15 replies to this topic

[bobisyahu]

I have been rummaging through this forum for a while and thought I'd finally post...

 

I'm a 28 y/o male who has been dealing with depression, extreme anhedonia, and concentration/attention/memory issues.  SSRIs do not give me any positive result.  Bupropion definitely helps a little, but not enough to get to the point where I can start making the lifestyle changes (better diet & exercise) that will help long-term.  

 

I know there is a bit of eye-rolling here when someone says, "I think I have a dopamine deficiency", but some of the non-cognitive symptoms I have read about suggest this as a possibility: cold hands and feet, lack of interest in eating (I have been hungry for the last 2 hours and still have not cared enough to make some food), slight but noticeable hand tremors.  These combined with the extreme anhedonia and the small but positive effect from the bupropion seem to strongly suggest a dopaminergic issue.

 

My psychiatrist thinks vyvanse might be worth trying again (I was on it for 2 years and it helped a lot, but I abandoned it 6 months ago).  My concern with psychostimulants is that they may only exacerbate the problem in the long-term.  

 

I am considering some dopamine precursors and cofactors and will probably start these soon.

 

My questions are, does anybody have any useful experience combining bupropion with anything else?

 

Would taking short-term mucuna pruriens be a valid way to test the dopamine-deficiency hypothesis?

 

[Mind_Paralysis]

Don't stare yourself blind on Dopamine.

Your issues could just as well be related to NOREPINEPHRINE (aka noradrenaline). I myself have cold hands and feet as well, and similar issues overall, to you.

 

I am afflicted by an ill-studied neurodevelopmental disease called SLUGGISH COGNITIVE TEMPO.

 

Have a look at the disease, and see if you recognise yourself in 6 or more symptoms.

https://en.wikipedia...cognitive_tempo

 

What little data there is on the disease suggests it's connected to the parts of the brain in the back of your head - the posterior and parietal networks - the Superior Parietal Lobe has the most compelling evidence right now - it seems to have the equivalent role of the Pre-Frontal Lobe in ADHD.

 

Have a look at the disease, and see if you recognise yourself in 6 or more symptoms.

 

It should be noted, that Bupropion has been proven to affect Norepinephrine to a greater extent than Dopamine...

 

 

Of course, you could also be afflicted with Atypical Depression - if so, I have written some about potential treatment here:

 

http://www.longecity...ndpost&p=825952

 

Sertraline and Bupropion is a common combo to try out for treatment-resistant atypical depression.

 

 

Refs:

--------

 

Use of Bupropion in Combination with Serotonin Reuptake Inhibitors

http://www.sciencedi...006322305008206

[Deaden]

Jahio. Jahio will tell you what you need.

Edited by Deaden, 05 September 2017 - 11:03 PM.

[Deaden]

Concentration and memory issues often come with anhedonia. You are depressed in the way that you feel less pleasure from things or you are completely anhedonic. Can you feel sadness/happiness ever since it set in? If not then you have anhedonia and it's normal Wellbutrin alone doesn't help you enough. I had tremors too when I was at my worst, they'd come after I did or took something that forces my brain to feel pleasure short term. Like sex or alcohol but I've been keeping away from those. Have you tried smoking cigarettes? They can help but don't make the same mistake as me and abuse them. Something like two a day can really make you feel strong emotions and pleasure like you used to be able to and be useful in making you more patient until you find a good med or combination of meds that works... shouldn't get you addicted. I'll let Jahio recommend you some good treatment options like he did to me and a few other people. I owe him.

[jaiho]

I'd recommend not starting nicotine :P

MAOIs actually reinforce nicotine addiction, so being on Nardil will make it harder to quit, Deaden. But still doable. Actually, adding Wellbutrin is useful since it blocks the pleasurable effects of Nicotine, reducing it's addictive qualities.

 

Anhedonia is hard to treat since most dopamine elevating drugs eventually gain tolerance.

Your best bet is trying a 5ht1a agonist based SSRI like Viibryd or Trintellix, or Fluoxetine (Prozac, 5ht2c antagonism aswell) and combining it with Wellbutrin or Nortriptyline.

