![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 4 to 28 of 28. Go back in thread:
Posted by zeugma on August 2, 2004, at 18:41:19
In reply to Re: Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 18:08:22
Well, this is just speculative on my part, from my experience with noradrenergic drugs (particularly Strattera) and the dopaminergic Provigil: Strattera did promote focused attention, but did not hook into the motor system very well. I felt like my mind was perfectly clear, but felt like an 'observer' at times of my state. The attention was there but the behavioral control was not. On Provigil it is markedly easier to direct my actions physically. This makes sense as dopaminergic drugs are used to combat Parkinson's which is a disorder of motor dyscontrol. Children with ADHD exhibit disinhibited movement. there are many variants of ADHD but there is clearly an interaction with the motor system that the DA drugs treat more effectively, although the NE drugs treat the cognitive symptoms to some extent by promoting attention itself.
This is more wild speculation, and those more knowledgeable about these things are free to object, but I found that nortriptyline has SOME effect on the motor system (reflected in a sense of 'slowing down' so I could use my attention to direct my actions) while Strattera had no effect on this at all. I wonder if this reflects a difference in the regional actions of the drugs, a claim Lilly (and my pdoc) were pushing. Provigil 'feels' more like nortriptyline than Strattera, because instead of promoting cognitive clarity, it promotes goal-directed action (which my scanning of the abstracts indicated was consistent with a DA effect). Provigil of course is much stronger than nortriptyline in this regard.
So in terms of energization and goal-directed activity: Provigil>nortriptyline>Strattera.
z
Posted by KaraS on August 2, 2004, at 18:56:15
In reply to Re: Norepinephrine vs. Dopamine, posted by zeugma on August 2, 2004, at 18:41:19
> Well, this is just speculative on my part, from my experience with noradrenergic drugs (particularly Strattera) and the dopaminergic Provigil: Strattera did promote focused attention, but did not hook into the motor system very well. I felt like my mind was perfectly clear, but felt like an 'observer' at times of my state. The attention was there but the behavioral control was not. On Provigil it is markedly easier to direct my actions physically. This makes sense as dopaminergic drugs are used to combat Parkinson's which is a disorder of motor dyscontrol. Children with ADHD exhibit disinhibited movement. there are many variants of ADHD but there is clearly an interaction with the motor system that the DA drugs treat more effectively, although the NE drugs treat the cognitive symptoms to some extent by promoting attention itself.
>
> This is more wild speculation, and those more knowledgeable about these things are free to object, but I found that nortriptyline has SOME effect on the motor system (reflected in a sense of 'slowing down' so I could use my attention to direct my actions) while Strattera had no effect on this at all. I wonder if this reflects a difference in the regional actions of the drugs, a claim Lilly (and my pdoc) were pushing. Provigil 'feels' more like nortriptyline than Strattera, because instead of promoting cognitive clarity, it promotes goal-directed action (which my scanning of the abstracts indicated was consistent with a DA effect). Provigil of course is much stronger than nortriptyline in this regard.
>
> So in terms of energization and goal-directed activity: Provigil>nortriptyline>Strattera.
>
> zz,
Could you please clarify more what you mean by "On Provigil it is markedly easier to direct my actions physically." Do you mean that it's easier to translate your intentions into action - or am I way off here?
Posted by Shawn. T. on August 2, 2004, at 19:08:28
In reply to Re: Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 18:08:22
You might want to check out these pages:
http://www.neurotransmitter.net/adhdda.html
http://www.neurotransmitter.net/adhdne.html
http://www.neurotransmitter.net/adhdgenetic.htmlOne hypothesis about stimulants such as the amphetamines is that they increase the number of spontaneously active dopamine neurons in regions such as the ventral tegmental area (http://jpet.aspetjournals.org/cgi/content/full/297/2/746 ). A possible result of reduced dopamine function in ADHD could be an intolerance of delays (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14624804&dopt=Abstract); this is consistent with the view that dopamine is involved in activational motivation. In neonatal rats that have had their dopamine neurons lesioned, dopamine D4 receptors increase in number and perhaps induce hyperactivity (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11927187&dopt=Abstract). The dopamine D4 receptor and other dopaminergic genes have been associated with ADHD. In general, dopamine may be involved in hyperactive-impulsive behavior while norepinephrine may be more involved in the cognitive aspects of ADHD; however, there may some overlap. Thus, a significant amount of evidence supports the use of stimulant drugs in a subset of the ADHD population. Future research should help to identify tests that could determine whether a person with ADHD would benefit most from a stimulant or non-stimulant drug.
