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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by psychobot5000 on April 29, 2007, at 12:35:53
I'm wondering what people's experiences have been with meds like desipramine, reboxetine and other noradrenaline-enhancing meds have been, for symptoms like low motivation, anhedonia, low concentration.
I have tried to find dopaminergic solutions to these problems (as was recommended to me), but the options of that nature are rather few. Now I'm wondering how useful meds that focus on noradrenaline might be, as some theory seems to offer it as an alternative. Have people found them useful for driveless, anhedonic depression? What about concentration? Which meds in particular? I'd of course welcome any other thoughts anyone might have on the subject.
Psychbot5000
Posted by linkadge on April 29, 2007, at 13:57:02
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
I have tried strattera. It just seems impossable to separate the peripherial noradrenergic effect from the central.
Strattera was a good adjunct but it caused tachycardia, chest pain, etc.
I wish it didn't.
I didn't want to get into the whole noradrenergic + beta blocker thing.
Linakdge
Posted by Ines on April 29, 2007, at 14:44:21
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
Hi there, I tried reboxetine to treat depression, exactly because my depression comes with lethargy, lack of concentration, motivaton and all that. It really didn't work for me. It made me manically energetic for about 5 days- but in a very uncomfortable way, I was bursting with energy that wouldn't go away even after vigorous exercise, but my mind was very agitated, jumping from thought to thought, and couldn't focus on anything at all. I also couldn't sleep for being wired up, but still felt sleepy and exhausted- I know it sounds weird, but it was unlike anything I've ever experienced. After about 5 days the energetic effect wore off and I felt the same as before only MUCH more anxious and wired up in a bad way. The anxiety was so bad I eventually had to reduce dosage by half. I stayed on it for 2.5 months but had no change in depression and anxiety never went away.
This is not to discourage you- it seems to have done wonders for many people. It's just information about possible effects. This sounds obvious, but it might be worth consulting an experienced pdoc- I was perscriped reboxetine by the GP, but when I eventually made it to the pdoc he said immediately that he didn't think reboxetine would work in my particular case- that I needed dopamine not noradrenaline.
Posted by mattdds on April 29, 2007, at 14:51:37
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
I'm a functional anhedonic (i.e. I need an environment that basically puts a (proverbial) gun to my head to get 'motivated'.)
I've tried this route - the noradrenergics - to improve my energy, focus, and interest in life. My experience, is that they push me into irritability and anxiety very quickly. So far, I'm left to choose between functional anhedonia and overstimulation. Overstimulation, with absolutely no renewed interest in life or motivation. Personally, I'll take anhedonia anyday.
My most recent trial was Provigil. I was exquisitely sensitive to that med, and had to d/c because I experienced a panic attack for the first time in years. I had to double my usual 2mg of clonazepam to terminate it.
Let me know if you figure it out!
Regards,
Matt
Posted by mattdds on April 29, 2007, at 15:02:47
In reply to Re: Noradrenergics for motivation, focus, anhedonia?, posted by Ines on April 29, 2007, at 14:44:21
Ines,
Wow, your story sounds exactly like mine. Those meds do nothing (for me) to improve mental acuity or motivation. They certainly give me energy, but in a very uncomfortable, overstimulated manner. Like you, my mind was everywhere and nowhere at once, my insomnia worsened, and after a few days, my mind was torched! Another notable AE was body aches and malaise.
When I tell a psychiatrist it increased my energy, they naturally get excited, thinking it's a successful treatment. But, at least for me, it worsened the overall situation.
Regards,
Matt
Posted by Declan on April 29, 2007, at 15:30:51
In reply to Re: Noradrenergics for motivation, focus, anhedonia? » Ines, posted by mattdds on April 29, 2007, at 15:02:47
This should be on Alternative, but has anyone tried green oat extract (which presumably is different to oatstraw extact).
MAO-B and PDE4 inhibitor, apparently, so higher levels of dopamine and Cyclic AMP.
Must get some.
Posted by Ines on April 29, 2007, at 17:41:52
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
Have you come across the selegiline (deprenyl)+ DPLA combo? If you haven't it might be worth checking it out, I've heard it can have good results for drive deficient depression.
Posted by psychobot5000 on April 29, 2007, at 21:16:34
In reply to Re: Noradrenergics for motivation, focus, anhedonia? » psychobot5000, posted by mattdds on April 29, 2007, at 14:51:37
>
> I've tried this route - the noradrenergics - to improve my energy, focus, and interest in life. My experience, is that they push me into irritability and anxiety very quickly. So far, I'm left to choose between functional anhedonia and overstimulation. Overstimulation, with absolutely no renewed interest in life or motivation. Personally, I'll take anhedonia anyday.
>That sounds like my brief experience on T3 (which I understand is supposed to enhance noradrenergic effects of meds somehow), and in that case, I too found anhedonia preferable to being a ball of tightly wound irritable anxiety. Wellbutrin felt much the same way, though not as bad.
