of Agmatine - 0.0001 mg/kg! Whereas the top hit for agmatine as a workout supplement recommends - *"240 lbs* - 175 to 698 mg per day" which is roughly 3mg/kg. A difference of 10,000!

I am guessing the higher dose will make me look like this:








I guess I will pick it up at GNC. I should probably notify my doctor... but he is difficult to reach if I don't see him in person. Tempted to just give it a try and notify him if it works.


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## jaiho (Feb 14, 2015)

Haha, i think thats a typo dose in the study. then again its mice
the studies on depression with agmatine they use 1.5-3 grams a day in humans. definitely worth a try


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## SFC01 (Feb 10, 2016)

@Gillman fan, make sure you keep us updated on the agmatine, like you say, sounds interesting.


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## jaiho (Feb 14, 2015)

Something even more interesting about Agmatine, it seems to mimic some of Ketamine's AD effects, via mTOR AMPA modulation & GSK3 inhibition.
http://www.sciencedirect.com/science/article/pii/S0924977X16300074

Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling

It also makes marijuana far more potent, as well as opiates.

https://examine.com/supplements/agmatine/

They even did a small pilot study of 3 depressed people, and achieved full remission, which was not reversed by shutting off serotonin via parachlorophenylalanine.


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## Gillman fan (Sep 24, 2016)

So I just got my "100% pure" package of 100g Agmatine Sulfate. It is kind of chunky when I open it, probably due to no anti-caking agents. 
I don't have a milligram scale, and the stuff isn't portioned out in any way and doesn't come with a scoop of any kind. Luckily there is a dosage conversion chart:
1/4 teaspoon = 562 mg
1/3 teaspoon = 750 mg
1/2 teaspoon = 1125 mg
I will take one 1/4 teaspoon dose now (3:30 pm CST) in a protective envelope of peanut butter. It tastes AWFUL and the peanut butter helps to disguise the awful taste. Like I just ate a bunch of pool chemicals. Agmatine sulfate with ketamine chaser? Yummmm....

I was JUST ABOUT to post everything below here when my package arrived.
Thanks Jaiho. That examine.com page is extremely high quality.

Safety first! It does appear that agmatine is NOT metabolized by MAO and does not directly act as a precursor to the monaminergic neurotransmitters. No problems with MAOs

This med does have some truly fascinating synergy. As you mentioned, it seems to work in the same way as Ketamine via AMPA (current theory) but it also boosts MK-801 which is a pure, clean, NMDAR antagonist. I think whatever NMDARergic effects it has are likely responsible for the huge range of drug interactions.

Re: the first study you linked, the dose is not a mistake. The first part of the experiment was aimed at determining the minimum effective dose (MED) of Agmatine to act as an antidepressant in its own right.


> In a second set of experiments, agmatine administered at a sub-effective dose (ten times less than MED, 0.001 mg/kg) in combination with sub-effective doses of conventional antidepressants, elicited a synergistic antidepressant-like effect with all the antidepressants tested.


The idea being they are measuring the synergy of a therapeutic dose of another medication + a tiny sprinkle of agmatine that is too little to do anything by itself. The interactions of these two meds support that agmatine does something special to the NMDA / Glutamate system.

Anyway I should also get my pramipexole RX in a day or two... will take weeks of nausea before I titrate to a therapeutic dose, but I consider it a conventional medicine that works on fairly well understood indications and mechanisms of action. Whereas something like agmatine is more of a "wild card."

Will probably dose again in a few hours together with Ketamine. I could potentially take this sublingually but the taste is vile. And 1/4 teaspoon is more than you think!

Thanks again for the heads up on this jaiho.


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## Gillman fan (Sep 24, 2016)

Fascinating! Less than an hour later it is having some effect. Not unpleasant, hard to draw a good parallel here. It is a noticeable feeling throughout my body. Feels like less adrenaline maybe(?) I normally channel nervous energy through my body, usually by bouncing my leg slightly up and down, but I feel no need to move now. Kinda CNS depressant-ish but without making me feel tired or drowsy. Less anxious / distracted better focus.

Time to add Ketamine?


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## Gillman fan (Sep 24, 2016)

Screw it it. I am trying to put all these effects together in my head. Reliance on 5ht signalling - could NTP be hurting me? Synergy with MK-801, synergy with Wellbutrin, this is truly beyond my ability to comprehend. 

The dosages are even worse. It is very clear that Agmatine functions as a bell curve, more is not always better, but I also believe that there are *different* bell curves depending on which signalling is at play - E.g. imadozoline/nitric oxide signalling, NMDA antagonism, adrenal antagonism, 5ht signalling(?), etc. etc. 

So sod the theory! Trial and error! Time to add some Ketamine! Got one errand to run first that requires driving my car, after that I can just chillax with my 100% legal and medically grade K.


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## jaiho (Feb 14, 2015)

I also read that bit that 5HT antagonism seems to block its AD effects, i have combined it with NTP and still noticed it somewhat, but perhaps not as much as when i tried it without being on anything.
Its strange because it doesnt have much effect on 5HT yet its AD effects are blocked by 5HT antagonism.. I would have thought most of its action was via mTOR>AMPA and some other actions i dont understand on synergism.
It does an absolute load of things for such a simple supplement.

and you're dead right it tastes bloody awful. I mix it with juice.


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## Gillman fan (Sep 24, 2016)

So Jaiho you have been taking this for a while? I would love to hear your experience, with and without Nortriptyline. What dosage are you taking? Did you experiment with different dosages? IMO dose is the real question to figure out with this med. 

I just took my 30 mg Parnate "evening" dose, another ~500 mg Agmatine, and now I am sitting and relaxing while I wait for Ketamine to work its way into my sublingual blood vessels.

I generally don't focus on my "mood" because so many variables impact it. But I notice some behavioral changes right away:

I went to the Walgreens drive through and complimented the female clerk for her hair. Which is very unusual for me. 
I get back home and use a different method to pack my pills into the little one week pill caddies. I have always been frustrated because Parnate pills are so small and so slippery, I frequently drop them, but I normally do it the same way every time. Better technique.
Also a different technique for retrieving incorrectly inserted pills into the caddy... normally I have to close every compartment and turn the whole thing upside-down, but I have had chopsticks sitting in front of me for like months now. It just seems quite obvious to me to use them, and it works.

These are pretty small things... but I try to record objective behavioral changes, looks like it is having an impact on learning.

Aaannnd the Ketamine has fully kicked in. I feel marvelous, basically just from the immediate dissociative and dopaminergic effects of Ketamine. Much more pleasant than normal. More relaxing, cognition not impacted at all, and a nice little body buzz (dopamine). I have not learned anything useful about the therapeutic effects but K is clearly being potentiated by Agmatine.


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## jaiho (Feb 14, 2015)

Agmatine had the same effect on me. I became a smooth operator in a way, i could access words much easier, and felt more confident talking to people randomly which is unlike me as well, haha.
I recommended Agmatine to people over on reddit for depression, and it seems some people reported back to me with full remission of their depression and continue taking it long term.

For me it completely destroyed depression, but i still felt i needed something more for anhedonic symptoms. I think it would be good for people here suffering anxiety, though thats never been a huge problem for me.

I noticed it increased my libido which nothing seems to help with so thats a plus. It definitely potentiates dopaminergic substances, perhaps thats why Ketamine feels more punchy, as it is a D2 agonist.

I used to take 1.5G a day, i havent taken it daily for awhile as ive been trying other things.

Most of my trials with it were without taking anything else, and my later trials adding it to NTP didn't seem to produce as good results, mostly a mild lift in mood.


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## Gillman fan (Sep 24, 2016)

I cried for the first time in... years? Not a bad thing. It wasn't some major trauma, I just saw some art done by one of my sons and all of a sudden I missed him. The truth is that I have been so used to being emotionally frozen, for such a long time, that my skills at coping with normal emotions are pretty low. I am sure it is Agmatine. Being sad is actually quite different from being numb, much better, you can experience some catharsis, ultimately you feel alive and connected to reality. 

Parnate is the only other med that has had anything like this effect on me... I did feel emotionally freer but I was pretty task oriented / getting stuff done. I wonder how much of this is synergy with Agmatine? I do feel more energized... just not the motivation that I really want. Pramipexole is pretty specialized and I hope it deals with my residual anhedonia. 

Jaiho can you get an Rx for Pramipexole or one of the other dopamine agonists? It seems like a logical next step, a fairly well targeted answer to anhedonia. Our symptoms and issues are quite similar. Or you could just let me be your guinea pig 

Edit: I got my Pramipexole Rx. Protocol with Pramipexole is .125 g titrations. I asked for .5 g pills, thinking it would be easy to cut them into 1/4s. It is NOT easy, they are the size of a grain of rice. Among the smallest pills I have ever seen. I can barely manage to shear them with cuticle trimmers. Shoulda gotten .25 g pills.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> I cried for the first time in... years? Not a bad thing. It wasn't some major trauma, I just saw some art done by one of my sons and all of a sudden I missed him.


Bless you mate !!

I`ve done that a few times as I dont live with the tin lids (kids) anymore - my daughter loves writing me little notes that I have to pin to my bedroom wall - they have set me off a few times


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## Gillman fan (Sep 24, 2016)

Yup this is amazing. Parnate is working at full strength now, I would say full remission but I still want to trial Pramipexole  so maybe I am at 70% motivation. Whether or not it is "medically indicated" it will really help me to get my life on track since I have developed so many poor habits / life skills. 

Jaiho I can't thank you enough. If some random dude on the internet recommended this, I disregard what they say completely. But I do listen to you. Agmatine is an amazing med that, like MAOIs, doesn't get used because it isn't patented and therefore isn't marketed. Now if only I could hire 1000 very buxom ladies in low cut blouses to get the "attention" of doctors and tout this drug, it would be a blockbuster, if not by itself then as an augment.


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## jaiho (Feb 14, 2015)

You're welcome Gillman Fan. I sure hope it lasts for you. There's a small strong following for the effects of Agmatine, i try to spread the word but it usually falls on deaf ears as people can't believe such a simple supplement sold in bodybuilding stores could have drastic effects.
As Gillman says, Capitalism is bad for science & your health  Agmatine is not as profitable as the latest SSRI, as it cannot be patented. Such is the way our system works.

I've abit wary of potent dopamine agonists like Pramipexole, ive seen a few reports of people getting full anhedonia relief, but then later tolerance is developed, and once the drug is ceased they fall into a deeper Anhedonia.


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## Gillman fan (Sep 24, 2016)

I just realized I am on a triple Australian cocktail - Dr. Gillman recommended MAOIs, Dr. Hyde (author of sublingual ketamine book) is Australian and recommended sublingual K, and jaiho recommended Agmatine. Of course the full combo is my idea.

I think your caution is healthy Jaiho. There may be multiple interactions which make agonist poop out really bad. https://www.ncbi.nlm.nih.gov/pubmed/25511804



> Collectively, these data suggest that prolonged treatment with dopaminergic D3 agonists provokes a reduction in DA reuptake by dopaminergic neurons related to a hitherto-unsuspected modification of the DAT interactome.


Yeah I think there is even a name for withdrawing from that stuff - Dopamine Agonist Withdrawal syndrome. I haven't read into it. Your caution may be warranted. I think at this point I don't really need Pramipexole. I need the normal **** like diet and exercise which doctors always recommend but I never really cared enough to try. I guess the thing is it is probably the most targeted and specific class of meds for residual anhedonia.