Shawn
Posted by KaraS on August 2, 2004, at 19:23:06
In reply to Re: Norepinephrine vs. Dopamine » KaraS, posted by Shawn. T. on August 2, 2004, at 19:08:28
> You might want to check out these pages:
> http://www.neurotransmitter.net/adhdda.html
> http://www.neurotransmitter.net/adhdne.html
> http://www.neurotransmitter.net/adhdgenetic.html
>
> One hypothesis about stimulants such as the amphetamines is that they increase the number of spontaneously active dopamine neurons in regions such as the ventral tegmental area (http://jpet.aspetjournals.org/cgi/content/full/297/2/746 ). A possible result of reduced dopamine function in ADHD could be an intolerance of delays (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14624804&dopt=Abstract); this is consistent with the view that dopamine is involved in activational motivation. In neonatal rats that have had their dopamine neurons lesioned, dopamine D4 receptors increase in number and perhaps induce hyperactivity (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11927187&dopt=Abstract). The dopamine D4 receptor and other dopaminergic genes have been associated with ADHD. In general, dopamine may be involved in hyperactive-impulsive behavior while norepinephrine may be more involved in the cognitive aspects of ADHD; however, there may some overlap. Thus, a significant amount of evidence supports the use of stimulant drugs in a subset of the ADHD population. Future research should help to identify tests that could determine whether a person with ADHD would benefit most from a stimulant or non-stimulant drug.
>
> Shawn
That makes perfect sense - those with pure ADD would need the NE but the ADHD would (also?) need the DA D4 activity. I have my reading cut out for me!!I think I need both noradrenergic and dopaminergic assistance. I definitely need help with focus and concentration but I also need the motivation badly.
Thank you.
Posted by zeugma on August 2, 2004, at 21:46:13
In reply to Re: Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 18:56:15
z,
Could you please clarify more what you mean by "On Provigil it is markedly easier to direct my actions physically." Do you mean that it's easier to translate your intentions into action - or am I way off here?you've got it :)
i'll try to explain more tomorrow.
z
Posted by pablo1 on August 2, 2004, at 22:19:39
In reply to Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 16:47:03
Excellent question!
The ADD stimulants have a significant NE component (as well as the primary dopamine action) so it's pretty hard to sort out. There aren't many pure dopamine medications, even cocaine & crystal meth work on NE to some degree.
In rough terms NE is the tense adrenaline, stress, fight/flight system and dopamine is the pleasure/reward system. I have no clue how concentration fits into those physical body descriptions. Motivation versus activity makes sense though. I wonder which effects obsessive behavior (which I associate with adrenaline/NE) but it's a motivation (avoidance) powered thing as well.
Ack, I'm confused now. Gotta read up on those links and will get back. As always, there is a counterintuitive factor where too much or too little gives the opposite effect.
The basic contradiction is that NE sounds more stimulating and DA more euphoric/sedating but the traditional mixture is something like 80% DA, 20% NE to get what we call a stimulant.
The pure DA meds can make people jittery but 'jittery' is something I'd be more likely to associate with adrenaline.
Posted by Sad Panda on August 2, 2004, at 23:31:29
In reply to Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 16:47:03
> Forgive me if I've asked something like this before but I'm trying to figure out whether I need noradrenergic and/or dopaminergic assistance. How much is each of these involved with energy and motivation? From the reading I've done it seems that they overlap quite a bit (unless I'm interpreting what I'm reading the wrong way). How does one know if they need more of one (or exclusively one) rather than the other? Is there any way to tell other than through trial and error of various meds?
>
>You should try some Desipramine to get a feel for an NE increase with less side effects, you can add it to any AD that you are taking. The NE boost I get from Nortriptyline gives me a feeling of alertness & a more awake feeling. Dopamine drives motivation via reward, doing or achieving something gives a natural dopamine boost which motivates you to do it again, this is why the stimulants are so addictive & a trap. Personally I think that tampering with dopamine should be avoided unless you actually need it for ADD problems.
Cheers,
Panda.
