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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by linkadge on December 11, 2003, at 19:23:41
http://www.hhmi.org/news/caron2.html
Strange.
Linkadge
Posted by scott-d-o on December 12, 2003, at 13:37:25
In reply to Ritalin Boosts serotonin !?, posted by linkadge on December 11, 2003, at 19:23:41
> http://www.hhmi.org/news/caron2.html
>
> Strange.
>It doesn't sound so strange to me.. Ritalin is very similar to cocaine, albeit with a longer half life. Cocaine actually blocks the reuptake of all the monoamines and is actually most selective for the serotonin transporter although this doesn't get very much attention since it's not responsible for the drug's "stimulant" and euphoric effects. I believe the "dulling of emotions" that one gets from cocaine use is the same effect many experience with the SSRI antidepressants.
Does this mean SSRI's could help with attentional problems? I don't think so, but they may work just as well at turning your "hyperactive" kid into a zombie, if that's what you're looking for. That being said, for many severely depressed individuals this emotional dulling is much preferrable to the pains of depression.
Have you ever wondered why Clonidine is used for "ADHD" in children when it is essentially the exact opposite of a stimulant and actually *suppress* the release of catecholamines? Are things becoming clearer now? :-)
scott
Posted by Festus on December 12, 2003, at 20:39:03
In reply to Re: Ritalin Boosts serotonin !? » linkadge, posted by scott-d-o on December 12, 2003, at 13:37:25
My 8 yr. old girl takes Concerta and a half a Clonidine at lunch,then a whole one at bedtime.I thought the Clonidine helped"ease-off"the rest of the lingering Ritalin so she could fall asleep easier.Is that close to what it does?Festus
Posted by zeugma on December 13, 2003, at 14:35:52
In reply to Re: Ritalin Boosts serotonin !?, posted by Festus on December 12, 2003, at 20:39:03
If Ritalin's primary effect in terms of ADD symtomology is by blocking 5-HT reuptake, why have SSRI's been shown to be clinically useless in treating ADD? And why would TCA's, and Strattera, which affect norepinephrine, relieve ADD symptoms?
By the way, cocaine's primary effect is not on 5-HT either. It is much more powerful as a dopamine and norepinephrine reuptake inhibitor.
Posted by scott-d-o on December 13, 2003, at 16:31:41
In reply to Re: Ritalin Boosts serotonin !?, posted by zeugma on December 13, 2003, at 14:35:52
> If Ritalin's primary effect in terms of ADD symtomology is by blocking 5-HT reuptake, why have SSRI's been shown to be clinically useless in treating ADD? And why would TCA's, and Strattera, which affect norepinephrine, relieve ADD symptoms?
Is this post intended for me? If so, I think you need to re-read what I posted. I never said that norepinephrine, or dopamine for that matter, do not play a role in attention and focus. In fact, I think NE plays the greatest role of all the monoamines in these problems. I also never said that SSRI's are useful in this regard.
I am saying, however, that it is very probable that Ritalin's "calming effect" is associated with it's effect as a very potent 5-HT reuptake inhibitor. I think hyperactivity and attention deficit symptoms have been grouped together too closely under the umbrella of the disorder "ADHD". It seems to me that this has inevitiably led to a lot of misdiagnosis as far as assuming a child has ADD just because he has a lot of energy, doesn't like to sit still for long periods, has difficulty focusing in school, etc. Most children have these types of problems. I wonder how many parents have taken their children into a psychiatrist thinking their child may have ADHD, and were told after the session, "nope, he doesn't have ADHD, sorry.." Probably not a likely occurence, I'm sure the majority just pull out the prescription pad and send them on their way.
I have never seen any clinical trials testing the efficacy of SSRI's in ADHD. I think if a SSRI was administered to a "hyperactive" child it may have a very similar calming effect but perhaps it may not do anything for attention and focus. However, can you imagine what it would do to the medical community if trials did show that a SSRI was just as effective as methylphenidate in treating ADHD in children? I am sure there are not very many people willing to conduct such a study whose outcome might demonstrate that we have been giving an analog of nature's most powerful stimulant to our children for decades and for no particular reason.
I have seen just as many children with attentional difficulties that are not hyperactive at all. They may be very quiet during school and do nothing but stare off into space all day. Sadly, these children are almost never diagnosed. I have seen studies that have shown that methylphenidate is relatively ineffective in treating adult ADD compared to ADD in children. Why do you think this is?
>
> By the way, cocaine's primary effect is not on 5-HT either. It is much more powerful as a dopamine and norepinephrine reuptake inhibitor.Much more powerful? That's kind of a relative term. It is more selective than the *SSRI's* are at blocking dopamine and norepinephrine reuptake, however it is actually a very powerful reuptake inhibitor of all the monoamines including serotonin, where it has an impact on the serotonin transporter much greater than any SSRI. I have read many articles stating the actual percentage increase of extracellular 5-HT is actually greater than that of DA, and it is more selective for DA then NE. I don't feel like looking for the article right now, but this should at least demonstrate that cocaine/methylphenidate's affects on serotonin should not to be ignored.