You might want to contact this guy: http://psychiatry.unm.edu/about/faculty-biosketches/Fawcett_Jan.html. He is a clinician who also publishes in the academic literature, I think he may be one of the more experienced persons in Pramipexole treatment for depression. Note that US doctors are tremendously reluctant to offer medical advice without doing an in-person diagnosis. Do not tell him anything about your personal health, just ask him *in general *what his experience is like re: agonist poop out. If you want to impress him you can also say agonist tachyphylaxis.

Also re: Agmatine I am going to start posting my experiences in thread in the general forums. This is something other people should know about.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> Also re: Agmatine I am going to start posting my experiences in thread in the general forums. This is something other people should know about.


Will be able to post my experience as I have some coming next week.


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## jaiho (Feb 14, 2015)

What can i say Gillman fan, us Aussies both know & love our drugs.. The most common anti depressant being available at the pub with mates.



> So help me god if this isn't the worst and best thing in the world.
> If I overdose, or forget a day or two, I have to start the titrating all over again. I feel sick to my ****ing guts and sweat more than on 2 grams of DNP and a boner that could cut a vial in half without shattering the glass. Somehow it always gives me the absolute ****tiest feeling the entire next day if I overdose. Like I'll have no energy for anything. The only way I know to deal with it without vomiting is get really ****ing cold. Like srs lvl cold, I woke my fiancée and said ****s going down. Sat on the toilet taking a huge dopamine dump while the fiancée was soaking a towel in ice water while I'm dropping turds like it's Vietnam. Don't even understand how she puts up with my ****. Of everything I've ever taken, this is the single thing that has made me contemplate my lifestyle. This even after going through a thyroid storm at the hospital from some UG overdosed T3 with a resting heartrate of 221 bpm.
> I've evolved now, I buy pramipexole in liquid form, 2mg/ml and 1 drop is 0.1mg. Once you get the prami dose right, your life is the best ****ing life of all the lives in the life. It makes good life seem like not good life compared to your life. BONERS THAT WOULD SCARE A LION, ORGASMS NOT SEEN SINCE THE TIME OF OUR LORD AND SAVIOUR PETER NORTH, SLEEP LIKE YOU'RE ON 15 UNITS OF GROWTH AND A RAGING ADDICTION FOR ALL THINGS SEX THAT MAKE YOU CONTEMPLATE IF YOU'RE A NYMPHO.
> I'M THINKING THE TREN DICK ISN'T ACTUALLY TREN DICK, IT'S JUST YOUR DOPAMINE AGONISTS ****ING U UP FAM.
> TLR; Worst ****ing best drug ever.


This pramipexole experience made me chuckle.
I read another of a happily married family man suddenly became a sex crazed beast, regularly seeing prostitutes & 'massage' therapists. Or becoming full fledged gambling addicts.

Interesting drug for sure, and would love to try it except for if i had to come off it.


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## porkpiehat (Feb 13, 2017)

*Now I get "social anhedonia"*



Gillman fan said:


> In this post I want to briefly share my experiences. I am on Parnate 50mg and right now it isn't doing much, if anything. BUT it was working and I have learned about the drug and about myself. I also have questions for the more experienced users here re: high dose Parnate, side effect management, and certain meds used with it.
> 
> For reference, I was taking 900mg lithium, 150mg lamictal, 150 mg Wellbutrin XL.
> 20 mg - feeling of things being interesting. Everything is more interesting and pleasureable. Unfortunately this does not motivate me in any way.
> ...


Yup. This has been my issue with many drugs. I feel serene, almost like I'm full of valium, But I open my mouth to talk or joke, and nothing comes out. It makes interacting with people exhausted because everything requires an effort and scripting. Full doses of Celexa and Prozac did this, as did Viibryd. With effexor it carried a tinge of anger and annoyance. I usually feel best when I'm washing out SSRI or on a low dose but then concentration and completing sentences becomes a problem

I started Parnate hearing that the MAOI's wouldn't cause this, but I'm rounding my first week and there it is! I immediately thought of your wording Gillman Fan after I left my office. I wonder if it will improve with dose? I tried 5mgs ritalin yesterday to cut through some of the fog and I got very chatty, more nervous than I would normally be on it. I actually started to lose control a little and say everything. Klonopin and propranolol tamped down the nervousness but I don't think my doc would get on board with this combo long-term.


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## Gillman fan (Sep 24, 2016)

I had so many side effects and so little efficacy that I gave up on SSRIs pretty quickly, ironically, this was for the best. 

Basically pleasure and motivation are tied together in your brain. You can find other reasons to do things or motivate yourself, but in the end you are hiding from your own emotions (or lack thereof) and therapy does jack sh*t here. Parnate's dopamine boost is completely dissimilar to SSRIs. They were marketed as "serenics" but feeling serene constantly is not always a good idea if you have a native lack of motivation / emotions. May be better for anxiety. 

I did find a serotonin bump around 80mg of Parnate, where I started experiencing a little apathy and some SSRI type symptoms. This is quite rare but I am also pretty vulnerable to that sort of thing.

Anyway I am glad you found my thread. I documented pretty much everything, including my tips for dealing with some of the side effects. You will encounter the worst side effects around 20-40 mg usually. Eventually these side effects will go away, then the next time you raise dose the will experience side effects, but not so severe... keep on raising dose and they will mostly go away.

As far as high dose causing hypomania/mania, talk to your doctor. I feel calmer but I think Nortriptyline helps there too.

You can read my thread for more advice/ experiences, not sure what else to say. Try drinking coffee before going to stimulants IMO. Stimulants + Parnate can be more mood stabilizing, cofffee does not hit the dopamine button too hard.

As for me, I am quite stable with my cocktail. No side effects, except for inability to sleep without meds. Ultimately I think I can drop the various meds except 150 MG Parnate and the two important augments. Not sure about Nortriptyline, I feel I need the anxiolytic properties less now, although the SNRI stuff is quite attractive. 

Generally people at the official "top end" dose of 60 mg generally feel some degree of tiredness for a big chunk of the day and end up using caffeine/ stimulants to get alertness. Now there is not hard data (large, randomized controlled trials) proving high dose Parnate is better, but neither is there any data showing that 60 mg or less should be the normal dose. Parnate came out 60 years ago and this is way before dose-finding studies existed. Also sounds like the FDA decided to "make an example" of Parnate by reducing its indications and requiring a lower dose, without any evidence. Dr. Gillman writes about this and it is quite interesting.

Oh one other thing - IIRC you are bipolar? For many doctors it is dogma that antidepressants are dangerous for bipolar patients. But if you read the academic literature the evidence simply isn't there. The only apparent danger for antidepressant without mood stabilizer is that it shortens the time between mood cycles - and there isn't even consensus on this. Heinjen et. al. recently aggregated a bunch of Parnate trials on bipolar patients, 450 total patients, 6% rate of mood switch vs 18% for control. Unfortunately, your doctor is likely afraid of Parnate and doesn't have time to learn about the actual evidence on this topic.


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## watertouch (Nov 4, 2013)

One should probable read this forums thread on DAWS, think 2 of the posters are not "around" anymore.
http://forum.mindandmuscle.net/36005-daws-dopamine-agonist-withdrawal-syndrome

Otherwise @*Gillman fan* noticed any effect/side effects on Prami?, 
Tiredness and sometimes feeling little "ill" was something i noticed, So i took it towards night! :wink2:


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## Gillman fan (Sep 24, 2016)

Just hunger. I never felt full, just wanted to keep eating. Wore off after 1 week.

Jaiho as far as the danger of agonist poop out, I am going to speculate and say Memantine + Agmatine is very strong insurance against poop out... here is my chain of reasoning.
1) Ketamine has shown in numerous studies in anaesthesiology journals that it can potentiate meds and lower required dosage to achieve same effect;
2) All that stuff about Memantine + poop out prevention.
3) Ketamine and Memantine share affinity at NMDAR.
4) Ketamine probably prevents poop out too, memantine is just too weak to show any real synergy. I think it is the same effect.
5) In that study you linked that we discussed, MK-801, which is a pure, clean (and super potent) NMDAR showed tremendous potentiation with Agmatine, 1/10th normal dose of each was just as effective.
6) Agmatine is itself an NMDAR among other things.
7) So the combo of Agmatine + another NMDAR should be more than twice as effective at potentiation and poop out prevention.

I don't think a pure NMDAR effect is good as an anti-depressant by itself, but it has the strongest correlation to potentiation / poop out prevention.

Shouldn't be too difficult to get a script for memantine. 

Of course, you could just try Parnate again. I feel like Parnate is doing the majority of the work in lifting my mood, it is the formula racecar, but the racecar needs people in the pit to give it gas, change tires, etc. 

I had one final dose of Ketamine left, figured what the hell its the weekend, took it on an empty stomach this AM and ended up tripping balls... not really hallucinating but just very strong dissociative effect, 3x as much as normal with just K.


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## Gillman fan (Sep 24, 2016)

Haven't had much to update this thread with, but I noticed an energy drop last two days. I waited too long to refill Wellbutrin and my Ketamine was starting to get "old." It breaks down in liquid form and has to be refridgerated. Not sure which.


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## porkpiehat (Feb 13, 2017)

Gillman fan said:


> You can read my thread for more advice/ experiences, not sure what else to say. Try drinking coffee before going to stimulants IMO. Stimulants + Parnate can be more mood stabilizing, cofffee does not hit the dopamine button too hard.
> 
> As for me, I am quite stable with my cocktail. No side effects, except for inability to sleep without meds. Ultimately I think I can drop the various meds except 150 MG Parnate and the two important augments. Not sure about Nortriptyline, I feel I need the anxiolytic properties less now, although the SNRI stuff is quite attractive.
> 
> ...


Nothing resembling hypomania anymore. Today marked my first day of notable postural hypotension, although sedation and weakness has been with me for a bit. I got the visual whiteout after standing up and climbing the stairs; it got progressively worse until half my vision was gone for about 90 mins. Migraine followed for most of the day. Propranolol helped the headache.

about 9pm I found myself more fluid in speaking and focusing on conversations vs distraction and scripting. Mood's a little better. Granted I took 10mg Ritalin ER afternoon to keep myself moving. This shows some promise.

To answer your question, I definitely have some kind of complex trauma; but the bipolar II vs borderline component is unclear. Right now I feel too sedated to experience anything like hypomania. Interestingly Lamictal after 10 years has become something that can cause mixed episodes and hypervigilance, plus cognitive problems when mixed with some drugs. It still stabilizes me if I'm feeling racy and anxious from stimulants.

Had a hypertensive crisis the other night. Ate a taco salad at the same time I took the parnate and it had what I thought was a safe amount of cheese. BP climbed over 210 and pulse was below 40. Ok by noon the next day but I was surprised to find out I'm up to 150 tonight and I haven't eaten since noon. I wonder if freely taking ritalin and propranolol might be destabilizing.


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## Apexio (Jan 20, 2017)

Ketamine is a fasctinating drug. Seems like it does not only help with depression, but has some long term anxiolytic effects: study

For those who can't get it prescribed, there is still the somewhat experimental option of 2f-Ketamine, which can be bought legally online. At least its direct subjective effects are indistinguishable from normal Ketamine... My only concern with taking Ketamine long-term would be bladder issues. How often do you take your Ketamine, Gillman Fan?


