Study Ganaxolone Study

[Girl3]

Psychiatrists that are up to date in PTSD research are absolutely aware that the startle response is over-generalized and hyperactive in many people with PTSD. While many people with Borderline Personality Disorder also have PTSD, they are not the same condition. Dissociative issues can arise with either BPD or PTSD.

For instance, though I experienced sexual, physical, mental/emotional abuse from the time I was a small child, I do not have BPD. I do have PTSD and DID, however.

Memory is complex and includes both limbic (primitive emotional responses) and cortical (memory as a function of cognitive recall) components. The genetic predisposition to develop PTSD probably arises out of a limbic system that functions in a fundamentally different way than the limbic system of people who don't have PTSD. In other words, the limbic system is preset in certain people to act in a PTSD fashion. It is a biologic brain maladaptation that once upon a time was probably quite useful. But without trauma, a person would not develop PTSD. They might be a worrier, or OCD, but it is the combination of trauma and a particular limbic system that results in PTSD.

Cognitive Behavioral Therapy can physically change the brain - reroute neuronal impulses. But it takes a knowledgeable therapist, a willing patient, and time to achieve those changes . And because each individual has different experiences, different or multiple traumas, the CBT needs to be tailored to the patient. While we may all have certain characteristics common to PTSD, we each experience our lives very differently.

 

[ikop]

girl3 - you are a very erudite person and have a lotof knowledge about ptsd.

You mentioned Cognitive Behavioral Therapy.
A standart technique for most of the anxiety disorders,it can ease and teach how to cope , but it has one big problem when we are talking about ptsd.
And i repeat here what i said before , when a Iraq veteran, a person who was attacked at the street or a women who was raped hears a surprising sound of a barking dog- and all the 3 of them are jumping out of their skin despite of thier different and unrealted traumatic backround, this means that the process of the overreactivity is not thoughs ralatet, and cannot be corrected or normalized by CBT.

This reaction means that somthing more deeper than thoughs is totally wrong , and if we would be able to correct this abnormality I am allmnost sure that most of the ptsd symptoms will dissaper , ( exept from the memory dysfunction - that is unrealted to the amygdala but to other arias that become dysfunctional when a massive amounts of stress hormones flooded the brain )

The so called benzodiazapines can temporary depress the wholle nervous system activity , including the amygdala , and that is exactly the reason that they are very effective in a short run for ptsd. but they are extremly phisical adictive and the amount needed to get the same results growing avery week of use - making them totally unefffective for managing ptsd in a long term.

But if we could normlize this hyperactive lymbic system (particulary the right amgdala- the center of fear ) theoretecly it will alliviate ptsd.

i will quot some info from a veru interesting article :

The amygdala as a target for behavior surgery
Dead Link Removed

"Functional neuroimaging studies can rarely establish a causal effect between areas of activity and the underlying condition. However, lesioning studies are more successful in this regard. Koenigs et al. [28] studied veterans in the Vietnam Head Injury Study (VHIS) to see if there was a correlation between the location of the brain damage and the incidence of PTSD. In the control group (i.e. combat veterans without brain injury), the prevalence of PTSD was 48%. However, the prevalence dropped to 0% in the group where the damage was to the amygdala. [28]"

"Taken together, these results reveal the importance of the amygdala in mediating the symptoms of PTSD. Functional inhibition of the amygdala using DBS may therefore prove successful at treating PTSD. We tested this hypothesis [30] in a rat model using inescapable shocks which produce long-lasting behavior changes that mimic PTSD faithfully. [36] Recently, Mikics et al. [37] demonstrated that rats traumatized by inescapable shocks, in the presence of a conspicuous object, had the tendency to bury the object when re-exposed to it 28 days later. Burying behavior does not occur normally in rats. In this experiment, 10 rats underwent the implantation of an electrode in the right basolateral nucleus of the amygdala (BLn) and then were subjected to inescapable shocks in the presence of a miniature ball. Half of the animals received DBS therapy for 4 hours/day for 7 days, whereas the other half was connected to the pulse generator but received no stimulation (i.e. sham). Seven days later, all the rats were re-exposed to the ball and the burying behavior was timed. The difference in behavior was striking. The sham control rats spent, on average, 13 times more time burying the ball then the DBS-treated rats (P < 0.005). [30] More recently, we used the same animal model to compare the effects of DBS to paroxetine. Paroxetine is a selective serotonin-reuptake inhibitor approved for the treatment of PTSD. Our results confirmed the superiority of DBS over paroxetine"


