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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 dcruik518 on June 16, 2008, at 19:11:12
Pramipexole for bipolar II depression: a placebo-controlled proof of concept study
Carlos A. Zarate, Jr. , a, b, , Jennifer L. Paynea, Jaskaran Singha, Jorge A. Quiroza, David A. Luckenbaughb, Kirk D. Denicoffb, Dennis S. Charneyb and Husseini K. Manjia
a Laboratory of Molecular Pathophysiology (CAZ, JLP, JS, JAQ, HKM), Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA
b Experimental Therapeutics and Pathophysiology Branch (CAZ, DAL, KDD, DSC), Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Human and Health Services, Bethesda, Maryland, USA
Received 30 December 2003; Revised 18 February 2004; accepted 15 March 2004. Available online 10 May 2004.Abstract
Background
The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression.Methods
In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale.Results
All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p = .02). One subject on pramipexole and two on placebo developed hypomanic symptoms.Conclusions
The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.
Posted by Bob on June 16, 2008, at 23:01:06
In reply to Mirapex found effective in TR Depression and BP II, posted by dcruik518 on June 16, 2008, at 19:11:12
Why are dopamine agonists so novel if we already have drugs like Nardil that have dopamine reuptake? Many people still don't respond to MAOIs either.
Posted by blueboy on June 17, 2008, at 10:03:15
In reply to Re: Mirapex found effective in TR Depression and BP II » dcruik518, posted by Bob on June 16, 2008, at 23:01:06
> Why are dopamine agonists so novel if we already have drugs like Nardil that have dopamine reuptake? Many people still don't respond to MAOIs either.
I don't follow the theoretical side of psychopharmacology, mostly because I don't think the science is advanced enough to actually be of help. In other words, I would agree with the initial assessment of the study, LOL. But I don't know everything and I'm not a scientist.
Anyway, one thing I have noticed is the large number of people on this board who praise MAOIs, mostly Nardil and Parnate, despite the serious side effects and the spate of newer SSRI/SSNI drugs. I'm a prime example -- Nardil is the only non-addictive drug that ever really helped me, and I took it for about two years until I had to stop due to side effects. I was willing to stay on it, even though I really got a lot of the side effects.
So, I'll leave it to the more technical-minded whether that is at all helpful, i.e. an anecdotal statement that might support Mirapex usage.
Also, I have taken Mirapex, 1 mg as needed, for Restless Leg Syndrome in the past (I now use Requip); it gave me no noticeable side effects and stopped RLS completely.
Posted by linkadge on June 17, 2008, at 11:32:46
In reply to Re: Mirapex found effective in TR Depression and B, posted by blueboy on June 17, 2008, at 10:03:15
>Why are dopamine agonists so novel if we already >have drugs like Nardil that have dopamine >reuptake? Many people still don't respond to >MAOIs either.
Like mentioned the side effect profile of different drugs can be different. MAOI's can cause significant insomnia for some users.
While Nardil "theoretically" should raise dopamine, some studies have not found a strong effect in this regard:
http://biopsychiatry.com/phenelzine.htm
Dopamine agonists are also selective to certain dopamine receptors. Not all dopamine agonsts have the same antidepressant effect. The d3 receptors may be implicated.
Serotonin also has inibitory actions on dopamine neurotransmission along certain neural pathways. Some people don't do well on agents that increase serotonin.
Linkadge
Posted by Phillipa on June 17, 2008, at 13:03:43
In reply to Re: Mirapex found effective in TR Depression and B, posted by linkadge on June 17, 2008, at 11:32:46
I mail with a person whose depression is gone after ECT, MAOI's and EMSAM on low requip, trileptal, and one other med. So it must work for some. Phillipa
Posted by blueboy on June 18, 2008, at 14:12:05
In reply to Re: Mirapex found effective in TR Depression and B, posted by linkadge on June 17, 2008, at 11:32:46
> >Why are dopamine agonists so novel if we already >have drugs like Nardil that have dopamine >reuptake? Many people still don't respond to >MAOIs either.
