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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 63 to 87 of 317. Go back in thread:
Posted by SLS on January 4, 2012, at 13:58:40
In reply to Re: Adding Parnate and prazosin., posted by sigismund on January 4, 2012, at 12:39:24
> Scott, can you explain simply how prazosin is different to clonidine.
Prazosin (Minipress) was originally developed as a treatment for hypertension. It was discovered by accident at a VA hospital that it was useful to treat PTSD.
Clonidine works the reverse of mirtazapine. It actually stimulates the NE alpha-2 receptors located on the presynaptic membrane. This, in effect, turns off the presynaptic NE neuron. Prazosin, on the other hand, blocks the postsynaptic NE alpha-1 receptor, thereby reducing NE activity.
Prazosin seems to be particularly successful at treating the disturbed sleep and nightmares associated with PTSD. I guess you are already aware that clonidine can produce or make worse depression. I find prazosin to be extremely clean. I noticed that I don't remember my dreams as much as I had before starting prazosin.
Good luck with whatever you decide to do.
- Scott
Posted by sigismund on January 4, 2012, at 14:14:09
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on January 4, 2012, at 13:58:40
> Prazosin, a highly lipophilic α1-adrenergic receptor blocker that is traditionally used to treat hypertension and benign prostatic hyperplasia,
Maybe two birds with one stone?
Posted by SLS on January 4, 2012, at 14:24:30
In reply to Re: Adding Parnate and prazosin., posted by sigismund on January 4, 2012, at 14:14:09
> > Prazosin, a highly lipophilic α1-adrenergic receptor blocker that is traditionally used to treat hypertension and benign prostatic hyperplasia,
>
> Maybe two birds with one stone?
Poor birds. :-(Is PTSD involved in your case?
If it were me, and PTSD were suspected, I would try the prazosin first. Also, Topamax is good for PTSD.
- Scott
Posted by Bob on January 4, 2012, at 14:50:31
In reply to Re: Adding Parnate and prazosin. » Bob, posted by SLS on January 4, 2012, at 5:55:26
>
> Chronic (long-term) antidepressant treatment with certain drugs causes the norepinephrine NE alpha-1 receptors to downregulate by reducing their numbers. Prazosin blocks these same receptors, thereby producing the same net effect.
>
> - Scott
>
I'm still lost. Is causing NE alpha-1 receptors to downregulate a desired effect or something that that we are trying to offset? Logically it would seem to me that if you are blocking the receptors it would reduce the available NE to the brain?Bob
Posted by Bob on January 4, 2012, at 14:51:41
In reply to Re: Adding Parnate and prazosin. » Bob, posted by SLS on January 4, 2012, at 5:55:26
> Hi Bob.
>
> It was nice of you to notice my post. It might be an important observation that prazosin has produced such a significant improvement in my condition.
>
> Just to let you know, I performed an experiment to verify that prazosin was the agent responsible for my improvement. I discontinued it for 36 hours and observed that I relapsed pretty hard. I was able to recapture the antidepressant response immediately upon the reintroducton of prazosin. Upon titration, I settled on 6 mg as the dosage. Hopefully, this is the dosage that will bring about a full remission. My instincts tell me that it will.
>
> > OK, so in lay terms what does this mean?
>
> Chronic (long-term) antidepressant treatment with certain drugs causes the norepinephrine NE alpha-1 receptors to downregulate by reducing their numbers. Prazosin blocks these same receptors, thereby producing the same net effect.
>
> I am, of course, extremely interested in the way prazosin might work for others as it now works for me. (Please God, let it continue). Perhaps prazosin has been overlooked in the treatment of TRD.
>
> For now, I would say that prazosin might work best as an adjunct to antidepressants for people who have a history of childhood physical abuse, emotional abuse (including bullying), or neglect. It may be that some people have a backdrop of PTSD acting to drive depression. Does pazosin also work for other subtypes of depression? I don't know.
>
>
> - Scott
>
>
> -------------------------------------------------
>
>
> > > This is an interesting abstract that reports a downregulation of NE alpha-1 (prazosin) binding with antidepressant use.
> > >
> > > -----------------------------------------
> > >
> > > J Neural Transm. 2010 Dec;117(12):1423-30. Epub 2010 Dec 7.
> > >
> > > Differential modulation of a-1 adrenoceptor subtypes by antidepressants in the rat brain.
> > >
> > > Ramakrishna D, Subhash MN.