As for Ines's comments on Reboxetine:
"Hi there, I tried reboxetine to treat depression, exactly because my depression comes with lethargy, lack of concentration... It made me manically energetic for about 5 days- but in a very uncomfortable way...but my mind was very agitated...and couldn't focus on anything at all. I also couldn't sleep for being wired up...."I took Reboxetine for...perhaps only a week--stopped it because I also felt anxious and wired up in a bad way...it doesn't seem a very effective AD from the experiences I read here. I'm sure Reboxetine has helped people, but I think it might not be an accident that they couldn't muster enough evidence of AD effect for the FDA to approve it.
Selegiline and DLPA is something I've sometimes wondered about--seems likely worth trying, but perhaps likely to cause insomnia too. I sometimes wonder why so many energyless, apathetic depressives have trouble getting to sleep as well. In any case, perhaps that would be a viable option, with something added for sleep--thanks for suggesting it.
Link, sorry to hear that Strattera made you tachycardic. I'm a little surprised, as I'm normally sensitive to that, and it didn't for me. But its positive effects disappeared very quickly anyway. I noticed you mentioned the idea of using beta-blockers with a noradrenergic. Does that seem like it would be a good combination? Since beta-blockers have the reputation for causing depression, I'd always wondered if one could get away with using them to control antidepressant or stimulant-induced tachycardia, without losing the mood benefits. Amineptine and nortriptyline made my heart race, damn them.
Interesting oats should be mentioned...likely nothing, but at some points in my childhood I insisted on eating oatbread, in part because I thought it made me feel better. ...Seems silly...
Anyway,
Psychbot
Posted by notfred on April 29, 2007, at 23:01:34
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
Noradrenergic AD's have been my mainstay for over 20 yrs. None of the SSRI's has proven effective.
I have never had problems with irritability; in fact I tend to like the AD's that have this side effect. For the most part I have been in remission for over 20 yrs,Effexor and Wellbutrin ahve been the AD's I liked the most.
Posted by rvanson on April 30, 2007, at 3:20:40
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
> I'm wondering what people's experiences have been with meds like desipramine, reboxetine and other noradrenaline-enhancing meds have been, for symptoms like low motivation, anhedonia, low concentration.
>
> I have tried to find dopaminergic solutions to these problems (as was recommended to me), but the options of that nature are rather few. Now I'm wondering how useful meds that focus on noradrenaline might be, as some theory seems to offer it as an alternative. Have people found them useful for driveless, anhedonic depression? What about concentration? Which meds in particular? I'd of course welcome any other thoughts anyone might have on the subject.
>
>
I'll go with what mattdds said. NE medications cause lots of anxiety problem in those prone to them and in my case I become a person with a short fuse and a big temper, which is not how I am normally, being adhedonic in nature since my depressive disorder started back 27 years ago.I think dopamine plays a much larger role in the symptoms of ahedonia, with NE and SER taking a back seat, but to each his own.
Posted by mattdds on April 30, 2007, at 3:35:56
In reply to Re: Noradrenergics for motivation, focus, anhedoni, posted by rvanson on April 30, 2007, at 3:20:40
Symptom patterns vary so much from person to person. Until there are some significant advances in science, we'll just have to go with what works for us as individuals.
Maybe our response to these meds will eventually shed some light on the nature of our condition. Isn't it great to be part of this experiment?
Matt
> I'll go with what mattdds said. NE medications cause lots of anxiety problem in those prone to them and in my case I become a person with a short fuse and a big temper, which is not how I am normally, being adhedonic in nature since my depressive disorder started back 27 years ago.
>
> I think dopamine plays a much larger role in the symptoms of ahedonia, with NE and SER taking a back seat, but to each his own.
Posted by linkadge on April 30, 2007, at 18:02:05
In reply to Re: Noradrenergics for motivation, focus, anhedoni, posted by mattdds on April 30, 2007, at 3:35:56
I see noradrenaline as energy and drive but not necessarily motivation or interest.
I remember reading an article about a pure dopaminer reuptake inhibitor in the pipelines (ie no noradrenergic uptake inhibition). Supposedly somnolence was a major side effect.
People associate stimulant with dopamine reuptake inhibition, but I have a feeling that dopamine reuptake inhibitors would be a class on their own.
Linkadge
Posted by psychobot5000 on April 30, 2007, at 18:19:06
In reply to Re: Noradrenergics for motivation, focus, anhedoni, posted by linkadge on April 30, 2007, at 18:02:05
> I see noradrenaline as energy and drive but not necessarily motivation or interest.
What do you see as being the difference between 'drive' and 'motivation?'
>
> People associate stimulant with dopamine reuptake inhibition, but I have a feeling that dopamine reuptake inhibitors would be a class on their own.
>Stimulants tend to work about as much on noradrenaline as on dopamine, anyway. It's strange that people associate them so much with DA. I suppose it's because both the theoretical benefits for ADHD, and the abusability are often perceived as deriving from the dopaminergic action. It's frustrating that no-one has come up with something like a pure (and market-viable) DA reuptake inhibitor, though--amineptine possibly excepted.