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## Gillman fan (Sep 24, 2016)

Yes Ketamine is still quite mysterious I think. I have heard rumors about drug companies trying to develop a "new" Ketamine for a long time, at least as of 10 years ago... I haven't been following this too closely, but I haven't heard of any wildly successful trials. Ketamine works perfectly well and is quite easy to prescribe and use in the sublingual form. 

Dose - 200 mg 2x / week. The initial dissociation and dopamine hit is very strongly potentiated by Agmatine. The therapeutic effects are hard to measure because of the rest of my cocktail. 

I have considered switching to Memantine at some point just to make things easier, but for now I think I will just stick with my K. 

As far as bladder damage - that is a legitimate concern, but not at this dosage range. Recreational dosages in the range of 1 gram - 3 gram daily result in bladder problems. Many psychiatrists treat Ketamime as a new, dangerous street drug that is totally untested. But pain management doctors have been using it for years around the dosage range I am using it, even higher, with no issues.


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## Gillman fan (Sep 24, 2016)

Oh - btw porkpie re your blood pressure - that sucks. You may consider adding a norepinephrine reuptake inhibitor. Four good ones with mild side effects that are MAOI friendly are atomoxetine, reboxetine, nortriptyline, and desipramine.

A NE reuptake inhibitor will completely block the pressor response. Three of these that I just listed show some affinity for the serotonin transporter (i.e. reuptake inhibition) but they are ok - not potent enough to cause any symptoms of serotonin poisoning. The various SSNRIs are completely off limits.

And note that an NE reuptake inhibitor, won't make _serotonin poisoning _any better or worse, it just turns the world into an "all the cheese you can eat" buffet.

Edit - oh and Porkpie, I am happy to have you post here but if you make your own thread you might get responses.

Borderline vs. bipolar 2 - you need to talk to your doctor, this is one area where most psychiatrists I have seen use pretty good judgment. IMO the distinction does matter -
1. First there is a perception that borderlines shouldn't be medicated at all, or do not respond to medication. This is false, this perception is simply because SSRIs suck and you need more powerful drugs;
2. Another dogma is that bipolars shouldn't be prescribed antidepressants. The only "FDA approved" treatment is Symbax, some horrible combination of fluoxetine plus an antipsychotic. In fact bipolars do respond, just not to ****ty SSRIs. The Heinjen study I just referenced showed great results for bipolar patients with fewer manic switches to boot. My pet theory here is that serotonin is mood destabilizing and bipolar patients respond better to dopaminergic meds.
3. Someone with bipolar can expect a full or nearly full remission if their mood is stabilized and boosted from a quality antidepressant. 
4. Full remission with medication alone isn't quite possible with BPD. And some medications may cause tradeoffs - an anxiolytic may cause disinhibition leading to more "acting out" behavior. That said, medications on the whole are worth it, but you won't be able to get a full remission. 
5. Someone with BPD who is truly committed to therapy can show 90% improvement over the course of a few years, therapy does not do much to help manic switching.

Sorry for being pedantic at times... I just like helping people get the knowledge they need to make decisions in their own treatment instead of relying on doctors who often rely on medical myths to make their decisions.


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## Gillman fan (Sep 24, 2016)

Just a little update, I have had symptomatic remission for like a month now, I think I had a cautious attitude because I didn't know if it would last. Also I think depression can start out being just symptoms, but it also turns into habits, assumptions about the way the world works, etc. 


Some of the little things in life are so different now. I took a taxi and talked with the driver, the conversation did not feel forced and I was able to pay attention to what he was saying without being bored or withdrawing into my inner world. I go to the airport and no agoraphobia. It was never crippling for me but it was always constant, just one of the many things that made life unpleasant, and I was so used to it that I barely considered it a problem. I am annoyed by the stupid security procedures so I joke with the TSA guy to blow off steam. 


I was in a long distance relationship that had no prospect of becoming a short distance relationship in the foreseeable future, I decided I didn't want that. Got some stuff I need to do first, I wanna get back on my own feet etc. but suddenly it occurs to me that I want something with a woman, relationship or not, and I can do it on my own terms. Internet dating sucks, I have no interest in bars. Going to start reaching out to the friends I had, that might lead somewhere but in general I am not interested in developing 1000 friendships. But it occurred to me I could easily do something like speed dating. Before I always thought about the expectations that others would have for me. I am not a "normal" person now that I am medicated and I don't want to be. I am my own brand and I still have little interest in small talk. I will just skip that **** and go straight for what is interesting, what lies beneath the surface. I suck at small talk but I can often understand people from the inside out, what makes them tick, etc. and at the same time I am plenty "mysterious," very few people can understand the way my mind works. That is just me being me... superficial people might not like it but I am indifferent to their approval anyway.


Also I don't see as much of this in the med forum, but in others people love to complain about being "beta males" and talk about how the world is run by and women only pay attention to "alpha males." As if they want to be transformed into That Guy who just walks into a bar and charms all the women at once with a perfect pickup line. As if that was the person they were meant to be. I think this is stupid BS, moreover it makes it impossible to make change in your life when you are measuring yourself up to some fake ideal inspired by TV ads. It is so much easier to be yourself.


Anyway this isn't an attempt to humble brag, I guess I just see some posts from people like "the drugs work, I am cured!" But for me I spent years learning about life as a depressed person, now I gotta unlearn all of that and open myself to new possibilities. 


Fortune cookie wisdom.


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## Gillman fan (Sep 24, 2016)

So amphetamines... I didn't like them before because they seemed to flatten me out emotionally. But after finishing the rest of the cocktail, they seem to affect me differently. I am sure its Ketamine + Agmatine combo. 20 mg of Vyvanse is just amazing now.

I am pretty good emotionally but just so used to being physically lazy. I want to dump some other meds and add a smidge of amphetamines for energy. A tiny dose is just so much more effective than Wellbutrin.


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## Apexio (Jan 20, 2017)

Gillman fan said:


> So amphetamines... I didn't like them before because they seemed to flatten me out emotionally. But after finishing the rest of the cocktail, they seem to affect me differently. I am sure its Ketamine + Agmatine combo. 20 mg of Vyvanse is just amazing now.
> 
> I am pretty good emotionally but just so used to being physically lazy. I want to dump some other meds and add a smidge of amphetamines for energy. A tiny dose is just so much more effective than Wellbutrin.


As Wellbutrin is indeed just a weak NE releaser/Reuptake Inhibitor, Vyvanse should be much more effective. I'm not feeling much of 300mg Wellbutrin daily taken for the 3 days, other than more physical strength and maybe a little bit more motivation. Are you taking just 150mg of Agmatine as your signature says? That seems like a very small dose! Hard to wrap my head around the fact it is helping you that much.

Edit: Just read that you are taking it sublingual. I can't find data for oral bioavailability, so it could be that it is much more effective when taken sublingual. I have to check if that is possible with the fillers in my capsules.


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## Gillman fan (Sep 24, 2016)

Naw I don't take Agmatine sublingual on a regular basis. I just suggested that when someone joked about snorting it. I *strongly* believe that Agmatine does not have a linear dose/response curve, that said I do not know that 150 mg is the right dose. Keep in mind I also weigh 280 lbs, which is 130 kilos for people in civilized countries that insist upon using a logical measurement system.

Wellbutrin is a mystery. It isn't strong enough as a reuptake inhibitor to block the tyramine pressor response, and it isn't strong enough as a releaser to cause any hypertensive issues. 
I have been on and off of it maybe 8 or 9 times. I did notice a benefit in terms of MAOI weakness even at a low dose, but the various doses from 300-450 mg I have been on SO many times have done nothing.

When my current doctor asked for me to trial Wellbutrin again, I insisted that we push the dose until it had a noticeable impact. Sure enough, *750 mg XL* gave me insomnia, swapped this out for a blend of XL and SR and I:
- Wrote 100 pages of erotic fiction to share with my long distance girlfriend
- Cleaned my room thoroughly, dusting every single flat surface
- Built a very large snow fort, easily 100 lbs of snow, 3 feet high, using my bare hands.
Surprisingly I didn't feel that different, the behavior was quite noticeable but the subjective effect was not.

Of course my doctor wasn't comfortable with that dose since a genetic test indicated I should be metabolizing it normally, I think the test is wrong but that is another topic.

Anyway I am just trying to explain what pure NE should be doing... it takes massive doses of Wellbutrin for me to notice anything, but tiny doses of amphetamines do so much more for me.


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## Gillman fan (Sep 24, 2016)

Apexio said:


> Are you taking just 150mg of Agmatine as your signature says? That seems like a very small dose! Hard to wrap my head around the fact it is helping you that much.


I don't know if you read the study that got me to plump down for Agmatine next day air off Amazon. Courtesy of jaiho. Feel better jaiho 
http://www.sciencedirect.com/science/article/pii/S0091305714003475

Here are a few money shots:
---------------------------------------------------------

A sub-effective dose of agmatine (*0.0001 mg/kg, p.o.*) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 *decreased immobility time *in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and *100-fold (MK-801). *

--------------------------------------------------------------------------------------------------------------------------------------
..... Besides having a synergic effect with conventional antidepressants, a sub-effective dose of agmatine administered in combination with a range of sub-effective doses of MK-801 was also able to reduce the MED of MK-801 by 100-fold. Although previous studies have shown that agmatine may enhance the antidepressant-like effect of MK-801 in the TST (Neis et al., 2014) and in the FST (Zeidan et al., 2007), no previous study had reported the potency of this synergism. Reinforcing the notion that the mechanism underlying the antidepressant-like effect of agmatine is dependent on the inhibition of NMDA receptors, previous studies have reported that agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal (Olmos _et al_., 1999 ; Wang _et al_., 2006) and cortical (Gilad _et al_., 1996 ; Zhu _et al_., 2003) neurons. In addition,* agmatine reverses the NMDA receptor-induced intracellular Ca2 + overload and the decrease of monoamines (including norepinephrine, epinephrine and dopamine) content in PC12 cells* (Y.F. Li et al., 2003). Accordingly, NMDA receptor antagonists, including MK-801, are known to produce antidepressant-like effects in various animal models of depression (Mantovani _et al_., 2003; Sanacora _et al_., 2008 ; Skolnick, 1999), and the combination of traditional antidepressant drugs and NMDA receptor antagonists was reported to produce enhanced antidepressant effects in the FST (Rogoz et al., 2002).


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## Gillman fan (Sep 24, 2016)

Added 20 mg Lisdexamphetamine (Vyvanse). Apparently the starting dose for a _child_ is 30 mg, but this 280 lb man does great with 20 mg.

I tried Vyvanse before Agmatine and it had a horrible effect on my emotional range. I felt like a zombie.

Decided to try a little after Agmatine and I am blown away. Generalized pleasure feelings for a few days, mostly gone at this point.

Better energy, more outgoing

My orgasms are indescribably intense. My body spasms and my head involuntarily jerks this way and that.

But the most surprising has been the change in my innate preference for delayed (planned) gratification vs. immediate gratification. My relationship to food as totally changed. I don't crave carbs or sugars. I don't feel the need to overeat, in fact I feel full after eating a healthy portion size. Even when I have some of my favorite food I don't pig out! I have been a chronic user of tobacco for years, yesterday I did not even notice that I was using the same packet of Snus for ~8 hours, I guess I did not crave the nicotine at all.

I did a little research and it is plausible that a dopamine boost can do all of this for me. The ventral tagmentum area of brain is generally linked to immediate gratification, and the prefrontal cortex is more involved in planning, long term goals etc. Both areas do a lot of dopamine signalling. Vyvanse plus the rest of my cocktail is somehow managing a delicate balancing act that modulates dopamine levels in both areas to where it is just right.

