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MUST READ (deprenyl, klonopin, adderall, wellb..)

Posted by Jason911 on February 8, 2002, at 4:01:05

THE PERSON WHO READS THIS IS CARING AND PATIENT (IT'S LONG) AND WILL TRY TO GIVE ME SOME SUGGESTIONS AS TO WHAT THEY THINK OF MY SITUATION, EITHER FROM EXPERIENCE OR SPECULATION, AND IF MY PLAN FOR MY NEXT VISIT IS HEADED IN THE RIGHT DIRECTION :) WHO EVER READS THIS THROUGH IS GREATLY APPRECIATED!! YOU MAY EVEN LEARN SOMETHING NEW... I TRIED TO KEEP IT AS DETAILED AS POSSIBLE...

* * *

About two months ago I was diagnosed with depression. The depressed mood started when I was in about the 7th grade. I, however, was pretty young and thought this was just normal and me being what my mother called "a lazy-ass who's give a sh*t was broke". In the 9th grade, I experimented with pot and instantly fell in love (which my doctor now describes as "self-medicating") with it's effects. That was (except for shrooming a couple of times) the only drug I've ever done. I didn't even (and still don't) smoke cigarettes, or drink, or do acid, or anything like that. From what I read on the net, for the most part, pot didn't seem extremely harmful except for possible lung damage over the long term. But that was long-term... besides, I was a basketball player and stayed in great shape anyway. It was the only way I felt good. It was so easy to just go smoke a bowl and be set for a while. I am 17 now (senior in high school) and recently was put on probation for possesion of pot. So I HAD to quit, which wasn't hard to do, but I went back to feeling like crap. A month later I decided to get help from a doctor.

I live in a suburb of Kansas City and am seeing one of the most highly regarded doctors in the area. My Mom is a nurse and told me that, anyway. The doctor told me that he thought I did indeed have depression and, based on the info that I gave him about myself (low motivation, lack of concentration, everything seems flat, low sex drive, short fuse/easily agitated, pot user for a few years as well), he said it was probably dopamine related. He put me on Wellbutrin to start out with. Our insurance didn't cover the SR form so I had to go with the older version and worked my way up (as instructed) to 150mg/morning and 150/mg noon. The first week sucked: my heart would beat pretty hard (in class, I could look at my chest and see my shirt flapping with every beat) which worried me and of course led to an increased heart rate :( Worse, it was IMPOSSIBLE to get to sleep. I called him about these problems and he then prescribed 1/2mg of Klonopin (clonazepam) before bedtime and told me that the heart thing was my body getting use to it and that it should go away "soon". Klonopin helped almost the first or second night on it (I got to sleep anyway) and my heart situation went away shortly thereafter. On my next scheduled visit a month later, I told him I didn't think it was helping my mood, concentration, or anything other than the fact that it relieved my short-fuse and helped my frequent anger problems (which was progress, I guess). This explained why, which I told the doctor, teachers had told me that they said I was "more pleasant to be around" or I didn't "look as angry all the time." I said I didn't notice anything other than that. Everything was still flat. I still wasn't motivated to do things as easy as get up and go to the movies with my friends or go to school basketball games. He said "You're still taking the Wellbutrin like I said right? 300mg a day?". I told him I was, and then prescribed me 5mg of Adderall in the morning and another 5mg at noon (to help concentration and further increase dopamine levels).

