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Dr. Bob is Robert Hsiung, MD,
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Posted by alesta on August 17, 2004, at 7:29:04
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by SLS on August 17, 2004, at 7:04:16
no wonder we don't know the answer. no one else does, either!:) so, scott, you agree with panda that dopaminergic drugs are not the answer in the long run? did wellbutrin even work for you in the beginning?
> A little dopamine here, and you chase yourself around in circles; a little dopamine there, and you chase members of the opposite sex in straight lines.
interesting way of putting it.:)amy
Posted by SLS on August 17, 2004, at 8:27:35
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by alesta on August 17, 2004, at 7:29:04
> no wonder we don't know the answer. no one else does, either!:)
I know. Somehow, I find this reassuring. If they did understand everything, AND STILL COULD NOT GET US WELL, we would be pretty much well doomed. It's that uncertainty that keeps hope alive for me.
> so, scott, you agree with panda that dopaminergic drugs are not the answer in the long run?
At this point in time, for the average sufferer of depression, I would say that I agree. Regulation of DA circuits might be one of the final pathways to remission, but it might be that it is those regulatory processes upstream that is necessary for long-term stable improvements. If you fine tune the inputs and interactions between the NE locus ceruleus and 5-HT raphe, perhaps you can re-regulate the activities of DA circuits in the mesolimbic cortex and watch depression disappear.
> did wellbutrin even work for you in the beginning?
No, not at all. I found nothing dopaminergic about it. But then again, a nosefull of cocaine did little for me when I experimented with it at my bachelor's party. It did do something positive, though. Or maybe it was the way the dancing girl... Never mind.
- Scott
Posted by alesta on August 17, 2004, at 9:24:39
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by SLS on August 17, 2004, at 8:27:35
thank you, scott! i appreciate it. take it easy with those bachelor parties......
amy :)
Posted by Emme on August 17, 2004, at 9:43:52
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by SLS on August 17, 2004, at 7:04:16
Hi Scott,
> A little dopamine here, and you chase yourself around in circles; a little dopamine there, and you chase members of the opposite sex in straight lines.
I'll be happy to be able to chase anything! :) Where do you find the time, energy, mental focus, to develop your knowledge of pharmacology? Impressive considering the severity of your depression.
Okay, got any thoughts? I had not thought about pursuing drugs with NE promoting effects. Maybe that would be helpful in keeping me motivated and out of sluggishness? Or would it make anxiety worse...? Wellbutrin was great when I first used it with Serzone. After a while that combo stopped working and I found Wellbutrin to be intolerably stimulating. A retrial didn't pan out - I couldn't control the stimulation and it didn't help depression. I can't tolerate Effexor.
BTW, aricept is probably out. My liver enzymes are a little elevated and my pdoc thinks that's the culprit. Now we're trying Mirapex. I think it's helping. I'm getting a little more done. But I'm still having a hard time having any optimistic thoughts like I had a few weeks back. It's probably worth continuing the Mirapex trial though.
But anyway, I'm wondering if I shouldn't ask my pdoc about a microdose of a tricyclic as mentioned above. I think she's leery of ADs since so many have pooped out on me, not helped, caused some cycling, or been intolerable. But I've never tried a tricyclc.
The L-theanine suggestion sounds interesting.
Sometimes I can't help but feel that we're feeling our way in the dark trying to match symptoms to neurotransmitters.
Emme
Posted by Sad Panda on August 17, 2004, at 9:58:20
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by alesta on August 17, 2004, at 2:00:57
> hey, panda,
> interesting. why does supplementing with dopamine have the opposite effect? do you know of a web site that i can read about this? then why do people even bother taking wellbutrin, which boosts dopamine? sorry for all the questions. thank you.