This is a welcome surprise. I should be able to lose a great deal of weight without any effort. My favorite snack is now carrot sticks.

I will admit to gorging myself on video games for the first few days, going to see if I can resist playing or cut back to a more reasonable amount of time.

My current results remind me very much of what jaiho said at the start of this thread, that a punchy combo like Parnate + Nortriptyline helps with Anhedonia by generally making all activity more fulfilling, which is not necessarily helpful because negative behaviors are also more rewarding. I did not expect this result at all.


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## Gillman fan (Sep 24, 2016)

At this point my cocktail is done. In some areas I think my functioning is well above "normal." 

I need to cut out some of the unnecessary drugs. I experience no side effects aside from insomnia, and Trazodone works. So... there isn't a real urgency to change things. I am also in a bit of a deadlock with my doctor - I want to go off Wellbutrin, he considers it a gift from god, I am reluctant to drop Nortriptyline (already at bottom of therapeutic range) partially due to its advantage in blocking pressor response. He always wants to drop it first. Keeping lithium at a low dose is handy in case we need to raise it. Lamictal may be providing synergy or modulation of different parts of the cocktail in a subtle way. 

I plan on scaling back my involvement on these forums. I would like to finish the FAQ as a legacy but that may not work. My doctor has expressed interest in working with me on some of his other patients, i.e. I might come up with research or ideas, maybe eventually be paid, this would be a far more satisfying hobby for me instead of posting here because my recommendations are often impractical. 

The next step for me is emotional development. I do not see many people talk about that here, maybe this isn't the right forum for it? Basically I want to talk about my experience with others IRL, make sense of what I have been through. I experienced a lifelong deficit of emotional development / maturation that isn't simply cured by a pill. In a sense, I did not develop a normal identity, I felt a hostage to fate and took the path of least resistance so many times. I never experienced the feeling of freedom and making my own choices. This space has opened for me now. I want to explore what is new, and I want to mourn the past as well. I was deaf and mute to my suffering. Now I can give voice to it. Finding myself and healing the scars of my past will be a lifelong process... but I want to start now rather than later.


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## Cassoulet94 (Apr 3, 2014)

Gillman fan said:


> The next step for me is emotional development. I do not see many people talk about that here, maybe this isn't the right forum for it?


I think you can make a bigger difference speaking with people IRL than on an online forum.

I read a book where some psychiatrist wrote that social anxiety was a pathology of freedom. I found it very true but I guess it can be said for a lot of other conditions.

Good luck with your life !


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## Apexio (Jan 20, 2017)

Gillman fan said:


> At this point my cocktail is done. In some areas I think my functioning is well above "normal."
> 
> I need to cut out some of the unnecessary drugs. I experience no side effects aside from insomnia, and Trazodone works. So... there isn't a real urgency to change things. I am also in a bit of a deadlock with my doctor - I want to go off Wellbutrin, he considers it a gift from god, I am reluctant to drop Nortriptyline (already at bottom of therapeutic range) partially due to its advantage in blocking pressor response. He always wants to drop it first. Keeping lithium at a low dose is handy in case we need to raise it. Lamictal may be providing synergy or modulation of different parts of the cocktail in a subtle way.
> 
> ...


I'm very happy for you and how your life is going at the moment! Finding a med cocktail that works is a very important step forward and gives you more room to work on your emotional issues. If you are able to mobilize only half of the passion, energy and intellect you show when you are engaged with pharmacological topics and the communication of your knowledge to others, there can't be anything that can stop you from making substantial progress with your personal development in the next month and years.

Of course I (and probably some other members) won't be so happy to hear that you won't be here that often in the future. But as you say, you will be doing more or less the same thing you did here, BUT in the real world, for money and with a better chance to actually realize your ideas. Good luck with that!

Somewhat unrelated question: Do you think you might have experienced some kind of trauma in the past?


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## Gillman fan (Sep 24, 2016)

Don't worry I will still pop in from time to time  There is some good research and discussion btw. 

Actually I stayed up late and spoke with Ken Gillman, mainly I wanted suggestions on how to slim down my cocktail, he just suggests waiting a few months to see if it is stable. I think he is probably critical of much of what he sees, but I he called my cocktail "rational" which counts as pretty effusive praise from him 

As for trauma, I had years of therapy and never was able to answer that question until relatively recently. Therapists are looking for emotional pain that is present. The best explanation is that I have a strong predisposition towards leaning on the logical side of my brain and ignoring the emotional side. 174 verbal IQ. Which simply means I have thought out response to stimuli before an emotional one "comes through." So I experienced the pain of absence - of not being emotionally present. It is a trauma but it isn't the kind that therapists really seem to look for. 

This predisposition led to something like trauma because my parents were both pretty emotionally disconnected, but logical people. I never really had to cope with others presenting me with their emotional states either. My mother probably did not "mirror" my emotional state but was very proud of my intellect and imagination and that is how we were engaged. And I knew about my intellectual side from an early age and was taught to consider it something was something valuable and good. I mean she was REALLY proud of me and she loved having an uber-rational mini-me that she could have discussions with, in her "native" language. 

I had some friends, I was always interested in classes, I had other entertainments, but I never had a sense of who I was or what I wanted. And with girls it was terrible. Plenty of them threw obvious signs of interest in my direction, or even more blunt direct interest in sex. I was attractive enough and always came across as supremely confident and funny in class. And I would be completely unaware of their interest, I was so involved in simulating a real person. I couldn't respond to this sort of thing in real time, but afterwards I would "watch a video" of the day when I was in a more comfortable and private place, run the events through my head and decide what had happened. I was a virgin to 26 when the woman seducing me was nice enough to give me time to think about it before I put a move on her. I had to rehearse and weigh all of the social signs we had gone through in my head, all the current signs she was sending me, the consequences if I messed up, and a staged response to romance that looked natural - touching, arm around, get closer, eye contact, kiss, groping etc. She laid so many obvious signals and yet me make the first "move" which I really appreciated. 

Meh I can go on but basically my emotional drives were fundamentally not integrated with the rest of my brain, this is quite similar to anhedonia but I am giving a more fine-grained description. Personal achievements meant very little because I did not really want them, friendships didn't feel meaningful because I could never engage emotionally. When things were at their best I was able to repress basically everything they felt and manage in spite of this disconnection. But eventually repressing everything was too taxing, even for me, and all the fear, loathing, etc. I had been holding inside took hold. I had no capability of soothing myself emotionally. 

That is a very long answer to a short question. I feel an urgency to speak and express myself that never existed before, but my self-analysis of my stuff is also rather complicated. I think you are someone who can understand and has experienced some aspects of this. My latest psychiatrist helped me with looking at and acknowledging my differences, but it is only now that I am in remission that I can truly see what happened to me. I was deaf and mute to my own pain, unable to sense it as anything but a foreign presence in my mind, unable to communicate it in a meaningful way. My cocktail has helped with more than just "mood" and "anxiety" - I am much better integrated now, I have hope, but I am still scarred in a way.

*Edit* - Cassoulet I didn't notice your post until I finished, I would agree that I had a pathology of freedom. I never experienced before.

Believe me I am talking to a LOT of people in my life. No need for therapists. I just didn't want to drop off the planet here, and I also wanted to explain that even with my 100% awesome med cocktail the healing isn't done yet.


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## porkpiehat (Feb 13, 2017)

I visited a new doctor lately who prescribes parnate and I thought he would be more familiar with combos, but he was uncomfortable with -- and failed to find research proving the therapeutic value of -- adding Nortriptyline to Parnate. The whole general fear of mixing TCA.

Gillman Fan can you elucidate a definite difference with the Nortriptyline? I've stayed at 20 mgs Parnate which kept me solidly out of depression but still kinda apathetic. Playing around with Lamictal dosing got me doing dishes and cleaning the litter, but there's no sex drive or planning for the future.

I can argue for it if there's some anecdotal proof of it helping in these areas.


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## Gillman fan (Sep 24, 2016)

Porkpie - I already did a lengthy writeup for SFC, I will PM you.

So the 20mg Vyvanse "pooped out." Went off it for a week, then my psychiatrist recommends going on 30 and then 40 mg. 

The funny thing is that I have done sooo much research, but my doctor is an expert on stimulants because he treats a LOT of ADD. So I just do what he says! It is nice being the patient.

Anyway it is stable so far, but this is just 5-6 days in. Vyvanse is working wonders now that I have the Ketamine + Agmatine combo. Lots of energy to do stuff, and the external world is just more interesting. I don't spend as much time in my head. I would say I have experienced mild pleasure/euphoria but honestly I don't care about that, I am looking at my functioning - I have a lot of stuff I need to get done, 2 small boys to take care of, I am unemployed, etc. 

Anyway I won't say my cocktail is "done" until I am stable for a month or so. I have loved Nortriptyline for a long time, but I don't think I need it anymore, I would like to swap it and Buproprion for Desipramine or Atomoxetine. I just like not having to worry about eating the wrong foods.


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## jaiho (Feb 14, 2015)

What's the reason for swapping out Nort, Gillman fan? It's potency as an NRI should be more than enough to eliminate the need for the MAOI diet.


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## Gillman fan (Sep 24, 2016)

Nort: Weight gain, plus I consider it mildly sedating. Its overall effects are great but I don't need the help with my mood anymore. The one issue I want to focus on now is energy. I am happy with my cocktail results re: anhedonia and mood but I would like more energy to do things. I might not like the change but I think it is at least worth a try. 

Right now though my doc is having me try some low dose amphetamines, quite easy and safe with Nort's NRI, but the effect isn't stable yet. Vyvanse provides tremendous energy for a few days and then poops out. I haven't decided anything for sure but my cocktail is certainly in the "tweaking and optimization" phase.

I wish more people could get an Rx for Ketamine sublingual. It is good for acute depression but IMO doesn't treat chronic symptoms that well. Fantastic combo with Agmatine.


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## tcprocks (Aug 17, 2017)

Gillman fan said:


> Parnate is still working quite smoothly at 150 mg. It is great. I feel energized, I don't feel as neurotic, I want to get stuff done, AND I am more normal emotionally. I feel more emotionally labile - I was emotionally constipated before. I mean I don't have mood swings on a day to day basis but I can feel situationally appropriate emotions where I couldn't before.
> 
> I had a week of confusing sleep issues that really got me down. I would sleep for 12 hours, not be sleepy at a normal bedtime, go to bed later, sleep for 12 hours, rinse repeat. I would wake up feeling barely functional, tired but also kind of sedated and anergic. I thought this was my sleeping pill causing problems. Turns out this is Parnate WITHDRAWAL! So moving part of my dose later in the day is fine. I have to go up to 150 mg Trazodone but that is fine, I like the feeling it gives me as I drift off to sleep  and this is still a low dose.
> 
> ...


Glad it finally worked.

I met Dr Gillman on the net some months ago and I am just starting treatment on Parnate. I am a fan of his site as well, it is difficult to find quality information like that.

I am really astonished with your psychiatrist. In Spain, I have not been able to find a pdoc that will even prescribe Parnate !!


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## tcprocks (Aug 17, 2017)

Gillman fan said:


> Just a little update, I have had symptomatic remission for like a month now, I think I had a cautious attitude because I didn't know if it would last. Also I think depression can start out being just symptoms, but it also turns into habits, assumptions about the way the world works, etc.
> 
> Some of the little things in life are so different now. I took a taxi and talked with the driver, the conversation did not feel forced and I was able to pay attention to what he was saying without being bored or withdrawing into my inner world. I go to the airport and no agoraphobia. It was never crippling for me but it was always constant, just one of the many things that made life unpleasant, and I was so used to it that I barely considered it a problem. I am annoyed by the stupid security procedures so I joke with the TSA guy to blow off steam.
> 
> ...


