![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by psychobot5000 on August 27, 2006, at 13:07:02
This Pubmed abstract sounds like the opening to a very useful article:
Dopaminergic-based pharmacotherapies for depression.
Eur Neuropsychopharmacol. 2006 AugHas anyone read the full article, or found out how to read it? It must have some interesting things to say about various dopaminergics treatments for depression!
Pbot
Posted by redbeach on August 27, 2006, at 14:03:39
In reply to Dopaminergic-based pharmacotherapies for Depressio, posted by psychobot5000 on August 27, 2006, at 13:07:02
I wouldnt hold your breath about dopamine based treatments. Get too much dopamine activity and people can become addicted, to all sorts of things such as gambling. Dopamine is so closely linked to the science of addiction that the FDA will never allow it. There was a dopamine based anti depressent but it was killed off by the FDA. Not because it isnt effective, believe me it can be for some people, but rather the legal nightmare when people sue when they lose money due to gambling addictions. Of course its an extreme minority who have problems however thanks to lawyers who will sue to the max you will never see an effective dopamine agonist or upate inhibitor that is marketed for depression. However if yiou can convince your docter that you have parkinsons then you might be in luck.
While in ranting mode, I might as well add after the Vioxx scandal, the chances of any effective medication coming out is about nil. I could well believe that in future pharmaceutical companies will promote products that have less chance of courting legal proceeding due to side effects rather than how efficient it is. I know that the makers of Paroxetine SKG actually found a more effective product but refused to market it due to the fact that it had to be taken twice a day to be effective. Once again, the customer comes last and marketing men win. The whole pharmaceutical industry is in a sad state of affairs. This has just been reinforced even more by Vioxx as mentioned before. Fewer products are coming on line than ever. This is not due to lack of research or effort, but more for the impossible job of finding an affective product with no side affects. I have given up waiting for a solution from the pharmaceutical industry. I now take St John's Wort, which ironically does have a dopamine reuptake inhibitor, which works more effectively for me than any other drug prescribed to me. I do believe though, that there are more effective solutions out there, but many of them will never be made. For example, some of the isolated compounds out of St John's Wort are effective and are worthy of further research. However, since you cannot put copyright a chemical found in nature, no pharmaceutical company will show interest. No money to be made, so no product for you or me. As someone who staunchly believes in capitalism, I believe that it is a process that is failing in regards to drug research wholy due to legatious lawyers. Anyway, that's enough ranting for me for one day!
Cheers
Redbeach
Posted by linkadge on August 27, 2006, at 16:42:38
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by redbeach on August 27, 2006, at 14:03:39
I have to agree. All the drug companies put comercials on the air making it sound like they're so very interested in helping people. The truth is that it is about money. Effective treatments have come and gone time and time again.
SSRI's are great for everbody. Sure. They make you serene and easy to manage. Lie around all day and eat those little white powdered donuts. No danger to society.
I think it is possable to create dopaminergically based meds with no abuse potential. Dopamine agonists have no abuse potential, and neither does SJW.
Wellbutrin doesn't really have that strong a dopaminergic mechanism. Its effects on dopamine do not appear to be sufficiant to explain its antidepressant effect.
There was a triple uptake inhibitor in the pipelines for depression. DOV 216 303. But, I don't think that it will ever see the light of day. Withdrawl too from this drug would likely make effexor withdrawl seem like a piece of cake.
Linkadge
Posted by Tom Twilight on August 27, 2006, at 16:44:36
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by redbeach on August 27, 2006, at 14:03:39
Yes the status of domperminagic treatments for depression is very frustrating!
The article probably has good suggestions, but no doubt they'l be ignored.
A pity we can't set up our own Drug's company!
The need to treat Parkinson's means that a few dopamine based medications are being developed.
Posted by linkadge on August 27, 2006, at 17:55:10
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by Tom Twilight on August 27, 2006, at 16:44:36
You just need to find a doctor who is willing to be creative and try things off lable.
Mirapex for instance has increasingly demonstrated efficacy in depression, some doctors are willing to give that a try.
Linkadge
Posted by jealibeanz on August 27, 2006, at 18:02:37
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by redbeach on August 27, 2006, at 14:03:39
Your right in saying that dopamine increases when one engages in addictive behaviors, but a drug that increases dopamine in the brain does not lead to such actions. If anything, it would prevent one with deficient dopamine from seeking out such risky behaviors to get a "high" from, since their brain chemicals are already being enhanced. People taking stimulants or dopaminergenic medications, such as Wellbutrin, don't demonstrate a higher prevelance of addiction.