Serotonin transporters upregulate with chronic cocaine use.
Mash DC, Staley JK, Izenwasser S, Basile M, Ruttenber AJ.
Department of Neurology, School of Medicine, University of Miami, Miami, FL 33136, USA. dmash@newssun.med.miami.edu
Cocaine potently inhibits serotonin (5-HT) reuptake in cell bodies and at nerve terminals and 5-HT has been implicated as a modulator of dopaminergic neurotransmission. Chronic use of cocaine may lead to a "serotonin-deficit" form of 5-HT dysregulation. We have examined the status of the 5-HT transporter (SERT) using ligand binding and autoradiographic methods in subgroups of cocaine overdose deaths. Quantitative autoradiography of [125I]RTI-55 was used to map and measure the effect of chronic cocaine use on SERT densities in the striatum, substantia nigra, amygdala, and adjacent paralimbic cortical areas of cocaine overdose (CO) victims with and without preterminal evidence of excited delirium (ED). SERT densities were elevated in the nucleus accumbens and throughout the anterior and posterior sectors of striatum in CO victims compared with age-matched and drug-free control subjects. In contrast, SERT densities were increased significantly in the anterior striatum, but not the posterior sectors in ED victims. Significant elevations in SERT were measured in the orbitofrontal gyrus (Brodmann area 11), the anterior portion of the insular cortex and the cingulate gyrus (Brodmann area 24) in CO and ED victims. Saturation binding site analysis demonstrated an increase in the density of RTI-55 binding sites with no change in the affinity of the radioligand for the SERT. Chronic cocaine exposure upregulated SERT densities in the substantia nigra of the CO, but not ED victims. The lack of SERT upregulation in the substania nigra and posterior striatum suggests the possibility of a distinct phenotype for fatal ED victims that exhibited an acute onset of bizarre and violent behavior prior to death. Adaptive changes in the SERT densities may contribute to depressed mood and drug craving associated with acute cocaine abstinence.
PMID: 11207425 [PubMed - indexed for MEDLINE]
Posted by scott-d-o on December 13, 2003, at 16:42:07
In reply to Re: Ritalin Boosts serotonin !?, posted by Festus on December 12, 2003, at 20:39:03
> My 8 yr. old girl takes Concerta and a half a Clonidine at lunch,then a whole one at bedtime.I thought the Clonidine helped"ease-off"the rest of the lingering Ritalin so she could fall asleep easier.Is that close to what it does?Festus
Clonidine is a alpha2 adrenergic receptor agonist. These receptors are presynaptic and act as a feedback mechanism for the release of the catecholamines (dopamine, epinephrine, and norepinephrine). Therefore, agonising them causes less of these neurotransmitters to be released. Since epinephrine is what causes stimulants to elevate heart rate and blood pressure by binding to beta adrenergic receptors in the heart, clonidine has the effect of lowering BP and heart rate and reducing activity of the sympathetic nervous system. This is why it is primarily used to treat hypertension.
Only you know how this translates to real-world results in your child.
scott
Posted by zeugma on December 13, 2003, at 18:04:15
In reply to Re: Ritalin Boosts serotonin !?, posted by scott-d-o on December 13, 2003, at 16:31:41
> > If Ritalin's primary effect in terms of ADD symtomology is by blocking 5-HT reuptake, why have SSRI's been shown to be clinically useless in treating ADD? And why would TCA's, and Strattera, which affect norepinephrine, relieve ADD symptoms?
>
> Is this post intended for me? If so, I think you need to re-read what I posted. I never said that norepinephrine, or dopamine for that matter, do not play a role in attention and focus. In fact, I think NE plays the greatest role of all the monoamines in these problems. I also never said that SSRI's are useful in this regard.I wasn't writing in regard to your post, though i see how it seemed like I was. I was responding to the study posted early in the thread. I interpreted your remarks (correctly) as expressing skepticism about the role of SSRI's in ADD treatment, particularly in regard to children. Or am I causing further confusion? :-)
>
> I am saying, however, that it is very probable that Ritalin's "calming effect" is associated with it's effect as a very potent 5-HT reuptake inhibitor. I think hyperactivity and attention deficit symptoms have been grouped together too closely under the umbrella of the disorder "ADHD".Agreed, this is one reason ADHD (and Ritalin) have gotten a bad name.