I didn't feel anything... other than the fact that it was screwing with my appetite so much that I was only eating one meal a day for a bit and had to force myself to eat a second for the next couple days! Those last couple days I was out of school as well, and slept-in to about 11 AM and took my morning dose with the noon dose with the mentality of keeping the same amount of medicine going in my system every day. My Dad, though, would kindly wake me up at 8 or so to give me my Wellbutrin. The Adderall, I figured, would wake me up and I wanted to sleep so I simply postponed it. After using the Adderall for those 4 or 5 days, with no apparent change (except for loss of appetite), I finally decided to call and tell him of my troublesome results. The nurse said he was out for the day, so I left a message with her (BTW, she also told me never to double up doses again) and said she'd try to get ahold of him. She called back later that evening and said he wanted me to try 15mg in the morning but none at noon and if I still wasn't feeling any change in mood to call her back in two days. Whatever. 2 days passed and I still wasn't feeling a thing (which, after doing research on the net recently, I find quite strange.. I should have been feeling SOMETHING), told that to the nurse and she then instructed me to quit the Adderall altogether for two days to see if I really was kidding myself (or whatever the reason was) and call her back after that time and tell her how I felt. 2 days and sure enough, nothing. I called her (which was 2/7/02- the day I wrote this) and told her, at which point I said I was going to stop taking the Adderall for reasons I wanted to explain to the doctor, and scheduled to see him 3 weeks earlier (which will be Wednesday the 13th). Here is where I then developed what I believe will be my soution.

This past week, I have been spending hours upon hours trying to find information on all kinds of medicine from all kinds of places: from www.erowid.com to this very forum, Psycho-Babble! By the way, I just became a member (it's past midnight now and officially 2/8/02) today and am going to be an active participant in all further discussions and help people based on my experiences with current and upcoming medications, by the way. Anyhoo, I came across an article somehow on deprenyl. The more and more I researched it, the more and more exited I began to get. I found a 5 or 6 page bio of deprenyl's discoverer, Dr. Joseph Knoll, and the uses of the medicine. It explained basically everything I spent hours researching on in a single report which I have printed out and am bringing to my visit next week. It talks about it's unique selective MAO-B inhibiting properties, catecholamine activity enhancing ability, neuroprotection from various neurotoxins, anti-aging possibilities, and most importantly its effectiveness in teating depression.

I brought it up the last time I met with the doctor but he said that, to his knowledge, it didn't work very well with depression and that he'd never heard of it used for this in quite some time and was mainly used as a medicine for Parkinsons and that it wasn't the best choice, in his opinion. Knowing as much as I know now, I believe he is unaware of some of deprenyl (selegiline HCL - Eldepryl in the US)'s potential benefits and recent findings. Who could blame him? He deals with psychotropic drugs that deal with depression and few doctors use deprenyl for this purpose. All that he knew was that at MAO-B selective doses (above 15mg, it becomes a full MAOI) it was not SOLELY effective at treating depression. My paper describes the studies that were done on atypical depressives, tretment-resistant depressives, and major despressives, and that effective treatment levels required dosages in the 20-30, even 60mg range. Well above MAO-B selective doses. Even though the treatments were effective and had low side-effects, there are risks involved with all-out MAOI's like diet restrictions (such as the "cheese effect"). So I can see where he's coming from in this light. But, there were three studies that suggested effective antidepressant action at selective MAO-B inhibiting doses.

That study was just the beginning of the paper's deprenyl-depression studies. What's eye-catching is what followed: "In 1978 Mendelwicz and Youdim treated 14 depressed patients with low-dose deprenyl (< or =10mg) plus 300mg 5-HTP 3 times daily for 32 days. Deprenyl potentiated the antidepressant effect of 5-HTP in 10/14 patients. 5-HTP enhances brain serotonin metabolism, which is frequently a problem in depression, while deprenyl enhances dopamine/noradrenalin activity" (how? - I'll explain in a bit). "Under activity of brain dopamine, noradrenalin (norepinephrine), and serototin neural systems are the most frequently cited biochemical causes of depression. So, deprenyl plus 5-HTP would seem a natural antidepressant combination."

