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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by SLS on October 19, 2001, at 16:44:56
Hi Doctor.
I suffer from TRD chronic bipolar depression. Several medications make me feel significantly worse, including mirtazepine and idazoxan. I recently attempted to add mirtazepine to an ongoing trial of venlafaxine. Within 12 hours of my first 7.5mg dose, my condition began to deteriorate in a manner similar to those previous. Might this suggest trying a drug that exerts an opposite effect at NE alpha-2 receptors (e.g. clonidine) ?
I’m upset because the two drug combinations using venlafaxine that my doctor thought would have the best chances of working for me involve using drugs to which I have previously experienced negative reactions – bupropion and mirtazepine.
Thanks.
- Scott
Posted by petters on October 20, 2001, at 13:46:26
In reply to Nierenberg - Clonidine for bipolar depression?, posted by SLS on October 19, 2001, at 16:44:56
> Hi Doctor.
>
> I suffer from TRD chronic bipolar depression. Several medications make me feel significantly worse, including mirtazepine and idazoxan. I recently attempted to add mirtazepine to an ongoing trial of venlafaxine. Within 12 hours of my first 7.5mg dose, my condition began to deteriorate in a manner similar to those previous. Might this suggest trying a drug that exerts an opposite effect at NE alpha-2 receptors (e.g. clonidine) ?
>
> I’m upset because the two drug combinations using venlafaxine that my doctor thought would have the best chances of working for me involve using drugs to which I have previously experienced negative reactions – bupropion and mirtazepine.
>
> Thanks.
>
>
> - ScottHi Scott...
About Clonidine. I know some folks who find it usefull in social phobia. In bipolar depression...I have never heard anything about it-Sorry.
By the way What about the Citalopram add to your current regim? Ziprasidone didn´t do so mutch, for you state, it I remeber it right.
Have you ever tried yohimbin?
What about Amantadin? I know one doc who use it in TRD as an add on. Since it enhance the efect on the other meds.Sincerely
Petters
Posted by JohnX on October 22, 2001, at 23:25:53
In reply to Nierenberg - Clonidine for bipolar depression?, posted by SLS on October 19, 2001, at 16:44:56
Scott,
One thing is curious.
Bupropion is thought to inhibit firing of neurons
in the primary area affected by the alpha-2 receptors.
Remeron's alpha-2 antagonism increases firing.-john
> Hi Doctor.
>
> I suffer from TRD chronic bipolar depression. Several medications make me feel significantly worse, including mirtazepine and idazoxan. I recently attempted to add mirtazepine to an ongoing trial of venlafaxine. Within 12 hours of my first 7.5mg dose, my condition began to deteriorate in a manner similar to those previous. Might this suggest trying a drug that exerts an opposite effect at NE alpha-2 receptors (e.g. clonidine) ?
>
> I’m upset because the two drug combinations using venlafaxine that my doctor thought would have the best chances of working for me involve using drugs to which I have previously experienced negative reactions – bupropion and mirtazepine.
>
> Thanks.
>
>
> - Scott
Posted by Dr. Bob on October 23, 2001, at 11:12:22
In reply to Nierenberg - Clonidine for bipolar depression?, posted by SLS on October 19, 2001, at 16:44:56
From Dr. Nierenberg:
Bipolar depression is notoriously difficult to treat. You should probably seek out a consult of an expert in bipolar disorder in your area.
Posted by Mitch on October 23, 2001, at 12:43:15
In reply to Re: Nierenberg - Clonidine for bipolar depression?, posted by JohnX on October 22, 2001, at 23:25:53
> Scott,
>
> One thing is curious.
> Bupropion is thought to inhibit firing of neurons
> in the primary area affected by the alpha-2 receptors.
> Remeron's alpha-2 antagonism increases firing.
>
> -john
John, thanks for that info! That is VERY peculiar, because I get God-awful irritability on any meds that antagonize alpha-2 receptors. Strangely, when I am on Wellbutrin I am a little edgy and nauseous, BUT I never noticed any irritability or hypomania...Mitch
Posted by JohnX on October 23, 2001, at 19:20:50
In reply to Re: Nierenberg - Clonidine for bipolar depression? » JohnX, posted by Mitch on October 23, 2001, at 12:43:15
Heres what happens with things like Remeron,
in case you are interested. The alpha-2 antagonism
increases firing in an area of the brain predominately
associated with (nor)adrenaline and the flight,or,
fight mechanism. These nerve impulses actually
propogate to serotonin neurons and increasing
the firing rate of some serotonin neurons.
