![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 45. This is the beginning of the thread.
Posted by jerrympls on January 27, 2004, at 20:22:46
...meds like Mirapex, Amantadine, etc?
I talked to my pdoc about adding a dopamine antagonist like Mirapex (it's an antagonist right?) she said that antipsychotics would do the same thing. But I thought antipsychotics hit different Dopamine sub receptors??
Can anyone help me sort this out??
Jerry
Posted by Sebastian on January 27, 2004, at 21:46:22
In reply to Do anti-psychotics act on dopamine the same as..., posted by jerrympls on January 27, 2004, at 20:22:46
Read the prescribing information on each medicin. You can find it at the brand name web site. google search, or abilify.com for example. They all are a little different in the type of dopamine and how much they affect it. The info is usualy at the top of the document.
Sebastian
Posted by scott-d-o on January 27, 2004, at 22:10:35
In reply to Do anti-psychotics act on dopamine the same as..., posted by jerrympls on January 27, 2004, at 20:22:46
antipsychotics are dopamine antagonists and sometimes have effects at a bunch of other receptors as well, usually in hopes of reducing the risk of tardive dyskinsia.
of the drugs you mention, one of them, mirapex, is a dopamine agonist, and the other is an indirect dopamine agonist; really it is the opposite action from antipsychotics.
however, your pdoc is right that at *low doses* antipsychotics can increase dopaminergic transmission because they antagonise these receptors in yo brain called presynaptic or "autoreceptors." These receptors are located on dopamine-producing neurons and act as a feedback mechanism for how much dopamine is in the synaptic space (i.e. between neurons.) antagonizing *these specific receptors* causes the neuron to release more dopamine, therefore there is more dopamine in the synaptic space to "agonize" the postsynaptic receptors naturally.
you just have to be careful because some antipsychotics don't preferentially antagonise autoreceptors at any dose, and in any case, taking a dose past the point where more postsynaptic receptors are being antagonized than presynaptic ones can really f*ck up a person who has a dysfunctional dopaminergic system (ask me how I know)....
dopamine agonists *may* actually cause a *decrease* in dopamine transmission using the same logic.. obviously higher doses would be desirable in their case if increasing dopamine transmission is your goal.. understand?
scott
Posted by Karen Moore on January 27, 2004, at 22:31:41
In reply to Re: Do anti-psychotics act on dopamine the same as » jerrympls, posted by scott-d-o on January 27, 2004, at 22:10:35
>
> you just have to be careful because some antipsychotics don't preferentially antagonise autoreceptors at any dose, and in any case, taking a dose past the point where more postsynaptic receptors are being antagonized than presynaptic ones can really f*ck up a person who has a dysfunctional dopaminergic system (ask me how I know)....
>
OK, I'm asking, "how do you know"??!! I've been on Seroquel for years, initially it was the only thing that kept me from tearing my head off during mixed mania (which was triggered by Effexor, I had know idea it was mania then...). Now I take it for sleep, nothing else works, but I suspect overall it may be making me worse. I have comorbid ADD which I highly doubt is helped by the Seroquel. I strongly suspect my dopamine system is a wreck and now I'm beginning to wonder if Seroquel has made it worse....But without it I don't sleep and end up again in dysphoric mania!
Thanks for your posts,
KM
Posted by jerrympls on January 27, 2004, at 22:32:43
In reply to Re: Do anti-psychotics act on dopamine the same as » jerrympls, posted by scott-d-o on January 27, 2004, at 22:10:35
> antipsychotics are dopamine antagonists and sometimes have effects at a bunch of other receptors as well, usually in hopes of reducing the risk of tardive dyskinsia.
>
> of the drugs you mention, one of them, mirapex, is a dopamine agonist, and the other is an indirect dopamine agonist; really it is the opposite action from antipsychotics.
>
> however, your pdoc is right that at *low doses* antipsychotics can increase dopaminergic transmission because they antagonise these receptors in yo brain called presynaptic or "autoreceptors." These receptors are located on dopamine-producing neurons and act as a feedback mechanism for how much dopamine is in the synaptic space (i.e. between neurons.) antagonizing *these specific receptors* causes the neuron to release more dopamine, therefore there is more dopamine in the synaptic space to "agonize" the postsynaptic receptors naturally.
>
> you just have to be careful because some antipsychotics don't preferentially antagonise autoreceptors at any dose, and in any case, taking a dose past the point where more postsynaptic receptors are being antagonized than presynaptic ones can really f*ck up a person who has a dysfunctional dopaminergic system (ask me how I know)....
>
> dopamine agonists *may* actually cause a *decrease* in dopamine transmission using the same logic.. obviously higher doses would be desirable in their case if increasing dopamine transmission is your goal.. understand?