>
> amy
>Wellbutrin is one of the drugs that people really don't know how it works. It is an average NRI & a weak DRI, mg for mg I think Zoloft is a stronger DRI than Wellbutrin is. I have seen written somewhere(can't remember) that Wellbutrin is a nicotinic acetylcholine antagonist which is said to be the reason that you are twice as likely to quit smoking using Wellbutrin(as Zyban) than using nicotine gums & patches. It also may have activity at NMDA receptors.
Cheers,
Panda.
Posted by alesta on August 17, 2004, at 10:46:22
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin » alesta, posted by Sad Panda on August 17, 2004, at 9:58:20
hi, panda,
thanks for the info. and it's nice to finally know how it helps smokers to quit. i wonder how it takes away the sexual side effects of SSRIs. (don't answer that <g>)
well, in conclusion:), i have decided not to augment the prozac. here's something interesting: linkadge told me that the lowering of the dopamine is part of the mechanism of action of the SSRIs, and that raising dopamine levels would probably make it less effective. strange. so maybe i could go with the norepinephrine-raising meds, but i don't know if that's a good idea, either. i think i'll just forget the augmentation for now. thanks for working through this with me. :0)
appreciate it,
amy
> > hey, panda,
> > interesting. why does supplementing with dopamine have the opposite effect? do you know of a web site that i can read about this? then why do people even bother taking wellbutrin, which boosts dopamine? sorry for all the questions. thank you.
> >
> > amy
> >
>
> Wellbutrin is one of the drugs that people really don't know how it works. It is an average NRI & a weak DRI, mg for mg I think Zoloft is a stronger DRI than Wellbutrin is. I have seen written somewhere(can't remember) that Wellbutrin is a nicotinic acetylcholine antagonist which is said to be the reason that you are twice as likely to quit smoking using Wellbutrin(as Zyban) than using nicotine gums & patches. It also may have activity at NMDA receptors.
>
> Cheers,
> Panda.
>
>
Posted by SLS on August 17, 2004, at 10:52:52
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbut » SLS, posted by Emme on August 17, 2004, at 9:43:52
> Where do you find the time, energy, mental focus, to develop your knowledge of pharmacology? Impressive considering the severity of your depression.
That's flattering.
Most of what I learned about psychopharmacology came during a 3 week burst in 1983 when I responded to a combination of Nardil + amitriptyline. (all the ipsilateral and contralateral stuff) Since then, I've enjoyed a handful of opportunities to be able to read, learn, and remember, but they are rare and short lived. For everything else, it is
POUND POUND POUND POUND POUND POUND POUND
with very little reward, but it is better than nothing. I feel so very, very, stupid. Reading anything is a difficult enough chore that it produces anticipitory anxiety at the mere thought of it.
Thanks for the ego boost.
:-)
- Scott
Posted by alesta on August 17, 2004, at 11:38:50
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbut, posted by SLS on August 17, 2004, at 10:52:52
scott,
i can't believe you feel stupid. this is very upsetting to me (i am an empathetic person--feel others emotions *very* easily). and if there's little reward, why pursue it? you don't need to. you know plenty to help people on this board with the experiences you've already had with meds. it's your charm, your presence that people are drawn to. why not just pursue happiness instead? sorry--don't mean to tell you how to live your life--i can never stop being an amateur counselor. i think i've finally overstepped my bounds on this site....i think that rejection sensitivity is setting in right about now...be gentle, people....
amy
Posted by SLS on August 17, 2004, at 12:12:40
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI---SLS, posted by alesta on August 17, 2004, at 11:38:50
Hi Amy.
You have me smiling and enjoying the warm fuzzies that effervesce from your kind words.
Thanks.
:-)
- Scott
> scott,
>
> i can't believe you feel stupid. this is very upsetting to me (i am an empathetic person--feel others emotions *very* easily). and if there's little reward, why pursue it? you don't need to. you know plenty to help people on this board with the experiences you've already had with meds. it's your charm, your presence that people are drawn to. why not just pursue happiness instead? sorry--don't mean to tell you how to live your life--i can never stop being an amateur counselor. i think i've finally overstepped my bounds on this site....i think that rejection sensitivity is setting in right about now...be gentle, people....