 

The idea behind this, is that serotonin is mostly inhibitory via 5HT2C receptors, and SSRIs increase the density of DAT (Dopamine transporter)

Sometimes just adding Wellbutrin is enough to counter the dopamine reducing effects of SSRIs, but others need further additions (Agomelatine, or Nortriptyline)

 

It's important to note that serotonin also increases DA release by activation of various 5HT receptors. 

 

https://www.ncbi.nlm...les/PMC2562467/

This paper explains the different 5HT receptors and which inhibit or facilitate DA release.

 

The other option is going straight for MAOIs like Nardil or Parnate. They increase dopamine more than any other anti depressant, via MAO-B inhibition.

[Deaden]

Yeah yeah I was just talking for him I don't think two cigarettes a day will make him addicted. And it's true I read that MAOIs made some people smoke way more than before. Maybe when I get my Nortryptline delivery + start taking Agmatine again it will be enough to help me quit. Right now I haven't really gave it a real attempt tbh. Smoking will give me pleasure from music or social situations, but I wish I didn't start I made a mistake I know...it killed the effects of Nardil which I remember really helped me when it started working. Wasn't enough to bring back my emotions alone but...  I've heard of a few meds that act on nicotinic receptors and have better success rate than Wellbutrin, but have no idea if they have bad interactions with MAOIs. I wonder if it will be impossible for me to gain emotions back from anything again as long as I keep smoking.

 

By the way about NAC and Sarcosine, why don't you try this combination now while still taking what you are taking? They don't affect neurotransmitters no? Shouldn't it be safe? Do you plan on trying that combo alone? You'll have to endure being numb again and take the risk of it not working as well as you expect it. Or might be better...

Edited by Deaden, 06 September 2017 - 03:44 AM.

[RedStaR]

 

I have been rummaging through this forum for a while and thought I'd finally post...

 

I'm a 28 y/o male who has been dealing with depression, extreme anhedonia, and concentration/attention/memory issues.  SSRIs do not give me any positive result.  Bupropion definitely helps a little, but not enough to get to the point where I can start making the lifestyle changes (better diet & exercise) that will help long-term.  

 

I know there is a bit of eye-rolling here when someone says, "I think I have a dopamine deficiency", but some of the non-cognitive symptoms I have read about suggest this as a possibility: cold hands and feet, lack of interest in eating (I have been hungry for the last 2 hours and still have not cared enough to make some food), slight but noticeable hand tremors.  These combined with the extreme anhedonia and the small but positive effect from the bupropion seem to strongly suggest a dopaminergic issue.

 

My psychiatrist thinks vyvanse might be worth trying again (I was on it for 2 years and it helped a lot, but I abandoned it 6 months ago).  My concern with psychostimulants is that they may only exacerbate the problem in the long-term.  

 

I am considering some dopamine precursors and cofactors and will probably start these soon.

 

My questions are, does anybody have any useful experience combining bupropion with anything else?

 

Would taking short-term mucuna pruriens be a valid way to test the dopamine-deficiency hypothesis?

 

 

Don't stare yourself blind on Dopamine.

Your issues could just as well be related to NOREPINEPHRINE (aka noradrenaline). I myself have cold hands and feet as well, and similar issues overall, to you.

 

I am afflicted by an ill-studied neurodevelopmental disease called SLUGGISH COGNITIVE TEMPO.

 

Have a look at the disease, and see if you recognise yourself in 6 or more symptoms.

https://en.wikipedia...cognitive_tempo

 

What little data there is on the disease suggests it's connected to the parts of the brain in the back of your head - the posterior and parietal networks - the Superior Parietal Lobe has the most compelling evidence right now - it seems to have the equivalent role of the Pre-Frontal Lobe in ADHD.

 

Have a look at the disease, and see if you recognise yourself in 6 or more symptoms.

 

It should be noted, that Bupropion has been proven to affect Norepinephrine to a greater extent than Dopamine...