>
> scott
Hey Scott-Thanks for the info. Yeah I understand. I used to know all this stuff - however all these meds have my brain in a fog. I certainly believe that my dopamingeric system is wy out of whack. Amphetamines help - but after a while it seems as if they cause the opposite reaction - as described by the negative feedback system you explain above. So I'm wondering about Ritalin/Concerta because it blocks reuptake of dopamine as well as release it - from what I understand. THEN I'm thinking about augmenting with Mirapex - about which I have heard some extraordinarily postive stories from others on this board - saying that it renewed their creativity, pleasure, motivation, etc.
My depression is rescurrent/refractory/resistant - you name it - and SSRI's just dull me. SNRI's aren't much different from SSRI's for me. Opiates work very well.
I don't want to add an anti-psychotic to be honest. I'm already on 200mg of Seroquel for insomnia. My doc said that Geodon or Abilify may help - but all I can imagine is brain dulling and sleepiness and/or akathesia.
So, we agreed to start Adderall XR 10mg. I've been on Adderall before at this dose and it had a MUCH MUCH more powerful effect the first time I was on it (about 3 years ago). Now it's like I'm taking nothing. My receptors are all screwed up.
What to do? What to try? ugh....
But thanks for your help....I greatly appreciate it.
Jerry
Posted by jerrympls on January 27, 2004, at 22:35:16
In reply to Re: Do anti-psychotics act on dopamine the same as » scott-d-o, posted by Karen Moore on January 27, 2004, at 22:31:41
>
> >
> > you just have to be careful because some antipsychotics don't preferentially antagonise autoreceptors at any dose, and in any case, taking a dose past the point where more postsynaptic receptors are being antagonized than presynaptic ones can really f*ck up a person who has a dysfunctional dopaminergic system (ask me how I know)....
> >
> OK, I'm asking, "how do you know"??!! I've been on Seroquel for years, initially it was the only thing that kept me from tearing my head off during mixed mania (which was triggered by Effexor, I had know idea it was mania then...). Now I take it for sleep, nothing else works, but I suspect overall it may be making me worse. I have comorbid ADD which I highly doubt is helped by the Seroquel. I strongly suspect my dopamine system is a wreck and now I'm beginning to wonder if Seroquel has made it worse....But without it I don't sleep and end up again in dysphoric mania!
> Thanks for your posts,
> KM
>
>Karen-
I'm in the same boat - I think the Seroquel is exerting a dampening effect and making me worse. I'm a terrible insomniac and I need something strong to get me to sleep and Seroquel has worked the best - but I feel terribly blunted for most of the morning and stimulants don't work as well, etc......
Jerry
Posted by Karen Moore on January 27, 2004, at 22:38:49
In reply to Re: Do anti-psychotics act on dopamine the same as » scott-d-o, posted by jerrympls on January 27, 2004, at 22:32:43
Posted by Karen Moore on January 27, 2004, at 22:44:35
In reply to Re: Do anti-psychotics act on dopamine the same as » scott-d-o, posted by jerrympls on January 27, 2004, at 22:32:43
Jerry,
Sorry, meant to forward this other post (from scott-d-o) to you earler, in case you didn't catch it...http://www.dr-bob.org/babble/20040122/msgs/305199.html
KM
Posted by jerrympls on January 27, 2004, at 22:52:28
In reply to I think we need to start a Dopamine Club here... (nm) » jerrympls, posted by Karen Moore on January 27, 2004, at 22:38:49
I completely agree. It's so sad that doctors are so set on the serotonin theory model of depression. They Dopamine system is where I - and many - many others need help.
Posted by scott-d-o on January 28, 2004, at 1:00:41
In reply to Re: Do anti-psychotics act on dopamine the same as » scott-d-o, posted by Karen Moore on January 27, 2004, at 22:31:41
> OK, I'm asking, "how do you know"??!! I've been on Seroquel for years, initially it was the only thing that kept me from tearing my head off during mixed mania (which was triggered by Effexor, I had know idea it was mania then...). Now I take it for sleep, nothing else works, but I suspect overall it may be making me worse. I have comorbid ADD which I highly doubt is helped by the Seroquel. I strongly suspect my dopamine system is a wreck and now I'm beginning to wonder if Seroquel has made it worse....But without it I don't sleep and end up again in dysphoric mania!
> Thanks for your posts,
> KM
>hey karen,
the fact that seroquel alleviated your effexor-induced mania does not suprise me, since it is a alpha-1 adrenergic antagonist. mania is usually caused by an excess of norepinephrine, of which effexor blocks it's reuptake into presynaptic neurons. central alpha-1 adrenergic receptors are postsynaptic and central alpha-2 adrenergic receptors are presynaptic. therefore, the alpha-1 antagonism of seroquel blunted your brains response to the increase norepinephrine from effexor.