Posted by blueberry on August 27, 2006, at 18:29:44
In reply to Dopaminergic-based pharmacotherapies for Depressio, posted by psychobot5000 on August 27, 2006, at 13:07:02
Dopaminergic options do exist. Ritalin, adderall, modafinil, adrafinil, st johns wort, selegiline, mirapex, bromicriptine, cabergoline, OFC (olanzapine fluoxetine combination). Probably the king of the hill, in my own opinion, is amisulpride.
Posted by psychobot5000 on August 27, 2006, at 19:56:20
In reply to Re: Dopaminergic-based pharmacotherapies for Depressio » psychobot5000, posted by blueberry on August 27, 2006, at 18:29:44
I agree with almost all of what is said. Odd that depressive patients have to leach off of the Parkinson's disease drug pipeline to get dopaminergic medications.
Still, given how little academic attention seems to be given to dopaminergics--largely because of lawsuits, addiction and etc--I would have liked to see what those researchers were saying about treatments available. What comparisons are made? What evidence is there for dopaminergic targets? What might be in the pipeline in the future?
As for the general situation on pharm development and marketing, it seems to me that the profit motive and patent laws are an inadequate stimulus for bringing the best drugs to market. There should be laws passed to provide a profit motive for those willing to investigat saint-john's wort, and older, safer medictions like tianeptine, whose patent is to old, but which may have advantages over other medications.
Or national governments could subsidize research on such non-patent-protected substances as seem best, so patients don't suffer from the lack of them.
Legal liabilities also should probably altered subtly, so as not to prevent drug development as much. Not an easy thing to do, I suppose, but I think it ought to be tried. Well, I suppose these are difficult problems.
Pbot
Posted by jealibeanz on August 27, 2006, at 21:48:49
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by psychobot5000 on August 27, 2006, at 19:56:20
Yeah, it seems a little strange that since I don't want what is considered first line treatment for depression, I'd like to suggest first line treatment for Parkinson's. This should't happen. (I know we know acknowlegde norepinephrine, along with serotonin can contribute to depression. It's actually acknowledged through the use of Wellbutrin, that dopamine contributes as well, but that's where it stopped in terms of currently used meds. Why????)
Maybe we should get some people who have struggled with depression and medication trials and failures on committees for drug development. Something other that a Prozac-copycat may have been produced over the last 20 years!
Posted by Tom Twilight on August 28, 2006, at 4:42:21
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by jealibeanz on August 27, 2006, at 21:48:49
Problem with things like Wellbutrin is that they affect Noradrenaline more than dopamine.
Thats "good" for pharms and doctors because it has "low abuse potential" (God I hate that phrase!)
The reason that more dopermanagic therapies are not being brought out is simply politics, weired morality, and lazyness!
What we should do is form a group to do something about this!
Sorry if I sound angry, I am!
People are suffering needlessly, that makes me angry.
Doperminagic medications are not nessecerilly adictive.
There was a drug called Nomifensine which was very effective and inhibited dopermine re-uptake, but had little abuse potential.It was withdrawn because it could cause a blood disorder, nothing to do with abuse.
A dopermine re-uptake inhibitor Vanorexine is being developed, but it doesn't raise dopermine much, this is seen as an advarntage!
Here a ling anway
http://en.wikipedia.org/wiki/Category:Dopamine_reuptake_inhibitors
Sorry for Bad spelling and rant, I just feel there must be something we can do!
Posted by linkadge on August 28, 2006, at 16:11:11
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by jealibeanz on August 27, 2006, at 18:02:37
>Your right in saying that dopamine increases >when one engages in addictive behaviors, but a >drug that increases dopamine in the brain does >not lead to such actions.
Its all about the area of the brain. Dopamine too isn't the magic pleasure chemical. The pleasurable effects of cocaine for instance are dependant on serotonergic and dopaminergic mechanisms.
The problem with dopamine is that it turns on "wanting" circutry. Illegal drugs like amphetamines can make you feel good in some ways but they don't leave you satisfied, you just want more. Its not really about the level of the chemical since the brain experiences pleasure in gradients. It will adapt to a higher level of the substance to try and maintain normal hedonic capacity.
You can increase dopamine in non-reward areas of the brain to try and increase motivation etc.
>If anything, it would prevent one with >deficient dopamine from seeking out such risky >behaviors to get a "high" from, since their
>brain chemicals are already being enhanced.Perhaps. Pretty much anybody can become addicted to illegal drugs. I don't thing it depends a whole lot on baseline neurotransmitter levels.
When it comes to neucleus accumbens activation, more is better. Thats why if you give mice one illegal drug, they'll still self inject other illegal drugs, the more the better.
>People taking stimulants or dopaminergenic >medications, such as Wellbutrin, don't >demonstrate a higher prevelance of addiction.In terms of wellbutin its hard to say since it isn't a very strong inhibitor of dopamine uptake. A high dose might only give you 20-30% inhibition of dopamine uptake. Its antidepressant effects are through other mechanisms.
