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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by qbsbrown on January 16, 2008, at 22:15:09
Just wondering. Seems that the zyprexa im taking counteracts the ritalin, doesn't it. one is increasing the dopamine and norep, while the zyprexa does the opposite, right?
Brian
Posted by tecknohed on January 16, 2008, at 22:15:10
In reply to Do stimulants induce mania?, posted by qbsbrown on January 12, 2008, at 16:32:47
> Just wondering. Seems that the zyprexa im taking counteracts the ritalin, doesn't it. one is increasing the dopamine and norep, while the zyprexa does the opposite, right?
>
> BrianYes they do. Hence why people abuse them to get high. When I used to get high on amphetamines I'd say it definitely mimicked hypomania & definitely full blown mania at times when I'd taken enough. Most symptoms of mania are identical to amphetamine abuse. Not taken Zyprexa myself but normal doses probably do antagonize DA.
Why were you prescribed them? Was the Ritalin making you hyper but still helping? Maybe thats why he/she added Zyprexa to calm you whilst aiming to keep most of Ritalin's theraputic qualities? I'm just guessing.
teck
Posted by cumulative on January 16, 2008, at 22:15:10
In reply to Do stimulants induce mania?, posted by qbsbrown on January 12, 2008, at 16:32:47
Yes, definitely, and I don't really buy the idea that only "hidden" bipolars can react in this way.
The more classic mood stabilizers seem more pertinent than antipsychotics here (since, for one, they will probably do more to directly counter the therapeutic effects of stimulants), but whatever works for you.
Posted by tecknohed on January 16, 2008, at 22:15:10
In reply to Re: Do stimulants induce mania?, posted by cumulative on January 12, 2008, at 17:14:28
> Yes, definitely, and I don't really buy the idea that only "hidden" bipolars can react in this way.
Ditto. If I had 'hidden' bipolar that appeared when I used stims then that meant all my friends at the time had it too! Unlikely.
Posted by qbsbrown on January 16, 2008, at 22:15:10
In reply to Re: Do stimulants induce mania?, posted by tecknohed on January 12, 2008, at 17:30:45
Posted by ShawnThomas on January 16, 2008, at 22:15:10
In reply to Do stimulants induce mania?, posted by qbsbrown on January 12, 2008, at 16:32:47
Stimulants can definitely increase mania, and Ritalin inhibits the reuptake of dopamine and norepinephrine. It is has more potent effects at the dopamine reuptake transporter.
You are asking several questions, and the correct answer to the last one is really intriguing. Zyprexa actually increases the release of dopamine and norepinephrine in areas of the brain such as the prefrontal cortex and striatum (see Westerink et al., 2001 - http://www.ncbi.nlm.nih.gov/pubmed/11165224 and Li et al., 1998 - http://www.ncbi.nlm.nih.gov/pubmed/9551772).
Also, the drug can increase cerebrospinal fluid levels of homovanillic acid, a key metabolite of dopamine that can be viewed as the best indicator of the total amount of dopamine release in the central nervous system (Scheepers et al., 2001 - http://www.ncbi.nlm.nih.gov/pubmed/11557160).
What qualifies as an opposite depends on one's perspective, but I do not view Zyprexa as an opposite of Ritalin in any sense. The two actually share a common indirect effect: increases in dopamine release!
On the one hand, Ritalin's mechanism of action is rather simple. On the other hand, Zyprexa is an inverse agonist at dopamine D2 receptors. It is also a low potency antagonist at dopamine D1 receptors. The drug is an antagonist at dopamine D3 and D4 receptors. At serotonin 5-HT2A and 5-HT2B receptors, Zyprexa is a potent antagonist. It also exhibits potent antagonist effects at histamine H1 receptors and alpha-1 adrenoceptors. Finally, Zyprexa is a low affinity antagonist at M1 and M5 muscarinic acetylcholine receptors (go to http://www.neurotransmitter.net/drug_reference.html and scroll down to the entry for olanzapine for references that support these claims).
Although Zyprexa can block some of the effects of Ritalin- induced increases in extracellular dopamine on dopamine receptors, the two drugs cannot totally cancel one another out. From a practical perspective, Zyprexa can reduce symptoms of mania that are caused by Ritalin. I would not make it my first choice for that application, but some people might.
Shawn
Posted by cumulative on January 16, 2008, at 22:15:10
In reply to Re: Do stimulants induce mania? » qbsbrown, posted by ShawnThomas on January 12, 2008, at 21:34:33
The HVA test measures dopamine metabolite. However, this isn't a reliable test of overall dopaminergic function, especially in the presence of a general (as you note) dopamine receptor antagonist like Zyprexa. Methylphenidate doesn't significantly increase the rate of dopamine release except at very very high doses -- the primary effect in increasing dopaminergic transmission is inhibition of the reuptake pumps.
The PFC/striatum DA release increase from olanzapine is very interesting, as is the fact that it's a stronger antagonist at serotonin receptors than dopamine, but note that the classic side effects that remain associated with olanzapine (particularly olanzapine, in fact) include apathy, sedation, weight gain, loss of motor skills, loss of volition, etc. ... these symptoms are certainly associated with impaired dopaminergic function, and are to some extent the sort of symptoms that typical therapeutic application of methylphenidate seeks to repair.