Some people will say that dbs is very invasive procedure , yes it is , but it is not new , it's been around for 20 years , and it is an experemental treatment for depression and ocd .

A very severe ptsd is actually a condition that is the mother of all the anxiety disorders , it will make you agarophobic, agressive , social phobic, it will give you pannic attacks , sleep problems ,anxiety realted pain issues, hundred of startlre response a day al of this will lead to stronf depresssion .

And that is what we usually see at what is called "combat ptsd" the person could be so frighened ,anxious and jumpy , that any option of working ,socializing or even going out of the house will become an allmost impossible mission , when you see a once cool brave fighter jumping from a small barking dog or loosing his mind because of a slamming dor- you understand how much seriuos this conditon is.
In this case a Functional inhibition of the amygdala using DBS will be a life safer .

 

[Girl3]

Oy vay - I am not erudite, I am an MD. I have PTSD and have studied enough to pass the exam to be a neuropsychiatry MD.

The orignal studies were looking at vets - but unfortunately weren't looking at receptors or signalling. I am going to make a very gross comparison, but bear with me. If someone assumes that the size of a man's penis determines his ability to make babies - they'll come to a null conclusion: penis size doesn't predict fertility. So all of the studies looking at size of the amygdala were erroneous because size is relative. Function is everything. We still don't even know all the receptors or signalling issues with the amygdala. So we still don't know how to perfectly characterize who has PTSD based on brain scans.

I am getting ready to participate in yet another study looking at the brain - another fMRI and PET - which whill help further delineate the issue of PTSD vs 'normal'.

Cognitive behavioral therapy - if you are willing to do it - does begin working immediately because it asks you to start looking immediately at your thought processes. Did that person really mean to attack me, or were they saying something glib? Is that man really looking at me to attack or is he just scoping me out as a 'horn-dog' would? Did that surgeon really mean to attack, or is he just being an ass like most surgeons are? I can attest to the functionality of CBT - but the patient must be willing to do the work. Over time, CBT changes the brain - physcially and neurobiologically.

While I agree DBS is not experimental in the gross -this is how the surgery is done sense - it is experimental when it comes to PTSD. When anyone has their brain transgressed by surgery, they have to accept that bad things can happen. My sister-in-law went from being a research coordinator for a large internation corporation to being a nursing-home patient when she got MRSA in her brain after a successful surgery for a cavernous hemangioma. At post-op day 7 she was nearly perfect. At post-op day 14 she was comatose. So anyone having their brain entered needs to understand that they are at risk for infection, infarction , and hazards as yet unknown. If something happens 1% of the time, that means it happens in 1:100 people. You know 100 people. Who would you choose to suffer bad consequences? I am not willing to suffer a 1% risk at this point. A 1% risk means you're more likely to have a bad outcome than die in a car wreck or of a drug overdose.

I have had PTSD since before I went to elementary school, so I know how it can affect one's life. But I don't encourage anyone to pursure anything so radical that it could worsen their life.