>
> amy
>
>
Posted by alesta on August 17, 2004, at 12:29:26
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI---SLS » alesta, posted by SLS on August 17, 2004, at 12:12:40
your welcome, scott. same here. i loved that post!!! now *that* is interesting to read...
amy :)
> Hi Amy.
>
> You have me smiling and enjoying the warm fuzzies that effervesce from your kind words.
>
> Thanks.
>
> :-)
>
>
> - Scott
>
>
> > scott,
> >
> > i can't believe you feel stupid. this is very upsetting to me (i am an empathetic person--feel others emotions *very* easily). and if there's little reward, why pursue it? you don't need to. you know plenty to help people on this board with the experiences you've already had with meds. it's your charm, your presence that people are drawn to. why not just pursue happiness instead? sorry--don't mean to tell you how to live your life--i can never stop being an amateur counselor. i think i've finally overstepped my bounds on this site....i think that rejection sensitivity is setting in right about now...be gentle, people....
> >
> > amy
> >
> >
>
>
Posted by zeugma on August 17, 2004, at 14:15:50
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI---SLS, posted by alesta on August 17, 2004, at 12:29:26
hi all. last week, when i started Ritalin, and had combined it with about 50 mg Provigil, I had mydriasis (enlarged pupils). The last time I had this side effect was on Wellbutrin, which makes me think all three drugs are dopaminergic. LSD also had this effect, and I think it also affects dopamine function, although I am less familiar with its pharmacology (I know it also functions as a serotonin agonist).
About DA and depression, I really shouldn't say, as I know for sure that I have ADHD, and that is a dopaminergic disorder beyond doubt. Attempts to correlate noradrenergic function to ADHD via genetics have been politically driven and unsuccessful, while abnormalities in dopaminergic function have been established for some years now. But there is a link, I am convinced, between ADHD severity and depression. I used to think that the ADHD caused depression as a secondary matter, i.e. by producing multiple failures in school, socially, etc., leading finally to a reactive depression. I don't believe this any more, because I think that abnormalities of DA expression strain the balance of the other amines, and that if, e.g. the dopamine transporter is overexpressed, leading to a chronically low level of synaptic dopamine, one is going to be in a constant state of hypoarousal that the brain is going to try to compensate for somehow, and this could well lead to other amines becoming hyperfunctional to the point where they themselves break down and depression results.
I think a similar thing may happen on long-term SSRI therapy, but in reverse. The hyperfunction of the serotonin system causes the dopamine system to break down to some extent. I think that it is unfortunate that so many with comorbid ADHD are treated with SSRI's, as they appear capable of creating ADHD-like symptoms in those without the disorder.Btw, someone made a suggestion a while ago that AD poop-out was so frequent on SSRI's because of a mild serotonin syndrome induced by unnecessarily high dosages. Recovery from depression requires all aminergic systems to function properly, and doctors have become so fixated on serotonin that they have been utilizing the pharmacopeia very unwisely, in my opinion. This is especially unfortunate given that the official catecholinergic alternative since the TCA's and MAOI's have fallen from favor is Wellbutrin. In my experience and in the experience of those I know, it is an extremely unpredictable drug, has an ambiguous effect on symptoms, and appears far more prone than any other AD to induce serious allergic reactions.
Posted by jrbecker on August 17, 2004, at 21:14:26
In reply to Wellbutrin DA? and digression on ADHD, posted by zeugma on August 17, 2004, at 14:15:50
Combining a Dopamine Agonist and Selective Serotonin Reuptake Inhibitor for Treatment of Depression: A Double-Blind, Randomized Study
Posted by alesta on August 18, 2004, at 1:15:58
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI, posted by jrbecker on August 17, 2004, at 21:14:26
jrbecker, you're a lifesaver! Wow. So now we’re back to square one. They are proposing that you *can* augment with something to raise dopamine levels and that it is a good idea to augment an ssri with a dopamine antagonist! so now we’re back to my original question. larry or chemist, i know this is a long series of posts, but if you could at least read my first one i would be most grateful. i won't ask another one for a loooong time.....:)...:).....please?