>
> Like mentioned the side effect profile of different drugs can be different. MAOI's can cause significant insomnia for some users.
>Wow, let me give anecdotal approval to that! When I got to 60mg/day (not a huge dose) I would lie wide awake until 5 am. It was actually a bit of fun, as the hypomania allowed me to spin wild fantasies that were rather entertaining, LOL.
It never went away, although it did subside a bit. I was on klonopin, Ambien, Lunesta constantly to get a decent night's sleep. Not that I needed it to function, but I was very worried about my health getting 5-6 hours' sleep per night. (Sometimes as little as 3.5 hours, although I would take a major nap in the afternoon when that happened. Like a "dead to the world" nap.)
Posted by Bob on June 18, 2008, at 15:10:22
In reply to Re: Mirapex found effective in TR Depression and B, posted by blueboy on June 18, 2008, at 14:12:05
I'm taking little tiny bits of Abilify, and it causes some insomnia. Unbelievable considering how small of an amount it is. I tried Mirapex once and a single dose caused immmediate insomnia that night, after the severe drowsiness of the hit on the bloodstream subsided.
ECT also induced insomnia, and has me wondering whether it elevates dopamine levels to a significant degree. Of course it just as easily could be something else entirely, like glutamate, or who the heck knows what.
Posted by Dopamine123 on June 20, 2008, at 21:08:49
In reply to Re: Mirapex found effective in TR Depression and B » linkadge, posted by Phillipa on June 17, 2008, at 13:03:43
I tried requip which has the same mechanism of action as mirapex. I found the cognitive side effects to be really bad. Requip tends to cause executive dysfunction because of reduced stimulation of the d1 receptors in the prefrontal cortex. The D2/D3 receptors are stimulated by the drug, but this actually reduces the amount of real dopamine in the synapse leading to a decreased activation of d1 receptors.
So my verbal fluency (ability to talk) and concentrate took a huge hit when on the drug.
Posted by dcruik518 on June 21, 2008, at 18:41:48
In reply to Didn't like Requip, posted by Dopamine123 on June 20, 2008, at 21:08:49
> I tried requip which has the same mechanism of action as mirapex. I found the cognitive side effects to be really bad. Requip tends to cause executive dysfunction because of reduced stimulation of the d1 receptors in the prefrontal cortex. The D2/D3 receptors are stimulated by the drug, but this actually reduces the amount of real dopamine in the synapse leading to a decreased activation of d1 receptors.
>
> So my verbal fluency (ability to talk) and concentrate took a huge hit when on the drug.
>
> My blog:
> http://brainstimulant.blogspot.comHi,
I'm taken requip and bromocriptine and have noticed something similar, I think. If I take a lot I get drowzy and a bit dopey, similar to taking too many benzos. this wasn't the case, however, when first started taking either one, though, so somehting must change in the brain's reaction to the med or perhaps it builds up the blood.
What I've found works well is to just take small amounts a bedtime and once during the day. I also take Adderall which I suspect stimulate the D1 receptor and the frontal lobes in general.
DRC
Posted by cactus on June 24, 2008, at 6:11:34
In reply to Didn't like Requip, posted by Dopamine123 on June 20, 2008, at 21:08:49
> I tried requip which has the same mechanism of action as mirapex. I found the cognitive side effects to be really bad. Requip tends to cause executive dysfunction because of reduced stimulation of the d1 receptors in the prefrontal cortex. The D2/D3 receptors are stimulated by the drug, but this actually reduces the amount of real dopamine in the synapse leading to a decreased activation of d1 receptors.
>
> So my verbal fluency (ability to talk) and concentrate took a huge hit when on the drug.
