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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 17 of 17. This is the beginning of the thread.
Posted by Bob on September 17, 2011, at 16:01:06
http://www.sciencedaily.com/releases/2011/09/110916121150.htm
As far as I know, BDNF has been completely ignored with today's drugs so far. Is this because we haven't know about it at all, or because we don't know how to modulate it?
Posted by linkadge on September 17, 2011, at 16:24:00
In reply to BDNF connection?, posted by Bob on September 17, 2011, at 16:01:06
The BDNF thing is far from conclusive. Some studies conclude that BDNF signalling is actually elevated in depression:
"Research suggests that aberrant signaling by a chemical called Brain-Derived Neurotrophic Factor (BDNF) through its receptor TrkB, may contribute to anxiety and depression, and inhibiting this pathway in mice can reduce anxiety and depression-related behaviors. "
BDNF may indirectly be influenced by antidepressant treatments. For instance, a metabolite of serotonin n-acetyl-serotonin is a potent trk-b agonist. This is the same receptor that BDNF activates. Also the antidepressant amitriptyline is a direct trk-b agonist.
But, I don't think they've got a clue whats going on, because all of the findings are contradictory.
Linkadge
Posted by Bob on September 17, 2011, at 20:20:11
In reply to Re: BDNF connection?, posted by linkadge on September 17, 2011, at 16:24:00
> The BDNF thing is far from conclusive. Some studies conclude that BDNF signalling is actually elevated in depression:
>
> "Research suggests that aberrant signaling by a chemical called Brain-Derived Neurotrophic Factor (BDNF) through its receptor TrkB, may contribute to anxiety and depression, and inhibiting this pathway in mice can reduce anxiety and depression-related behaviors. "
>
> http://news.drugs-expert.com/depression-news/researchers-identify-trkb-antagonist-with-anxiolytic-antidepressant-activity/
>
Well that's one thing I certainly agree with... they definitely have very little idea what's going on. As I look back over the course of my illness, I can see that in the beginning treatments gave me some hope, but as the years ticked by there was less and less response and more and more sickness. Most things didn't work at all, and those that "worked" did only for a short time. I am now a shadow of my former self, even on "good days". As for the bad days - those are the ones where I really don't think I'm gonna make it.
> BDNF may indirectly be influenced by antidepressant treatments. For instance, a metabolite of serotonin n-acetyl-serotonin is a potent trk-b agonist. This is the same receptor that BDNF activates. Also the antidepressant amitriptyline is a direct trk-b agonist.
>
> But, I don't think they've got a clue whats going on, because all of the findings are contradictory.
>
> Linkadge
>
>
>
>
>
Posted by SLS on September 17, 2011, at 23:52:51
In reply to Re: BDNF connection? » linkadge, posted by Bob on September 17, 2011, at 20:20:11
> Well that's one thing I certainly agree with... they definitely have very little idea what's going on. As I look back over the course of my illness, I can see that in the beginning treatments gave me some hope, but as the years ticked by there was less and less response and more and more sickness. Most things didn't work at all, and those that "worked" did only for a short time.
Your story sounds vaguely familiar to me.
:-(
> I am now a shadow of my former self,
I am familiar with the deteriorations of the body, mind, and spirit that result from depression. It is enough to demoralize one to the point of contemplating suicide.
> even on "good days". As for the bad days - those are the ones where I really don't think I'm gonna make it.
Is there anything that can provide you with even the smallest degree of relief on a steady basis? I managed to eek out a 15% improvement combining nortriptyline and Lamictal.
Which drugs made you feel dramatically worse?
- Scott
Posted by Bob on September 18, 2011, at 12:31:24
In reply to Re: BDNF connection? » Bob, posted by SLS on September 17, 2011, at 23:52:51
> > Well that's one thing I certainly agree with... they definitely have very little idea what's going on. As I look back over the course of my illness, I can see that in the beginning treatments gave me some hope, but as the years ticked by there was less and less response and more and more sickness. Most things didn't work at all, and those that "worked" did only for a short time.