The Remeron has a property that blocks a particular
type of sertonin receptor (the 5ht-2 series), generally
associated with anxiety. The increased serotonin
firing hits the other receptors and a balance is
supposed to be achieved that reduces anxiety in the
net. But the two areas of the brain , the one with
the noradrenaline, and the one with serotonin projections
can reactly very differently amongst different people.
In particular people with stress disorders will probably
be hyperactive on the noradrenergic path and may
experience anxiety on remeron.Interestingly, Buspar attempts
to decrease the firing rate of those serotonin neurons
to decrease anxiety, but one of its side metabolites
is an alpha-2 antagonist. I think this could kill
some of its anti-anxiety potential, but at higher
doses for some people the alpha-2 antagonism is
actually an anti-depressant (probably for people
who aren't generally anxious too).-john
> > Scott,
> >
> > One thing is curious.
> > Bupropion is thought to inhibit firing of neurons
> > in the primary area affected by the alpha-2 receptors.
> > Remeron's alpha-2 antagonism increases firing.
> >
> > -john
>
>
> John, thanks for that info! That is VERY peculiar, because I get God-awful irritability on any meds that antagonize alpha-2 receptors. Strangely, when I am on Wellbutrin I am a little edgy and nauseous, BUT I never noticed any irritability or hypomania...
>
> Mitch
Posted by Mitch on October 23, 2001, at 23:41:11
In reply to Re: Nierenberg - Clonidine for bipolar depression? » Mitch, posted by JohnX on October 23, 2001, at 19:20:50
>
> Heres what happens with things like Remeron,
> in case you are interested. The alpha-2 antagonism
> increases firing in an area of the brain predominately
> associated with (nor)adrenaline and the flight,or,
> fight mechanism. These nerve impulses actually
> propogate to serotonin neurons and increasing
> the firing rate of some serotonin neurons.
> The Remeron has a property that blocks a particular
> type of sertonin receptor (the 5ht-2 series), generally
> associated with anxiety. The increased serotonin
> firing hits the other receptors and a balance is
> supposed to be achieved that reduces anxiety in the
> net. But the two areas of the brain , the one with
> the noradrenaline, and the one with serotonin projections
> can reactly very differently amongst different people.
> In particular people with stress disorders will probably
> be hyperactive on the noradrenergic path and may
> experience anxiety on remeron.
>
> Interestingly, Buspar attempts
> to decrease the firing rate of those serotonin neurons
> to decrease anxiety, but one of its side metabolites
> is an alpha-2 antagonist. I think this could kill
> some of its anti-anxiety potential, but at higher
> doses for some people the alpha-2 antagonism is
> actually an anti-depressant (probably for people
> who aren't generally anxious too).
>
> -john
Well, it obviously turns on the *fight* response! I really felt concerned about the level of hostility I was experiencing with Remeron (and with Buspar). I was having fantasies about all sorts of violence. It almost became obsessive. I had several heated arguments (over nothing, really) at work that made me worried about getting fired. I really felt I had little control over physically assaulting somebody. The only time that happened (in an impulsive manner) was when I was in my early 20's and my Dad jumped my ass about something relatively piddly and I sucker-punched him. At the time I was being prescribed Valium and it seemed to make me very hostile occasionally. The ADHD I was dx'ed with (a few years ago)seems to fits this paradoxical reaction pattern. The only meds that I have ever found truly dangerous (in grave lack of impulse control) were Remeron, Buspar, Valium.My question is do you have any more detail about how Wellbutrin *inhibits* NE firing with respect to the area of the brain you talked about earlier?
Mitch
Posted by JohnX on October 24, 2001, at 22:30:01
In reply to Re: Nierenberg - Clonidine for bipolar depression? » JohnX, posted by Mitch on October 23, 2001, at 23:41:11
Mitch,
I read a paper on the proposed mechanism of
Wellbutrin, but I don't remember the details
off the top of my head. I believe the partial jist of
it was that the norepinephrine reuptake inhibition
causes the alpha-2 adrenoreceptors to downregulate
long term. I.e. they become less sensitive to
repeated exposure to norepinephrine in the synapse,
thus boosting norepinephrine levels because of
the reuptake inhibition but curbing
the rate of firing of the neurons themselves due
to the alpha-2 downregulation.Alpha-2 antagonists have often been a test for
panic attacks which would indicate symtoms of
post traumatic stress disorder. Yohimbine is
a very powerful alpha-2 antagonists that will
oftern times induce a panic attack in many people.