>
> My blog:
> http://brainstimulant.blogspot.comwow, I had the opposite response. I posted a more detailed response up higher on the board. It was good and bad for me
Posted by satsumas on June 30, 2008, at 16:51:45
In reply to Didn't like Requip, posted by Dopamine123 on June 20, 2008, at 21:08:49
can you explain a bit more detail? i'm currently taking 2.0 mirapex a day in divided doses, with effexor 150 (in the process of tapering off), desipramine 75 (in the process of tapering up), and lithium 450.
at first, i thought the mirapex was helpful for the 'desire' and anhedonia elements of the depression, but i think that may have just been the effexor kicking in at a higher dose. my main reason for having my pdoc Rx mirapex was that i think i have a serious dopamine disfunction, as no matter what AD i've been on in teh past two years, the apathy, anhedonia, low motivation, and poor libido/romantic interest elements were always there.
focalin (ritalin) helped a bit for the motivation and focus, but not for anything else. and it was too speedy. i'm hoping the mirapex is a bit more targeted in the emotional part of the brain (mesolimbic?) rather than the frontal cortex like I believe ritalin targets.
i'm curious as to what your specific experience with mirapex was, how you noticed the cog. disfunction kicking in, and what specific aspects of your experience you felt were hit the most.
why would d2/d3 agonists lower d1? and what does d1 do?
thanks so much...your post got me a bit worried!
Posted by Dopamine123 on June 30, 2008, at 18:11:45
In reply to Re: Didn't like Requip » Dopamine123, posted by satsumas on June 30, 2008, at 16:51:45
>i'm curious as to what your specific experience with mirapex was, how you noticed the cog. disfunction kicking in, and what specific aspects of your experience you felt were hit the most.
First, my concentration got really bad. I also found that my verbal fluency and overall ability to talk decreased considerably. It was like I couldn't think of anything to say when being around people. I just became very untalkative and quiet. Also my motivation levels took a hit.
I did notice a mild increase in the pleasure response, but I felt somewhat demented due to the executive dysfunction. The pleasure response rapidly dissappeared too probably due to tolerance. I actually found women more attractive which is probably due to agonism of d2/d3 receptors in the pleasure center.
So it was kind of weird. It decreased my apathy in certain instances, but seemed to increase it in regards to other aspects of functioning.
I take adderall now. This drug is much more consistent in improving apathy, verbal fluency, motivation and anhedonia. Probably because it stimulates D1, D2, and D3 receptors at the same time.
>why would d2/d3 agonists lower d1? and what does d1 do?
Mirapex is like fake dopamine. It increases activation at d2/d3 receptors, but it isn't an agonist at d1 receptors. It also hits d2/d3 autoreceptors that control the synthesis and release of dopamine. So what happens is that the amount of real dopamine in the synapse actually decrease because it is hitting those autoreceptors. The autoreceptors are like feedback mechanism in your brain to make sure you don't get too much dopamine. So your d2/d3 receptors end up getting activated to a greater degree because of mirapex, however the amount of real dopamine decreases. Your brain thinks there is an overload of dopamine so it compensates by reducing output. However while mirapex stimulates d2/d3 receptors it doesn't stimulate the d1 receptor. So the d1 receptor is activated less than it normally would because there is less dopamine.
Sorry if that's confusing, that's the best I can do.
Activation of the D1 receptor is associated with cognitive functioning, verbal fluency, interest (as opposed to apathy).
It's complex and you might not necessarily get the same response that I did. I think it all depends on your original brain functioning.
As cactus said
"wow, I had the opposite response. I posted a more detailed response up higher on the board. It was good and bad for me"
Posted by satsumas on June 30, 2008, at 18:57:08
In reply to Re: Didn't like Requip, posted by Dopamine123 on June 30, 2008, at 18:11:45
thanks for the explanation.
CACTUS: can you point me to your thread? i tried searching and couldn't find anything recent so i'm not sure if it was an old thread or not.
now i'm worried about mirapex in the long term. i've been on focalin (ritalin) before...how does adderall compare, if you have any experience with both? does it hit all parts of the brain, not just the prefrontal cortex?
i guess if mirapex poops out, then i stop taking it....seems like not a good discontinuation scenario. how did you taper off? did you notice things getting even worse when you were off of it?
thanks,
sat
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