Amy
Posted by alesta on August 18, 2004, at 6:05:31
In reply to Re: Dopaminergic Drug/Supp.LARRY or CHEMIST help!, posted by alesta on August 18, 2004, at 1:15:58
OOPS....i meant to say dopamine agonist, not antagonist....sorry!
Posted by chemist on August 18, 2004, at 9:40:49
In reply to Re: Dopaminergic Drug/Supp.LARRY or CHEMIST help!, posted by alesta on August 18, 2004, at 6:05:31
> OOPS....i meant to say dopamine agonist, not antagonist....sorry!
hello there, chemist here...interestingly, the subject of L-theanine has reared its head on the alternative board...i am not the right person to ask about it, as i am not familiar with the chemistry of this derivative of glutamine...i think that the responses you have received are coming from folks who know their stuff, although here i go with my thoughts, you asked for it: i tend to lean towards benzodiazepines/alprazolam for anxiety issues, and am a fan of dexedrine (and adderall) to address ADD/ADHD-like problems. my experience with antidepressants has been checkered, and i glowingly endorse parnate or, failing that, luvox (fluvoxamine). if you want dopamine - and want it fast - i suggest one of the CNS stimulants. however, perhaps you can get some closure on the L-theanine issue, and this might be worth examining......do check the post on the alternatives board, as the person taking a concentrate of L-theanine did not report favorably, but you can judge the quality of information......all the best, chemist
Posted by alesta on August 18, 2004, at 9:47:28
In reply to Re: Dopaminergic Drug/Supp.LARRY or CHEMIST help! » alesta, posted by chemist on August 18, 2004, at 9:40:49
Thank you, Chemist, and it's nice to meet you! i really appreciate it. welcome back!
(: amy :)
Posted by alesta on August 18, 2004, at 9:56:11
In reply to Re: Dopaminergic Drug/Supp.LARRY or CHEMIST help! » chemist, posted by alesta on August 18, 2004, at 9:47:28
hi, chemist,
if i could just bother you for one more quick question...do the benzos slow or reduce your cognitive processes in any way?
thanks again,
amy:)
Posted by chemist on August 18, 2004, at 10:15:33
In reply to CHEMIST--quick question, posted by alesta on August 18, 2004, at 9:56:11
> hi, chemist,
>
> if i could just bother you for one more quick question...do the benzos slow or reduce your cognitive processes in any way?
>
> thanks again,
> amy:)
hello amy, pleased to meet you....my experience with benzos and xanax has been very favorable, but do keep in mind that i am biased that way. having gotten that disclaimer off my chest, i can report that aside from short-term memory problems (some of which i attribute to the meds and some to honest-to-goodness inattention), i have not had any unpleasant experiences on the meds, cognitive or otherwise. although my self-evaluation might be more grand than that of someone who can make the assessment in a more objective light (e.g., my doctor and/or therapist), all parties involved with the current regimen of luvox, dexedrine, and xanax are apparently satisfied....having tried many benzos in addition to xanax over the years, i prefer xanax but have had success with ativan, klonopin, and valium, the latter being (for me) somewhat physically sedating. i did not find tranxene to work as well as the ones i have mentioned, and did find restoril, halcion, and dalmane all appropriate for sleep, although when it has been an issue, i prefer ambien. anyhow, i do hope i have answered your question.....all the best, chemist
Posted by alesta on August 18, 2004, at 11:33:32
In reply to Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by alesta on August 16, 2004, at 14:38:41
you can add a modest amount of methylphenidate to an SSRI to boost dopamine function.
woo hoo!
