Is an NMDA antagonist the answer to treatment-resistant depression?

[666illuminati]

Thanks to shitty psychiatrists that throw random medication at you, I've taken matters into my own hands. Me being 16, I'm a little worried about the safety and effects of what I'll be discussing, but my brain is probably already screwed up from 6 years of SSRIs/SNRIs and stimulants. I'm assuming my problem is the downregulation of my DA receptors due to years of porn/internet/videogames and stimulants, mainly adderall. I've been prescribed countless srris that only make the problem worse from the dopamine blockade, see ref. 1.
Now there was a week where I experienced a strange awakening moment, about a month or two ago, and my theory is that I somehow increased my DA receptor density. During this week I broke my nofap record and lasted a whole week. During this week I jogged more than I have in my entire life (Exercise increases D2 receptors), and during this week I also started at a new school where I was one of the best looking and more wealthy kids (It's a shitty school). I'm bringing this up not to toot my own horn but because of the study done that social dominance has shown to increase dopamine receptors, see ref 2. What we have here is a massive increase in dopamine density. Let it be known that during this week I was on wellbutrin 150mg and adderall 20 or 30mg I don't remember. Let it also be known that during this week I experienced a very noticeable deepening of my voice and my gynecomastia/puffy nips also shriveled up and went away! This all ended when I fapped again, ending my nofap streak. A month later and I still haven't gotten back to this state. I'm on day 50 of nofap and I have no libido. I've also been taking 40mg cymbalta, 150mg wellbutrin and 30mg adderall. I still have gynecomastia and my voice is hoarse. I'm discontinuing my cymbalta today because of the dopamine blockade. I'm suffering from anhedonia, social phobia, and depression. I used to the funniest kid and had tons of friends. I think my problem's solution is a simple increase of DA receptors. What I've read is that taking an NMDA antagonist just once can completely restore all sorts of faults in your brain. Is this true? Should I go load up on cough syrup?

#1 - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674976/
#2 - http://www.csub.edu/~isumaya/prosem/SocialdomMorgan.pdf

 

[666illuminati]

What else confuses me is that I got my blood checked while I had gynecomastia (I still have it) and my prolactin levels were normal, as were my estradiol. I don't know how accurate those tests are, but something is causing it. To simplify my post, what can I do to fix my anhedonia/depression? Assuming DA is the problem, what can I do to upregulate my DA receptors?

 

[gingerbaker]

I'm pretty sure that NMDA antagonists don't "completely restores all faults in your brain" or they would be a miracle drug.

It sounds like the anhedonia/depression could very well be due to either the underlying depression or you playing doctor and going off your meds. Downregulation of DA would most definitely cause anhedonia and depression. Traditional anti-psychotics like haloperidol seem to cause up-regulation of DA but I doubt you want to be on those based on what you are feeling.

What I would recommend is that you talk to your doctor and tell him about your problems (side-effects) and ask him for his help. If you don't feel happy with the answers he gives you, talk to him openly about what you've found with your research. Normally, doctors hate this kind of thing especially when coming from a teenager (trust me, I used to go in to my psych apts with journal articles, systematic reviews, etc printed out). As much as you might not like it, they are psychiatrists for a reason and do have more education than you do (not discounting your intelligence or the role you should play in your own care). On the other hand, they also are notorious for using their patients like lab rats. "Oh, you're having X side effect, here take Y and that will help" "Oh, so Y is causing a negative side-effect, here, take Z" and on and on.

That being said, playing doctor isn't usually the most productive way to go about this. At least talk to your doctor.

 

[666illuminati]

I'm pretty sure that NMDA antagonists don't "completely restores all faults in your brain" or they would be a miracle drug.

It sounds like the anhedonia/depression could very well be due to either the underlying depression or you playing doctor and going off your meds. Downregulation of DA would most definitely cause anhedonia and depression. Traditional anti-psychotics like haloperidol seem to cause up-regulation of DA but I doubt you want to be on those based on what you are feeling.

What I would recommend is that you talk to your doctor and tell him about your problems (side-effects) and ask him for his help. If you don't feel happy with the answers he gives you, talk to him openly about what you've found with your research. Normally, doctors hate this kind of thing especially when coming from a teenager (trust me, I used to go in to my psych apts with journal articles, systematic reviews, etc printed out). As much as you might not like it, they are psychiatrists for a reason and do have more education than you do (not discounting your intelligence or the role you should play in your own care). On the other hand, they also are notorious for using their patients like lab rats. "Oh, you're having X side effect, here take Y and that will help" "Oh, so Y is causing a negative side-effect, here, take Z" and on and on.

That being said, playing doctor isn't usually the most productive way to go about this. At least talk to your doctor.

While I was on the cymbalta I couldn't even make it to school, I had awful social phobia and started crying for no reason. I had completely flat emotions. I got in to my doc a week ago and she gave me lamictal which is a mood stabilizer. This isn't exactly going to make me happy again. My next appointment is in a month and I'd prefer to not feel this way for a whole month if I know the answer is out there. I'm waiting for blood test results to check my thyroid which has been acting up.

 

[Hammilton]

Lamictal as a mood stabilizer is known for its ability to raise mood, actually.

 

[gingerbaker]

That sounds awful, I'm sorry man. I've definitely had my fair share of that extreme social phobia (which kava helps TREMENDOUSLY). I'd recommend trying some kava to help with the anhedonia and social phobia. Kava is extremely benign in regards to dependence (ie. there is none) and many, including myself, have found great benefits from using kava. It will also help in regards to lifting your mood as it is a very weak, reversible MAOI-b and has been shown to increase levels of NE and DA. Also, and maybe more importantly, it exerts an effect of voltage-gated Na+ and Ca+ ion channels (much like lamictal, but I think the affinities are actually greater) as well as some GABA-b affifnity.