The next one gets even more promising! "In 1984 Birkmayer, Knoll, and colleagues published their successful results in 155 unipolar depressed patients who were extremely treatment-resistant. Patients were given 5-10mg deprenyl plus 250mg phenylalanine daily. Approximately 70% of their patients achieved full remission, typically within 1-3 weeks. Some patients were continued up to 2 years on treatment without loss of antidepressant action. The combination of deprenyl plus phenylalanine enhances brain PEA activity, while both deprenyl and PEA enhance brain catecholamine activity. Thus deprenyl plus phenylalanine is also a natural antidepressant combination."

Almost equally impressive: "In 1991 H. Sabelli reported successful results treating 10 drug-resistant major depressive disorder patients. Sabelli used 5mg deprenyl daily along with 100mg vitamin B6, and 1-3 grams phenylalanine twice daily as treatment. 6 of 10 patients viewed their depressive episodes terminated within 2-3 days! Global Assessment Scale scores confirmed the patients' subjective experiences. Vitamin B6 activates the enzyme that converts phenylalanine to PEA, so the combination of the three is a bio-logical way to enhance both PEA and catecholamine brain function, and thus to diminish depression."

Here is why the catecholamine enhancement is so important in treating depression, especially in those whose depression can be related directly to dopamine under-activity (as in my case). You see, even if deprenyl's oringinally hypothesized mode of action - directly increasing synaptic dopamine levels through MAO-B inhibition - is false, deprenyl's MAO-B inhibition still provides part of its benefit.

It wasn't until the 1990s that Knoll's deprenyl research took a new direction. Working with rat brain stems, rabbit pulmonary and ear arteries, frog hearts and rats in shuttle boxes, Knoll discovered a new mode of action of deprenyl that he believes explains its widespread clinical utility. Knoll discovered that deprenyl [selegiline] (and it's cousin, PEA) are "catecholamine enhancers". Catecholamines refers to the inter-related neurotransmitters dopamine, noradrenaline, and adrenaline. Catecholamines are the transmitters for key activating brain circuits - the mesolimbic-cortical circuit and the locus coeruleus. The neurons from these two brain circuits project from the brain stem, through the mid-brain, to the cerebral cortex. They help to maintain focus, concentration, alertness and effortful attention. One of the reasons the doctor put me on Adderall! - but it seems obvious Adderall is only a temporary fix as it is well documented that the human body develops tolerance (whether it's 6 days or 2 years, everyone's different) to amphetamines, including d-amphetamine, quite quickly. Plus, amphetamines are known to damage dopamine cells but whether or not the damage is done at clincally prescribed doses is not yet known and that scares me especially after long term use AND from what I hear, discontinuing use just sends the person right back into the hole it once lifted them out of). Deprenyl would seem much better (it even protects your dopamine cells from damage/neurotoxicity) :) Dopamine is also the transmitter for a brainstem circuit - the nigrostriatal tract - which connects the the substantia nigra (which deprenyl enhances) and the striatum, a nerve tract that helps control bodily movement.

Here's how it works: when an electrical impulse travels down the length of a neuron - from the recieving dendrite, through the cell body, and down the transmitting axon - it triggers the release of packets of nerotransmitters into the synaptic gap. These transmitters hook onto receptors of the next neuron, triggering an electrical impulse which then travels down that neuron , causing yet another transmitter release. What Knoll and colleagues discovered through their highly technical experiments is that deprenyl and PEA act to more efficiently couple the release of neurotransmitters to the electrical impulse that triggers their release. In other words, deprenyl (and PEA) cause a larger release of transmitters in response to a given electrical impulse. It's like "turning up the volume" on catecholamine nerve cell activity. And this may be clinically very useful in depression where there may be under-activity of both dopamine and noradrenalin neurons. And the key here is the addition of the supplement phenylalanine to the deprenyl to help significantly increase PEA levels (one need only look to the results of the above studies to come to that conclusion). Even deprenyl in itself has shown in autopsy studies to not only increase dopamine levels by 40-70% in Parkinson patients but increase PEA levels 1300-3500%! You see, PEA is the preferred substrate for MAO-B, the MAO that deprenyl inhibits. PEA has an extremely rapid turnover due to its rapid and continuous breakdown by MAO-B. Thus deprenyl's catecholamine activity enhancer has a dual mode of action. At MAO-B inhibiting doses, deprenyl has a huge catecholamine enhancing effects due to the major increases in PEA levels. Many authors have pointed out the probable dopamine neuron activity enhancing effect of PEA in Parkinson patients taking deprenyl. Knoll's discovery of PEA's catecholamine activity enhancer effect now explains this PEA dopamine-enhancing effect.