I agree the effects of seroquel on your dopaminergic system at that dose cannot be helpful. Surely there is another drug out there that will help you sleep. I assume you've already tried benzos, ambien, sonata?
If your insomnia does not respond to gaba potentiating meds then what about trazodone? It acts solely via serotonin receptors.
If seroquel is the only thing that keeps you sane while on effexor, than perhaps you should not be on effexor. Are you taking the effexor for ADD? Do you have the same manic reaction to stimulants?
scott
Posted by scott-d-o on January 28, 2004, at 1:31:25
In reply to Re: Do anti-psychotics act on dopamine the same as » scott-d-o, posted by jerrympls on January 27, 2004, at 22:32:43
> Thanks for the info. Yeah I understand. I used to know all this stuff - however all these meds have my brain in a fog. I certainly believe that my dopamingeric system is wy out of whack. Amphetamines help - but after a while it seems as if they cause the opposite reaction - as described by the negative feedback system you explain above. So I'm wondering about Ritalin/Concerta because it blocks reuptake of dopamine as well as release it - from what I understand. THEN I'm thinking about augmenting with Mirapex - about which I have heard some extraordinarily postive stories from others on this board - saying that it renewed their creativity, pleasure, motivation, etc.
actually, you have ritalin and amphetamines backwards. yes, ritalin is a monoamine reuptake blocker with a high affinity for dopamine.however, it is the amphetamines that bind to the dopamine transporter and actually reverse its action, not only blocking reuptake but causing a release of dopamine into the synapse, as opposed to transporting dopamine back into the presynaptic neuron like it's supposed to do. cocaine and methylphenidate merely block the transporter causing it to do jack sh*t.
augmenting your adderall with mirapex doesn't sound like a great idea to me if you are non-responsive to stimulants due to supersensitive dopamine autoreceptors. if this is the case, the mirapex will most likely cause these receptors to activate and decrease dopamine release. NMDA antagonists can help with stimulant tolerance. magnesium supplementation (300% of the RDA of a highly bioavailable compound) is the natural way to go about this; memantine is a med that has this direct action on these receptors.
>
> My depression is rescurrent/refractory/resistant - you name it - and SSRI's just dull me. SNRI's aren't much different from SSRI's for me. Opiates work very well.
>
> I don't want to add an anti-psychotic to be honest. I'm already on 200mg of Seroquel for insomnia. My doc said that Geodon or Abilify may help - but all I can imagine is brain dulling and sleepiness and/or akathesia.
>
> So, we agreed to start Adderall XR 10mg. I've been on Adderall before at this dose and it had a MUCH MUCH more powerful effect the first time I was on it (about 3 years ago). Now it's like I'm taking nothing. My receptors are all screwed up.
>
> What to do? What to try? ugh....
>
> But thanks for your help....I greatly appreciate it.
>
> Jerry
an antipsychotic could help you at low-dose; I haven't tried abilify but I had a terrible experience with geodon. it is definitly not dopaminergic even at it's lowest dose of 20mg. I didn't try splitting the capsules for a lower dose. sulpiride or amisulpride are the two antipsychotics that are the most selective for dopamine autoreceptors. at low doses they can increase dopamine release without disturbing DA transmission too badly. unforunately, they are not approved in the usa; you could get a script and order from overseas thou. if you want to stick w/fda-approved meds the closest thing is stelazine (trifluoperazine). start at only 1mg don't go over 2mg.hope this helps,
scott
Posted by Karen Moore on January 28, 2004, at 1:37:14
In reply to Re: Do anti-psychotics act on dopamine the same as, posted by scott-d-o on January 28, 2004, at 1:00:41
Excellent, thanks for your thought provoking response, Scott.
I dropped Effexor ages ago and found out quickly with other trials that SSRIs make me absolutely miserable. ADD is the least of my problems, I was taking it for agitated depression, but now I find myself fitting into the bipolar spectrum. Stimulants make me a little hypomanic if I'm not careful, but it's the pleasant sort rather than the dysphoric flavor. As for sleep drugs, I've tried benzos, trazadone, sonata, anti-convulsants, all nada, my brain just doesn't want to ever shut down. And if I don't sleep I get downright manic. I just finished putting together a summary sheet to see a psych. researcher tomorrow (s.dubovsky) and counted 31 prescription drug trials in the last 2 and half years! And that doesn't count some of the other unsanctioned pharmacology experiments I've put myself through...
OK. There's my whine for the evening.
Thanks again,
KM
P.S. Have you ever heard of anyone having LOW blood pressure problems on stimulants? And I don't mean orthostatic hypotension... My only theory so far is cortisol, but that hasn't proven to be the problem (yet).