It seems to me that this has inevitiably led to a lot of misdiagnosis as far as assuming a child has ADD just because he has a lot of energy, doesn't like to sit still for long periods, has difficulty focusing in school, etc. Most children have these types of problems. I wonder how many parents have taken their children into a psychiatrist thinking their child may have ADHD, and were told after the session, "nope, he doesn't have ADHD, sorry.." Probably not a likely occurence, I'm sure the majority just pull out the prescription pad and send them on their way.
> I have never seen any clinical trials testing the efficacy of SSRI's in ADHD. I think if a SSRI was administered to a "hyperactive" child it may have a very similar calming effect but perhaps it may not do anything for attention and focus. However, can you imagine what it would do to the medical community if trials did show that a SSRI was just as effective as methylphenidate in treating ADHD in children? I am sure there are not very many people willing to conduct such a study whose outcome might demonstrate that we have been giving an analog of nature's most powerful stimulant to our children for decades and for no particular reason.Actually, I think when Prozac was first released, an awful lot of people wanted it to replace the stimulants as treatment for ADHD. I do know it was researched extensively and failed to demonstrate clinical effectiveness in treating symptoms.
>
> I have seen just as many children with attentional difficulties that are not hyperactive at all. They may be very quiet during school and do nothing but stare off into space all day. Sadly, these children are almost never diagnosed.yes, these are the children who 'fall through the cracks.'
I have seen studies that have shown that methylphenidate is relatively ineffective in treating adult ADD compared to ADD in children. Why do you think this is?
I didn't know MPH was relatively ineffective in adults. I do know Strattera is the first drug to be FDA approved for treatment of adult ADHD, for what that's worth.
>
> >
> > By the way, cocaine's primary effect is not on 5-HT either. It is much more powerful as a dopamine and norepinephrine reuptake inhibitor.
>
> Much more powerful? That's kind of a relative term. It is more selective than the *SSRI's* are at blocking dopamine and norepinephrine reuptake, however it is actually a very powerful reuptake inhibitor of all the monoamines including serotonin, where it has an impact on the serotonin transporter much greater than any SSRI. I have read many articles stating the actual percentage increase of extracellular 5-HT is actually greater than that of DA, and it is more selective for DA then NE. I don't feel like looking for the article right now, but this should at least demonstrate that cocaine/methylphenidate's affects on serotonin should not to be ignored.
> Serotonin transporters upregulate with chronic cocaine use.
>
> Mash DC, Staley JK, Izenwasser S, Basile M, Ruttenber AJ.
>
> Department of Neurology, School of Medicine, University of Miami, Miami, FL 33136, USA. dmash@newssun.med.miami.edu
>
> Cocaine potently inhibits serotonin (5-HT) reuptake in cell bodies and at nerve terminals and 5-HT has been implicated as a modulator of dopaminergic neurotransmission. Chronic use of cocaine may lead to a "serotonin-deficit" form of 5-HT dysregulation. We have examined the status of the 5-HT transporter (SERT) using ligand binding and autoradiographic methods in subgroups of cocaine overdose deaths. Quantitative autoradiography of [125I]RTI-55 was used to map and measure the effect of chronic cocaine use on SERT densities in the striatum, substantia nigra, amygdala, and adjacent paralimbic cortical areas of cocaine overdose (CO) victims with and without preterminal evidence of excited delirium (ED). SERT densities were elevated in the nucleus accumbens and throughout the anterior and posterior sectors of striatum in CO victims compared with age-matched and drug-free control subjects. In contrast, SERT densities were increased significantly in the anterior striatum, but not the posterior sectors in ED victims. Significant elevations in SERT were measured in the orbitofrontal gyrus (Brodmann area 11), the anterior portion of the insular cortex and the cingulate gyrus (Brodmann area 24) in CO and ED victims. Saturation binding site analysis demonstrated an increase in the density of RTI-55 binding sites with no change in the affinity of the radioligand for the SERT. Chronic cocaine exposure upregulated SERT densities in the substantia nigra of the CO, but not ED victims. The lack of SERT upregulation in the substania nigra and posterior striatum suggests the possibility of a distinct phenotype for fatal ED victims that exhibited an acute onset of bizarre and violent behavior prior to death. Adaptive changes in the SERT densities may contribute to depressed mood and drug craving associated with acute cocaine abstinence.
>
> PMID: 11207425 [PubMed - indexed for MEDLINE
Hmmmm. I wonder if this has any bearing on the current debate about whether some people are liable to commit bizarre and violent acts when starting SSRI's.
Posted by scott-d-o on December 13, 2003, at 20:24:58
In reply to Re: Ritalin Boosts serotonin !?, posted by zeugma on December 13, 2003, at 18:04:15
> I didn't know MPH was relatively ineffective in adults. I do know Strattera is the first drug to be FDA approved for treatment of adult ADHD, for what that's worth.
