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Dr. Bob is Robert Hsiung, MD,
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Posted by SLS on February 24, 2012, at 14:31:48
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by ed_uk2010 on February 24, 2012, at 13:33:07
> > Eddy, does Scott's response to prazosin surprise you?
>
> It did initially Sigi, but less so now. I read a bit about how it might augment noradrenergic ADs.
>Ed, if it isn't too big an imposition, could you post a link to anything you find regarding prazosin. I would really like to see the stuff you have found already regarding augmentation of noradrenergic ADs.
Thanks.
If you don't have the time or energy, that's okay.
- Scott
Posted by ed_uk2010 on February 24, 2012, at 16:49:55
In reply to Re: Adding Parnate and prazosin. » ed_uk2010, posted by SLS on February 24, 2012, at 14:31:48
> > > Eddy, does Scott's response to prazosin surprise you?
> >
> > It did initially Sigi, but less so now. I read a bit about how it might augment noradrenergic ADs.
> >
>
> Ed, if it isn't too big an imposition, could you post a link to anything you find regarding prazosin. I would really like to see the stuff you have found already regarding augmentation of noradrenergic ADs.
>
> Thanks.
>
> If you don't have the time or energy, that's okay.
>
>
> - ScottHi Scott,
It was only an animal study - the one that Franz posted a few days ago. Prazosin seemed to augment imipramine and it was hypothesised than it might augment noradrenergic ADs.
Posted by sigismund on February 24, 2012, at 17:07:05
In reply to Re: Adding Parnate and prazosin. » SLS, posted by ed_uk2010 on February 24, 2012, at 16:49:55
> it was hypothesised than it might augment noradrenergic ADs.
Because it acted in a similar way or an opposite way or because it mixed well (and so on and so forth)?
In my simple way I was thinking about how Scott mainlt takes ADs that increase dopamine and NE, and since prazosin blocks NE (this is ridiculous, but anyway) it might be that which helped.
Perhaps someone can amplify.
Posted by Phillipa on February 24, 2012, at 18:19:10
In reply to Re: Adding Parnate and prazosin., posted by sigismund on February 24, 2012, at 17:07:05
I thought the same thing about the norepineprine when googled the med also saw that 40 was was used in hypertension.
Posted by ed_uk2010 on February 25, 2012, at 2:43:14
In reply to Re: Adding Parnate and prazosin., posted by sigismund on February 24, 2012, at 17:07:05
> > it was hypothesised than it might augment noradrenergic ADs.
>
> Because it acted in a similar way or an opposite way or because it mixed well (and so on and so forth)?Prazosin does block the effects at NE, but only at one type of receptor (alpha-1 group). It doesn't block the effects of NE at any other type of receptor. Perhaps it could 'augment' noradrenergic ADs such as nortriptyline by allowing the increased levels of NE to bind to other receptors but not alpha-1?
TCAs also block alpha-1 receptors but like Scott said, they are not very potent at the alpha-1b subtype, which may be the relevant receptor in the brain. TCAs are more active at alpha-1a, which is why they tend to reduce standing BP.
Interestingly, reboxetine, an NRI which does not block alpha-1 receptors at all, does not appear to be such a reliable AD as nortriptyline. Reboxetine is highly selective for the NE transporter whereas nortriptyline also binds to a variety of other receptors. Lack of alpha-1 blockade also means that reboxetine can make it difficult to urinate. This is less of a problem with nortriptyline because it blocks alpha-1a receptors in the prostate and urinary tract.
Posted by SLS on March 2, 2012, at 16:31:25
In reply to Adding Parnate and prazosin., posted by SLS on December 29, 2011, at 6:55:56
Just a quick update:
I am still gradually improving. It never happens fast enough, though. However I am so very grateful for any improvement at all. I don't always see a difference day to day, but I can see a difference week to week. The trend is definitely towards continued improvement. I will have a few days in a row when I feel less well. I lose ground during these times, and it is a little frustrating if not scarey to feel worse. I guess this is the "saw-tooth" effect that Robert Post would tell his patients about. Two steps up and one step down.
Currently:
Parnate 80 mg
nortriptyline 150 mg
Lamictal 200 mg
Abilify 10 mg
lithium 300 mg
prazosin 6 mgYay for polypharmacy!