 

[ikop]

Md girl3 I know that you are a medical doctor, (respect)
and the reason i hightli respect your knowledge.
it is not a secret that the amygdala is the key structure at the disorder.
the research that willing to found the exact with all of it aspects reason for ptsd symptomalogy ofthe ptsd redicilous ,expensive and might take decete.
we need to find a solution in the near futre.
at all studies that had been produced till now the only structure at the brain that is definetly responsible for ptsd is the amygdala. it has been proved by nomerous of stuied , not the hipocampus, not the front cortext , insula cortex.
the amygdale as you know is the basic primative structure of the defense system and it projects " commands the other arias including the arias respond ing for (creation?) of stress hormones .

remmember the women without the amygda who could not feel any anxiety or fear, the soldiers from vietnam aria with a injury to amygda that none of them developed ptsd , the hyperactivy of the amygdala observed in ptsd patients in this aria . it is correct that other arias as well effected by ptsd , like the hipocampus . (but this hypocampus theory was not conclusive enough . and of course the amygdala is in charge for the defence startle response (key factor of ptsd ) -without it this repond (startle ) is drasticlly dimminished.
the ventromedial prefrontal cortex and the medial one have to implicated at the disorder , but they are all progecting to the amygdla which decides what phisiological respond produce from the sensory and emotional input .
mokeys without an amygdla are not responds to normal u fear situation and does not produce agression.
i wish i could provide the links for the scientific articles (just cant find it )
theoreticly if you go to that fear centere and shut down the hyperactivity, the results in my opinion would be close to normalization of the person functionig.

Yes .
lke you said the procedure is invasive and carry risks much more that the usual drugs therapy but in many cases when the person is unfuctional , and the standart therapies does not work for him, he must try it.

there is no reason for this kind of intervention would be ingonred when thousand of people underwent it for depression and ocd ,not talking about movement disorders , would try it.
it all depends on the severity of the symptoms :
when a person life is hell ,when the average sleep is about 3 hours (not because of nightmares , when drug therapy does not work , when a person not only unable to work but he is startled of every movement , every sound, every person stands close to him
(including family members ) - this unfortunatelyis the solution for him that can give him some normal life .

And there are many like that.
ptsd is not an homogeneous , and has many face , and digress and i am talking about the peoplpe that are in the edge ,
they should consider it.
up to date i do not believe in our date drugs - the ssri , even paxil the first in line, is not effective in most cases because the serotonin dysfunction is not the primary reason for ptsd , it cane easy in some cases depression and slightly remove anxiety, the trick to correct memories with propronolol is a medical mistake , and I am not not talking about drugs like respredal and etc.

i believe that shutting down the lymbic hyperactivty will result in outstanding, life changing results much more that any drug or psychological help (even if it does by invasive procedure like dbs)

In my opinion PTSD Is the name of many disorders that has some similar characteristics but in fact they are different "diseases "

the "pure form of ptsd is what we see after a violent attack, similar in what hapinig in rape, combat, car incedent , civilian gung attack and etc.
The disorders that has some similarities with ptsd are disorders that there was not real (or perceived) as real by the person attack to the individual life.

That is kind of the disorders that there wore not resulted in so sirious functional and anatomical changes, but more psychological trauma .
What i called a real ptsd is usually resulted in extreme starltle reponse , 24/7 anxiety feelings, moderate to severe memory loose , it can cause dyslexia ,trembling, epilepsia attacks , tinnitus .hyperacusis (acute hearing ) confusion very similar to those with brain injuries and much more.

the reason in my opinion that there is a strong connection between borderline personality with traumatic events at childhood disorder and ptsd is due to a past mistake - those are to differnt disorders that need different aproach .


I am almost sure that many people have been brainwashed to believe they have ptsd by they doctors just because the existence of psychological problems (at the bpd clusster )+ childhood trauma to have ptsd.

I AM NOT Saying that bpd is not a serious condition , not at all , it is very serious, but it just not ptsd.

bpd is a serious condition that need to get aמappropriate treatment but different treatment than ptsd .

by the way i do believe that ganaxolone might help a lot to ptsd sufferers and other anxiety problems but time would say .
(please do do not delete this post because of grammar rulels (and used dictionary and tired as hard as i could . i am not a native in English_

 

[Girl3]

Ikop - first you have to understand that the brain is both simple and complex: the amygdala is sort of like a bypass-processor; that is when circuits need to connect faster, the bypass-processor kicks in. Why it kicks in in PTSD patients is still part of the puzzle - just like CB1 recpetors are part of the puzzle. We know from the most recent intelligently designed research, that CB1 recpetors are massively upgraded in the PTSD patient. However - pure suppression of CB1 receptors doesn't result in cure of PTSD. Stopping the amygdala from bypass-processing may suppress the symptoms of PTSD - but we don't know enough yet to know what the next bad thing will be.