> >
>
> hey karen,
>
> the fact that seroquel alleviated your effexor-induced mania does not suprise me, since it is a alpha-1 adrenergic antagonist. mania is usually caused by an excess of norepinephrine, of which effexor blocks it's reuptake into presynaptic neurons. central alpha-1 adrenergic receptors are postsynaptic and central alpha-2 adrenergic receptors are presynaptic. therefore, the alpha-1 antagonism of seroquel blunted your brains response to the increase norepinephrine from effexor.
>
> I agree the effects of seroquel on your dopaminergic system at that dose cannot be helpful. Surely there is another drug out there that will help you sleep. I assume you've already tried benzos, ambien, sonata?
>
> If your insomnia does not respond to gaba potentiating meds then what about trazodone? It acts solely via serotonin receptors.
>
> If seroquel is the only thing that keeps you sane while on effexor, than perhaps you should not be on effexor. Are you taking the effexor for ADD? Do you have the same manic reaction to stimulants?
>
> scott
>
Posted by scott-d-o on January 28, 2004, at 3:42:22
In reply to I think we need to start a Dopamine Club here... » scott-d-o, posted by Karen Moore on January 28, 2004, at 1:37:14
> Excellent, thanks for your thought provoking response, Scott.
> I dropped Effexor ages ago and found out quickly with other trials that SSRIs make me absolutely miserable. ADD is the least of my problems, I was taking it for agitated depression, but now I find myself fitting into the bipolar spectrum. Stimulants make me a little hypomanic if I'm not careful, but it's the pleasant sort rather than the dysphoric flavor. As for sleep drugs, I've tried benzos, trazadone, sonata, anti-convulsants, all nada, my brain just doesn't want to ever shut down. And if I don't sleep I get downright manic. I just finished putting together a summary sheet to see a psych. researcher tomorrow (s.dubovsky) and counted 31 prescription drug trials in the last 2 and half years! And that doesn't count some of the other unsanctioned pharmacology experiments I've put myself through...
> OK. There's my whine for the evening.
> Thanks again,
> KM
hi karen,sounds like you've been thru a lotta meds.. assuming I was correct about your insomnia being provoked by excess NE, believe it or not, I can still sit here all nite and name meds that could help until I come up with one you haven't tried..
how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does, however it is also a very potent antihistamine (sedative), and also has alpha-1 antagonism (which I assumed was the reason seroquel helps your insomnia.) In fact, the only reason effexor was supposed to be an improvement over older tricyclics, such as doxepin, is because effexor doesn't have the sedative and anticholinergic action of TCA's. doxepin also happens to be a 5-HT2a antagonist, again like seroquel, and this should help with the insomnia as well.. sounds like the best of both meds for you..
> P.S. Have you ever heard of anyone having LOW blood pressure problems on stimulants? And I don't mean orthostatic hypotension... My only theory so far is cortisol, but that hasn't proven to be the problem (yet).
yeh.. sounds like your on the right track.. raised cortisol levels in plasma.. for the insomnia you should definitly try the alpha-2 agonist clonidine; assuming you don't like the doxepin idea. but go slow; I know for sure the clonidine will knock ya out like never b4 ;-)
scott
Posted by Sad Panda on January 28, 2004, at 23:14:54
In reply to Re: I think we need to start a Dopamine Club here. » Karen Moore, posted by scott-d-o on January 28, 2004, at 3:42:22
> how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does, however it is also a very potent antihistamine (sedative), and also has alpha-1 antagonism (which I assumed was the reason seroquel helps your insomnia.) In fact, the only reason effexor was supposed to be an improvement over older tricyclics, such as doxepin, is because effexor doesn't have the sedative and anticholinergic action of TCA's. doxepin also happens to be a 5-HT2a antagonist, again like seroquel, and this should help with the insomnia as well.. sounds like the best of both meds for you..
>Doxepin is an extremely weak serotonin reuptake inhibitor but it is powerful at blocking histamine, the only thing stronger is Mirtazapine. Efexor is a weak norepinephrine reuptake inhibitor. Benzos don't make me drowsy but Mirtazapine certainly does.
Cheers,
Panda.
Posted by scott-d-o on January 29, 2004, at 0:43:09
In reply to Re: I think we need to start a Dopamine Club here. » scott-d-o, posted by Sad Panda on January 28, 2004, at 23:14:54
> > how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does, however it is also a very potent antihistamine (sedative), and also has alpha-1 antagonism (which I assumed was the reason seroquel helps your insomnia.) In fact, the only reason effexor was supposed to be an improvement over older tricyclics, such as doxepin, is because effexor doesn't have the sedative and anticholinergic action of TCA's. doxepin also happens to be a 5-HT2a antagonist, again like seroquel, and this should help with the insomnia as well.. sounds like the best of both meds for you..