> > > Source
> > >
> > > Kamineni Institute of Medical Sciences, Sreepuram, Narketpally, Nalgonda 508254, Andhra Pradesh, India. drramakrishna@klsindia.com
> > > Abstract
> > >
> > > The aim of the present study was to examine the effect of chronic antidepressants treatment on the density of a1-adrenoceptor (AR) subtypes in rat brain. Density of total a1 and a(1A)- and a(1?)-ARs was measured in cortex and cerebellum of rats treated with amitriptyline (AMI), desipramine (DMI) and fluoxetine (FLX), (10 mg/kg body wt), for 30 days, using [³H]prazosin in presence and absence of WB-4101. The density of cortical total a1-ARs was significantly decreased with AMI (54%) and DMI (25%) treatment, without altering the affinity of the receptor. Fluoxetine did not alter the density of cortical a1-ARs. The density of cortical a(1A)-ARs was also significantly decreased with AMI (85%) and DMI (50%) treatment, without affecting the affinity. The density of cerebellar total a1-ARs was significantly decreased with AMI (37%), DMI (50%) and FLX (70%) treatment, without affecting the affinity for [³H]prazosin. The density of a(1A)-ARs was significantly decreased with AMI (67%), DMI (59%) and FLX (92%) treatment. a(1B)-AR density was decreased only with FLX (47%) and DMI (47%) treatment. Correspondingly the basal IP3 and NE (10 µM) stimulated IP3 levels were significantly decreased in AMI (47%), DMI (22%) and FLX (48%) treated rat cortex. The results suggest that chronic antidepressant (AD) treatment down-regulates the cortical and cerebellar total a1-ARs in rat brain. However, a(1A) subtype is predominantly down-regulated by AMI and DMI, where as FLX affects cerebellar a(1A)-ARs. The region-specific and subtype specific down-regulation of a1-ARs density, which occurs after prolonged AD treatment, may underline the therapeutic mechanism of action.
> > >
> > > PMID:
> > > 21136124
> > > [PubMed - indexed for MEDLINE]
>
I thought you were attributing your response to the Parnate, not the Prazosin.Bob
Posted by Phillipa on January 4, 2012, at 19:59:28
In reply to Re: Adding Parnate and prazosin. » Bob, posted by SLS on January 4, 2012, at 5:55:26
Scott does this mean it could also help someone with anxiety ocd with emotional abuse? Jan/P
Posted by Phillipa on January 4, 2012, at 20:07:14
In reply to Re: Adding Parnate and prazosin. » SLS, posted by Bob on January 4, 2012, at 14:51:41
What if your blood pressure runs low? Jan/P
Posted by SLS on January 4, 2012, at 22:44:12
In reply to Re: Adding Parnate and prazosin. » SLS, posted by Phillipa on January 4, 2012, at 19:59:28
> Scott does this mean it could also help someone with anxiety ocd with emotional abuse? Jan/P
I really don't know what other conditions prazosin will demonstrate efficacy in treating. It is certainly a benign drug to try. A friend of mine uses it for sleep. It has been studied for PTSD.
How do you sleep? Do you ever have nightmares?
Prazosin often causes dizziness when you first start taking it. Mine went away for the most part.
- Scott
Posted by SLS on January 4, 2012, at 23:39:33
In reply to Re: Adding Parnate and prazosin. » SLS, posted by Bob on January 4, 2012, at 14:50:31
> I'm still lost. Is causing NE alpha-1 receptors to downregulate a desired effect
Apparently, it is. It should reduce NE activity, thereby reducing anxiety.
> Logically it would seem to me that if you are blocking the receptors it would reduce the available NE to the brain?
Prazosin does not reduce the amount of norepinephrine neurotransmitter in the brain.
When NE attaches to a receptor, that receptor is stimulated to perform a function (either excitatory or inhibitory). Blocking this receptor using an antagonist or using an inverse agonist serves to prevent this function. Prazosin is an antagonist at excitatory NE alpha-1 receptors, thus reducing the number of receptors available for stimulation.
I hope this helps. Maybe I'm confusing things.
- Scott
Posted by Bob on January 5, 2012, at 0:08:09
In reply to Re: Adding Parnate and prazosin. » Bob, posted by SLS on January 4, 2012, at 23:39:33
> > I'm still lost. Is causing NE alpha-1 receptors to downregulate a desired effect
>
> Apparently, it is. It should reduce NE activity, thereby reducing anxiety.
>
> > Logically it would seem to me that if you are blocking the receptors it would reduce the available NE to the brain?