- Scott
Posted by Phillipa on March 2, 2012, at 21:07:03
In reply to Re: Adding Parnate and prazosin., posted by SLS on March 2, 2012, at 16:31:25
Scott I'm impressed for sure. In all the years been here this is the best. And I need to remember two steps forward and back myself. I must say you are the most courageous and positive person and always with hope. And this time is paying off. You finally got a winning combo!!! Phillipa
Posted by Beckett on March 3, 2012, at 14:55:22
In reply to Re: Adding Parnate and prazosin., posted by SLS on March 2, 2012, at 16:31:25
Good news. I was wondering how it was going. Glad to hear it.
:-)
Posted by sigismund on March 3, 2012, at 17:18:59
In reply to Re: Adding Parnate and prazosin., posted by SLS on March 2, 2012, at 16:31:25
>Yay for polypharmacy!
Maybe.
Before the prazosin polypharmacy was not so good, was it?
A pity you could have not tried it first.
I will see if my doc will write a script for it.
Posted by sigismund on March 3, 2012, at 20:29:50
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on March 3, 2012, at 17:18:59
By which I mean 15% for whatever effort it was back then made me feel I would rather (I don't know) watch TV or stare at the wall.
All I can recall is it was Parnate, probably nortriptylline and a couple of others.
Posted by SLS on March 3, 2012, at 21:26:21
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on March 3, 2012, at 17:18:59
> >Yay for polypharmacy!
>
> Maybe.
>
> Before the prazosin polypharmacy was not so good, was it?Is that question meant to relate to my condition in particular of to those of everyone else?
Polypharmacy has certainly served me better than all of the monotherapeutic treatments I have tried over the last 30 years.
I recently tried to discontinue Abilify. I relapsed after two weeks. Fortunately, I was able to recapture a response within two days.
Is there something inherently unscientific about using more than one drug at a time to treat an illness? I really don't understand on what basis polypharmacy should be discouraged. CV diseases often require 3 drugs to manage hemodynamics and cardiac conduction. Is there something about the fundamental nature of mental illness that dictates that a single pharmacological action always be sufficient to treat it? Unfortunately, it would seem that the converse is true. Most of the drugs we currently use possess more than one pharmacological property. Perhaps a single biological target will one day emerge as the only site necessary to modulate. But that is not today.
Ed_Uk2010 mentioned that prazosin might work in conjunction with a norandrenergic drug to treat depression. I don't know what condition or symptoms you are trying to treat, though. I have always been unclear on this. It won't hurt to try prazosin as monotherapy, but I wouldn't forever cast the drug aside if it doesn't help treat MDD or BD.
- Scott
Posted by sigismund on March 3, 2012, at 21:42:27
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on March 3, 2012, at 21:26:21
>Is that question meant to relate to my condition in particular of to those of everyone else?
No, just you.
>Polypharmacy has certainly served me better than all of the monotherapeutic treatments I have tried over the last 30 years.
Yes, but it isn't saying much if it is only 15% hey?
>I recently tried to discontinue Abilify. I relapsed after two weeks. Fortunately, I was able to recapture a response within two days.
I recall you saying that.
>Is there something inherently unscientific about using more than one drug at a time to treat an illness?
No, not unscientific.
>I really don't understand on what basis polypharmacy should be discouraged.
The inadequacy of our knowledge, our ability to get it wrong, the shortcomings of the drugs?
>Is there something about the fundamental nature of mental illness that dictates that a single pharmacological action always be sufficient to treat it? Unfortunately, it would seem that the converse is true.
But how many years had you been on treatment to reach 15% 3 or 4 years ago? You get what I am trying to say? I hope you don't get me wrong. Treatment should have a better outcome than benign neglect
>Ed_Uk2010 mentioned that prazosin might work in conjunction with a norandrenergic drug to treat depression. I don't know what condition or symptoms you are trying to treat, though. I have always been unclear on this. It won't hurt to try prazosin as monotherapy, but I wouldn't forever cast the drug aside if it doesn't help treat MDD or BD.If it could help with sleep I would be happy. People who take it sleep longer. I don't sleep deeply enough to dream or have nightmares. PTSD? Could be.
Please take this the right way. I am just interested.
Posted by papillon2 on March 3, 2012, at 23:07:48
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on March 3, 2012, at 21:42:27
I'd take 15% over nothing. 15% could be the difference between life and death.
Posted by sigismund on March 3, 2012, at 23:44:12
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by papillon2 on March 3, 2012, at 23:07:48
>I'd take 15% over nothing. 15% could be the difference between life and death.
Yes. But you might wish for more after such a lot of effort.
Still, you should see me with all the stuff I take. There is a rationale. It's not always effective, AFAIK. There's a lot of polypharmacy in it (especially with TCM). When people question it I become quite irritated.