Posted by Sad Panda on August 2, 2004, at 23:35:56
In reply to Re: Norepinephrine vs. Dopamine, posted by zeugma on August 2, 2004, at 18:41:19
> Well, this is just speculative on my part, from my experience with noradrenergic drugs (particularly Strattera) and the dopaminergic Provigil: Strattera did promote focused attention, but did not hook into the motor system very well. I felt like my mind was perfectly clear, but felt like an 'observer' at times of my state. The attention was there but the behavioral control was not. On Provigil it is markedly easier to direct my actions physically. This makes sense as dopaminergic drugs are used to combat Parkinson's which is a disorder of motor dyscontrol. Children with ADHD exhibit disinhibited movement. there are many variants of ADHD but there is clearly an interaction with the motor system that the DA drugs treat more effectively, although the NE drugs treat the cognitive symptoms to some extent by promoting attention itself.
>
> This is more wild speculation, and those more knowledgeable about these things are free to object, but I found that nortriptyline has SOME effect on the motor system (reflected in a sense of 'slowing down' so I could use my attention to direct my actions) while Strattera had no effect on this at all. I wonder if this reflects a difference in the regional actions of the drugs, a claim Lilly (and my pdoc) were pushing. Provigil 'feels' more like nortriptyline than Strattera, because instead of promoting cognitive clarity, it promotes goal-directed action (which my scanning of the abstracts indicated was consistent with a DA effect). Provigil of course is much stronger than nortriptyline in this regard.
>
> So in terms of energization and goal-directed activity: Provigil>nortriptyline>Strattera.
>
> z
>
>Hi Z,
It's intersting that you say that about Nortriptyline. The info I have is all the TCA's are weak but measurable Dopamine reuptake inhibitors & that Nort is the stongest of the bunch.
Cheers,
Panda.
Posted by jlbl2l on August 3, 2004, at 0:25:17
In reply to Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 16:47:03
NE is made from DA.
Posted by sb417 on August 3, 2004, at 0:43:00
In reply to Re: Norepinephrine vs. Dopamine » KaraS, posted by Sad Panda on August 2, 2004, at 23:31:29
> > > You should try some Desipramine to get a feel for an NE increase with less side effects, you can add it to any AD that you are taking. >
> Cheers,> Panda.
>It is not necessarily true that you can add desipramine to any antidepressant. You shouldn't add it to an MAOI, and if you are particularly sensitive to medication combinations and/or if you have a genetic polymorphism for some of the cytochrome P450 enzymes, especially the 2D6 enzyme, you probably could not add a tricyclic to any antidepressant. Some people have no problem with polypharmacy; others are extremely sensitive to drug combos and can get very sick or die from indiscriminate mixing of medications. It is best that any attempts to mix medications are done under a doctor's supervision.
Posted by Sad Panda on August 3, 2004, at 1:22:42
In reply to Re: Norepinephrine vs. Dopamine » Sad Panda, posted by sb417 on August 3, 2004, at 0:43:00
> It is not necessarily true that you can add desipramine to any antidepressant. You shouldn't add it to an MAOI
>
>You can actually add some TCA's to MAOI's. If the TCA isn't a serotonin reuptake inhibitor then it will actually improve the safety of an MAOI. Desipramine, Nortriptyline, Doxepin & Trimipramine can all be added to an MAOI depending on if you need stimulating or sedating. Clomipramine & Imipramine are dangerous due to risk of serotonin syndrome & I would not risk Amitriptyline either although you can find it combined with an MAOI in a pubmed search.
>
>
> and if you are particularly sensitive to medication combinations and/or if you have a genetic polymorphism for some of the cytochrome P450 enzymes, especially the 2D6 enzyme, you probably could not add a tricyclic to any antidepressant. Some people have no problem with polypharmacy; others are extremely sensitive to drug combos and can get very sick or die from indiscriminate mixing of medications. It is best that any attempts to mix medications are done under a doctor's supervision.
>
>That's true, but I wasn't suggesting starting desipramine at 100mg either. Starting at 25mg would be fine.
Cheers,
Panda.
Posted by sb417 on August 3, 2004, at 1:29:26
In reply to Re: Norepinephrine vs. Dopamine » sb417, posted by Sad Panda on August 3, 2004, at 1:22:42
I am aware of the MAOI+TCA combos that you mention, but they are not for everyone. In some cases, even low doses of TCA do not work. These combinations should be done with great care under a doctor's supervision.