> >
>
> Doxepin is an extremely weak serotonin reuptake inhibitor but it is powerful at blocking histamine, the only thing stronger is Mirtazapine. Efexor is a weak norepinephrine reuptake inhibitor. Benzos don't make me drowsy but Mirtazapine certainly does.
>
> Cheers,
> Panda.
>not sure what you're correcting from my post, I believe my exact words were that doxepin is a "very potent antihistamine."
mirtazapine isn't nearly as strong an antihistamine as doxepin, doxepin binds very strongly to both histamine receptors, while mirtazapine only has a weak action at the h1 receptor.
the antagonism at 5-HT2/3 serotonin receptors is probably more responsibile for the drowsiness you experience from remeron.. and by no means is effexor a "weak" NE reuptake inhibitor, although it does like the serotonin transporter a bit more.. you are right however if you were just pointing out that, comparitively, doxepin has a higher affinity for the NE trans, and effexor has a higher affinity for the SERT rather than the NET.
scott
Posted by Sad Panda on January 29, 2004, at 1:09:59
In reply to doxepin, remeron, whatever.. thread is off-topic » Sad Panda, posted by scott-d-o on January 29, 2004, at 0:43:09
> > > how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does, however it is also a very potent antihistamine (sedative), and also has alpha-1 antagonism (which I assumed was the reason seroquel helps your insomnia.) In fact, the only reason effexor was supposed to be an improvement over older tricyclics, such as doxepin, is because effexor doesn't have the sedative and anticholinergic action of TCA's. doxepin also happens to be a 5-HT2a antagonist, again like seroquel, and this should help with the insomnia as well.. sounds like the best of both meds for you..
> > >
> >
> > Doxepin is an extremely weak serotonin reuptake inhibitor but it is powerful at blocking histamine, the only thing stronger is Mirtazapine. Efexor is a weak norepinephrine reuptake inhibitor. Benzos don't make me drowsy but Mirtazapine certainly does.
> >
> > Cheers,
> > Panda.
> >
>
> not sure what you're correcting from my post, I believe my exact words were that doxepin is a "very potent antihistamine."
>
> mirtazapine isn't nearly as strong an antihistamine as doxepin, doxepin binds very strongly to both histamine receptors, while mirtazapine only has a weak action at the h1 receptor.
>
> the antagonism at 5-HT2/3 serotonin receptors is probably more responsibile for the drowsiness you experience from remeron.. and by no means is effexor a "weak" NE reuptake inhibitor, although it does like the serotonin transporter a bit more.. you are right however if you were just pointing out that, comparitively, doxepin has a higher affinity for the NE trans, and effexor has a higher affinity for the SERT rather than the NET.
>
> scottScott, I think if you do some research you will find that Mirtazapine is stronger than Doxepin at blocking H1. 5-HT2a is similar for both while the 5-HT3 abilites of Mirtazapine is great for reversing SSRI & Efexor induced nausea.
>>>how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does
These 2 meds are nearly opposite to each other. Efexor main effect is on Serotonin while Doxepin has practically no effect on Serotonin.
Karen, if you haven't tried either Mirtazapine or Doxepin for sleep then I think they are worth a try.
Cheers,
Panda.
Posted by scott-d-o on January 29, 2004, at 4:02:57
In reply to Re: doxepin, remeron, whatever.. thread is off-topic » scott-d-o, posted by Sad Panda on January 29, 2004, at 1:09:59
> > Scott, I think if you do some research you will find that Mirtazapine is stronger than Doxepin at blocking H1. 5-HT2a is similar for both while the 5-HT3 abilites of Mirtazapine is great for reversing SSRI & Efexor induced nausea.
>
> >>>how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does
>
> These 2 meds are nearly opposite to each other. Efexor main effect is on Serotonin while Doxepin has practically no effect on Serotonin.
>
> Karen, if you haven't tried either Mirtazapine or Doxepin for sleep then I think they are worth a try.
>
>
> Cheers,
> Panda.
>
>Umn, they are not opposite to each other at all. they both inhibit the reuptake of serotonin and norepinephrine, sounds similar to me. so effexor has a little higher affinity for the serotonin transporter relative to norepinephrine than does doxepin, so what?
I don't kno where u get your info but doxepin was the most powerful antihistamine of the tricyclics and remeron is a second-generation AD that is a very weak antihistamine. here's some abstracts off medline.. note the words *very weak* in the first abstract and *weaker* in the second abstract in regard to mirtazapine's antihistaminic properties..
--------------------------------------------
Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression.Fawcett J, Barkin RL.
Department of Psychiatry, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612, USA.
Mirtazapine is a presynaptic alpha-2 antagonist that has dual action by increasing noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors because mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist. In addition, mirtazapine has only a weak affinity for 5-HT1 receptors and has very weak muscarinic anticholinergic and histamine (H1) antagonist properties.