Ha ha, I want some of that. Doing things on my own terms... would be great.

I suck at small talk as well, that is probably why I hate it... or maybe it is because small talk sucks at being interesting !


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## tcprocks (Aug 17, 2017)

I am presently at 40 mg and starting to see some improvement on mood. More energy.

The main side effects is close to zero libido and sleepiness on the afternoon. I am spacing my doses every 1.5-2 hours to avoid blood pressure spikes after taking it. Apparently few people is affected but I am one of those.

BTW, the MAOIs + TCAs combination is known to be safe since the 70´s

The link is jamamanetwork.com/journals/jamapsychiatry/article-abstract/490464


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## Gillman fan (Sep 24, 2016)

Just an update:

I have been in full symptomatic remission for 2ish months now. Amphetamines (Vyvanse) could make me feel super duper good, ready to take on the world, but then result in a huge crash/ or make me feel like a robot. Actually I have not given up 100%, I want to trial a small dose of adderall, Rx is for 20 mg, will see how it goes.

I think for a while I was really disappointed that the meds didn't solve all my problems, I mean I didn't feel depressed but I wasn't eager to re-engage with reality either. My expectations for meds were a bit inflated due to my Vyvanse response too. Right now I am pursuing psychotherapy with my wonderful, creative, odd and disorganized Dr. After years of therapists running we are doing a completely different approach with a focus on me articulating my ideal self, what I am capable of, etc.

FWIW I occasionally add psychological commentary to this thread, basically my overall understanding of my illness has been that even from a very early age I had an extremely strong preference towards logical/linear/verbal thinking, and I came to rely on it to such an extent that my ability to understand/experience/integrate emotions was crippled. I guess people in a depression/anxiety forum may think emotions are bad, but the truth is you *need* emotions in order to experience joy, a drive, a sense of who you are and what you want to accomplish... and so much more. Chronic anhedonia and depression are more "medical" ways of describing this.

Parnate has relieved me of depression and "anxiety" (also more complicated but I will skip another lengthy explanation), but it hasn't instantly given me drive. It has enabled me to have an awareness of my own emotions for the first time in my life, I mean a real *experiential* awareness and not the sort of "awareness" that a therapist can give you.

So I need to discover my drives, who I am, what I want, or at least integrate these abstract-sounding things into my emotional experience of self. I think, first and foremost, I suffered from a rare, chronic issue that can only be addressed through psychiatry, and frankly it has required a massive and "heroic" amount of medication to help me. But the emotional issues that I am describing (e.g. drives) are an outgrowth of my long-standing emotional stunting - areas where emotionally normal people develop from children into adults. In some ways I am emotionally more like a teenager than anything else.

To elaborate more on this, read the "four identity states" in this article https://en.wikipedia.org/wiki/James_Marcia#Identity_diffusion. Basically I bounced between the three immature states, I would elaborate more upon his definition of foreclosure but I don't want to write another mega post. A diagnosis in conventional psychological terms would be something like personality disorder, not otherwise stated. Of course I disagree with some of the dogma here but... must stop ranting.

Years and years of medication and the best psychotherapists that money could buy got me nowhere, but my current doctor PLUS the super-powerful med cocktail I have pursued with his support have gotten me far! But basically, I am still unemployed, isolated, etc. after withdrawing into my shell for a long time.

Anyway I am writing about myself but I hope that others find this useful. Meds can be 100% necessary in some cases, but not sufficient. I think SFC experienced illness for the first time later in life, debilitating symptoms that were completely treated with Nardil, but he has a good emotional foundation that I (and others) may lack. SFC sorry if this is an oversimplification but I think of you as the poster boy for 100% insta remission from MAOIs.

Also I have been posting a lot less, I am probably not going to be posting as often trying to solve people's problems. But if you say my name three times (like the movie "Beetlejuice") you can temporarily summon me to a thread, or feel free to send PM.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> Anyway I am writing about myself but I hope that others find this useful. Meds can be 100% necessary in some cases, but not sufficient. I think SFC experienced illness for the first time later in life, debilitating symptoms that were completely treated with Nardil, but he has a good emotional foundation that I (and others) may lack. SFC sorry if this is an oversimplification but I think of you as the poster boy for 100% insta remission from MAOIs.


:smile2:

@watertouch also called me the nardil poster boy but yes, completely agree with you on this mate.


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## UKguy (Sep 30, 2013)

Gillman fan said:


> Just an update:
> 
> I have been in full symptomatic remission for 2ish months now.
> 
> ...


Glad to hear you are getting positive results these last couple of months.

I can identify a lot with the two paragraphs quoted. I have emotions obviously but as you say it is the ability to experience, understand and then act on them on all levels that is a challenge.

I struggle to know 'who I am, what I want' as well, although I'm not sure how uncommon this is really. Plenty of people just bumble along in life without really discovering who they are or what they want, at least on a deep level. In fact I think it is probably quite normal but there is a lot of the crap that is shoved down our throats that makes us think otherwise. Very few people can achieve success in life as it is portrayed in the media and viewed by society.

I just went up to 30mg Parnate but experiencing some weird BP/HR issues and anxiety again. Maybe I should have listened to Nardil poster boy @SFC01 :band and gone with Nardil, sigh. It is early days I guess.

btw where do you find a doctor to RX that combo of meds?


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## SFC01 (Feb 10, 2016)

UKguy said:


> I struggle to know 'who I am, what I want' as well, although I'm not sure how uncommon this is really. Plenty of people just bumble along in life without really discovering who they are or what they want, at least on a deep level. In fact I think it is probably quite normal but there is a lot of the crap that is shoved down our throats that makes us think otherwise. Very few people can achieve success in life as it is portrayed in the media and viewed by society.
> 
> I just went up to 30mg Parnate but experiencing some weird BP/HR issues and anxiety again. Maybe I should have listened to Nardil poster boy @*SFC01* :band and gone with Nardil, sigh. It is early days I guess.
> 
> btw where do you find a doctor to RX that combo of meds?


Yeah its quite common to struggle with the who am I ****, which is why I dont bother with that anymore - I`m run of the mill average with a good life so that does it for me. I read a lot of cosmology stuff and I`ve always liked the Carl Sagan's Pale Blue Dot quotes -it makes you realise just how insignificant we all are and that puts life into a nice perspective for me.

If you cut me in half I'll have nardil written through me like a stick of rock ! :smile2: They need to do an advert for nardil with me in it - I`m up for it !!

I want Gillman Fan's pdoc too !! I`d be trying to get everything under the sun off of him.


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## Gillman fan (Sep 24, 2016)

As far as the "who I am" bit, it is less metaphysical than it sounds. It is linked directly to behavior. In the past when I interacted with people, unless they tickled my intellectual curiosity, I would deliberately be unfailingly polite, listen to what they have to say, maybe mumble something in exchange, and politely find an excuse to end the conversation. This was kind of a default behavior... kind of noncommittal. I then had to spend time analyzing my interactions with people in order to grade them as trustworthy/ not, interesting/not etc.

Now I realize how blunt I am. I don't want a life of making small talk and avoiding confrontation. I don't want my recreation to be roaming the streets at night with a huge group of drunken "friends." In fact the quantity of my friends means almost nothing to me now, one or two good ones is enough. I have a very good idea what I want in a woman  intellectual curiosity (but with a more feminine touch, I am still uber rational) is probably at the top of the heap, together with a rich inner life and a desire to share it. Also hint hint - not gonna say this at first but "openness to experience" is the #1 variable that corresponds to a woman's sex drive. In long term relationships... what men want in terms of sex doesn't really matter, the woman decides, best to choose one that matches up with you.

So basically, even if I am interacting with someone I find boring, I know *why* I am interacting with them, I am not vaguely angry, I don't feel trapped in my own head and my own routines. Also I have felt the need to hide my intellect in order to not be threatening to people. ***** that too.

as far as my doctor :lol: good luck finding another like him. Much like Steve Jobs he has a "uniform" - black pants, a black T shirt and a cheap unbuttoned shirt worn over top, always blue. Unlike Steve Jobs he always looks kinda dishevelled. He is trained in psychoanalysis and psychiatry, and generally turns away clients who are not *weird* enough. I am dead serious, one of the first thinks he asked me was 1) whether I can afford him and 2) whether I could benefit from his special skill set. Doctors normally have no question in their minds that they can help you, and the display of diplomas, professional dress, a well-appointed office etc. are made to reassure you of their expert authority.

He understood me within an hour, I mean actually understood how I think and feel rather than the psychologists "well maybe you unconsciously are angry" schtick. I am never at a loss for words but I was nearly dumbfounded.

Now as far as the drugs  he looks at each patient individually and while he does care about safety, he has made it clear that he doesn't care about legal liability. He wants to make people better and also doesn't give a ***** what other doctors are doing.

It wasn't like I went into our first meeting and said "ok I want to try a combination of Parnate, stimulants, ketamine etc." Instead we tried a few drugs that didn't work out. I was resolved to be 100% involved in this process and I researched the hell out of his recommendations and kept detailed journals for dose/response, blood pressure, etc. Nuedexta was a wash, Ketamine monotherapy didn't last, and Trintellix made me apathetic.

Then I dropped the MAOI request. He is just old enough that he worked with them briefly long ago... he was worried because he swallowed the propaganda about MAOIs being "dangerous" but I carefully explained my research to him, and the important thing is he trusted me to give him accurate, OBJECTIVE analysis. He never had the time to research everything I have.

Getting on this cocktail has required a lot of effort, some experimentation, and a tremendous amount of discussion. I want him to understand the essential reasoning, risks and benefits of each med I research or request, and he has been crucial to planning a lot of the logistics. Multi-drug cocktails can be really hard to manage, it requires skill and judgment. We have had hour long meetings on more or less an "as needed" basis to discuss all of this. Basically he *is* a very liberal doctor, but more importantly he has no ego - he doesn't need to feel that he *needs* to know more than me. And he has also made it clear that he would not prescribe this cocktail to a regular patient due to safety concerns and not understanding the details.

So this bears little in common with the typical psychiatrist-patient relationship. He does have final say on everything and there have been a few times where he has wanted to titrate a drug more slowly, and after he explains it I agree with his reasoning. Literally every decision has been a consensus. And the stimulants? He is an expert in ADHD and is quite comfortable with them, I think adding the first stimulant was his recommendation lol.

So yeah  he is a very unique doctor, but I am also a pretty unique patient. Also Dr. Ken Gillman's research and expertise have been invaluable in this whole process since he is completely authoritative and addresses all the health/safety stuff.

If you are in the Chicago area I can hook you up. He should be accepting new patients in the near future.


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## porkpiehat (Feb 13, 2017)

I hope to sit down and really read through what you've written. I think I can relate to it more than I want to right now, in the middle of a med change, last thing I need is internal doubt and second guessing.

I experienced a lot of good from Parnate, namely cognitive stuff, self possession. But I did really dislike the distance I felt from people and the lack of motivation to do anything. I was able to rationally look at some of my emotions, dulled although they were, and kind of make sense of why they were occurring. I also realized that I wasn't as trapped in certain behavioral patterns as I thought I was. I might have felt a drive to do nothing or just fish but if I could muster willpower to change directions my brain would follow. I just couldn't handle the "speedy and nervous/super exhausted" axis I was on.