Posted by Sad Panda on August 3, 2004, at 2:01:32
In reply to Re: Norepinephrine vs. Dopamine » Sad Panda, posted by sb417 on August 3, 2004, at 1:29:26
> I am aware of the MAOI+TCA combos that you mention, but they are not for everyone. In some cases, even low doses of TCA do not work. These combinations should be done with great care under a doctor's supervision.
>
>That's true, but I assume that we are only talking about doing legal things on this board & since you have to get a doctor to prescibe these things, then it would be under a doctors supervision.
Posted by sb417 on August 3, 2004, at 2:41:41
In reply to Re: Norepinephrine vs. Dopamine, posted by Sad Panda on August 3, 2004, at 2:01:32
> >> That's true, but I assume that we are only talking about doing legal things on this board & since you have to get a doctor to prescibe these things, then it would be under a doctors supervision.
>
>I don't think we should assume anything. I know there is at least one poster on this thread alone who has no medical insurance. She is stuck in the Catch-22 of being too sick to work, so she doesn't have insurance, but she can't get the medical help she needs to get well until she has a job that provides insurance. She is in a desperate situation, and I'm concerned that she may act out of desperation and do something dangerous. And, if you think about the number of people without insurance, there are probably hundreds of other readers in the same predicament. The practice of obtaining medications illegally will go on, regardless of Dr. Bob's prohibition against broadcasting it.
Posted by KaraS on August 3, 2004, at 3:17:31
In reply to Re: Norepinephrine vs. Dopamine, posted by sb417 on August 3, 2004, at 2:41:41
I am the aforementioned desperado who is stuck in that Catch-22. I really appreciate all of your advice and concern. At least in my case, you don't have to worry. The only medication I am taking right now is a minute amount of Effexor. I should be off of it entirely soon. The things I'm going to be trying now are a couple of brands of Rhodiola and then, separately, Perika (SJW). All of the info I'm gathering now is for future reference.
Posted by Sad Panda on August 3, 2004, at 3:55:24
In reply to Re: Norepinephrine vs. Dopamine, posted by sb417 on August 3, 2004, at 2:41:41
> > >> That's true, but I assume that we are only talking about doing legal things on this board & since you have to get a doctor to prescibe these things, then it would be under a doctors supervision.
> >
> >
>
> I don't think we should assume anything. I know there is at least one poster on this thread alone who has no medical insurance. She is stuck in the Catch-22 of being too sick to work, so she doesn't have insurance, but she can't get the medical help she needs to get well until she has a job that provides insurance. She is in a desperate situation, and I'm concerned that she may act out of desperation and do something dangerous. And, if you think about the number of people without insurance, there are probably hundreds of other readers in the same predicament. The practice of obtaining medications illegally will go on, regardless of Dr. Bob's prohibition against broadcasting it.
>
>
>I think you may be being a bit too strict. If we all gave out advice adhering to the rules as you see them then the only advice we could give or get would be to go seek medical advice from an actual doctor.
I also seriously doubt anyone ever died from taking 25mg of Desipramine, IMHO.
Posted by SLS on August 3, 2004, at 6:13:42
In reply to Re: Norepinephrine vs. Dopamine » sb417, posted by Sad Panda on August 3, 2004, at 3:55:24
I think each poster decides where to place the fine line he walks. I move mine around from time to time.
It can be argued that even the advice coming from an M.D. might not be of sufficient value to submit in a forum such as this when so little patient information is made available as would be necessary to acquire in a proper medical interview for the sake of making diagnoses and treatment decisions.
I've been pretty conservative lately with giving suggestions - the "do no harm" thing, I guess.
- Scott
Posted by Philidor on August 3, 2004, at 11:34:27
In reply to Re: Norepinephrine vs. Dopamine » zeugma, posted by Sad Panda on August 2, 2004, at 23:35:56
It's important to know whether we're talking about depression or ADHD here. Ritalin expert Dr. Patrick Cosgrove thinks, in a nutshell, that ADHD is ALL about dopamine and that many ADHDs who are dejected from their disorder are misdiagnosed as depressive, and put on SSRI's which do little or nothing for them. Read this fascinating interview:
Posted by Racer on August 3, 2004, at 12:19:26
In reply to Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 16:47:03
Don't lose sight of the question of balance. I don't think that most of the mood disorders are caused by a simple deficiency in one or another of the neurotransmitters, so much as an imbalance of the ratios between them. My 'theory' is that that's why trial and error is so important in finding the right med or combo for each of us.