Posted by alesta on August 18, 2004, at 12:19:03
In reply to Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by alesta on August 16, 2004, at 14:38:41
here is a web site concerning augmentation with ritalin, etc.
http://www.mhsource.com/expert/exp1012698e.html
Posted by Dave001 on August 19, 2004, at 3:28:13
In reply to Dopaminergic Drug/Supp to Aug SSRI-Not Wellbutrin, posted by alesta on August 16, 2004, at 14:38:41
> I really need some dopamine in my system. i'm starting to feel happy with the prozac, but i know i've got to replace the depleted dopamine (due to no motivation, anhedonia, etc.). i don't want to add wellbutrin because i suffer from anxiety and don't need anything anxiogenic. i really want to try l-theanine with it (it increases dopamine *and* GABA, the effect on serotonin is debatable). i just wonder if this is safe. i don't like not knowing how they will interact, and i can't find any info on this combo. does anyone know how these might interact or have any suggestions on how i can *safely* increase my dopamine levels with prozac besides adding wellbutrin? if not, and no one responds, that's ok, then i'll at least have closure and then can move on to parnate (or nardil + provigil) with certainty.
>
> you can skip this part..just venting..(And I’m used to being on the prozac now, and like its prosocial aspects, it’s how I used to be, and don’t know what’s going to happen on the next drug, or when I go off this one. I don’t even know if I would’ve posted on this board if I hadn’t started the prozac. I don’t know...maybe I’ll be okay on the parnate...I don’t know why I’m freaking out.... I just needed to vent that. I have my rare negative moments.:))
>
> amy
>There are many. One you might want to consider is pramipexole, as it has been used successfully in a number of studies (albeit not all well controlled/designed) to elicit an antidepressant response in both uni and bipolar depression.
I'm about to give pramipexole and escitalopram a try, and I've tried *a lot* of things, including high-dose Parnate + Dexedrine + Provigil + Klonopin (and yes all at the same time). Suprisingly, I didn't have to adhere to any dietary restrictions at all. I guess I just had a high tolerance to the pressor amines. Dunno.
Good luck.
Dave
Posted by alesta on August 19, 2004, at 9:09:23
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI-Not Wellbut, posted by Dave001 on August 19, 2004, at 3:28:13
thank you, dave. mirapex, huh? i'll have to look into that.
my god, you took all that stuff at the same time, and it still didn't work? talk about drug-resistant! (FYI i'm one of those people that gets drunk off one beer <g>. that combo would probably do me in.)
Good luck to you, too! keep me posted with whatever you try. :)
take care,
amy
Posted by Dave001 on August 20, 2004, at 18:25:25
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI--DAVE, posted by alesta on August 19, 2004, at 9:09:23
> thank you, dave. mirapex, huh? i'll have to look into that.
>Keep in mind that that is only one of the many options though. Have you ever tried Amantadine? Selegeline can also be used with SSRIs if the dose isn't too high (I think <= 10 mg/day). There has been at least one study on the safety of combining selegeline with an SSRI. I do share the same basic mentality with you in that I feel that SSRI monotherapy is a prescription for failure (ugh, not to get anyone discouraged though! :-) in most cases because of the effects inherent with raising serotonin, such as reduced dopamine activity and elevations in prolactin, even if subclinical. I've also seen decreased expression of nitric oxide synthase in most of the SSRI studies, including Effexor; the one exception I've found has been citalaprom/escitalaprom (Celexa/Lexapro). Incidentally, it seems that Lexapro and Mirapex are going to be used in that clinical study posted earlier in this thread.
See the URL:
http://clinicalstudies.info.nih.gov/detail/A_2004-M-0227.htmlIf you scroll down toward the bottom of the page, you'll see both "Pramipexole" and "Escitalopran" (sic) listed as "Keywords."
> my god, you took all that stuff at the same time, and it still didn't work? talk about drug-resistant! (FYI i'm one of those people that gets drunk off one beer <g>. that combo would probably do me in.)