I look forward to reading further posts


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## tcprocks (Aug 17, 2017)

SFC01 said:


> Yeah its quite common to struggle with the who am I ****, which is why I dont bother with that anymore - I`m run of the mill average with a good life so that does it for me. I read a lot of cosmology stuff and I`ve always liked the Carl Sagan's Pale Blue Dot quotes -it makes you realise just how insignificant we all are and that puts life into a nice perspective for me.
> 
> If you cut me in half I'll have nardil written through me like a stick of rock ! :smile2: They need to do an advert for nardil with me in it - I`m up for it !!
> 
> I want Gillman Fan's pdoc too !! I`d be trying to get everything under the sun off of him.


Ha, ha, count me in. Everybody wants Gillman Fan's pdoc :-D
If only mine would prescribe Parnate...

I am glad for you Gillman Fan that you got such a mix working.

I have been on 40 mg Parnate for four weeks now and anxiety, fear, ...begin to increase for no apparent reason. This is disturbing because there was a time @30 mg when I felt immune to anxiety.

Maybe it is time to increase to 50 mg but will wait a little bit because my agmatine just arrived !!

Eagerly waiting for tonight to see if it augments trazodone. Keep you posted.


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## porkpiehat (Feb 13, 2017)

tcprocks said:


> Ha, ha, count me in. Everybody wants Gillman Fan's pdoc :-D
> If only mine would prescribe Parnate...
> 
> I am glad for you Gillman Fan that you got such a mix working.
> ...


What is the agmatine for? just to help the trazodone get you to sleep?
I got the anxiety and fear also on Parnate. It is a stimulant after all and a stronger inhibitor of MAO-B to boot. If you are sensitive to these chemicals...especially with trauma/fibromyalgia or BP component, I think this reactions is more likely. Just a thought.

Anywhooo, I think small, small doses of klonopin or propranolol were helpful to me in these situations.


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## Gillman fan (Sep 24, 2016)

Porkpie - pls read Agmatine thread I explain it. It is safe, but extremely complicated in how it works.


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## porkpiehat (Feb 13, 2017)

Gillman fan said:


> Porkpie - pls read Agmatine thread I explain it. It is safe, but extremely complicated in how it works.


I just ordered some. I tend to not do so well with many "harmless" supplements like SAMe, NAC, and sarcosine...that last one made me feel AWFUL.

On day 6 of Marplan I should probably let it go longer before adding stuff, but thought I'd have a faster reaction with the inhibition from 30 mgs parnate still in my system from the hot switch.

I'd love to have my sex drive back, sociability etc.


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## tcprocks (Aug 17, 2017)

porkpiehat said:


> I just ordered some. I tend to not do so well with many "harmless" supplements like SAMe, NAC, and sarcosine...that last one made me feel AWFUL.
> 
> On day 6 of Marplan I should probably let it go longer before adding stuff, but thought I'd have a faster reaction with the inhibition from 30 mgs parnate still in my system from the hot switch.
> 
> I'd love to have my sex drive back, sociability etc.


Me too.

I have tried SAMe in the past. It is activating/stimulating but it doesn´t add anything positive, especially if you have anxiety. I found it helpful for arthritic pain though.

I have been taking NAC as well just in case. It does no harm in me. I take to improve chronic nasal congestion so that I do not depend so much on oxymetazoline.


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## Gillman fan (Sep 24, 2016)

I am doing more "therapy-esque" stuff with my doctor - meeting more frequently, talking about my goals and what is holding me back, etc. I had to wait a long time to see him and I considered seeing a regular psychologist, but I am so glad I waited for him. The funny thing is that his son and his partner are both INTJs. So he knows how to deal with us, and he also knows how frustrating we can be! 

I am having problems with Trazodone. 100 mg used to put me to sleep all night and I would wake up feeling like a million bucks. Now I am at 200 mg and I am waking up every night almost. So I proposed to my doctor that I switched to a "Z drug" for a week. 

Right away he brings up how much exercise helps you sleep... new studies on this topic showing it is more effective than sleep meds, etc. I understood this as him not wanting to help with sleep meds and got quite frustrated and angry. At the end he did agree to help me, we have a "deal" that I will engage in mild exercise in exchange for the eszopiclone Rx, and the truth is I am more likely to engage in exercise knowing that I received something in exchange. So I am no longer frustrated regarding this exchange. 

I tried adjusting my dosage schedule to see if I could improve insomnia a bit. For a long time I have been taking 30 mg Parnate at 6 pm because it helped me wake up without feeling like I am going through a mini-stimulant withdrawal. It helps with sleep onset somewhat but I felt incredibly tired this morning... often I want to stay in bed and end up oversleeping because I am daydreaming, or thinking about a dream, or feel warm and comfortable etc. and I am often tired, but this morning I felt dead. No Parnate since noon the previous day. 

My doctor was happy to prescribe Vyvanse, but I explained that it lasted 18-24 hours with me. I explained my success with Adderall at very low doses in the past and requested regular adderall, I do have an Rx for that now. Right now I nibble on the 10 mg tablets and eat 1-2 mg at a time at most, never at night of course. Ironically I think the adderall makes me feel more tired when it is bed time, which is a good thing!

Anyway I am still tweaking the meds a little, but the main thing for me now is translating by better emotional state and newfound confidence into action and better life habits on my part. It takes effort. I can boost my mood and energy further via higher dose amphetamines so that it does NOT take effort, but this has never been stable. The 3 mg dose I mentioned is a large dose for me!

*over and out*


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## porkpiehat (Feb 13, 2017)

Gillman fan said:


> . Right now I nibble on the 10 mg tablets and eat 1-2 mg at a time at most, never at night of course. Ironically I think the adderall makes me feel more tired when it is bed time, which is a good thing!
> 
> Anyway I am still tweaking the meds a little, but the main thing for me now is translating by better emotional state and newfound confidence into action and better life habits on my part. It takes effort. I can boost my mood and energy further via higher dose amphetamines so that it does NOT take effort, but this has never been stable. The 3 mg dose I mentioned is a large dose for me!
> 
> *over and out*


Hmmm. I'd love to understand the sleeping better on adderal thing. I've taken ritalin after waking mid-night when my thoughts are disorganized and out of control, and it worked. However I think I was coming down from some "partying" at that time.

When do you take your agmatine? I tried 500 mgs this morning for the first time. It slowed me down a little but helped me feel more upbeat and less anxious on a long car ride with an aquaintance. Around 5pm I found myself more fearful and less self possessed for the rest of the day, even after taking my last 20mgs of marplan and an extra 50mgs of lamictal. I read that it stimulates alpha 2, which may be detrimental in someone with trauma history; and that it impacts NMDA (?) centers, which I think are partially a lamictal target.

I'd like to try a second 500mgs later in the day but I don't know if it would interfere with sleep meds.


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## tcprocks (Aug 17, 2017)

porkpiehat said:


> Hmmm. I'd love to understand the sleeping better on adderal thing. I've taken ritalin after waking mid-night when my thoughts are disorganized and out of control, and it worked. However I think I was coming down from some "partying" at that time.
> 
> When do you take your agmatine? I tried 500 mgs this morning for the first time. It slowed me down a little but helped me feel more upbeat and less anxious on a long car ride with an aquaintance. Around 5pm I found myself more fearful and less self possessed for the rest of the day, even after taking my last 20mgs of marplan and an extra 50mgs of lamictal. I read that it stimulates alpha 2, which may be detrimental in someone with trauma history; and that it impacts NMDA (?) centers, which I think are partially a lamictal target.
> 
> I'd like to try a second 500mgs later in the day but I don't know if it would interfere with sleep meds.


I would start on a smaller dose and see how you react. 500 mg was quite noticeable in my case.


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## tcprocks (Aug 17, 2017)

Gillman fan said:


> I am doing more "therapy-esque" stuff with my doctor - meeting more frequently, talking about my goals and what is holding me back, etc. I had to wait a long time to see him and I considered seeing a regular psychologist, but I am so glad I waited for him. The funny thing is that his son and his partner are both INTJs. So he knows how to deal with us, and he also knows how frustrating we can be!
> 
> I am having problems with Trazodone. 100 mg used to put me to sleep all night and I would wake up feeling like a million bucks. Now I am at 200 mg and I am waking up every night almost. So I proposed to my doctor that I switched to a "Z drug" for a week.
> 
> ...


Me too here.

I have tried to change the dosage schedule as well to see if I can start sleeping more easily. First I checked if I could take the whole 40 mg in one shot. Regarding the blood pressure it was ok (during the weekend). Then I did a test for three days, and it was a mess. It is too "activating"/stressing when working. Heart beat/pounding increase easily which is an uneasy sensation. Then orthostatic hypotension is more marked and all in all I had a harder time getting to sleep which was what I was after. Ok, I did not maintain this schedule for too long but...

Now I am trying the opposite, take one pill every three hours even though the last one is at 6 pm or whenever. Indeed, a last dose closer to bedtime helps the sleep onset. However, this sleep is maintained for about 1-1 1/2 hours.

I have noticed that Parnate is changing my sleep patterns, maybe trazodone is partially responsible for that. I get to dream more and now I can sleep about 6 hours (vs. 4 or 5 previously) which makes me less tired in the morning. Previously I slept 4-5 hours and woke up early morning really tired but had no problem with sleep onset.

Before Parnate I could not get back to sleep if I woked up, no matter the time. I had used Z drugs, benzos, trazodone, mirtazapine/mianserin. Nothing could make me sleep longer.

Now the main problem is falling asleep with Parnate when I reached 30 mg/day. I have now 100 mg trazodone and 7.5 mg mirtazapine and it takes me 1-2 hours to fall asleep.

I have tried 200 mg trazodone and it gives me a headache in the morning plus a stuffy nose that makes me snore. Those are known secondary effects. I do not want to increase Mirtazapine further because of its own effects as a potent antihistamine. I cannot gain weight as my back would resent.

It is true, exercise helps. But I already practice exercise daily and has its limitations. First, excercise does not have to be exhausting otherwise It will make me sleep worse. Second, there is a practical limit on how many hours you can devote to exercise. Now I do two hours daily including the necessary stretches (as important as exercise itself).

So yes, exercise is good but in the end you will develop tolerance to it as you get more fit, like with meds !! Unless you can spend eight hours a day doing exercise... then lesions will appear more easily.

I find excruciating when people/doctors cure everything with exercise. BTW, exercise makes me feel better, better like in better shape. In my case has zero impact on mood even when I spent 4 hours a day. And does not make me fall asleep more easily. More exercise makes me... more tired. If I am too tired I cannot sleep well.


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## Gillman fan (Sep 24, 2016)

TCProcks: I have a one-month belated reply to your sleep problems. If you specifically have a problem with waking up too early, I would suggest bright-light therapy an hour BEFORE you go to sleep. I believe that MAOIs do more than just cause insomnia, they specifically interfere with circadian rhythms. Basically MAOIs trick your body into trying to have two circadian rhythms per day... this is why people wake up early but then feel sleepy in the afternoon. Trying to medicate circadian rhythm issues is often ineffective. I am not an "alternative treatment" guru but I believe the evidence is excellent for bright light therapy. I discussed this with Dr. Gillman, he has a strong vein of skepticism but at least he found my reasoning plausible and I believe he recommended this to one other patient.