For these types of patients alpha-2 agonists are helpfull. This
would include Clonidine (Catapres) and Guanfacine
(Tenex). These meds are generally anxiolytic
, sometimes used to detox from benzodiazepines and
also control hyperactivity disorders (as in ADHD),
and can be taken concurrently with other anti-depressants.If you are curious about any other meds effect in
the brain's locus coerulus (the area I am referring too),
I can probably dig it up.-john
> >
> > Heres what happens with things like Remeron,
> > in case you are interested. The alpha-2 antagonism
> > increases firing in an area of the brain predominately
> > associated with (nor)adrenaline and the flight,or,
> > fight mechanism. These nerve impulses actually
> > propogate to serotonin neurons and increasing
> > the firing rate of some serotonin neurons.
> > The Remeron has a property that blocks a particular
> > type of sertonin receptor (the 5ht-2 series), generally
> > associated with anxiety. The increased serotonin
> > firing hits the other receptors and a balance is
> > supposed to be achieved that reduces anxiety in the
> > net. But the two areas of the brain , the one with
> > the noradrenaline, and the one with serotonin projections
> > can reactly very differently amongst different people.
> > In particular people with stress disorders will probably
> > be hyperactive on the noradrenergic path and may
> > experience anxiety on remeron.
> >
> > Interestingly, Buspar attempts
> > to decrease the firing rate of those serotonin neurons
> > to decrease anxiety, but one of its side metabolites
> > is an alpha-2 antagonist. I think this could kill
> > some of its anti-anxiety potential, but at higher
> > doses for some people the alpha-2 antagonism is
> > actually an anti-depressant (probably for people
> > who aren't generally anxious too).
> >
> > -john
>
>
> Well, it obviously turns on the *fight* response! I really felt concerned about the level of hostility I was experiencing with Remeron (and with Buspar). I was having fantasies about all sorts of violence. It almost became obsessive. I had several heated arguments (over nothing, really) at work that made me worried about getting fired. I really felt I had little control over physically assaulting somebody. The only time that happened (in an impulsive manner) was when I was in my early 20's and my Dad jumped my ass about something relatively piddly and I sucker-punched him. At the time I was being prescribed Valium and it seemed to make me very hostile occasionally. The ADHD I was dx'ed with (a few years ago)seems to fits this paradoxical reaction pattern. The only meds that I have ever found truly dangerous (in grave lack of impulse control) were Remeron, Buspar, Valium.
>
> My question is do you have any more detail about how Wellbutrin *inhibits* NE firing with respect to the area of the brain you talked about earlier?
>
> Mitch
Posted by Mitch on October 25, 2001, at 0:01:27
In reply to Re: Nierenberg - Clonidine for bipolar depression? » Mitch, posted by JohnX on October 24, 2001, at 22:30:01
> Mitch,
>
> I read a paper on the proposed mechanism of
> Wellbutrin, but I don't remember the details
> off the top of my head. I believe the partial jist of
> it was that the norepinephrine **reuptake inhibition**
> causes the alpha-2 adrenoreceptors to downregulate
> long term. I.e. they become less sensitive to
> repeated exposure to norepinephrine in the synapse,
> thus boosting norepinephrine levels because of
> the reuptake inhibition but curbing
> the rate of firing of the neurons themselves due
> to the alpha-2 downregulation.Thanks John, that makes a lot of sense. I have taken Remeron at therapeutic dosages for several weeks (and Buspar for several weeks), and the hostility seemed to be exacerbated rather than reduced with time. So, this makes me wonder whether the alpha-2 receptors are indeed *downregulated* with mirtazipine and buspirone. It seems that receptor downregulation seems to be exclusively limited to agents that affect the *transporters*. Given that both these agents do not appear to block reuptake of NE as their primary mechanism. So, otherwords without downregulation of alpha-2 receptors the hostility should NOT resolve with time (seems to fit).
Mitch
This is the end of the thread.
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