>Yeah, well it did have some effect; it's just that the positives didn't outweigh the negatives. I was on the Dexedrine for a long time before starting the Parnate, though, so it had already lost much of its effectiveness. I started Dexedrine when I was about 17/18 for "ADD", but I really want to stop due to concerns of neurotoxicity. The problem is finding an opportune moment where I can just say, "OK, now seems like a good time to begin months of amphetamine withdrawal."
> Good luck to you, too! keep me posted with whatever you try. :)
>
Thanks, you too!Dave
Posted by dondon on August 20, 2004, at 18:47:49
In reply to Re: Dopaminergic Drug/Supp.LARRY or CHEMIST help! » chemist, posted by alesta on August 18, 2004, at 9:47:28
Sertraline is a fairly potent dopamine reuptake inhibitor. MUch more potent than wellbutrin and nomifensine. HIgh doses of sertraline such as 300 mg has an amphetamine(psychostimulant effect)
200 mg of zoloft has only moderate affinty for dopamine reuptake. But when you push the sertraline to 300 mgs it has high affinity for dopamine reuptake(amphetamine effect) .
300 mg of sertraline is the same as 60 mg of paxil. I had to squeeze a dopaminergic effect out of sertraline because my doctors would never give me a stimulant such as dexedrine or adderal.
my 2 cents.
Posted by alesta on August 21, 2004, at 17:32:26
In reply to Re: Dopaminergic Drug/Supp to Aug SSRI--DAVE, posted by Dave001 on August 20, 2004, at 18:25:25
Hi, dave, :)
good to hear from you! Excellent job! There is so much quality information in your post that I still need to sort through. I was looking for which medications they were using in the study, but didn’t see them; guess I didn’t look hard enough.:) I checked on mirapex and it didn’t look that great from a side-effect point-of-view (e.g. hair loss!) lexapro, I don’t know too much about. I’m definitely going to check on that.
Question: you said you wanted to quit Dexedrine due to neurotoxicity. Do you feel that all stimulants are neurotoxic? I ask because I am considering augmenting prozac with low-dose Ritalin for dopamine and to combat the ssri-related fatigue.
Thank you again for your wealth of pertinent information. You’re really helpful.:)
Take care,
Amy :)> > thank you, dave. mirapex, huh? i'll have to look into that.
> >
>
> Keep in mind that that is only one of the many options though. Have you ever tried Amantadine? Selegeline can also be used with SSRIs if the dose isn't too high (I think <= 10 mg/day). There has been at least one study on the safety of combining selegeline with an SSRI. I do share the same basic mentality with you in that I feel that SSRI monotherapy is a prescription for failure (ugh, not to get anyone discouraged though! :-) in most cases because of the effects inherent with raising serotonin, such as reduced dopamine activity and elevations in prolactin, even if subclinical. I've also seen decreased expression of nitric oxide synthase in most of the SSRI studies, including Effexor; the one exception I've found has been citalaprom/escitalaprom (Celexa/Lexapro). Incidentally, it seems that Lexapro and Mirapex are going to be used in that clinical study posted earlier in this thread.
>
> See the URL:
> http://clinicalstudies.info.nih.gov/detail/A_2004-M-0227.html
>
> If you scroll down toward the bottom of the page, you'll see both "Pramipexole" and "Escitalopran" (sic) listed as "Keywords."
> > my god, you took all that stuff at the same time, and it still didn't work? talk about drug-resistant! (FYI i'm one of those people that gets drunk off one beer <g>. that combo would probably do me in.)
> >
>
> Yeah, well it did have some effect; it's just that the positives didn't outweigh the negatives. I was on the Dexedrine for a long time before starting the Parnate, though, so it had already lost much of its effectiveness. I started Dexedrine when I was about 17/18 for "ADD", but I really want to stop due to concerns of neurotoxicity. The problem is finding an opportune moment where I can just say, "OK, now seems like a good time to begin months of amphetamine withdrawal."
>
> > Good luck to you, too! keep me posted with whatever you try. :)
> >
> Thanks, you too!
>
> Dave
>
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