>
> Your story sounds vaguely familiar to me.
>
> :-(
>
> > I am now a shadow of my former self,
>
> I am familiar with the deteriorations of the body, mind, and spirit that result from depression. It is enough to demoralize one to the point of contemplating suicide.Yes, the deterioration and build-up of emotional pain over the years has unquestionably brought me much closer to suicide.
>
> > even on "good days". As for the bad days - those are the ones where I really don't think I'm gonna make it.
>
> Is there anything that can provide you with even the smallest degree of relief on a steady basis? I managed to eek out a 15% improvement combining nortriptyline and Lamictal.
It's the "steady basis" part that presents a significant problem. I have found things that help for a little while but sooner or later I reach a point where the side effects are just too burdensome in one way or another. Then it becomes necessary to experiment with yet another drug combo which inevitably involves yet another withdrawal and another ramp up on a new drug. I am exquisitely sensitive to meds and med changes and it has all taken a severe toll.Currently I am taking nortriptyline and zoloft and it has helped a little, but if I heed the lessons of the past, it won't be so for too much longer. I have to somehow try to accept the low grade life I am living on a less-than-optimum drug cocktail but it is very difficult to do.
>
> Which drugs made you feel dramatically worse?
The drugs and treatments that did the most damage would be these I think:- Effexor (non-XR) This drug was okay until it quit working, and then the withdrawal was life threatening.
- Topirimate
- Gabapentin
- Electro-convulsive therapy
- Klonopin withdrawal
This is by no means a complete list but rather the highlights of some of my biggest crises. I have had significant problems on many different meds and combinations of meds and would be writing page after page here if I describes all of it.
>
>
> - Scott
>
>
Posted by Bob on September 18, 2011, at 14:11:54
In reply to Re: BDNF connection? » SLS, posted by Bob on September 18, 2011, at 12:31:24
Oh, by the way... when I say a med worked for a awhile and then quit, I mean "worked" in a very qualified manner. I've never been on a med that truly allowed me to truly feel like myself. I've never even been near 100% there and have always experienced troublesome side effects of one sort or another.
When you're maybe 50 to 60% of your former self do you stay with a med with troublesome side effects or take the very risky and more painful route of another change? Way back in the beginning I didn't hesitate to choose the option of change, and paid a heavy price many times.
Posted by zonked on September 20, 2011, at 21:36:30
In reply to Re: BDNF connection? » Bob, posted by SLS on September 17, 2011, at 23:52:51
> Which drugs made you feel dramatically worse?
>
>
> - ScottMay I?
Effexor XR (extreme anxiety/akathisia like feeling), Wellbutrin SR and XL (extreme anxiety and quickness to anger), nortriptyline (same as Wellbutrin), selegeline (depression somewhat relieved but anxiety very Wellbutrin-like.)
Meds that worked, but then pooped out: Zoloft (yay! best ever.), Nardil (seems to work in combination with testosterone but never as well as the first two times), Parnate (dose had to go so high over time as to provoke unacceptable hypomania, where the response became hypomania or nothing.)
My doctor once mentioned "super-dosing" SSRIs to regain response. One other professional mentioned this: a psychiatric NP I met who has bipolar disorder herself. Should I not regain the response I had recently after re-adding Testim, I dunno what I'm gonna do.
I will look to see what you have to say about Viibryd, that's for sure.
Hope I didn't offensively hijack the thread folks..
-z
Posted by SLS on September 20, 2011, at 22:15:24
In reply to Re: BDNF connection? » SLS, posted by zonked on September 20, 2011, at 21:36:30
>
> > Which drugs made you feel dramatically worse?
> >
> >
> > - Scott
>
> May I?
>
> Effexor XR (extreme anxiety/akathisia like feeling), Wellbutrin SR and XL (extreme anxiety and quickness to anger), nortriptyline (same as Wellbutrin), selegeline (depression somewhat relieved but anxiety very Wellbutrin-like.)