If you are willing to take an antipsychotic, risperidone (Risperdal) has been shown to up-regulate DA receptors. Possibly taking it at night would help with the extreme sedation that some people experience.

"Changes in members of the dopamine (DA) D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) receptor families in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after prolonged treatment (28 days) with the atypical antipsychotics olanzapine, risperidone, and quetiapine. Olanzapine and risperidone, but not quetiapine, significantly increased D(2) binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-putamen (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%, 30%). Olanzapine and risperidone, but not quetiapine, produced even greater up-regulation of D(4) receptors in CPu (61%, 37%), NAc (65%, 32%), and HIP (61%, 37%)."
[http://www.ncbi.nlm.nih.gov/pubmed/11303062]

 

[666illuminati]

That sounds awful, I'm sorry man. I've definitely had my fair share of that extreme social phobia (which kava helps TREMENDOUSLY). I'd recommend trying some kava to help with the anhedonia and social phobia. Kava is extremely benign in regards to dependence (ie. there is none) and many, including myself, have found great benefits from using kava. It will also help in regards to lifting your mood as it is a very weak, reversible MAOI-b and has been shown to increase levels of NE and DA. Also, and maybe more importantly, it exerts an effect of voltage-gated Na+ and Ca+ ion channels (much like lamictal, but I think the affinities are actually greater) as well as some GABA-b affifnity.

If you are willing to take an antipsychotic, risperidone (Risperdal) has been shown to up-regulate DA receptors. Possibly taking it at night would help with the extreme sedation that some people experience.

"Changes in members of the dopamine (DA) D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) receptor families in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after prolonged treatment (28 days) with the atypical antipsychotics olanzapine, risperidone, and quetiapine. Olanzapine and risperidone, but not quetiapine, significantly increased D(2) binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-putamen (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%, 30%). Olanzapine and risperidone, but not quetiapine, produced even greater up-regulation of D(4) receptors in CPu (61%, 37%), NAc (65%, 32%), and HIP (61%, 37%)."
[http://www.ncbi.nlm.nih.gov/pubmed/11303062]

Thanks for the kava tip. I've tried a lot of herbs like curcumin, forskolin and vitex. The vitex was great at first but led to depression which has been reported. I also tried yohimbe and that stuff did the trick but I don't want it interacting with my other medicine, plus my blood pressure is already really high without it. An anti-psychotic isn't the route to go for me, I was prescribed abilify and had to stop it within 2 days due to depression.

 

[Lopez]

i used memantine at 10 and 20 mg for about 2 months with success before using benzos. it was an AMAZING anxiolytic/antidepressant. no ruminating thoughts, no sense of despair, etc.

the only reason i stopped was because i kept feeling like i was on DXM which got annoying after about the first month. it was VERY dissociative but lacked hallucinogenic effects other than spatial disorientation.

i still remember being at the gym in a dissociative daze and lifting heavy weight on the squat felt so easy, because although i was aware of the fatigue, i couldn't associate with it so i would keep going, then i sprained my ACL which had already been reconstructed 2 years prior so i stopped...

it was also very expensive

 

[666illuminati]

I was also looking at the possibility of taking Parkinson's medication (Dopamine agonists). My case is a little similar, I have bad posture even though I'm in shape, which is probably associated with my depression, but when I try to correct my posture my extremities start shaking as if they're going against it. I also slur my speech when I'm depressed. Bromocriptine looks hopeful

 

[arctica]

Before you add another drug to the mix, check to see if the tremor goes away now that you've discontinued Cymbalta. I had crazy tremor and muscle spasms (and night sweats) on that drug. I found it rather unpleasant. Let your body equilibrate and maybe you won't need to swallow a spider to catch the fly.

 

[endotropic]

4a. Medical/psychiatric questions: in particular, we are not here to advise you on what drugs you should take to treat a disorder you have diagnosed in yourself--that's your physician's job. However, discussion of the mechanisms involved in psychiatric medications is encouraged.

This thread started off OK, I could tell you were at least trying to put some theory behind your post and not just asking for treatment advice, but now we're straying into the "advise you on what drugs you should take to treat a disorder you have diagnosed in yourself" territory. More science, less what should I take, and this thread can stay open.

 

[nAON]

Depression and psychiatric disorders are very complicated, we don't even understand the full mechanisms behind. You can't just simplify all your various states of mind to dopamine activation/inhibition.

I'd advise getting off all the drugs for a while and going through CBT if you haven't already, then re-evaluating what your symptoms and treatment options are.

 

[dingophone]

I'd be extremely cautious with using ketamine for depression at the moment.Keep in mind that these experimental studies are exactly that; experimental. My dad, who's a psychiatrist, recently had a psychotic patient come in and discovered that this patient had been treated off label with ketamine for depression. She was also withdrawing off of 5 benzos and speed though... but still. Be careful. Have you tried bupropion? Its worked well for my anhedonia.

 

[666illuminati]

I'd be extremely cautious with using ketamine for depression at the moment.Keep in mind that these experimental studies are exactly that; experimental. My dad, who's a psychiatrist, recently had a psychotic patient come in and discovered that this patient had been treated off label with ketamine for depression. She was also withdrawing off of 5 benzos and speed though... but still. Be careful. Have you tried bupropion? Its worked well for my anhedonia.

Bupropion hasn't done much for me. I'm thinking about bringing dopamine agonists up to my psychiatrist (Parkinson's medications). They seem like they have potential and have already had success in treating depression.