While I never wrote that the two are opposites (that's not really a meaningful statement in this complex, complex system), I am adamant that Zyprexa can easily diminish the positive therapeutic effects of stimulants.
Posted by your#1fan on January 16, 2008, at 22:15:10
In reply to Re: Do stimulants induce mania? ))ShawnThomas, posted by cumulative on January 12, 2008, at 22:40:14
I was on diffrent stimulants for almost 10 years, concerta, Adderall, Dexedrine, Dexedrine was the best but it didnt last very long at all, only 3 hours, so long days where called for frequenet redosing, and i felt washed out after it. I had to take off some days.
Stimulants will increase your intrest in things, talking, doing something that really intrests like looking at things online, and anything your brain has intrest in. It will increase that effect.
I stopped because of constant re-dose and some other things, i did have some abuse stimuants the last 2 years i was on it. But the reason was because its short half life. Too much energy, i rerember the bad things of which stimulants did to me.
But right now im always constantly losing my keys, STUDDERING sometimes because i dont know how to say things. When i was on stimulants, adderall, or Dexerine mainly i knew how exactly to do things, how do speeches, projects and everything, i had more friends because my "mind" was together. I knew what i was doing. The past 2 years have been absolute horridness to mind! im constantly in recent:
1)lost my keys for periods, which i would go hypomaina.
Including my phone, i've lost 2 phones. Mainly because of lack of thinking.
Forgetting where i parket my car. Forgetting People's names and look like an idiot.... like hey Frank! oh sorry i mean Ryan, Kevin?its Daniel! "opps sorry"
One of my saying i say much too much is: oh danmit! not again!
I have gone 2 year of going in circles and not know where im going, i've got on Strattera, Wellbutrin, i cant take them with Prozac (which is my life saver from depression really).
But Zyprexa will counter act (depending on what dose, but anything above 10mg your not going to feel much stimulant - from a stimulant such as Adderall) It will be like you didnt take it.
It will get you to sleep if your having bad times with insomnia (both manic, and from stiumlants) But the next day you wont that great...trust me! ;) Days when you feel exhausted from stimualnts. Its terrible! cant focus]]time will go by so slowly during the day especially when your at work]] oh its awful.
But at the same its was my best help for me, but the side effects caused for me, (now that is not everyone, some people can tolerate it) I tolerated it for 8 years then it was the last 2 years that really got not for me.
I wish you luck. Please pray for me....too
ok?
im your#1fan
Posted by ShawnThomas on January 16, 2008, at 22:15:11
In reply to Re: Do stimulants induce mania? ))ShawnThomas, posted by cumulative on January 12, 2008, at 22:40:14
As you suggest, I did mean to state that both Ritalin/methylphenidate and Zyprexa/olanzapine can increase extracellular levels of dopamine. I also agree that it can increase dopamine release as you suggest; however, I am not aware of any research that suggests that high, clinically relevant doses can cause that effect. Do you know of any?
Why don't you view CSF HVA as a reliable indicator of overall dopamine release in the CNS? Are you basing that on personal opinion or a journal article(s)?
thanks,
Shawn
Posted by linkadge on January 16, 2008, at 22:15:11
In reply to Re: Do stimulants induce mania? ))ShawnThomas » cumulative, posted by ShawnThomas on January 13, 2008, at 13:57:55
CSF HVA may be a reliable indicator of dopamine release, but not necessarily a reliable indicator of overall dopamine receptor interactions.
That olanzapine increases dopamine release in certain brain regions (5-ht2c antagonism?) doesn't necessarily mean it increases dopamine receptor responces. I heard an it argued that the dopamine receptor antagonism would to some extent negate proposed cognitive enhancing effects of dopamine release in the frontal cortex.
Stimulants don't always cause mania. They can. A large portion of those treated theraputically with stimulants don't display any symptoms of mania. There are even some case reports of high dose stimulants reducing otherwise intractable manic behavior (I'll look for the references).
Apparently bipolars have less dense prefrontal corticies. Improving metabolism in that brain regions may improve certian bipolar symptoms by improving executive function. I remember finding certain stimulants depressing.
Linkadge
Posted by Larry Hoover on January 16, 2008, at 22:15:11
In reply to Re: Do stimulants induce mania? ))ShawnThomas, posted by linkadge on January 13, 2008, at 17:35:20
Posted by linkadge on January 16, 2008, at 22:15:48
In reply to , posted by on December 31, 1969, at 18:00:00
My above post was not meant to be directed at anybody.
Linkadge
Posted by llurpsienoodle on January 18, 2008, at 7:57:30
In reply to Do stimulants induce mania?, posted by qbsbrown on January 16, 2008, at 22:15:09
how about provigil. I took provigil for a year, although my pdoc suspected that I had bipolar (the kind that they don't dx until DSMV comes out). I didn't find it addictive, or have any cause to raise my dose. It worked everytime pretty much the same. It has a different (and mostly unknown) mode of action.
Caffeine?
Theobromine?
lotsa stimulants out there. so little time...
sigh
-Ll
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