>
> Prazosin does not reduce the amount of norepinephrine neurotransmitter in the brain.
>
> When NE attaches to a receptor, that receptor is stimulated to perform a function (either excitatory or inhibitory). Blocking this receptor using an antagonist or using an inverse agonist serves to prevent this function. Prazosin is an antagonist at excitatory NE alpha-1 receptors, thus reducing the number of receptors available for stimulation.
>
> I hope this helps. Maybe I'm confusing things.
>
>
> - Scott
It would seem to me that the effect you're describing would possibly reduce anxiety, but might also take away energy to function as well.
Posted by Bob on January 5, 2012, at 0:09:11
In reply to Re: Adding Parnate and prazosin., posted by SLS on January 3, 2012, at 14:28:16
> Today is day 6 of my positive response to treatment. Still going strong.
>
> Relief. Finally.
>
> My mind is reawakening after 30 years of existing in a vegetative state.
>
> Keep those prayers coming!
>
>
> - Scott
>
>
> > This stuff is still working - robustly. It is as if a light switch was turned on. I haven't felt this well for as long as I can remember - decades. I am not even 1/2 well yet, but I feel that I am on my way to remission. See how optimistic I get? It is a sickness :-).
> >
> > Please pray for me. I could use all the help I can get.
> >
> >
> > Currently:
> >
> > Parnate 80 mg
> > nortriptyline 150 mg
> > Lamictal 200 mg
> > Abilify 10 mg
> > lithium 300 mg
> > prazosin 6 mg
> >
> >
> > - Scott
>
>
Scott,How do you know that the response you're experiencing is not the Parnate?
Bob
Posted by SLS on January 5, 2012, at 3:23:07
In reply to Re: Adding Parnate and prazosin. » SLS, posted by Bob on January 5, 2012, at 0:09:11
> How do you know that the response you're experiencing is not the Parnate?
http://www.dr-bob.org/babble/20111226/msgs/1006288.html
- Scott
Posted by SLS on January 5, 2012, at 3:26:11
In reply to Re: Adding Parnate and prazosin. » SLS, posted by Bob on January 5, 2012, at 0:08:09
> It would seem to me that the effect you're describing would possibly reduce anxiety
Yes.
> but might also take away energy to function as well.
Fatigue is a possible side effect of prazosin, but probably not depression or cognitive impairments.I find it very clean. It feels like a pure antidepressant without fatigue or apathy.
- Scott
Posted by sigismund on January 5, 2012, at 3:40:21
In reply to Re: Adding Parnate and prazosin. » Bob, posted by SLS on January 5, 2012, at 3:26:11
And there is the fact that you have been on this combo minus the prozasin and gave it up. Maybe it is not exactly the same combo? You have been on and off .Parnate a few times that I can recall.
So, OK, a failed (?) blood pressure med has at last given you relief. Do you feel this is mediated through improved sleep? It doesn't sound like it from what you say.
I would like to try it for sleep improvement. I often don't get to the stage of sleep where nightmares are possible. I guess for me it is either this or trimiprimine
Posted by sigismund on January 5, 2012, at 3:44:08
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on January 5, 2012, at 3:40:21
>So, OK, a failed (?) blood pressure med has at last given you relief.
And yet you speak/spoke about being slowed down and half dead rather than jumping out of your skin (as you might expect from someone who gains benefit from prozasin?).
I don't understand any of this of course.
Posted by SLS on January 5, 2012, at 4:13:22
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on January 5, 2012, at 3:40:21
> And there is the fact that you have been on this combo minus the prozasin and gave it up. Maybe it is not exactly the same combo? You have been on and off .Parnate a few times that I can recall.
There are two differences with my Parnate treatment this time. I am taking lithium 300 mg and prazosin 6 mg. This is why I discontinued the prazosin as an experiment. I relapsed within 36 hours of discontinuation and recovered within a few hours of reinstatement.
> So, OK, a failed (?) blood pressure med has at last given you relief. Do you feel this is mediated through improved sleep?
I don't think so. I have a tendency to oversleep when I am at my baseline depression. I never had a sleep study, so I don't know what my EEG looks like.
> It doesn't sound like it from what you say.
>
> I would like to try it for sleep improvement. I often don't get to the stage of sleep where nightmares are possible. I guess for me it is either this or trimiprimineYour thinking is sharp and well-targeted.
Have you tried nefazodone? I believe it improves sleep architecture.