That said, Sad Panda has a point about dopamine being involved in the reward system, and it's involved in motivation. Norepinephrine is involved in the whole system that ends up producing adrenaline, so I would associate it with energy. (And, since I'd like the motivation to use the energy that I would like to have, I'd look at something that maybe tweaks both... But I'm not only not a scientist, I couldn't even play one on TV!)
The Terrible Trio of neurotransmitters associated with mood disorders -- serotonin, dopamine, and norepinephrine -- are all monoamines -- so one of the monoamine oxydase inhibitors will hit all of them. If you're interested in getting more narrow in the target you're gunning for, I agree that desimpramine or nortryptyline are good bets.
In general, though, I think the trial and error process will give you the best results. It's frustrating, and there are very few tests that can help guide the choices made, and very few doctors who bother with any of those tests, but the only way to find out if you'll benefit from a specific drug is to try it. And, while the different neurotransmitters do have different effects, which makes you think (well, makes me think) that your symptoms can guide the choice of a target, the reality is that behavior and emotions are too complex to be attributed to a single cause. My own lack of energy, for example, when depressed, is actually an overflow of anxiety -- which you'd think would give me energy, right? Not all of it is intuitive.
(Then again, I tend to think that serotonin gets too much attention -- those other molecules are so cute! We oughta be petting them, too, before they start to sulk.)
Posted by KaraS on August 3, 2004, at 13:23:01
In reply to It's all a matter of balance » KaraS, posted by Racer on August 3, 2004, at 12:19:26
> Don't lose sight of the question of balance. I don't think that most of the mood disorders are caused by a simple deficiency in one or another of the neurotransmitters, so much as an imbalance of the ratios between them. My 'theory' is that that's why trial and error is so important in finding the right med or combo for each of us.
>
> That said, Sad Panda has a point about dopamine being involved in the reward system, and it's involved in motivation. Norepinephrine is involved in the whole system that ends up producing adrenaline, so I would associate it with energy. (And, since I'd like the motivation to use the energy that I would like to have, I'd look at something that maybe tweaks both... But I'm not only not a scientist, I couldn't even play one on TV!)
>
> The Terrible Trio of neurotransmitters associated with mood disorders -- serotonin, dopamine, and norepinephrine -- are all monoamines -- so one of the monoamine oxydase inhibitors will hit all of them. If you're interested in getting more narrow in the target you're gunning for, I agree that desimpramine or nortryptyline are good bets.
>
> In general, though, I think the trial and error process will give you the best results. It's frustrating, and there are very few tests that can help guide the choices made, and very few doctors who bother with any of those tests, but the only way to find out if you'll benefit from a specific drug is to try it. And, while the different neurotransmitters do have different effects, which makes you think (well, makes me think) that your symptoms can guide the choice of a target, the reality is that behavior and emotions are too complex to be attributed to a single cause. My own lack of energy, for example, when depressed, is actually an overflow of anxiety -- which you'd think would give me energy, right? Not all of it is intuitive.
>
> (Then again, I tend to think that serotonin gets too much attention -- those other molecules are so cute! We oughta be petting them, too, before they start to sulk.)
Thanks. I petted serotonin too much in the past myself. The future will be devoted to the adorable NE and DA.
Posted by RetiredYoung on August 3, 2004, at 13:44:15
In reply to Re: It's all a matter of balance, posted by KaraS on August 3, 2004, at 13:23:01
> > > Thanks. I petted serotonin too much in the past myself. The future will be devoted to the adorable NE and DA.
Hilarious!! But just remember, NE and DA, when too high, can turn from baby kittens into saber tooth tigers!
Posted by KaraS on August 3, 2004, at 14:17:38
In reply to Re: It's all a matter of balance, posted by RetiredYoung on August 3, 2004, at 13:44:15
> > > > Thanks. I petted serotonin too much in the past myself. The future will be devoted to the adorable NE and DA.
>
> Hilarious!! But just remember, NE and DA, when too high, can turn from baby kittens into saber tooth tigers!
Good analogy. I'll keep that in mind.