It's like when they used rimonabant (anti-pot) to suppress appetite. It suppressed appetite - and made people suicidal. I received an isotope labeled rimonabant-analogue to study my brain - especially my amydala. The isotope insured that it would be a 2-3 hour phenomenon - no longer than I needed to lay in the PET scan. The horror of having my amydala receptors occupied by essentially an anti-amygdala drug was worse than anything I experienced in my entire life. Imagine being unable to react, unable to feel anything except helplessness.

PTSD is more likely to occur in a person whose childhood was laced with trauma - and the more trauma in childhood, the more entrenched the PTSD. When you look at military personnel with PTSD, the ones who had terrible/traumatic childhoods are the ones generally with the worst, most entrenched PTSD. HOWEVER - no one can predict who will get PTSD at this point, nor an anyone say that people with BPD are less likely to have PTSD or be convinced therof.

A more likely scenario is that a therapist whose credentials are slim or knowledge-base weak - decides on a simple check list, who has what. In my own lifetime, I was wrongly diagnosed by several psychiatrists, a couple of LCSWs, and a psychologist. I take the blame for some of it because after my first suicide attempt I didn't say "gee I was raped repeatedly by my older brother - think that has anything to do with my decision to kill myself?"

If someone wants to submit to an experimental therapy, knowing it could hurt them, kill them, change them irrevocably - that is the choice of the experimental subject - but it HAS to be spelled out in the consent and it HAS to have plan B if crap goes wrong. Even down to what happens if your art line site bleeds or you get an infection.

Comorbidity is another issue. Can you have BPD and PTSD? Yes. Just like you can have diabetes and high blood pressure and they don't compliment each other, they don't cause each other - and you need treatment for both. So for anyone out there who has Borderline Personality Disorder and PTSD - God Bless you, the treatment is long, but stick to it.

Ultimately - all I can say is that there are not enough competent diagnosticians/therapists/PsyD/MDs and too many patients without adequate knowledge of what is out there in terms of diagnosis, therapy, and medication.

And I assure everyone - just like no two diabetic patients or hypertensive patients are the same, nor do they respond to the same medications, life-style modifications, etc - no two PTSD patients are going to be exactly alike. There will be more than one treatment plan even when they figure out how to do it all scientifically.

 

[ikop]

girl3 please explain in more details about CB1 receptors and their connection to fear. I am unfamiliar with the subject.

In my case cannabis (hashish , is most common where I live (Israel) does not has and positive effect ,it makes me more anxious, and exaggerate my startle response (which is in the roof ).

The only drugs that helped me were the benzodiazepines. But I developed such high tolerence that now I need 12 mg of clonazepam to fill somthing that is Equivalent to 240 mg of diazepam.
Equivalent table :
http://www.benzo.org.uk/bzequiv.htm

And we are not talking here about Stopping the amygdala from bypass-processing but about a decreasing the activity .

So going back to the women with damage to the amygdala on both sides of her brain:

".M. reported little-to-no symptoms of fear on the questionnaires and also rated herself as fearless most often during the emotional experience sampling. However, she did experience other emotions, such as joy, happiness and sadness normally, the researchers said."

http://abcnews.go.com/Health/MindMo...ala-shows-fear/story?id=12404875#.T86eoWOKWuI

So as you see suppressing the amugdala does not results ins suppression of all emotions .

I can say for my self that I do no have flashbacks ,
"memories, recurring distressing dreams, subjective re-experiencing of the traumatic event(s), or intense negative psychological or physiological response to any objective or subjective reminder of the traumatic event(s)."