As for Scott's question: what is my problem? Well, you won't get a psych diagnosis from me. And I don't know. Part of me has always hated being alive. Now it is almost over. That's it, really. I can cope.
Drugs that make me feel better rather than worse would interest me. Can't get them.
Posted by ed_uk2010 on March 4, 2012, at 3:45:06
In reply to Re: Adding Parnate and prazosin., posted by sigismund on March 3, 2012, at 23:44:12
Hi Sigi,
>But you might wish for more after such a lot of effort.
You certainly would, but it doesn't always work out that way.
>Part of me has always hated being alive. Now it is almost over.
Nearly over? You're not even old!
>Drugs that make me feel better rather than worse would interest me.
The problem with drugs that make you feel better straight away is that it's rarely long before they make things worse.
Anyway, I suppose you'll just be trying a small dose of prazosin at night? You could try 0.5mg before bed, increasing to 1mg then 2mg if necessary.
Posted by SLS on March 4, 2012, at 6:10:33
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on March 3, 2012, at 21:42:27
Hi Sigi.
15% is better than zero, I'm sure we could both agree. It allowed me to live independently instead of with my parents or a supportive residence. That 15% was primarily the product of combining nortriptyline and Lamictal. Everything else that I took at any one time was for the purpose of experimentation rather than as a treatment to commit to. Bringing in Abilify helped a bit - enough for me to choose to remain on it while searching for other things. Adding an MAOI to a TCA is what got me well the first time in 1987. So adding Nardil or Parnate to the nortriptyline was a no brainer unless I wanted to try something novel. For me, novel meant anything different than I had thusfar tried. For instance, I tried Lexapro. It didn't help. However, Celexa remains novel to me as my brain has never seen it before, despite the molecular similarities. Anyway, I brought lithium on board for its neurogenesis and neuroprotection. Unexpectedly, in combination with Parnate, it helped to smooth out "mood drift". It helped stabilize me and enhanced the antidepressant effects to the other drugs I was taking. That's five drugs. I added prazosin. That's six.
When I remove ANY ONE of the drugs I take, I relapse.
This logical progression of determining drug treatment is more than just a haphazard throwing of enough sh*t against the wall to see how much would stick. I hope you can understand why I felt somewhat insulted by your words. In a way, they were an insult to my intelligence and that of my doctors as well. I guess that is really my problem and not yours.
My sleep is significantly smoother for having added prazosin. I experience fewer awakenings. Experiments have shown that prazosin and clonidine each increase the spectral power of delta-wave (slow-wave) sleep as seen on an EEG. This should produce a greater period of time spent in deep sleep. I hope prazosin helps you.
- Scott
Posted by SLS on March 4, 2012, at 6:15:02
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by ed_uk2010 on March 4, 2012, at 3:45:06
> Hi Sigi,
>
> >But you might wish for more after such a lot of effort.
>
> You certainly would, but it doesn't always work out that way.
>
> >Part of me has always hated being alive. Now it is almost over.
>
> Nearly over? You're not even old!
>
> >Drugs that make me feel better rather than worse would interest me.
>
> The problem with drugs that make you feel better straight away is that it's rarely long before they make things worse.
>
> Anyway, I suppose you'll just be trying a small dose of prazosin at night? You could try 0.5mg before bed, increasing to 1mg then 2mg if necessary.You should really take prazosin 3 times a day if you want to glean an anxiolytic effect during the day. I started at 1 mg t.i.d. Dizziness was a problem at first, but it mitigated within a week. I am now taking 6 mg/day. It is a very clean drug.
- Scott
Posted by SLS on March 4, 2012, at 6:40:19
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by ed_uk2010 on March 4, 2012, at 3:45:06
Hi Ed.
I checked out a few studies on Google.
You are right. Some people respond well to dosages as low as 1 mg h.s. I wouldn't have thought so. Some people go to 6 mg and higher, though.
I don't know how you do it. I really don't.
You are amazing. I don't know how you can keep all of this important information and wonderful insights in your head.
- Scott
Posted by SLS on March 4, 2012, at 7:24:29
In reply to Re: Adding Parnate and prazosin., posted by sigismund on March 3, 2012, at 23:44:12
> My sleep is significantly smoother for having added prazosin. I experience fewer awakenings. Experiments have shown that prazosin and clonidine each increase the spectral power of delta-wave (slow-wave) sleep as seen on an EEG. This should produce a greater period of time spent in deep sleep. I hope prazosin helps you.