Posted by zeugma on August 4, 2004, at 11:46:45
In reply to Re: Norepinephrine vs. Dopamine, posted by KaraS on August 2, 2004, at 18:56:15
This is a passage from a book, "Synaptic Self", that devotes a whole chapter to the topic of motivation:
"the nucleus accumbens sits at the crossroads of emotion and movement, and... dopamine release in this region plays a crucial role in motivated or goal-directed behavior. This conclusion was based on four main sets of observations. First, the nucleus accumbens receives massive dopamine inputs from the tegmentum. Second, injection of methamphetamine or cocaine into the nucleus accumbens leads to behavioral activation: animals start exploring their environment as if in search of something. Third, the accumbens sends output to areas involved to areas involved in the control of movement (such as the pallidum, an area that connects with the movement-control regions in the cortex and brain stem). Today, it is widely accepted that the nucleus accumbens and areas with which it is connected constitute key elements of a circuit through which emotional stimuli direct behavior toward goals." [p.247]
A couple of comments. The author mentions that the brain stem is involved in movement control. This might explain why nortriptyline helped me more with the 'intention-motivation' linkage than Stattera, because as my pdoc and the Lilly Corp. said, TCA's work more in the brainstem, while Strat is selective for the prefrontal cortex. The PFC has been the presumed site of the dysfunctions involved in ADD/ADHD (see for example "The Executive Brain"). I would say that the PFC is closely involved with cloudy/unclear thinking, but according to the diagram on p. 248 of "Synaptic Self", the PFC is only remotely connected to the motor system, via a GABA inhibitory pathway to the nucleus accumbens, and thence via another GABA pathway to the pallidum. The ventral tegmental area sends DA pathways to both the nucleus accumbens and to the pallidum. So it much more closely involved in motor control than the PFC. Strattera made my mind perfectly clear, but did not enhance control of movements.
Also, the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues. In the 1960's, with the clinical success of the TCA's and MAOI's, norepinephrine was thought to be crucial to AD response as all these drugs enhanced NE transmission while many did nothing for 5-HT. So NE was extensively researched, but of course by using '60's technology, which is nothing compared to what we have now. Then about 1990 the SSRI's became the official 'antidepressants' of choice. So 5-HT became the transmitter of interest, and of course technical advances made 5-HT studies a lot more informative than those studies made while NE was the topic of choice. Now with CYMBALTA finally released we will no doubt see an explosion of studies on NE in mood disorders.
In terms of understanding the relative roles of norepinephrine and dopamine in pathophysiology, the most detailed examination I know of has been in the field of narcolepsy, where DA vs. NE- ergic drugs were compared using EEG studies on narcoleptic dogs. The upshot was that DA reuptake inhibitors enhanced wakefulness, while NE reuptake inhibitors had no effect on wakefulness but selectively blocked REM sleep:
http://www.sro.org/pdf/863.pdf
This result is interesting, because premature induction of REM has always been linked to the melancholic subtype of depression. I do hope CYMBALTA lives up to the symmetry implied in its name, and promotes greater understanding of the 'other' neurotransmitter involved in psychopathology. You know how I feel about misreaders of PubMed abstracts ;), so I would be remiss if I did not point out that the esteemed author whose diagrams and text I drew on above can make shocking misstatements such as this:
"These [SSRI's] are as effective as tricyclics in helping people, but probably not more so. This is to be expected, since both classes of drugs basically do the same thing- make more serotonin available at synapses. But the SSRI's do the job with fewer side effects- they are selective for serotonin, so the side effects caused by enhancing norepinephrine are eliminated." [p. 275]
This explains why it is hard to say exactly what NE's role is in a range of disorders. The author is a leading researcher in the field of neuroscience.