>
> Meds that worked, but then pooped out: Zoloft (yay! best ever.), Nardil (seems to work in combination with testosterone but never as well as the first two times), Parnate (dose had to go so high over time as to provoke unacceptable hypomania, where the response became hypomania or nothing.)
>
> My doctor once mentioned "super-dosing" SSRIs to regain response. One other professional mentioned this: a psychiatric NP I met who has bipolar disorder herself. Should I not regain the response I had recently after re-adding Testim, I dunno what I'm gonna do.
>
> I will look to see what you have to say about Viibryd, that's for sure.
>
> Hope I didn't offensively hijack the thread folks..
>
> -z
>
Intolerant of NE drugs, perhaps? Are there any drugs that you responded well to that were NE reuptake inhibitors? How about NE alpha-2 antagonists like Remeron > 45mg or Buspar (via metabolite 1PP).How about trimipramine (Surmontil)? Nefazodone? I agree with you that Viibryd might be worth a try.
My doctor would love for a drug to trigger mania in me. He would simply add anti-manics and retain the antidepressants. Depakote and Zyprexa squash my manic episodes within 12 hours of the first dose.
How about adding guanfacine when NE drugs agitate you? (wild guess). You might even want to try it regardless.
- Scott
Posted by zonked on September 20, 2011, at 22:54:01
In reply to Re: BDNF connection? » zonked, posted by SLS on September 20, 2011, at 22:15:24
> How about adding guanfacine when NE drugs agitate you? (wild guess). You might even want to try it regardless.
>
>
> - ScottWow, good call. Before I became disabled, I used to have a really good (but really expensive, no insurance) neuropsychiatrist who once suggested guanfacine (Tenex) as an adjunct. I had never heard of it, so I refused it. It sounds like something to bring up in the future if required.
Scott, I notice you haven't taken benzos in a long time or at least since I've corresponded with you. Is there a particular reason for this (loss of efficacy, cognitive concerns) or is it just incidental?
I actually don't really *like* the way benzos make me feel... I am dependent on Xanax now and do not want to taper though. Also, I need a benzo or Z-drug to sleep typically.
While on Nardil, did you get the insomnia and if so how did you manage?
I have found Ambien produces less of a depression nasty effect when I wake up compared to restoril. Both require mid-night dosing for a complete night's sleep.
My new drug plan includes coverage for Ambien CR, which I may give a try.
I'm kind of surprised we haven't seen commercials for Viibryd yet; although I never seem to remember Forest Labs advertising Lexapro on TV either.
-z
Posted by SLS on September 21, 2011, at 8:02:06
In reply to Re: BDNF connection? » SLS, posted by zonked on September 20, 2011, at 22:54:01
Hi Z.
> Scott, I notice you haven't taken benzos in a long time or at least since I've corresponded with you.
I have nothing against BZDs, but I prefer to do without them if I can so as not to complicate things too much. Anxiety is not generally a problem with me. However, I have had choppy sleep for about a year. I imagine Nardil contributed to this. Unfortunately, Nardil does not produce total insomnia and suppression of dreaming the same way it did twenty-five years ago. It is scary to think that one can become so brain-dead to no longer experience such potent effects of MAOIs. For sleep, I occasionally combine zaleplon with lorazepam. It works pretty well to get me through the night. I like to think that taking BZDs for sleep every third night helps prevent tolerance.
Coming off of Xanax must be hell if you are in some sort of hypernoradrenergic state.
I don't know what to think of Viibryd and my chances to respond to it. For now, I am treating it as an unknown entity rather than trying to apply the knowledge that it is a SSRI/5-HT1a partial agonist. There must be something more to this drug. People who have tried to replicate the combination of these two properties by taking Buspar and Prozac failed to improve. A mantra of mine is that for every new drug that becomes available, a certain percentage of previously treatment resistant people will respond.
I'll try to check in regularly while I am trialing Viibryd.
What things are you looking to try next?