- Scott
Posted by SLS on January 5, 2012, at 4:16:13
In reply to Re: Adding Parnate and prazosin., posted by sigismund on January 5, 2012, at 3:44:08
Subject: NE alpha-1 receptors in cingulate.
It occurred to me that prazosin might quiet those neurons that are observed to be hyperactive in cingulate cortex (Brodmann areas 24, 25) in indviduals with MDD. If so, it would effectively mimic DBS.
This is a wild guess for which I have little supportive evidence.
- Scott
Posted by SLS on January 5, 2012, at 4:21:00
In reply to Re: Adding Parnate and prazosin., posted by sigismund on January 5, 2012, at 3:44:08
> >So, OK, a failed (?) blood pressure med has at last given you relief.
>
> And yet you speak/spoke about being slowed down and half dead rather than jumping out of your skin (as you might expect from someone who gains benefit from prozasin?).
>
> I don't understand any of this of course.
Have you had psychological traumas early in life?Is it possible that there is a PTSD component to your condition?
How is your memory? Is it impaired? If so, something might have beat the hell out of your hippocampus - extreme stress.
- Scott
Posted by g_g_g_unit on January 5, 2012, at 6:22:46
In reply to Re: Adding Parnate and prazosin., posted by SLS on January 5, 2012, at 4:13:22
I genuinely pray you see continued success on this combination, SLS! I hope I don't sound disingenuous, but I've always found your struggle heartbreaking.
So do you think prazosin could you be used to treat MAOI insomnia?
Posted by SLS on January 5, 2012, at 7:48:02
In reply to Re: Adding Parnate and prazosin. » SLS, posted by g_g_g_unit on January 5, 2012, at 6:22:46
> I genuinely pray you see continued success on this combination, SLS! I hope I don't sound disingenuous, but I've always found your struggle heartbreaking.
That is EXTREMELY affirming. Thank you.
> So do you think prazosin could you be used to treat MAOI insomnia?I never thought of that. I am not sure, but I doubt it. I didn't sleep at all last night due to drinking too much Diet Coke. I think I am now too sensitive to caffeine.
Maybe prazosin would help stress or anxiety induced insomnia. It works very well for PTSD sleep disturbances and nightmares.
The two things that I can recommend for MAOI-induced insomnia is the combining of two BZD receptor agonists or low-dose Seroquel. I like the idea of combining Sonata with Ativan or Restoril.
- Scott
Posted by sigismund on January 5, 2012, at 12:11:40
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on January 5, 2012, at 4:21:00
>Have you had psychological traumas early in life?
Yes. I guess so. I came out of childhood frightened.
My memory now is impaired, but that is an age thing.
Posted by sigismund on January 5, 2012, at 15:16:44
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on January 5, 2012, at 4:21:00
I don't know what the situation is here, but in some places nefazodone was discontinued because of liver toxicity?
Agomelatine too is toxic to the liver. I don't know how toxic. Just from the taste you can tell it is likely to be bad. We are not meant to eat things that taste so acrid. As soon as my stomach absorbed it my sinuses filled with mucous. It was good at first with sleep. I loved it.
Posted by SLS on January 5, 2012, at 15:17:03
In reply to Re: Adding Parnate and prazosin. » SLS, posted by sigismund on January 5, 2012, at 12:11:40
> >Have you had psychological traumas early in life?
> Yes. I guess so. I came out of childhood frightened.
Me, too. The world was simply too big for me.
- Scott
Posted by SLS on January 5, 2012, at 15:24:35
In reply to Re: Adding Parnate and prazosin., posted by sigismund on January 5, 2012, at 15:16:44
> I don't know what the situation is here, but in some places nefazodone was discontinued because of liver toxicity?
I read that the incidence of liver toxicity was fairly low. 1 in every 250,000. You could screen for toxicity with blood tests.
A friend of mine who has N24 circadian rhythm disorder finds prazosin helpful.
- Scott
Posted by Phillipa on January 5, 2012, at 18:38:53
In reply to Re: Adding Parnate and prazosin. » sigismund, posted by SLS on January 5, 2012, at 15:24:35
And to think I read on here about the liver toxicity and the banning in Canada and Europe so would not take it when the pdoc here begged me too. Others here basically said don't. As for nightmares for last two years having them frequently. Fears of death and things haven't thought about in years. I think the 40 year old female across the road from me takes it for PTSD nightmare also said it works for her. She's on other meds also antipsycotic, antidepressant? Jan/P
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