As far as stimulants, the jury is still not out. Some doctors argue that taking stimulants early in life predisposes a person to crave stimulants later in life. We do know that people with ADHD are more likely to abuse other substances but it is hard to say if its the disorder or the treatmetns which lead to addictive behaviors.
Linkadge
Posted by linkadge on August 28, 2006, at 16:22:01
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by Tom Twilight on August 28, 2006, at 4:42:21
Amineptine was a very promising drug too. I heard that in several animal models of depression, that it relieved symptoms faster and more completely than imipramine.
Even the SSRI's and TCA's work down the road through a dopaminergic mechanism. You can abolish the antidepressant effect of SSRI's and TCA's by reducing activity at certain dopamine receptors. For non responders, that adaptive process probably never occurs.
It doesn't make a whole lot of sence to me. Doctors insist that depression can't resolve overnight, but even some of the most severe depression can remit very quickly with the right (illegal) drug.
I'm willing to bet that even the most severly depressed people would go into a (temporary) remission if given ecstacy.
Unless there is a change in thought about how to treat these disorders, theres not going to be much process.
Researchers want a silver bullit that they never find.
So, they take amineptine off the market for a small abuse potential, but why don't they work harder at regulating the drugs instead of banning them alltogether for people who could benifit?
Linkadge
Posted by jealibeanz on August 28, 2006, at 16:44:15
In reply to Re: Dopaminergic-based pharmacotherapies for Depre » jealibeanz, posted by linkadge on August 28, 2006, at 16:11:11
There may be some argument the early use of stimulants could lead to drug seeking if the stimulants are taken away from the patient. Probably this is because the patient experienced what is was like to live a better and more functional life!
In my opinion, people with ADHD, depression, anxiety, ect. do not seek drugs because of past antidepressant or stimulant use, it's because there's a true dysfuntion in their brains. We recognize this in ourselves and sometimes come upon substances with can relieve our symptoms partially.
Posted by psychobot5000 on August 28, 2006, at 20:13:10
In reply to Re: Dopaminergic-based pharmacotherapies for Depre, posted by jealibeanz on August 28, 2006, at 16:44:15
________
In my opinion, people with ADHD, depression, anxiety, ect. do not seek drugs because of past antidepressant or stimulant use, it's because there's a true dysfuntion in their brains. We recognize this in ourselves and sometimes come upon substances with can relieve our symptoms partially.
_________I can only assume that addiction takes -both- the addictive substance, and a disposition on the part of the person, either in character or biology.
The case of amineptine is particularly frustrating because, to the extent that it was studied, it seemed such a clean drug. The modest scale of its abuse potential is evident in the case studies: most amineptine abusers are documented as having previous dependence on opiates, cocaine, alcohol, cannabis, etc. The same holds true for abusers of tranylcipromine, prozac, and tianeptine--they nearly all have histories. This suggests to me that it takes a particular kind of person to make amineptine abuse a problem. Not that patients who benefited from it are unbiased (nor should they be), but many of them seem baffled by the attention payed to it.
Since I am not aware of it being possible to synthesize amineptine on the street, the way meth labs make possible that epidemic, I can't say removing amineptine makes sense to me. What danger was there? The abuse potential was not so great, and if it had to be carefully synthesized, then the source could be controlled. Perhaps the issue of drug-induced liver disease was more serious than we tend to realize.
I can only guess why Minaprine isn't available as a substitute dopaminergic antidepressant. Some pieces in the archives here make it sound very attractive.
Posted by linkadge on August 28, 2006, at 20:57:33
In reply to Re: Dopaminergics, amineptine, addiction, posted by psychobot5000 on August 28, 2006, at 20:13:10
The only issue is that there is a real distinction between the way a drug like prozac and a drug like ritalin work in the brain.
When the drugs are tested in mice it is simple enought to see. The mice do not have any chemical imballences to begin with, but they will self adminster cocaine and ritalin, because they like it. It is a pleasurable substance. This is because both directly activate the pleasure centres of the brain. Other antidepressants do not do this.
That is why you hear people who have done harder drugs say things like "don't even try it once".
Another clear difference between the activities of the drugs is how the stimulants are able to activate "addiction genes". A former coke, meth or even nicotine addict can still feel intense cravings for the drug many years after use. All of these substances lead to activation of certain genes involved in the addiction process. I think the gene is known as delta fos-B, also known as intermediate early genes.
Once these genes are swiched on, they do not turn of very easily. Ie, I don't think we have found a way to directly turn off these genes. The recent finding was that even the stimulants used to treat ADHD turn on these genes.