- Scott
Posted by zonked on September 21, 2011, at 10:53:20
In reply to Re: BDNF connection? » zonked, posted by SLS on September 21, 2011, at 8:02:06
> Hi Z.
>
> > Scott, I notice
> I'll try to check in regularly while I am trialing Viibryd.
>
> What things are you looking to try next?
>Hmm. The AndroGel (testosterone) augmentation was working well, it was as if it allowed the Nardil to work. Now that I'm having to ration it, that sort of went away.
But I do see the doctor this week and have switched drug plans to one that covers Testim, which is functionally equivalent.
I hope it works again. I really screwed up the testosterone twice; once by quitting smoking a few days into it (had to, financial reasons); another was the insurance company paying for it once, but requiring a clinical hypogonadism diagnosis to refill it. I am "low normal" testosterone by default, and my numbers are about 100 more than "clinical" hypogonadism. The new insurance plan does not require any prior auth for Testim.
Someone told me that hormones aren't like antidepressants though, that they either work, or they don't. I hope this is true. I see my doctor on Friday and I hope to get all this cleared up.
I won't be stopping anything in my regimen any time soon, except October 1 I will be adding daily testosterone topical back (instead of half my usual dose every other day, which I've had to do to make the remaining packets last.)
If I fail on this, God please forbid, I have never taken a tricyclic except nortrip. Too much norepinepherine...
The good days I've had have been really good - talkative, positive, optimistic, more energy. That was when I was applying one 2.5gm 1% testosterone gel every morning.. before and after the worst of the cigarette withdrawal which messed things up.
Now Viibryd, it seems to be getting better reviews than Pristiq did when it first came out. I can tell you, I know of one person for whom Pristiq really worked and it was his first AD. Still too new for me to have much of an impression of it.
Anyway, about me: we'll know if the current regimen is working a few weeks into daily testosterone application again. When I had good days on it, it actually made me wonder if I could taper the Nardil and if low T or some related hormonal problem has been the ultimate cause.
Not for me to do now, although I've gained 45 lbs since starting Nardil. Some lbs. are due to just being on Nardil, and some, I will admit, are due to binge eating on days I've felt like crap.
-z
Posted by SLS on September 22, 2011, at 9:40:34
In reply to Re: BDNF connection? » SLS, posted by zonked on September 21, 2011, at 10:53:20
It looks like my prescription plan will refuse to cover Viibryd, even with a pre-authorization request. I really would like to try this drug before moving on to Effexor.
- Scott
Posted by zonked on September 22, 2011, at 10:32:39
In reply to Re: BDNF connection?, posted by SLS on September 22, 2011, at 9:40:34
> It looks like my prescription plan will refuse to cover Viibryd, even with a pre-authorization request. I really would like to try this drug before moving on to Effexor.
>
>
> - ScottIf you have concurrent Medicaid coverage, sometimes they'll pick up something Medicare Part D won't. It depends on your state and in some cases your county.
Unlikely, but worth calling the pharmacy to see if Medicaid will cover it straight out.
I think in California I have the right to request Medicaid cover a non-formulary drug if my Medicare PDP refuses to cover it and it isn't formulary for Medicaid either, as long as it's for the approved indication. This is actually how Xanax gets covered for dual-eligibles in California - it can't be covered by Medicare by law, CA Medicaid removed it from their formulary in 2008 or 2009, but if you've tried and failed other drugs Medicaid will cover it with justification.
You could also ask your doctor to get a bunch of samples from Forest until you can make this work more permanently. I'm just a third party observer, Scott, but I think your case warrants a drug with a novel mechanism of action.
Good luck. I would think Forest would be mounting a massive physician "education" campaign by now and samples should be abundant.
-z
Posted by Bob on September 22, 2011, at 16:07:31
In reply to Re: BDNF connection?, posted by SLS on September 22, 2011, at 9:40:34
> It looks like my prescription plan will refuse to cover Viibryd, even with a pre-authorization request. I really would like to try this drug before moving on to Effexor.
>
>
> - Scott
Why are they refusing? Do you know?