Study is here https://www.ncbi.nlm.nih.gov/pubmed/16171276

As far as meds are concerned I was actually going to discuss my own sleep issues. 200 mg Trazodone was not doing it for me, I took a week off and switched to a "Z" drug (Eszopiclone) and then went back to 200 mg Trazodone. Trazodone is back to working its magic for me. It is common for me to wake up around 2 am but then I can go back to sleep in 10-15 minutes. I feel like my sleep is great on Traz. Going to try adding a bit of Agmatine before bedtime, see how that goes. Apparently Trazodone does build some tolerance, I may have to do this cycle every 6 months or so, but I did NOT experience "rebound insomnia" after ceasing Traz or anything like that. Traz isn't great for everyone but it just works wonders for me.

I am cutting back on the rest of my cocktail too. I went from 150 mg Parnate to 120 mg, haven't noticed any difference. Dropping Wellbutrin SR and Strattera completely makes me feel less sedated in the morning, with no apparent mood difference. I filled an Rx for Adderall and I am happy with the results, the Rx is for the smallest dose, 10 mg, but I typically just have a 3 mg "nibble" of the tablets in the AM and around noon.

Getting **** done is still a problem. Going to ask my doctor about Clonidine / Guanfacine. 0 problem in terms of MAOI interaction. I think my brain is as good as it is going to get in terms of overall neurotransmitter boosts, but if I could target the PFC it would be ideal.

I kinda took a hiatus from self-improvement due to my sister's terminal illness. I spent a week visiting her in California. She was only 40 years old but suffered a rare form of cancer that metastasized throughout her body. My mom was 100% supportive and basically paid for the best treatment my sister could get, my sister at least was happy because she felt her doctors were on the same page, I had the impression they were really excellent. So anyway I flew out to see her, the entire time she was in a hospital bed and her legs were so badly swollen she couldn't really move or take care of herself.

She had nurses to provide for her physical needs, but 1) being in a hospital a long time is super disorienting and 2) she was drugged up on pain meds most of the time. I ended up spending a big chunk of each day sitting with her in the hospital, she was asleep most of the time. I didn't provide any life-saving treatment but I helped her with little things like a towel on her head, talking with her, holding her hand, and listening when she complained about her situation.

Ironically my mom also needed my care too. She is diabetic and not in the best of health, and she was 110% devoted to taking care of my sister, meaning poor diet and not enough sleep. I was there for her too so that she could sleep more and I encouraged her to eat/ drink diabetes-safe foods.

I ended up on the "night shift" which I thought would be easy. Afterall the combination of an MAOI and a powerful sleep med means I do not really experience the need for sleep until I take Traz. Unfortunately, this did not work as planned, something about the circadian rhythm disruption really screwed with me, and when I missed two doses of Parnate it precipitated an acute episode of agitated depression... which felt really, really bad but I knew it was temporary. Cleared up within 4-6 hours of taking my Parnate dose, but this was also enough of a shock to my immune system that I caught a cold... and couldn't sit with my sister at all due to her compromised immune system.

The last time I saw her I knew that her end was nigh. My mom still had a positive outlook, basically because the surgeon always seemed to have another plan in mind, and I hardly wanted to rain on that parade. But she died less than a week after I left. Very hard on my mom but she was staying with her extremely supportive sister in CA.

Ultimately I am discussing this for the selfish reason of reflecting on my own emotions, thought processes here. I was not super-duper close to my sister. But we were close. Somehow I cannot think about her loss in the abstract, I think about the last bit of time I spent with her, and I guess I feel proud that I was supportive in a way that I didn't know was possible for me. It was sad to be with her but I was really focused on what she needed to feel the best she could. The stupid hospital encouraged her to eat "whatever she could" and "as much as she can" but she had only tasteless hospital food. Why not her favorite ice cream, Cherry Garcia? I got her some and she ate quite a bit, got her some Pho soup which she loved, etc.

Honestly by the time she died... I actually felt relieved, because she could have lingered on death's door for another couple of months, not feeling at all well and not getting any better. But I felt that taking care of her was taking a toll on my mom, physically, psychically and financially. I spent meaningful time with my sister, I didn't feel tremendously strong emotion but I showed my love through actions. And through it all I knew what I felt, how I felt... I did not feel cut off from myself.

So it is a weird reaction to someone's death, I feel the loss but I also experienced my own growth and resilience.

Another topic entirely - I have been feeling a strong need for female companionship. I haven't talked about it much in this thread but for a long time I had a long-distance relationship with a woman I met online, we ended breaking up but I learned so much about how I function in relationships, and what it is that I want from a woman, in the process. I was married for 3 years and we "got along" but I really wasn't myself... I simply got married because I wanted security and feared loneliness.

The plan is speed dating - it is random and old-fashioned in this day of Grinder and all the various dating sites but I think the subtle subconscious cues of in-person courtship are vital. And I know I am an odd duck, I think it will be easy to kind of explain myself and be honest about my needs and flaws in a 5 minute interaction with someone. I am really quite comfortable verbally explaining myself with transparency and (brutal) honesty - BUT I still feel nervous about the initial stages of courtship. Stating my preference (and need) for openness and explicit verbal communication early on is one thing, but there is a great deal of uncertainty and subtlety early on...

But somehow I feel stuck and don't want to proceed with relationship stuff until I clean up my goddamn house. I am a good father in many ways but a TERRIBLE housekeeper and having a 2.5 year old and 3.5 year old... it is like having a house party every weekend. I don't want to be dating but be ashamed to have someone see how messy my house is. +1 for trying clonidine/guanfacine.

Anyway long post... for those of you who are following thank you, I am happy to share and I hope you can learn from some of what I am going through. Also I am quite comfortable answering any questions, be it re: medication or more personal.


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## tcprocks (Aug 17, 2017)

Gillman fan said:


> TCProcks: I have a one-month belated reply to your sleep problems. If you specifically have a problem with waking up too early, I would suggest bright-light therapy an hour BEFORE you go to sleep. I believe that MAOIs do more than just cause insomnia, they specifically interfere with circadian rhythms. Basically MAOIs trick your body into trying to have two circadian rhythms per day... this is why people wake up early but then feel sleepy in the afternoon. Trying to medicate circadian rhythm issues is often ineffective. I am not an "alternative treatment" guru but I believe the evidence is excellent for bright light therapy. I discussed this with Dr. Gillman, he has a strong vein of skepticism but at least he found my reasoning plausible and I believe he recommended this to one other patient.
> 
> .....
> 
> .


Thank you for the tip. Will try that as it is simple enough. I have noticed the lack of light in winter could be a cause of decreasing mood. Correlation is not causation but.... who knows.

I am sorry about your loss. I have had recently a similar experience, not as close, with the sister of a friend. She was 43.

Don´t be too harsh on you, don´t try to have everything tidy with two children, it is the way it is. Just put a sign like "God bless this mess" or something and you are set up :grin2:

BTW, I have left trazodone. I had built tolerance and It was doing nothing lately. Sleep time was the same with and without.

I have to get back to exercise as I quit since the cold days arrived.


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## tcprocks (Aug 17, 2017)

BTW, using trazodone long term could be a bad idea according to this article:

https://www.researchgate.net/public...om_m-CPP_might_outweigh_benefits_of_trazodone


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## Hannes2 (Nov 4, 2016)

tcprocks said:


> BTW, using trazodone long term could be a bad idea according to this article:
> 
> https://www.researchgate.net/public...om_m-CPP_might_outweigh_benefits_of_trazodone


Would not trazodone's antagonism at the "bad" receptors - though with somewhat less affinity then m-CPP's agonism, but then in higher concentration - to some extent neutralize the bad effects of m-CPP?

50 mg trazodone keeps working for me against Parnate insomnia since months, but I always take a two days break at the weekends to avoid tolerance.


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## Gillman fan (Sep 24, 2016)

Read the footer on the bottom:


> "Articles published in the Viewpoint section of this Journal may not meet the strict editorial and scientific standards that are applied to major articles inThe World Journal of Biological Psychiatry. "


This is a shoddy publication that admittedly was published in the _opinion _section of a not very prestigious journal. It does not include citations for some of its most important points.

The existence of mCPP as *a* metabolite of Trazodone is no secret. It is the mirror universe version of Trazodone, the evil, moustache twirling twin, its opposite at virtually every receptor site. Everyone agrees that mCPP is bad.

The author raises issues about mCPP, and then implies that Trazodone should not be used because of these issues. OK, mCPP is bad, got it. But Trazodone works in the exact opposite way at each receptor site. Any in vivo study of Trazodone will necessary include the weighted effect of mCPP.

Did I say mCPP is the evil twin of Trazodone? Well, it is more like the parents had 10-100 children and mCPP is the black sheep of the family. This is an empirical question, one of many that the other should have discussed but didn't. The evidence weighs against his hypothesis... blood levels of mCPP are much lower than Trazodone. In the range of 10% to 1% as much. Trazodone actually has several metabolic pathways and mCPP is the product of only one of these metabolic pathways.

The author's poor reasoning is supported by a shocking lack of citations of empirical studies of Trazodone (and its sister compound, Nefazodone). The author concludes that Trazodone should be studied more. I certainly agree! But don't imply a total lack of empirical data when there is plenty.

Actual human studies on trazodone directly conflict with the author's conclusions. E.g. mCPP (and therefore Trazodone) is anxiogenic - nope, the opposite. mCPP (and therefore Trazodone) is dangerous because of hypertension. Actually the biggest risk of Trazodone in overdose is HYPOtension. The author raises question after question, questions that have already been answered!

Trazodone doesn't work for everyone. If you have an adverse reaction to Trazodone then stop taking it. There is probably a tremendous variation in response here for a number of reasons that the author does not discuss- for example, genetic variance for the enzyme expressed by the CYP 2D6 locus can be quite significant, with ultra-rapid individuals commonly requiring twice the dosage of normal (extensive) metabolizers, and poor metabolizers requiring half the dose. mCPP relies on 2D6 to a much greater extent than Trazodone, so a poor 2D6 metabolizer may have greater blood levels of mCPP than an extensive metabolizer. Similarly, slower 3A4 metabolism would tend to raise blood levels of Trazodone vis a vis mCPP.

I greatly prefer risks/ side effects that are immediately apparent upon starting a medication. Traz feels bad? Stop taking it. No harm done. Side effects that develop more slowly can be even more dangerous. Oh, it turns out the antipsychotic Seroquel causes insulin sensitivity? Well too bad, you can't undo that, you are now predisposed to developing diabetes. It turns out the pyramidal (muscle control related) side effects of Seroquel are permanent? Yeah, that can happen. You realize that you gained 30 lbs on Remeron? Oops. Long-term use of an antihistamine has built up a tolerance but you can't discontinue due to somatic symptoms as extreme itchiness and sensitivity to allergens? Not pleasant. Ambien has slowly impaired your memory, led to semi-conscious autonomic behavior that could land you in ER (and you won't remember), and has significant withdrawal symptoms of rebound insomnia, nightmares etc? Well it sure felt good when I started it; I thought the FDA approved this crap?

Trazodone does not exist in a vacuum, alternative sleep meds all carry their own risks and drawbacks. Trazodone carries risks and side effects that should be immediately apparent when treatment is started. The biggest risk is a 1 in 6,000 chance of priapism. Trazodone is evil, an evil that almost everyone should avoid but MAOI patients might find necessary. Nonetheless, it is like Diet Evil(R) compared to the alternatives.