>Yes, this is a good point.. Now that Strattera is out you have the company that manufactures the drug running television advertisements depicting an adult having problems focusing at work. The ad slyly never even mentions the name of the drug or that they are even a drug manufacturer. It seems like ADD wasn't even widely recognized as a disorder that occurred in adults until recently. My guess is that just as many adults have problems with ADD as do children. However, the liability of the substance abuse of stimulants caused much of the medical community to have "attention deficit" problems when it came to recognizing that the disorder even existed in adults. :-)
scott
Posted by linkadge on December 14, 2003, at 20:22:34
In reply to Re: Ritalin Boosts serotonin !? » zeugma, posted by scott-d-o on December 13, 2003, at 20:24:58
It really depends on what your symptoms are. Some children are very calm with regrards to locomoter activity, they can be very kind but have trouble putting their mind to one task, they can't really snap out of daydreaming. These kids may benefit from a more dopaminergic, or noradrenic medication.
However the children who tend to be overactive in their locomoter activity, the ones who are very capable but more defiant and tempered may indeed to better with a more serotogenic medication.
Linkadge
Posted by Mememe on December 16, 2003, at 1:04:16
In reply to Re: Ritalin Boosts serotonin !?, posted by linkadge on December 14, 2003, at 20:22:34
So what would be the effect of a depressed person taking Ritalin? Especially people experiencing fatigue and the blahs as side effects to the traditional antidps?
Posted by scott-d-o on December 16, 2003, at 2:35:54
In reply to Re: Ritalin Boosts serotonin !?, posted by Mememe on December 16, 2003, at 1:04:16
> So what would be the effect of a depressed person taking Ritalin? Especially people experiencing fatigue and the blahs as side effects to the traditional antidps?
Actually it works great for CFS and depression, for some people. However, studies have shown children exposed to Ritalin before adolescence can increase depression later in life but decreases the likelyhood of drug abuse as an adult. You can also be sure that any pdoc except the most liberal will make you try every antidepressant on the planet before resorting to Ritalin for treatment of these disorders.
Posted by Mememe on December 16, 2003, at 13:00:56
In reply to Re: Ritalin Boosts serotonin !?, posted by scott-d-o on December 16, 2003, at 2:35:54
> Actually it works great for CFS and depression, for some people. However, studies have shown children exposed to Ritalin before adolescence can increase depression later in life but decreases the likelyhood of drug abuse as an adult. You can also be sure that any pdoc except the most liberal will make you try every antidepressant on the planet before resorting to Ritalin for treatment of these disorders.<
What are the side effects of Ritalin? (Weightgain?) Can it be mixed with antidepressants? I seem to have tried every antidepressant under the sun. I'll ask my pdoc to see what he thinks about Ritalin.
Posted by scott-d-o on December 16, 2003, at 13:57:50
In reply to Re: Ritalin Boosts serotonin !?, posted by Mememe on December 16, 2003, at 13:00:56
> > Actually it works great for CFS and depression, for some people. However, studies have shown children exposed to Ritalin before adolescence can increase depression later in life but decreases the likelyhood of drug abuse as an adult. You can also be sure that any pdoc except the most liberal will make you try every antidepressant on the planet before resorting to Ritalin for treatment of these disorders.<
>
> What are the side effects of Ritalin? (Weightgain?) Can it be mixed with antidepressants? I seem to have tried every antidepressant under the sun. I'll ask my pdoc to see what he thinks about Ritalin.It depends on the antidepressant although I don't really see why this would be necessary because Ritalin increases all of the monoamines and combined with another antidepressant could cause unpredictable effects and it would probably not be necessary anyway. Possible side effects off the top of my head include euphoria and hence addiction, weight loss, loss of appetite, dry mouth, bruxism, increased sex drive, and anxiety.
Posted by Mememe on December 17, 2003, at 0:37:36
In reply to Re: Ritalin Boosts serotonin !? » Mememe, posted by scott-d-o on December 16, 2003, at 13:57:50
> > > Actually it works great for CFS and depression, for some people. However, studies have shown children exposed to Ritalin before adolescence can increase depression later in life but decreases the likelyhood of drug abuse as an adult. You can also be sure that any pdoc except the most liberal will make you try every antidepressant on the planet before resorting to Ritalin for treatment of these disorders.<
Well, Scott, you were right - my pdoc was not interested in even considering Ritalin. He said it does not affect serotonin. When I mentioned what I had read in the article on the topic, he argued with me and said that, since he is a licensed clinical psychiatrist, HE knows. In other words, he didn't believe me about the Ritalin. The weight loss would be great as a Ritalin side effect, by the way. Today he is adding Trazadone to help me sleep and deal with the insomnia from the Zoloft. I am hoping to still lose weight somehow. (After being a size 4 for 20 years, it's hard when I can't fit into a size 8 now. :( )
This is the end of the thread.
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