----------------------------------------------[Antidepressives of the 3rd, 4th and 5th generation]
[Article in Czech]
Svestka J.
Psychiatricka klinika Lekarske fakulty MU, Brno.
Antidepressants are classified into five generations. Preparations of the first generation affect various neurotransmitter systems and are therefore associated with many undesirable effects (e.g. tricyclic antidepressants, maprotiline). The second generation of antidepressants is already devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker (e.g. mianserine, mirtazapine, trazodone).
Posted by Sad Panda on January 29, 2004, at 7:44:35
In reply to Re: doxepin, remeron, whatever.. thread is off-top » Sad Panda, posted by scott-d-o on January 29, 2004, at 4:02:57
> > > Scott, I think if you do some research you will find that Mirtazapine is stronger than Doxepin at blocking H1. 5-HT2a is similar for both while the 5-HT3 abilites of Mirtazapine is great for reversing SSRI & Efexor induced nausea.
> >
> > >>>how about switching the effexor to the old tricyclic doxepin.. it blocks reuptake of serotonin and norepinephrine, like effexor does
> >
> > These 2 meds are nearly opposite to each other. Efexor main effect is on Serotonin while Doxepin has practically no effect on Serotonin.
> >
> > Karen, if you haven't tried either Mirtazapine or Doxepin for sleep then I think they are worth a try.
> >
> >
> > Cheers,
> > Panda.
> >
> >
>
> Umn, they are not opposite to each other at all. they both inhibit the reuptake of serotonin and norepinephrine, sounds similar to me. so effexor has a little higher affinity for the serotonin transporter relative to norepinephrine than does doxepin, so what?
>
> I don't kno where u get your info but doxepin was the most powerful antihistamine of the tricyclics and remeron is a second-generation AD that is a very weak antihistamine. here's some abstracts off medline.. note the words *very weak* in the first abstract and *weaker* in the second abstract in regard to mirtazapine's antihistaminic properties..
>
> --------------------------------------------
>
>
> Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression.
>
> Fawcett J, Barkin RL.
>
> Department of Psychiatry, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612, USA.
>
> Mirtazapine is a presynaptic alpha-2 antagonist that has dual action by increasing noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors because mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist. In addition, mirtazapine has only a weak affinity for 5-HT1 receptors and has very weak muscarinic anticholinergic and histamine (H1) antagonist properties.
>
>
> ----------------------------------------------
>
>
>
> [Antidepressives of the 3rd, 4th and 5th generation]
>
> [Article in Czech]
>
> Svestka J.
>
> Psychiatricka klinika Lekarske fakulty MU, Brno.
>
> Antidepressants are classified into five generations. Preparations of the first generation affect various neurotransmitter systems and are therefore associated with many undesirable effects (e.g. tricyclic antidepressants, maprotiline). The second generation of antidepressants is already devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker (e.g. mianserine, mirtazapine, trazodone).
>Scott, I am familiar with the first abstract, it says
1. Mirtazapine is a presynaptic alpha-2 antagonist
2. Mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist
3. Mirtazapine has a weak affinity for 5-HT1 receptors
4. Mirtazapine is a very weak muscarinic anticholinergic antagonist
5. Mirtazapine is a histamine (H1) antagonistIt DOES NOT say weak or very weak histamine anatgonist.
The second abstract is incorrect. Mianserin is a potent anti-histamine too as it is the older brother of Mirtazapine.
I will post some more about it when I find it again on the web.
Cheers,
Panda.
Posted by katrina1 on January 29, 2004, at 12:02:47
In reply to Re: doxepin, remeron, whatever.. thread is off-top » Sad Panda, posted by scott-d-o on January 29, 2004, at 4:02:57
Just my two cents: I take addrall and I take low dose zyprexa (2.5mg) & might add abilify (2.5 mg, tops), but boy do I get the stimulant resistance and low blood pressure thing...I could take 60 mgs. of adderall and still sleep like a cat at night. It's like the first 20mgs. does nothing. I've seen Dr. Dubovosky-he's insightful...
I'm gonna buy some magnesium...we were hoping the AP's could help with my profile that looks like the neg. side of scizophrenia (I'm not)??? It's such a crap shoot sometimes, I've never gotten remission-I'm even on subutex (partial opiate)...it helps take the teeth out of depression.
Posted by scott-d-o on January 29, 2004, at 14:44:47
In reply to Re: doxepin, remeron, whatever.. thread is off-top » scott-d-o, posted by Sad Panda on January 29, 2004, at 7:44:35
>
> Scott, I am familiar with the first abstract, it says
> 1. Mirtazapine is a presynaptic alpha-2 antagonist
> 2. Mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist
> 3. Mirtazapine has a weak affinity for 5-HT1 receptors
> 4. Mirtazapine is a very weak muscarinic anticholinergic antagonist
> 5. Mirtazapine is a histamine (H1) antagonist
>
> It DOES NOT say weak or very weak histamine anatgonist.