 

 

Of course, you could also be afflicted with Atypical Depression - if so, I have written some about potential treatment here:

 

http://www.longecity...ndpost&p=825952

 

Sertraline and Bupropion is a common combo to try out for treatment-resistant atypical depression.

 

 

Refs:

--------

 

Use of Bupropion in Combination with Serotonin Reuptake Inhibitors

http://www.sciencedi...006322305008206

 

 

Bupropion is a stronger DAT inhibitor/DA releaser, than NET/NE AFAIK, do you have a source for otherwise?

 

Your symptoms seem to be a case of hypothyroidism, not every problem we have is connected to neurotransmitter dysfunction. Try supplementing with high doses of Ashwagandha, and one serving of supplemental iodine. Take caffeine with L-Theanine as well if you can tolerate it, but go easy as caffeine isn't exactly healthy. 

Edited by RedStaR, 07 September 2017 - 11:12 AM.

[Mind_Paralysis]

 

 

I have been rummaging through this forum for a while and thought I'd finally post...

 

I'm a 28 y/o male who has been dealing with depression, extreme anhedonia, and concentration/attention/memory issues.  SSRIs do not give me any positive result.  Bupropion definitely helps a little, but not enough to get to the point where I can start making the lifestyle changes (better diet & exercise) that will help long-term.  

 

I know there is a bit of eye-rolling here when someone says, "I think I have a dopamine deficiency", but some of the non-cognitive symptoms I have read about suggest this as a possibility: cold hands and feet, lack of interest in eating (I have been hungry for the last 2 hours and still have not cared enough to make some food), slight but noticeable hand tremors.  These combined with the extreme anhedonia and the small but positive effect from the bupropion seem to strongly suggest a dopaminergic issue.

 

My psychiatrist thinks vyvanse might be worth trying again (I was on it for 2 years and it helped a lot, but I abandoned it 6 months ago).  My concern with psychostimulants is that they may only exacerbate the problem in the long-term.  

 

I am considering some dopamine precursors and cofactors and will probably start these soon.

 

My questions are, does anybody have any useful experience combining bupropion with anything else?

 

Would taking short-term mucuna pruriens be a valid way to test the dopamine-deficiency hypothesis?

 

 

Don't stare yourself blind on Dopamine.

Your issues could just as well be related to NOREPINEPHRINE (aka noradrenaline). I myself have cold hands and feet as well, and similar issues overall, to you.

 

I am afflicted by an ill-studied neurodevelopmental disease called SLUGGISH COGNITIVE TEMPO.

 

Have a look at the disease, and see if you recognise yourself in 6 or more symptoms.

https://en.wikipedia...cognitive_tempo

 

What little data there is on the disease suggests it's connected to the parts of the brain in the back of your head - the posterior and parietal networks - the Superior Parietal Lobe has the most compelling evidence right now - it seems to have the equivalent role of the Pre-Frontal Lobe in ADHD.

 

Have a look at the disease, and see if you recognise yourself in 6 or more symptoms.

 

It should be noted, that Bupropion has been proven to affect Norepinephrine to a greater extent than Dopamine...

 

 

Of course, you could also be afflicted with Atypical Depression - if so, I have written some about potential treatment here:

 

http://www.longecity...ndpost&p=825952

 

Sertraline and Bupropion is a common combo to try out for treatment-resistant atypical depression.

 

 

Refs:

--------

 

Use of Bupropion in Combination with Serotonin Reuptake Inhibitors

http://www.sciencedi...006322305008206

 

 

Bupropion is a stronger DAT inhibitor/DA releaser, than NET/NE AFAIK, do you have a source for otherwise?

 

Your symptoms seem to be a case of hypothyroidism, not every problem we have is connected to neurotransmitter dysfunction. Try supplementing with high doses of Ashwagandha, and one serving of supplemental iodine. Take caffeine with L-Theanine as well if you can tolerate it, but go easy as caffeine isn't exactly healthy. 