Speaking of polypharmacy, if prazosin helps, but is not wholly adequate, you can add clonidine to augment the prazosin. I don't know if anyone has tried this for PTSD, but it makes sense to me. If taken at night along with prazosin, any tendency towards dizziness might dissipate by morning. I'm not sure. Both clonidine and prazosin are used to treat hypertension. I don't know if the two drugs are synergistic with respect to lowering blood pressure. By the way, at 6 mg/day of prazosin, my blood pressure while seated is normal (120/76). I experience some mild to moderate orthostatic hypotension. Note that I am taking Parnate at the same time, which, itself, causes dizziness.
Topamax is also good for treating PTSD, just in case you are thinking along those lines. I don't know if it affects sleep architecture at all.
- Scott
Posted by ed_uk2010 on March 4, 2012, at 11:04:27
In reply to Re: Adding Parnate and prazosin. » ed_uk2010, posted by SLS on March 4, 2012, at 6:40:19
Very kind of you Scott.
I was thinking that Sigi does not like anything which makes him feel 'off' during the day. Taking prazosin as a single dose at night might improve sleep whilst avoiding daytime adverse effects. Disturbed sleep seems to be one of Sigi's main problems.
Posted by sigismund on March 4, 2012, at 13:18:34
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on March 4, 2012, at 6:10:33
>. I hope you can understand why I felt somewhat insulted by your words.
I guess so.
>In a way, they were an insult to my intelligence and that of my doctors as well.
I didn't mean it like that.
>I guess that is really my problem and not yours.
No, it's my problem as well. I certainly didn't mean to insult you. I'm sorry.
> This should produce a greater period of time spent in deep sleep. I hope prazosin helps you.
Thanks
Posted by SLS on March 5, 2012, at 6:36:43
In reply to Re: Adding Parnate and prazosin., posted by sigismund on March 4, 2012, at 13:18:34
Just to let you know, Some people with PTSD go as high as 12 mg/day with prazosin. The maximum recommended dosage is 20 mg, although some people go up to 40 mg. There is a lot of room to work with. Like I said, prazosin is a clean drug for me. At 6 mg/day, I experience no alterations in mental function. There is no "brain-fog" or sense of feeling "drugged". For the first 1 - 2 weeks, you might feel some fatigue and tiredness along with dizziness. However, these things might not surface if you start at 1 mg at night.
I understand that sleep is a an issue with you, and you can limit your intake of prazosin to a night dose. However, if anxiety and depression are problems during the day, you could take prazosin three times a day.
My only complaint is that prazosin reduces my sex drive. I was not happy about this, as depression all but abolishes it. I'm hoping that I recover some of it as I improve. I do experience occassional dizziness, but I am taking Parnate, which is known to do this on its own.
Prazosin has a short half-life (2-3 hours). That's why it is recommended to dose it two or three times a day to treat hypertension or daytime PTSD. If you should want to stop taking prazosin, it will take a day or two for it to completely leave your system.
- Scott
Posted by sigismund on March 9, 2012, at 16:14:22
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on March 5, 2012, at 6:36:43
>My only complaint is that prazosin reduces my sex drive.
Well I read that it can induce priapism, a mild dose of which would have been most welcome, but I did not experience this myself.
My sleep was greatly improved by 0.5mg. When I woke I woke later and without the usual feeling. I took some herbs and went back to sleep.
Which is good. I am suspicious of gabapentin and would prefer not to take it. That may not be why my PSA is so high but I am not keen to get prostate cancer quite yet.
Posted by SLS on March 11, 2012, at 7:48:16
In reply to Re: Adding Parnate and prazosin. » SLS, posted by ed_uk2010 on March 4, 2012, at 11:04:27
Hi Ed.
I found this. I believe it lends evidence to my pet theory that the neural hyperactivity of the sgACC seen in depression is reduced by prazosin via NE alpha-1b receptor blockade.
http://www.ncbi.nlm.nih.gov/pubmed/18704022
CNS Spectr. 2008 Aug;13(8):663-81.
The subgenual anterior cingulate cortex in mood disorders.
Drevets WC, Savitz J, Trimble M.
SourceSection on Neuroimaging in Mood and Anxiety Disorders, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA. drevetsw@mail.nih.gov
AbstractThe anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.
PMID:
18704022
[PubMed - indexed for MEDLINE]
PMCID:
PMC2729429Free PMC Article
Posted by ed_uk2010 on March 11, 2012, at 13:36:41
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on March 9, 2012, at 16:14:22
>My sleep was greatly improved by 0.5mg.
Excellent!
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