So my proposal on Wednesday will be to take 10mg a day of selegiline, 600mg of phenylalanine supplement, as well as a good amount of vitamin's C and E, and 1000mg of NAC. The reason for the latter is that deprenyl increases only 2 of the 3 main antioxidants made in the brain. SOD, and catalase to a lesser extent. But the third, glutathione isn't raised at all so it is recommended by Knoll that one take around 1000mg NAC (which increases glutathione levels) to normalize these levels. Good amounts of vitamin C and E help very much as antioxidants themselves. I will ask to discontinue Adderall and taper off the Wellbutrin as well. Wellbutrin is now said to be mainly a noradrenalin reputake inhibitor while only mildly binding to the dopamine uptake sites and actually decreasing the amount of dopamine that is manufactured! I believe that Eldepryl and around 600mg/day of phenylalaine will take care of the noradrenalin AND dopamine especially.

I also am going to tell him (and I don't know why the HELL I didn't tell him this before.. I didn't even think of it) that I want to take that Klonopin (2mg) in the morning as well as 1mg a night (.5mg isn't working anymore). I have some social anxiety/phobia characteristics that I need addressed and I hear it works wonders in people with SP or similar syptoms and is even enhanced by deprenyl! I get VERY nervous and tense at family gatherings, in the presence of women (I had a couple of "intimate" relations with some girls and had to halt their sexual advances before it got to THAT point...I was just too nervous), and it's unbearable. I have no chance of getting it up in those situations. It's not physical either, I wake up with an erection almost every morning. When I'm at home and relaxed it's not a problem in response to erotic thoughts or things I hear or see on television. Another is an example of my UA's that I have to take while on probation. You have to piss in a cup with someone watching you and that makes me so uncomfortable I can't even piss for the life of me! I have to drink enough water so that my bladder feels like it's going to explode before I go in and take a UA. I learned this after one time that I drank like 4 glasses of water before I went in and didn't piss and they had to close for lunch so I had to leave and come back in 30 minutes. So on the way home I almost DIED from the pain. I know it's kinda funny, and I wish I could've seen the look on my face (and other onlookers for that matter!) on the drive home. I've never been in so much pain in my life! No one else has that problem, though. I'm the only one who has to wait the 30 minutes to try again and it sucks. I just get way too nervous in situations like that. When I pull up next to cars at a stop light I'm uncomfortable looking to see who's pulled up beside me. WHY??? I found that there are alot of girls that have mentioned to me or my friends that they "want" me (all I'd have to do is give the OK and BAM! - I don't want to sound arrogant or anything - but that just makes this whole situation that much more bothersome, ya know? The opprotunities I'm missing!) but NOOOO! I'm too much of a pussy to relax and do my thing, so to speak. It's purely psychological. I'm proud of my body and if only I could put it to use! In public places I feel as if everyone is looking at me. It's wierd. Either I have a booger in my nose that I'm not finding or I have a problem. It's one of the two. There are so many other examples but my eyes are starting to smart and my fingers are getting tired. It's 3:40 in the morning now (it's taken me over 3 hours to write and edit this...that's gotta be something along the lines of obsessive-compulsive or something). Anyway, I hope I've found the solution to my problems and I hope the reader hasn't fallen asleep already... -Jason911




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poster:Jason911 thread:93294
URL: http://www.dr-bob.org/babble/20020208/msgs/93294.html