But I do have "decreased capacity (down to complete inability) to feel certain feelings"

And I do have :
"Persistent symptoms of increased arousal not present before"


In addition I developed hyperacsus (acute hearing ) , essential tremor ( a week after the attack ), memory and concentration problems , and I poor visual procceing .

I live in a feeling of constant symptoms of fear and cannot tolerate any person strands next to me.

That Was just a little introduction.

It is unlikely, in my opinion, that we could produce a real progress with drugs .

I still think that decreasing amygdala activity could be the answer to PTSD - at least to the majority of us. Up to this date the only way to target the amygdala is deep brain stimulation.

I wish I could be done with drugs , but developing such drug will be very very hard and might take years. And we do not have this years.

And I want to live now.

 

[Girl3]

If you look at the literature - by that I mean scholarly articles, not magazine blurbs - you would find that since 2003, the fact that people who get DBS have a higher rate of suicidal ideation AND suicide completion. In a metanalysis study by Appleby,MD et al in 2007, they looked at DBS trials published from 1996-2006 and more than 800 study articles were included.

While small case reports suggest OCD and major depression respond to DBS, the fact that suicidal ideation and completion is a problems means that until well controlled studies for patients with greater risk for suicide are undertaken, getting a deep brain stimulator for PTSD is a crap shoot.

In multiple trials of DBS, permanent sequelae (that's medicine-talk for bad outcome) remains about 4-5% of patients. Infection also occurs in about 5% of patients early on, but that risk increses over time.

So if you want a DBS, you have to go in knowing it may kill you 1-2% at the outset, you may suffer a bleed inside your brain (4-5%) or your suicidal ideation/completion may become worse (2-4%/0.16-0.32). If you pperform DBS on 1000 people, 16-32 of them will complete suicide. Personally, I don't like those odds. The conclusion of the Appleby study was that while DBS has been shown to work for movement disorders, people should be screened for depression and suicidality prior to receiving DBS.

Anyone receiving DBS should have close supervision regarding their emotional state - not just in the immediate post-operative period, but for the duration of the device. Anyone implanting DBS in patients with suicide as a component of the disease itself, should have competent psychiatric follow-up in place for patients.

 

[ikop]

I Think that is it a matter of ones functioning, of course a person that can work, have periodic flashback attacks, or dreams, will not take the risk of of this kind of procedure.

But a person who is completely unfunctioning, having 24/7 feelings of anxiety, isolated, have not sleep more than 3 hours at night for years, living a life 24/7 in physical fear up to the point that going to the bank or to to buy some food at a store becoming impossible mission ,and even cannot contact with his family will consider this operation regardless of the 5% risks.

I think that a depression in ptsd is not a symptom of ptsd , but a result of the things mention, in other words it is not a "brain based cased by luck of some neurotransmiters. Anybody with this high state of anxiety will be depressed.

 

[Girl3]

I do fear going to the grocery store, or meeting people in any new setting, going outside for a run, visiting ANY city, and I do not talk to anyone in my family. Right now there is a block party going on - I contributed food, and spoke to a few people. I did what I could stand to do, then excused myself to return to the safety of my house.

But I have forced myself over the years to do things - often by dissociation. Girl2, typically fueled by alcohol or drugs could do all sorts of extraverted activities. She sang in rock groups. Now I try to harness her cahones without her extra baggage and dangerous behaviors.

If I get 4 hours of sleep in a row, I consider it a blessing. I also know that if I dream - even if it feels like I am awake while I'm doing it - it is sleep. If too many nights go by without sleep, I take a sleeping pill. If it is horrific anxiety that is getting to me, I might take a Xanax. If it is the neuropathic pain, I take gabapentin. But I only do that a couple of times a month - because I don't want to be addicted or dependent. I also don't want to be like Michael Jackson, whose daily use of drugs actually interfered with his ability to sleep. Opiates especially inhibit entering into the deeper stages of sleep. My psychiatrist wants me on as few drugs as possible because he is a big believer in the brain can heal and do miraculous things - even though he is a researcher looking for new ways to treat, including medication-based therapy.