Posted by KaraS on August 4, 2004, at 16:29:32
In reply to emotion and movement and motivation » KaraS, posted by zeugma on August 4, 2004, at 11:46:45
> This is a passage from a book, "Synaptic Self", that devotes a whole chapter to the topic of motivation:
>
> "the nucleus accumbens sits at the crossroads of emotion and movement, and... dopamine release in this region plays a crucial role in motivated or goal-directed behavior. This conclusion was based on four main sets of observations. First, the nucleus accumbens receives massive dopamine inputs from the tegmentum. Second, injection of methamphetamine or cocaine into the nucleus accumbens leads to behavioral activation: animals start exploring their environment as if in search of something. Third, the accumbens sends output to areas involved to areas involved in the control of movement (such as the pallidum, an area that connects with the movement-control regions in the cortex and brain stem). Today, it is widely accepted that the nucleus accumbens and areas with which it is connected constitute key elements of a circuit through which emotional stimuli direct behavior toward goals." [p.247]
>
> A couple of comments. The author mentions that the brain stem is involved in movement control. This might explain why nortriptyline helped me more with the 'intention-motivation' linkage than Stattera, because as my pdoc and the Lilly Corp. said, TCA's work more in the brainstem, while Strat is selective for the prefrontal cortex. The PFC has been the presumed site of the dysfunctions involved in ADD/ADHD (see for example "The Executive Brain"). I would say that the PFC is closely involved with cloudy/unclear thinking, but according to the diagram on p. 248 of "Synaptic Self", the PFC is only remotely connected to the motor system, via a GABA inhibitory pathway to the nucleus accumbens, and thence via another GABA pathway to the pallidum. The ventral tegmental area sends DA pathways to both the nucleus accumbens and to the pallidum. So it much more closely involved in motor control than the PFC. Strattera made my mind perfectly clear, but did not enhance control of movements.
>
> Also, the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues. In the 1960's, with the clinical success of the TCA's and MAOI's, norepinephrine was thought to be crucial to AD response as all these drugs enhanced NE transmission while many did nothing for 5-HT. So NE was extensively researched, but of course by using '60's technology, which is nothing compared to what we have now. Then about 1990 the SSRI's became the official 'antidepressants' of choice. So 5-HT became the transmitter of interest, and of course technical advances made 5-HT studies a lot more informative than those studies made while NE was the topic of choice. Now with CYMBALTA finally released we will no doubt see an explosion of studies on NE in mood disorders.
>
> In terms of understanding the relative roles of norepinephrine and dopamine in pathophysiology, the most detailed examination I know of has been in the field of narcolepsy, where DA vs. NE- ergic drugs were compared using EEG studies on narcoleptic dogs. The upshot was that DA reuptake inhibitors enhanced wakefulness, while NE reuptake inhibitors had no effect on wakefulness but selectively blocked REM sleep:
>
> http://www.sro.org/pdf/863.pdf
>
> This result is interesting, because premature induction of REM has always been linked to the melancholic subtype of depression. I do hope CYMBALTA lives up to the symmetry implied in its name, and promotes greater understanding of the 'other' neurotransmitter involved in psychopathology. You know how I feel about misreaders of PubMed abstracts ;), so I would be remiss if I did not point out that the esteemed author whose diagrams and text I drew on above can make shocking misstatements such as this:
>
> "These [SSRI's] are as effective as tricyclics in helping people, but probably not more so. This is to be expected, since both classes of drugs basically do the same thing- make more serotonin available at synapses. But the SSRI's do the job with fewer side effects- they are selective for serotonin, so the side effects caused by enhancing norepinephrine are eliminated." [p. 275]
>
> This explains why it is hard to say exactly what NE's role is in a range of disorders. The author is a leading researcher in the field of neuroscience.
Thanks so much Zeugma!!!It has been very helpful to get the textbook answer along with how that translates to your personal experience. I feel like I have more of the full picture.
You wrote: "the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues." I can see someone questionning the role of NE in motivation but as an antidepressant? Wouldn't the success rate of the noradrenergic TCAs alone prove that statement false?
As for that shocking misstatement, I can't believe that the author meant it to read like that. Not only does it say something really silly and wrong, but the argument supporting it doesn't make any sense. This "expert" needs to get another editor!