 

 

I've talked to at least one Dr. on another forum whom was absolutely adamant that Bupe's effects on dopamine are negligible and our very own Finn showed a neat study that used the latest in-human data on the drug, and it does appear as if the first conclusions regarding Bupe's effects on dopamine in humans was incorrect - in rats it seems more selective for DA, but in humans it's NE.

 

The Psychopharmacology of Bupropion: An Illustrated Overview

https://psychopharma...hopharmacology/

 

 

In contrast to what was described in animal studies, human in vivo research suggests that bupropion effects on dopamine are relatively modest.

 

As far as I understand it, the confusion comes partially as well, not just from rat-studies, but from the fact that apparently most of the actions of bupe really comes from the METABOLITE, i.e, at first, it's a weak DA-selective drug, but very quickly it turns into a weak NE-selective drug.

 

 

I'll see if I can dig up the study's Finn found, but in essence I have been convinced that yes, it's more of a NE-agent than a DA-agent.

 

HOWever... This is, admittedly, something of an oddity, because Bupropion is provably addictive and euphoric via intravenous administration - as seen in the krokodil-like abuse that's started cropping up in Canada, for instance. (previously abused intranasally in prisons)

 

It might be that this changes the pharmacodynamics of the drug. There's of course also the fact that it treat anorgasmia in people using SSRI's, and is known to cause hypersexuality in some individuals - all in line with the idea of greater effects on DA than NE.

 

But the tests of regular use is what we have for clinical use, and then it's more of an NE agent.

 

BUT, I digress, because depending on your internal chemistry, Bupropion may not even have any NE-effects, because it's still first and foremost a Nicotinic antagonist, so those are the effects you're going to feel first, no matter what.

[Finn]

 

 

 

 

I'll see if I can dig up the study's Finn found, but in essence I have been convinced that yes, it's more of a NE-agent than a DA-agent.

 

 

 

Wikipedia's bupropion pharmacodynamics section explains it pretty well and has links to the studies.

 

https://en.wikipedia...harmacodynamics

[bobisyahu]

Thanks for the responses.

 

Stinkorninjor:

I have been looking into the Sluggish Cognitive Tempo page and there seems to be some similarity to how I'd describe myself. These are the most striking:

• Spacey or 'in a fog'
• Mind seems to be elsewhere
• Stares blankly into space
• Lethargic or more tired than others
• Trouble staying awake or alert in boring situations
• Gets lost in own thoughts
• Apathetic or withdrawn, less engaged in activities
• Loses train of thoughts
• Forgets what he/she was going to say
• Hard time putting thoughts into word

Also my original post (maybe 150 words) took about 20 mins to write.  Unrelatedly, most of my thoughts are intensely self-critical and negatively focused.

 

Deaden:

I dont really like smoking cigarettes anymore, but interestingly enough I  used a nicotine patch for two days last week and they were two of the best days I've had in months

 

Jaiho:

I have not responded well to SSRIs in the past but have never taken in combo with bupropion, will look into this as well as MAOIs....thanks

 

RedStaR:

I have been thinking about the possibility of hypothyroidism (my mom has it), I had hormone levels checked like 4 years ago and they were normal-ish, but I plan to see a GP in the next month to check again.

 

Lastly, I dont know if this is diagnostically informative or not, but I got the vyvanse prescription yesterday and took a small dose (~15mg) in the early afternoon.  Before taking it I had actually been in a decent mindset, enough to go to the gym for the first time in weeks.  After taking it I continued to feel well (except for stomach issues and mild physical anxiety), but when it started wearing off all traces of the good mood vanished.  This has continued into this morning...I think I will not try more of this. 

[RedStaR]

I've talked to at least one Dr. on another forum whom was absolutely adamant that Bupe's effects on dopamine are negligible and our very own Finn showed a neat study that used the latest in-human data on the drug, and it does appear as if the first conclusions regarding Bupe's effects on dopamine in humans was incorrect - in rats it seems more selective for DA, but in humans it's NE.[/size]

The Psychopharmacology of Bupropion: An Illustrated Overview


https://psychopharma...hopharmacology/

 
As far as I know, the PET method for imaging endogenous dopamine in the human brain is a rough estimate at best. We do not really know for sure unless a post mortem human brain was sampled.