Amygdala PET scan and fMRI studies are some of the ones I participated in - and the clinically interesting thing is going to be individual receptor types - because CB1r and FAAH receptors work differently in people. So eventually they will have drugs that will be tailored to the individual. Until they understand exactly what is going on with the over-or-underactive signalling, any treatment is just throwing things at the wall and seeing what sticks.

But in the meantime, I utilize cognitive behavioral therapy techniques and force myself to do things I don't want to do. Every time I think "I don't want to do ______" I say it's like brushing your teeth. You don't enjoy it, but you don't want them to rot. I don't want to rot.

It isn't that I am against anything new - I just believe that if someone is going to pursue a therapy, she should know what the risks are and if there is really good scientific evidence backing it up. I would caution anyone against using risperdone for instance - one of the trials looking at it was stopped early due to bad clinical outcomes. It has helped certain individuals who have psychotic features of their PTSD, but the vast majority of PTSD patients don't need to be on it. I submit the vast majority of PTSD sufferers should not undergo DBS at this juncture. In fact, I'd rather they go have stellate ganglion blocks than DBS, because the risk of having a really bad outcome with SGB is less.

The power to heal IS within each of us. Right now. It isn't fast, it isn't perfect, and we can and will have setbacks. But we can heal without bizarre or dangerous experimental treatments. If you had seizures that occurred every hour and were reducing your brain to mush, I'd say go get DBS because it is a known treatment. If you had Parkinson's so bad you couldn't walk or feed yourself, I'd say get DBS because you stand a 50% chance of having real results for up to 4 years. But right now, there isn't a scientist on the planet who can say more than "we put a DBS in two PTSD patients who felt 30% better." Did you know that just participating in a study has shown people improve in the short term even if they are in the placebo arm? It's called attention to your problem by people who care.

There are some studies in Israel that are recruiting participants:
ClinicalTrials.gov Identifier: NCT00965809

 

[ikop]

Oh, ClinicalTrials.gov - I know this site very well.... I am there almost every day looking for new trials to arrive...

I even participated in a TMS study ( magnetic pulses to the medial prefrontal cortex) but got a seizure at the 8 treatments so I was eliminated from the study , but anyway there was not any positive effects after 8 treatments, so it was unlike to be changed even if I did all the 12....

What is funny that they tried to manipulate by presenting the trial as a big success, but actually there was only a minor improvement.

[DLMURL]http://www.marketwire.com/press-release/brainsway-reports-final-results-of-ptsd-clinical-trial-with-deep-tms-tase-brin-1543616.htm[/DLMURL]

 

[Girl3]

Notice the website origin: Marketwire. One does not look for scientific proof at Marketwire. The company who stands to make money off of it have made a press release.

In a sham study that was done (google scholar TMS for PTSD), results degraded after 2 month - which doesn't mean it didn't work, it just means it isn't permanent and that results really don't last more then two months.

TMS for PTSD was one of those studies that resulted from a 20 year old technology with no real use. I remember using it in the neurosurgical intensive care unit patients who had severe traumatic brain injury - because the chair of neurosurgery thought it might help. Because it is non-invasive and doesn't seem to cause any long-term side-effects many people are 'throwing sh*t at the wall, and seeing if it will stick.'

If there are any major university psychiatry or psychology departments near you, you should check their websites for research information. ClinicalTrials.gov is just the largest, non-profit clearing house for studies and their contacts - that's why I refer to it.

 

[ikop]

yep ,tms for ptsd = no no .
but you must (i think ) to agree with me that the sciantific data about the role of the amygdala in the ptsd symptoms up today is close a fact.

please look to this :

http://c328287.r87.cf1.rackcdn.com/07-Langevin-1.mp4