>
> The second abstract is incorrect. Mianserin is a potent anti-histamine too as it is the older brother of Mirtazapine.
>
> I will post some more about it when I find it again on the web.
>
> Cheers,
> Panda.
>you're prob right about that abstract, like most abstracts, it is poorly worded.;-) I think doxepin has only slightly higher affinity than mirtazapine for h1 (I think mirtazapine binds with a pKi value around 9 and doxepin has a pKi around 10), but doxepin is not as selective and has much stronger h2 antagonism, so I think overall it is much more antihistaminic.. but then again I'm already sick of talking about it.. i guess a lot of it depends on where u get your data from also.
scott
Posted by scott-d-o on January 29, 2004, at 15:01:24
In reply to Re: doxepin, remeron, whatever.. thread is off-top, posted by katrina1 on January 29, 2004, at 12:02:47
> Just my two cents: I take addrall and I take low dose zyprexa (2.5mg) & might add abilify (2.5 mg, tops), but boy do I get the stimulant resistance and low blood pressure thing...I could take 60 mgs. of adderall and still sleep like a cat at night. It's like the first 20mgs. does nothing. I've seen Dr. Dubovosky-he's insightful...
> I'm gonna buy some magnesium...we were hoping the AP's could help with my profile that looks like the neg. side of scizophrenia (I'm not)??? It's such a crap shoot sometimes, I've never gotten remission-I'm even on subutex (partial opiate)...it helps take the teeth out of depression.
maybe it's time to take a little break from adderall and see if that helps.. the drug they use in cough syrups, dextromethorphan, is also a NMDA antagonist.. some people use it recreationally cause it feels like ketamine or PCP at high doses (disassociative).. normally you can only get it by itself in the disgusting syrups but I stumbled upon new "Robitussin CoughGels" at the pharmacy the other day.. not sure how they got it fda approved considering abuse potential.. liquid gelcaps with Dextromethmorphan 15mg as the only active ingredient.. I may have to try them out ;-) Not sure if it will do anything for my stim tolerance, which was so bad some years ago that at one point I fell asleep like 15 mins after doing 100mg of pure meth..
Posted by Sad Panda on January 31, 2004, at 9:12:21
In reply to Re: doxepin, remeron, whatever.. thread is off-top, posted by scott-d-o on January 29, 2004, at 14:44:47
>
> you're prob right about that abstract, like most abstracts, it is poorly worded.;-) I think doxepin has only slightly higher affinity than mirtazapine for h1 (I think mirtazapine binds with a pKi value around 9 and doxepin has a pKi around 10), but doxepin is not as selective and has much stronger h2 antagonism, so I think overall it is much more antihistaminic.. but then again I'm already sick of talking about it.. i guess a lot of it depends on where u get your data from also.
>
> scottHi Scott,
I'm not sick of talking about it yet :)
I don't know how strong Mirtazapine is at H2 antagonism, AFAIK H2 antagonism controls acid in the stomach, I'm only interested in H1 because of what it does for sleep. Stomach juice talk would be getting way off topic. ;)
Here is an article that says Mirtazapine is a potent H1 blocker & references the exact same paper by Fawcett J & Barkin RL. You can read it all at http://www.medscape.com/viewarticle/410902_print Here is a snip:
"Mirtazapine is also a potent antagonist at central and peripheral histamine (H1) receptors, which may explain its sedative effects. Unlike maprotiline, mirtazapine has little activity at muscarinic or peripheral a1adrenergic receptors.[1-4]
References
1. Holm KJ, Markham A. Mirtazapine: a review of its use in major depression. Drugs 1999;57:607-31.
2. Tetracyclic antidepressants. In: Olin BR, ed. Drug Facts and Comparisons. St. Louis: Facts and Comparisons. 2000:900-3.
3. Remeron® product information. Organon. April 1996.
4. Fawcett J, Barkin RL. A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry 1998;59:123-7."
Here is another snip from: http://www.psychotropical.com/notes/637.html"Mirtazapine (6-azamianserin) was, for good reasons***, first tested as a sedative around 1982 - 1985. It is of significance and interest to note one of the earliest papers in 1985; the title introduced it as a "new antidepressant" even though there was no evidence at that time of any antidepressant efficacy in humans. The paper actually investigated only the sedative effect. There is nothing like establishing the idea before the facts.
***good reasons:-- we now know it is the most potent anti-histamine on the world market, eclipsing even doxepin.""Like mianserin, mirtazapine is a potent H1 blocker (anti-histamine) and thus inevitably causes sedation and weight gain; indeed H1 blockade is the most potent property of both these drugs, mirtazapine being even more potent than doxepin."