Psychbot
Posted by linkadge on May 1, 2007, at 6:22:58
In reply to Re: Noradrenergics for motivation, focus, anhedoni » linkadge, posted by psychobot5000 on April 30, 2007, at 18:19:06
I see drive as more, "I have the energy to get things done", and motivation as "I can find some pleasure and interest in what I am going"
Perhaps those two words are too close. Perhaps I should have used, energy vs. motivation.
There is at least one selective dopamine reuptake inhibitor in the pipelines. Apparently it has low affinity for neucleus accumbens transporters and has little abuse potential.
I will try to find a chemical name.
Linkadge
Posted by kaleidoscope on May 1, 2007, at 15:35:36
In reply to Noradrenergics for motivation, focus, anhedonia?, posted by psychobot5000 on April 29, 2007, at 12:35:53
Noradrenergics do not increase my motivation, but at least they don't decrease it.
ED
Posted by psychobot5000 on May 1, 2007, at 16:17:06
In reply to Re: Noradrenergics for motivation, focus, anhedoni, posted by linkadge on May 1, 2007, at 6:22:58
Sounds as though most people on this thread seem to feel that noradrenergics may not directly be useful for these.
>
> There is at least one selective dopamine reuptake inhibitor in the pipelines. Apparently it has low affinity for neucleus accumbens transporters and has little abuse potential.
>This is good, but let me theorize what might be best: a dopamine reuptake inhibitor with -high- affinity for the nucleus accumbens, which could be bonded to a molecule that would make it inert until processed (and released from the bond) by the liver, at a rate limited by the quantity of liver-enzyme available--just as they've done with amphetamine.
Potentially, this might create a drug that might effectively fight anhedonia, without significant abusability. It would be impossible to flood the system with an active form of the chemical.
Aside from wishful thinking, it just occurred to me to mention that I found EPA fish oil (1-2g daily) seemed to help immediately with these issues. It was genuinely helpful beyond stimulants or any antidepressant I can think of, for anhedonia. Problem was, it wouldn't let me sleep, which naturally caused havoc. But maybe it would be useful for some anhedonics.
Psychbot
PS. Anyone find nomifensine any more useful for motivation or anhedonia than the NA specific meds?
Posted by linkadge on May 1, 2007, at 16:28:51
In reply to Re: NA/DA meds for motivation, anhedonia, posted by psychobot5000 on May 1, 2007, at 16:17:06
I think there are some studies that show abusability of dopamine reuptake inhibitors is (like you say) dependant on rate of inhibition.
I think that some found that you needed <50% inhibition of DAT within 10 minautes (or something like this) in order for a substance to posess significant risk of abuse.
Linkadge
Posted by jrbecker on May 2, 2007, at 1:41:04
In reply to Re: NA/DA meds for motivation, anhedonia, posted by psychobot5000 on May 1, 2007, at 16:17:06
> This is good, but let me theorize what might be best: a dopamine reuptake inhibitor with -high- affinity for the nucleus accumbens, which could be bonded to a molecule that would make it inert until processed (and released from the bond) by the liver, at a rate limited by the quantity of liver-enzyme available--just as they've done with amphetamine.
>
> Potentially, this might create a drug that might effectively fight anhedonia, without significant abusability. It would be impossible to flood the system with an active form of the chemical.
>you basically have a candidate in Vyvanse. it's a reconstituted amphetamine compound from Shire.
It's awaiting labelling authorization by the FDA and is being slated for a june/july launch. If you haven't responded to other ampthetamines in the past though, this will probably not induce drastically different effects. However, if a sustained reponse and/or rebound effects have been issues that have hampered their use by you in the past, then Vyvanse might be somewhat more suitable.
www.fda.gov/cder/Offices/ODS/MG/lisdexamfetamineMG.pdf
Posted by psychobot5000 on May 2, 2007, at 14:15:22
In reply to Re: NA/DA meds for motivation, anhedonia, posted by jrbecker on May 2, 2007, at 1:41:04
> > This is good, but let me theorize what might be best: a dopamine reuptake inhibitor with -high- affinity for the nucleus accumbens, which could be bonded to a molecule that would make it inert until processed (and released from the bond) by the liver, at a rate limited by the quantity of liver-enzyme available--just as they've done with amphetamine.
> >
> > Potentially, this might create a drug that might effectively fight anhedonia, without significant abusability. It would be impossible to flood the system with an active form of the chemical.
> >
>
> you basically have a candidate in Vyvanse. it's a reconstituted amphetamine compound from Shire.Vyvanse was what I modeled the idea of this hypothetical med on. It's probably a good idea on their part to prevent abusability, however, amphetamine is far from being a pure DA reuptake inhibitor. Dexamphetamine didn't do that much for me, as it happens--though I have no idea why. ...I guess my hope was that they could use this Vyvanse-type abuse-limiting formulation of drugs, to make it possible to release a dopaminergic drug that in its natural form is much more abusable and euphoric. If the liver-enzyme thing prevented anyone from binging, because the liver only released the drug into active form at a slow rate, perhaps BigPharma could release a powerful dopaminergic drug without upsetting the drug warriors and creating another drug of abuse.
Best,
Psychbot
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