One general proposition the article states is that "Trazodone should be studied more in order to ensure safety." Yeah that would be great! But it simply isn't true that Trazodone is some poorly researched anomaly, NO sleep meds have received adequate study in terms of their long term use.

TCProcks I understand where you are coming from. I did the same internet sleuthing and at first I was rather alarmed by mCPP. But, in my opinion and after reading more literature, Trazodone is the best choice for long-term treatment of insomnia.


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## SFC01 (Feb 10, 2016)

tcprocks said:


> BTW, using trazodone long term could be a bad idea according to this article:
> 
> https://www.researchgate.net/public...om_m-CPP_might_outweigh_benefits_of_trazodone


I tried trazodone for a while for sleep but it correlated with a downturn in mood which I had never experienced on nardil before so I dropped in the end - I always had the mCPP issue in the back of my mind as well - as depending on individual circumstances, it seems the mCPP metabolism rate can vary quite a bit.

Btw, I second GF's point on light therapy - I have never had SAD and I sleep fine but sticking my head in front of a light therapy lamp each morning in the dreary UK winter months just feels great !! I like closing my eyes right in front of it and it feels like you are sunbathing on a nice summer afternoon !


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## tcprocks (Aug 17, 2017)

Gillman fan said:


> Read the footer on the bottom:
> 
> This is a shoddy publication that admittedly was published in the _opinion _section of a not very prestigious journal. It does not include citations for some of its most important points.
> 
> ...


Agreed. Trazodone and/or a potent antihistaminic (Mianserin/Mirtazapine/Doxepin) are the best bets. I have used the first two because getting Doxepin here is nearly impossible.

This guy mentions there are better options but do not say which. That made me very suspicious. Probably it was not the best article on the subject but is one that is accessible. Well, one can use Sci-Hub (https://sci-hub.hk/) to get other articles but the server won´t last.

However, mCPP risks are for real so, if possible, we should decrease trazodone dosage as much as we can. I have quit it just because it was no longer effective *and* I was experiencing a mood downturn and suspecting this could be the cause just like SFC01 mentions.

Let´s see how light therapy results.


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## tcprocks (Aug 17, 2017)

Gillman fan said:


> Read the footer on the bottom:
> 
> ... Trazodone is evil, an evil that almost everyone should avoid but MAOI patients might find necessary. Nonetheless, it is like Diet Evil(R) compared to the alternatives.
> 
> .


:laugh::laugh::laugh::laugh::laugh::laugh: Diet Evil


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## Hannes2 (Nov 4, 2016)

I tried light therapy as recommend by Gillman fan but is has no effect on insomnia for me. I used in the morning, then in the evening, then also for the whole day, but insomnia persists. I'm still using the lamp every day, just in case there is some benefit for mood (which is difficult to determine though given all the drugs and supplements I'm taking).


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## Gillman fan (Sep 24, 2016)

Light therapy isn't going to replace sleep meds for most MAOI users and has little effect on sleep onset insomnia. I specifically recommend trying light therapy for:

Waking up too early; and/or feeling very sleepy at the same time each day in the afternoon.

Early waking insomnia is very difficult to treat. Any sleep med you take will be mostly wearing off by the time your body wants to wake up. If you take a longer acting sleep med it will make you drowsy after you wake up.


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## Gillman fan (Sep 24, 2016)

Haven't done an update in quite some time. Med cocktail is stable, adding 200 mg SAMe helps with physical energy / endurance.

One part of my life I was not managing very well was the neatness of my house. It was very messy, not in a way hazardous to health, it mainly just looked like a disaster. Based on my psychiatrist's recommendation I finally got a cleaning person to help me... spent a good 11 hours doing cleaning and she did 9.

I had no idea how much psychic energy my messy house would suck out of me. I would think of something like "oh I should reconnect to XYZ friend" or start dating, but then I would think of how much my house was disgusting. "Well I should clean up first." But it never got done, it was kind of a way of avoiding doing things. I know that I enjoy myself so much more and the meds are basically working... but some start of me is/was still afraid.

I have figured out exactly what is still wrong with me at this point. I am no longer "anhedonic," "anergic" etc. but I would say lack of hedonic feedback over the course of my life has conditioned me to be rather passive. I have had success, but it never felt good, and my inevitable depressions made it seem less and less attractive to devote energy to improving my life. The fundamental feelings have changed but I guess I have had a lifetime of "learning" impairment.



It is funny that I think rats illustrate my condition better than people. I have just done a lot of research, and a word like "depression" is virtually meaningless to me... but I find a study like this and it is very exciting because it illustrates a vital part of my impairment as well as the link between the dopaminergic and glutamate systems.


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## SFC01 (Feb 10, 2016)

Gillman fan said:


> Haven't done an update in quite some time. Med cocktail is stable, adding 200 mg SAMe helps with physical energy / endurance.


is the ketamine still doing it for you mate ?


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## jaiho (Feb 14, 2015)

> I have figured out exactly what is still wrong with me at this point. I am no longer "anhedonic," "anergic" etc. but I would say lack of hedonic feedback over the course of my life has conditioned me to be rather passive. I have had success, but it never felt good, and my inevitable depressions made it seem less and less attractive to devote energy to improving my life. The fundamental feelings have changed but I guess I have had a lifetime of "learning" impairment.


I know this feeling. My therapist would say the biggest healing has to be done within the window of experiencing freedom of anhedonia. If the work isn't done to get life back on check, then the benefits will fade, and perhaps the cause of many poop outs for alot of people.
I suppose alot of us look at it too much as a biological/chemical problem, when there could be deeper issues we arent aware of.


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## Gillman fan (Sep 24, 2016)

Yup the ketamine is still an important part of the cocktail.

Actually I have always been dosing Agmatine in the morning and Ketamine later in the day. A few weeks back I took them both in the morning because I had a long drive coming up in horrible weather conditions and I wanted absolute 100% focus on driving (with a little aid from 200 mg caffeine and 5mg adderall as needed). So I took both in the morning before I left, and I was blown away by the increase in potency.

Normally Ketamine is like 2-3 glasses of wine, and I am a big guy, so it is mildly relaxing without producing the "stupid" feeling of alcohol. I have little interest in alcohol now beyond, say, one drink of something delicious.

But this time I was halfway into a K hole. I tried sublingual doses of Ketamine up to 400-500 mg and really didn't notice that much of an increase in potency, but taking Agmatine at least tripled the effect. It wasn't unpleasant, just inconvenient because I wanted to be getting stuff done. The potency is intriguing because I think there is a very good chance Ketamine boosted with Agmatine can equal the strength of IV Ketamine, without the risks.

One other thing I forgot to mention - my doctor is actually prescribing Ketamine and Parnate to other patients now. It feels really rewarding to know that I played a part in this and made some difference. In particular, one patient made something like 200(!) suicidal "gestures" but Ketamine greatly alleviated this suffering. I don't think it is the most amazing anti-depressant ever but I strongly believe it is the best anti-suicidal. She did get hospitalized at one point, her doctor refused to administer Ketamine because he "didn't believe in it." She did much worse until she was released and able to resume her treatments. Funny story - a patient comes into his office with a stack of papers and starts talking about this "Australian doctor," thinking he needs to convince my doctor of the merits of MAOIs. And of course then my doctor a)namechecks Gillman and b)is able to talk about his significant experience with MAOIs ~30 years ago and more recent experience with me.

So Jaiho it isn't so much that I believe it is an emotional/ psychological issue per se. I know I have had several brief episodes with drastically increased motivation, energy and confidence to get **** done. I just don't think I can achieve a stable effect here.

The current plan with my doctor is not "psychological" but a behavioral intervention. This is the study of how to motivate people to do something and it does not presume "psychopathology" or neuroses etc. Conventional psychology is overwhelmingly concerned with resolving neurotic/ abnormal thoughts so people can be "normal." One really good example is Las Vegas - they hire behavior shaping PhDs who engineer every part of the experience, from the lighting to the smells to what you see - and they hire undercover employees to go around and help lift the mood. The target behavior here is very simple - making money for the casino! But there is a science behind it.

So essentially, I have not been working for a while, if I didn't have other financial means I would have been forced to get a job by now. But instead I am going to have to exercise initiative in this field and others, with incentives to make it more attractive to do stuff. I am so completely unused to making decisions because I want to, and not having some heavy avoidance baked in, for example, moving to a new place might make me feel better temporarily because I could tell myself I didn't need to change, everything would be better. And virtually every one of these positive changes in my life I was running away from my last depression, I had to tell myself that some change would fix everything... I had virtually no other choice because all the psychotherapy and meds I had for years did precisely nothing.

My experiences are just so different than many others on this forum. I can't tell you how many times in my life I felt very confident in relationships or my abilities. This wasn't so much feeling good about myself, just a logical assessment of how others saw me, etc. Nothing stuck. I succeeded in some ways before, I can succeed again, why bother? Why stick my head out when it is just going to be nailed down again? I participated in an intense group therapy style program for a while, and I gave it 100%, whatever doubt I felt was submerged as I focused on succeeding in terms of the program. So I went out of my way to talk to people openly, make friends, and help other people in my role as a peer. As I was leaving I had one final meeting with the staff. Most of the time was taken up by the irrelevant coincidence that my therapist was out of town, was my move out date coordinated to avoid him? lol. He didn't understand me more than 10-20% and I didn't understand myself either, I just realize now how little I care about the guy.

Anyway the purpose of this anecdote is that one of the staff pointed out things I had accomplished in my time there, being a "leader" and helping others blah blah and none of this was a coincidence, these were all goals I set for myself. This was infuriating... I didn't exactly have the words to express why it was infuriating, but in retrospect it is so obvious that anhedonia robbed me of any sense of accomplishment here. So many times in my life I was almost glad to throw everything away... everything I built, the friendships I made, because it felt totally unreal. Trying to live the life of a normal person I always felt like an imposter, I could make decisions etc. without much feeling inside, no one would notice the difference, but I was so hollow. Being depressed seemed more authentic in a way.

Also one way in which I differ from other people is that I was able to substitute verbal/logical ability for a lot of things that would normally be done via emotional processes, just in terms of interacting with people on a daily basis or whatever, this became so routine and automatic I was cut off from a lot of negative and positive emotions, but I also built coping skills. Gradually, I could understand other people very well, sort of from the "inside out," even if I was not particularly empathetic. I couldn't tune in with what other people were feeling in the moment, but I could understand people well enough that countless people opened up to me and trusted me completely. "cold empathy" mixed with intuition, I guess. Probably this is more a function of my personality and intelligence than my illness. In any event, I was damn near autistic at other times. My "model" of how other people worked was extremely rigid and incapable of coping on the fly. Best example being women... nothing logical about attraction. I did receive plenty of attention but anything from flirting to an outright proposition went straight over my head, couldn't fit in in the "model," mine as well have not been there. Actually I feel pretty confident in this area, I suck at flirting but I have little interest in casual relationships anyway, nor do I care what 90% of women think. I know I have a "type" where mutual attraction is easy and natural, just gotta find them.

This is more or less just thoughts floating around in my head at this point, a roundabout way of understanding myself because I spent so long without knowing what was really wrong. Not really trying to make a point with this last round of introspection lol. Maybe just that the impact of chronic anhedonia over the years... the damage is subtle, I seemed functional enough so many times, but each experience of being "functional" or "normal" made me feel more and more powerless to change the hollow feeling.

So yes this is a psychological way of looking at my illness... but simply talking about this would never have helped. Psychiatry is essential and a 100% cure would be great but I am at 70%, still optimistic overall.


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