"It is claimed to give relief from the ubiquitous anxiety symptoms of depression better and sooner than SSRIs, this is convincingly accounted for by its extremely potent sedative (and therefore anxiolytic) anti-histamine action. Indeed the first trial in 1985 was as a "pre-med" comparing its sedative / anxiolytic properties to diazepam. Mirtazapine 15 mg was equal to diazepam 10 mg."
Some receptor affinites from: http://www.psychotropical.com/notes/253.html
"Potency for blocking H1 and (A1) post-synaptic receptors
H1 blockade relates to a) sedation, and b) weight gain
A1 relates to postural hypotension and reflex tachycardiamirtazapine 0.12 (-)
Doxepin 0.2 (23)
Mianserin 0.4 (34)
Amitriptyline 1 (24)
Dothiepin 3.6 (450)
Nortriptyline 6.3 (55)
Clomipramine 15 (50)
Imipramine 37 (32)
Desipramine 60 (100)
Nefazodone 24000 (48)
trazodone 1100 (42)
Sertraline 24000 (380)
venlafaxine 35000 (35000)
Doxepin and mirtazapine are the most potent antihistamines on the world market, indeed, because of this doxepin has been marketed as a topical skin preparation."Mirtazapine is getting close to 2x stonger than Doxepin. People I have spoken with who have taken both say 15mg of Mirtazapine is about as potent as 25mg of Doxepin for sleep.
Here is another snip from http://www.biopsychiatry.com/
"Mirtazapine (Remeron) is a structural analogue of the off-patent mianserin (Bolvidon). It is a comparatively new drug - a so-called NaSSA. By blocking the inhibitory presynaptic alpha2 adrenergic autoreceptors and stimulating only the 5-HT1A receptors, mirtazapine enhances noradrenaline and serotonin release while also blocking two specific (5-HT2 and 5-HT3) serotonin receptors implicated in dark moods and anxiety. By contrast, stimulation of the 5-HT2A receptors accounts for the initial anxiety, insomnia and sexual dysfunction sometimes reported with the SSRIs; stimulation of the 5-HT3 receptors causes nausea. Unfortunately, mirtazapine is a potent blocker of the histamine H1 receptors too. So it tends to have a somewhat sedative effect. This profile may be good for agitated depressives and insomniacs."
Let me know if you want me to find some more info for you.Cheers,
Panda.
Posted by scott-d-o on February 1, 2004, at 1:31:33
In reply to Doxepin v Mirtazapine » scott-d-o, posted by Sad Panda on January 31, 2004, at 9:12:21
wow, you must have a lot of time on your hands :-)
keep in mind panda, doxepin is usually prescribed anywhere from 75mg all the way up to a max of 300mg, where as remeron has a *max* dose of 75mg.
according to your data, at the max dose that a pdoc will prescribe, u will get an overall sedative effect that is over 2 times as powerful from the doxepin than the remeron.
so if u have a h1 antagonism fetish, u best go ask your pdoc for doxepin.. ;p
anyhow, thanks for the info..
scott
Posted by Karen Moore on February 2, 2004, at 0:25:06
In reply to Re: Doxepin v Mirtazapine » Sad Panda, posted by scott-d-o on February 1, 2004, at 1:31:33
Hi folks,
Thanks for the in depth discussion here, I'm thinking that I've become a bit of a pharmacology nerd these days, I never thought I'd find these things so amusing and engrossing. But when it looks like there might be some solutions in this morass of information it seems like it might actually be worth spending all of this time trying to figure it all out! If it means there might be a possibility of "taming the beast", why not!
Funny thing is I tried Mirtazapine a few months ago, for exactly some of the reasons you two were debating. But on day three of a very low dose I ended up in the ER on oxygen and a saline drip! Still don't know what the hell that was...
Thanks,
KM
Posted by Karen Moore on February 2, 2004, at 0:40:54
In reply to Re: doxepin, remeron, whatever.. thread is off-top » katrina1, posted by scott-d-o on January 29, 2004, at 15:01:24
Hey Scott,
Yup, went off the Adderall for a while. That's partially why it took me so long to respond to your note. I was only on 10mg but my brain shuts down so violently it's just amazing (and a bit demoralizing).
As for NMDA antagonists, I'm also curious. I talked to Stephen Dubovsky a few days ago about a variety alternatives and included that in my list(his pets are thyroid hormone and Ca channel blockers). He mentioned using an NMDA antagonist called Memantine, but cautioned me (the bipolar "me") that it might just destabilize me more. Nonetheless, I got the feeling he had atleast some good results with TR patients.
I admit remembering one desperate evening of gulping Robitussin. I remember a vague high, but that was years ago, before I had any clue what bipolar was. Or NMDA antagonists, for that matter! Let me know if you try the gel caps...
KM
Go forward in 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.