Posted by SLS on September 22, 2011, at 17:25:51
In reply to Re: BDNF connection? » SLS, posted by Bob on September 22, 2011, at 16:07:31
> > It looks like my prescription plan will refuse to cover Viibryd, even with a pre-authorization request. I really would like to try this drug before moving on to Effexor.
> >
> >
> > - Scott
>
>
> Why are they refusing? Do you know?
The drug might be too expensive in the eyes of the insurance company to add it to their formulary when it is already full of other antidepressants. They act as if they know something about the clinical utility of a drug that practicing clinicians do not. They are playing doctor without a license.
- Scott
Posted by hyperfocus on September 23, 2011, at 14:36:57
In reply to Re: BDNF connection? » linkadge, posted by Bob on September 17, 2011, at 20:20:11
It's like the old joke about 3 blind men trying to describe an elephant. One says it's like a snake, another that it's sharp and pointy, the third that it's broad and flat. When observations on things like BDNF contradict each other it means there is a whole mass of hidden variables we don't yet know about. Clearly we''re still very much in the dark about mental illness and how psych drugs work.
A while back I read some speculative article similar to this about parts of the brain that begins to degenerate due to chronic anxiety and stress, causing dysregulation of thinking and memories as well as reducing the 'reward' we get for normally pleasurable activities, which of course leads to more anxiety and stress. The brain becomes trapped in a set of thinking it cannot biochemically escape because physical brain structures have degenerated to the point where there is not enough circuitry to support anything else. The actions of ADs were speculated to be primarily neurogenerative - repairing the brain so there is a higher payoff and more circuitry to support positive thinking and behavior and emotions and memories. BDNF was speculated to play a primary role in this.
I've observed that in those short periods of hypomania we all experience, my thinking remains the same. Like my mood might be significantly elevated, but it's like there are these deep groves in my mind that my thinking has to follow no matter what. The expectation is that someday these groves will eventually disappear due to less stress and more rewards from positive behavior, leading to more full-spectrum thinking.
Right now I guess we're still in the age of Galileo and Copernicus in psychiatry - we have some observations that are consistent and theories that partially work, but there's a lot we still can't make sense of. What we really need is some Isaac Newton to develop a theory that unearths all the hidden variables in mental illness.
Posted by Bob on September 23, 2011, at 17:49:57
In reply to Re: BDNF connection?, posted by hyperfocus on September 23, 2011, at 14:36:57
> It's like the old joke about 3 blind men trying to describe an elephant. One says it's like a snake, another that it's sharp and pointy, the third that it's broad and flat. When observations on things like BDNF contradict each other it means there is a whole mass of hidden variables we don't yet know about. Clearly we''re still very much in the dark about mental illness and how psych drugs work.
>
> A while back I read some speculative article similar to this about parts of the brain that begins to degenerate due to chronic anxiety and stress, causing dysregulation of thinking and memories as well as reducing the 'reward' we get for normally pleasurable activities, which of course leads to more anxiety and stress. The brain becomes trapped in a set of thinking it cannot biochemically escape because physical brain structures have degenerated to the point where there is not enough circuitry to support anything else. The actions of ADs were speculated to be primarily neurogenerative - repairing the brain so there is a higher payoff and more circuitry to support positive thinking and behavior and emotions and memories. BDNF was speculated to play a primary role in this.
>
> I've observed that in those short periods of hypomania we all experience, my thinking remains the same. Like my mood might be significantly elevated, but it's like there are these deep groves in my mind that my thinking has to follow no matter what. The expectation is that someday these groves will eventually disappear due to less stress and more rewards from positive behavior, leading to more full-spectrum thinking.
>
> Right now I guess we're still in the age of Galileo and Copernicus in psychiatry - we have some observations that are consistent and theories that partially work, but there's a lot we still can't make sense of. What we really need is some Isaac Newton to develop a theory that unearths all the hidden variables in mental illness.
That is one excellent and insightful post!
This is the end of the thread.
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