 

Also note that rat metabolism is much more extensive than humans with regards to its active metabolite (2S,3S)-Hydroxybupropion, where mice are more comparable. But studies are mixed on this issue for brain plasma levels.

 

 In contrast to what was described in animal studies, human in vivo research suggests that bupropion effects on dopamine are relatively modest.

 

 

Relatively modest falls in-line with animal studies, where DAT occupancy reached 25% for therapeutic doses in rat models.

 

 

Positron emission tomography with [11C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion.Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion.

 

 

Bupropion and its metabolites inhibited striatal uptake of the selective DAT-binding radioligand (11)C-betaCIT-FE in vivo. Three hours after the last dose of bupropion SR, average DAT occupancy by bupropion and its metabolites was 26%-a level that was maintained through the last PET assessment at 24 hours after dosing.

 

 

 

apparently most of the actions of bupe really comes from the METABOLITE

 

 

Well, not most, but a large part comes from an isomer of its main metabolite. Based on it's AUC and IC₅₀ , it is anywhere from 10—25x stronger than BUP for NET, DAT, and nAChR inhibition. A study on rat brain showed indeed, stronger DAT re-uptake inhibition.

 

 

 

It has also been hypothesized that BUP excites DA release through nAChR antagonism, leading to a downstream effect on the remaining DA-related subunits. We know that BUP works most potently on α3β2, and to some extent, α4β2, α3β4, and α7. 

 

 

 

More research (or cross-research by anyone here willing to) needs to be done here to determine the clinical effects of such.

Edited by RedStaR, 07 September 2017 - 09:47 PM.

[bobisyahu]

update:

 

for the last few days I have experimented with some vyvanse dosing.  At lower doses (20-30mg) it puts me into an unpleasant, spaced-out, anxious state.  At higher doses (70mg+) it had a largely positive impact on my mood, memory, and seemed to clear up the brain fogginess.  I have read that at lower doses it has a larger effect on nor-epinephrine while at larger doses impacts dopamine more heavily...can anybody confirm this?

[Finn]

update:

 

for the last few days I have experimented with some vyvanse dosing.  At lower doses (20-30mg) it puts me into an unpleasant, spaced-out, anxious state.  At higher doses (70mg+) it had a largely positive impact on my mood, memory, and seemed to clear up the brain fogginess.  I have read that at lower doses it has a larger effect on nor-epinephrine while at larger doses impacts dopamine more heavily...can anybody confirm this?

 

Vyvanse is lisdexamphetamine, predrug of d-amphetamine.

 

With d-amphetamine, I would say it is opposite of that, at lower levels DA goes up while NE effects are more lackluster, with higher doses NE starts to catch up. 

 

http://www.longecity...e-2#entry809865

Edited by Finn, 09 September 2017 - 07:20 PM.

[bobisyahu]

Thanks. 

 

I just got some supplements from Now and am going to add them to my bupropion dose tomorrow.

-Mucuna

-p-5-p

-methyl folate

 

...anyone have any thoughts, positive or negative, on this?

o, and also looking into sulbutiamine to help mitigate DA down-regulation

[Jiminy Glick]

Are you eating enough? If not you are not getting enough amino acids, minerals, and vitamins. Go out and get some amino acid powders. You probably don't get enough phenylalanine, tryptophan, and a lot of other stuff in your diet. 

I went through a phase where I wasn't really into food but protein shakes, maybe you are a person that would rather drink their food. It is quicker. 

Edited by Jiminy Glick, 10 September 2017 - 12:08 PM.

[Kinesis]

I've taken bupropion in combination with amitriptyline with excellent results.

There are some drawbacks though. Bupropion is a stimulant and amitriptyline is anticholinergic. Stimulants tend to lose effectiveness after a while and anticholinergics depress cognitive function. With the combination my cognitive function was excellent but I would still be concerned about the longer term. I'd consider this mostly just as a bridge to get you through until you settle on a better long term solution.