So, lets say some kid uses this kind of drug for all of their childhood, and then comes off it at adulthood. Even though the disorder may have abated, the genes are still turned on, and the patient may continuously feel like something is missing for their adulthood. Now, if they use use a harder drug like cocaine, they may be more likely to continue to use it based on the fact that the drug is now ameliorating a previously instilled predisposition.
Linkadge
Posted by linkadge on August 28, 2006, at 21:07:42
In reply to Re: Dopaminergics, amineptine, addiction, posted by psychobot5000 on August 28, 2006, at 20:13:10
But, ritalin works for ADHD not because it increases dopamine in the pleasure centres of the brain, but because it increases dopmaine in the frontal cortex.
The activity of dopamine depends on the receptor and on the region of the brain. I don't think that dopamine agonists like mirapex are acutely rewarding, but I don't know I havn't taken one.
The only antidepressant I found that was acutely rewarding was Parnate. Right after the first dose I felt warm pleasurable sensations all over my body. I imedately became more sociable, and had a mild overall sence of well being. That being said, it was the only one that made my mildy psychotic.
The antidepressant effect of the drug was probably sufficiant to supercede any desire to increase the dose, but I can kinda see how this one could be abused.
Linkadge
Posted by jealibeanz on August 28, 2006, at 21:34:27
In reply to Re: Dopaminergics, amineptine, addiction, posted by linkadge on August 28, 2006, at 20:57:33
And part of this solution is to recognize the ADHD does not go away for many people in adulthood, it just manifests in a different manner. Therefore proper treatment is necessary in these patients with appropriate monitoring of symptoms in conjunction with their ability to conform to the responsibilities that come with raising a family, holding a full-time job, ect.
Posted by Tom Twilight on August 29, 2006, at 1:51:31
In reply to Re: Dopaminergics, amineptine, addiction, posted by jealibeanz on August 28, 2006, at 21:34:27
I'm sorry this is early in the morning and I haven't slept well.
However I can't entially agree with what Linkadge is say, much as I respect him.
Firstly even potential addictive drugs that affect dopamine are not addictive to everyone.
For example I took Dexedrine for several months
Ignorant stimulant phobic UK docs told me I wouldn get addicted.
In my case this was just not true, I don't crave Dex in anyway!Secondly it deppends on the when and the where of the dopamine in the brain!
Sadly reasoning like Linkadges has produced a phobia of dopamine drugs.
Like I said we should do something about it, no ones going to listen otherwise.
P.S. Sorry for bad spelling-I'm tired and Dyslexic
Posted by linkadge on August 29, 2006, at 16:47:41
In reply to Dopaminergics-addiction-Not nesserilly, posted by Tom Twilight on August 29, 2006, at 1:51:31
>Sadly reasoning like Linkadges has produced a >phobia of dopamine drugs.
I am not against dopaminergically based medications at all. Please feel free to read all of the posts in this thread to see that I too believe that this is a very usefull avenue for future drug development.
For some people ADHD continues into adulthood, and for some people it does not. Just like how depression can be a one time thing, or it can be a chronic disorder.
I totally agree, it does depend on the part of the brain that the drug activates. It is possable to rase dopamine in motivation circutry without directly affecting reward circutry.
Not everybody gets addicted to stimulants I agree. There are many factors, duration of treatment being one.
If you give a mouse ritalin, for instance, through its childhood, and then discontinue the drug in its adulthood, it develops significant indications of reward deficit. Simply meaning, the rat becomes abnormally anhedonic for the rest of its life. That is because its brain has worked to accomidate the drug. I will look for that study.
Drugs like ritalin and amphetamines do turn on the same addiction genes as harder drugs, that is the truth. There is a risk, wheather you succumb to addiction or not. Drugs like straterra, do not however.
That is not to say that all dopaminergic medications activate such genes.
Linkadge
Posted by shasling on September 4, 2006, at 10:11:29
In reply to Re: Dopaminergics-addiction-Not nesserilly, posted by linkadge on August 29, 2006, at 16:47:41
It is possable to rase dopamine in motivation circutry without directly affecting reward circutry.
Hi Link,With respect to the above comment, do you know of specific methods to do this? Low dose Abilify is doing so pretty well for me now, but due to the ever-present poop-out factor, I'd be interested in more info on that, if you have any, for a plan B.
Thanks,
Suzie
Posted by linkadge on September 5, 2006, at 6:49:12
In reply to Re: Dopaminergics-addiction-Not nesserilly, posted by shasling on September 4, 2006, at 10:11:29
The only things I can thing of are dopamine agonists, like mirapex. They have been shown to have antidepressant effect buy I've never heard of abuse, so I don't think they're acutely rewarding.
Linkadge
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.