-K
Posted by Sad Panda on August 5, 2004, at 23:29:25
In reply to Re: emotion and movement and motivation » zeugma, posted by KaraS on August 4, 2004, at 16:29:32
> > This is a passage from a book, "Synaptic Self", that devotes a whole chapter to the topic of motivation:
> >
> > "the nucleus accumbens sits at the crossroads of emotion and movement, and... dopamine release in this region plays a crucial role in motivated or goal-directed behavior. This conclusion was based on four main sets of observations. First, the nucleus accumbens receives massive dopamine inputs from the tegmentum. Second, injection of methamphetamine or cocaine into the nucleus accumbens leads to behavioral activation: animals start exploring their environment as if in search of something. Third, the accumbens sends output to areas involved to areas involved in the control of movement (such as the pallidum, an area that connects with the movement-control regions in the cortex and brain stem). Today, it is widely accepted that the nucleus accumbens and areas with which it is connected constitute key elements of a circuit through which emotional stimuli direct behavior toward goals." [p.247]
> >
> > A couple of comments. The author mentions that the brain stem is involved in movement control. This might explain why nortriptyline helped me more with the 'intention-motivation' linkage than Stattera, because as my pdoc and the Lilly Corp. said, TCA's work more in the brainstem, while Strat is selective for the prefrontal cortex. The PFC has been the presumed site of the dysfunctions involved in ADD/ADHD (see for example "The Executive Brain"). I would say that the PFC is closely involved with cloudy/unclear thinking, but according to the diagram on p. 248 of "Synaptic Self", the PFC is only remotely connected to the motor system, via a GABA inhibitory pathway to the nucleus accumbens, and thence via another GABA pathway to the pallidum. The ventral tegmental area sends DA pathways to both the nucleus accumbens and to the pallidum. So it much more closely involved in motor control than the PFC. Strattera made my mind perfectly clear, but did not enhance control of movements.
> >
> > Also, the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues. In the 1960's, with the clinical success of the TCA's and MAOI's, norepinephrine was thought to be crucial to AD response as all these drugs enhanced NE transmission while many did nothing for 5-HT. So NE was extensively researched, but of course by using '60's technology, which is nothing compared to what we have now. Then about 1990 the SSRI's became the official 'antidepressants' of choice. So 5-HT became the transmitter of interest, and of course technical advances made 5-HT studies a lot more informative than those studies made while NE was the topic of choice. Now with CYMBALTA finally released we will no doubt see an explosion of studies on NE in mood disorders.
> >
> > In terms of understanding the relative roles of norepinephrine and dopamine in pathophysiology, the most detailed examination I know of has been in the field of narcolepsy, where DA vs. NE- ergic drugs were compared using EEG studies on narcoleptic dogs. The upshot was that DA reuptake inhibitors enhanced wakefulness, while NE reuptake inhibitors had no effect on wakefulness but selectively blocked REM sleep:
> >
> > http://www.sro.org/pdf/863.pdf
> >
> > This result is interesting, because premature induction of REM has always been linked to the melancholic subtype of depression. I do hope CYMBALTA lives up to the symmetry implied in its name, and promotes greater understanding of the 'other' neurotransmitter involved in psychopathology. You know how I feel about misreaders of PubMed abstracts ;), so I would be remiss if I did not point out that the esteemed author whose diagrams and text I drew on above can make shocking misstatements such as this:
> >
> > "These [SSRI's] are as effective as tricyclics in helping people, but probably not more so. This is to be expected, since both classes of drugs basically do the same thing- make more serotonin available at synapses. But the SSRI's do the job with fewer side effects- they are selective for serotonin, so the side effects caused by enhancing norepinephrine are eliminated." [p. 275]
> >
> > This explains why it is hard to say exactly what NE's role is in a range of disorders. The author is a leading researcher in the field of neuroscience.
>
>
> Thanks so much Zeugma!!!
>
> It has been very helpful to get the textbook answer along with how that translates to your personal experience. I feel like I have more of the full picture.
>
> You wrote: "the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues." I can see someone questionning the role of NE in motivation but as an antidepressant? Wouldn't the success rate of the noradrenergic TCAs alone prove that statement false?
>
> As for that shocking misstatement, I can't believe that the author meant it to read like that. Not only does it say something really silly and wrong, but the argument supporting it doesn't make any sense. This "expert" needs to get another editor!
>
> -K
>
>I think he is very wrong too. The TCA's that have higher efficacy than SSRI's, Clomipramine, Amitriptyline & Imipramine, have widely varying degrees of serotonin reuptake inhibition, but are all fairly equal & potent NE reuptake inhibitors. Initially, they are only mild NRI's, but after their first stage of metabolism, they become desmethy-Clomipramine, Nortriptyline & Desipramine which are all potent NRI's but have practically no power at all as an SRI. Also, these metabolites have longer half lives which further swings the balance in favour of NE.
Cheers,
Panda.
This is the end of the thread.
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