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#13 seanob

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Posted 06 July 2019 - 09:06 PM

I used naloxone and it didnt help me. I still have one injector left.



#14 teal

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Posted 23 October 2019 - 05:57 AM

I contacted the people in charge of the study requesting to be a part of the ongoing clinical trial so I might be able to get my hands on the drug.


Did they write back? We should let them know a pilot study on DPDR is warranted. Just some twenty patients would go a long way.

#15 Mayer-Gross

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Posted 23 October 2019 - 08:32 AM

Why is this thread even a debate?  There have been several with heroin addiction and depersonalisation disorder who has been on suboxone/buprenophine with a very low respons as 20 -30% reduction in symptoms. It has a high antagonistic effect on the kappa opioid receptor . It is the kappa opioid system that can shot drown for emotions and the reward system to stress, anxiety and addiction other parts of the opioid system cannot do that so they are excluded. Drugs like naltrexone, nalmefeme and naloxone have either a very short half-life or a very low affinity for the kappa-opioid receptor. The trails done with these drugs where small, not repeated and 20-15.years old. They have never been replicated in larger trails but many on this forum has tried them with no to limited effect effect. Those who have tried drugs like suboxone has had a limited effect. Here is one that had a 20-30% reduction in symptoms with suboxone;

 

 

"I wouldn't do it if I were you.  I have been on it long term.  It's a serious drug.  It's what they give heroin addicts to help during the withdrawal process.  Most people don't stay on it long term. If you do stay on it long term and want to quit at some point a Suboxone withdrawal is 4x worse than an actual heroin withdrawal.  I think it's insanely reckless that people on here are recommending Suboxone/Subutex for depersonalization treatment.  These are people who in large have probably not tried it themselves and if so are just being guinea pigs.  I highly doubt Suboxone is going to cure or help anyone with DP.  If you want to try it that's your call, but if it doesn't help I wouldn't stay on it long term. "

 

https://www.dpselfhe...ne/?hl=suboxone

 

But, depersonalisation is a disorder of cognitive regulation of emotions with many brainstructures involved. This emotional regulation emotions starts at the prefrontal cortex and one structure can use dynorphin in the inhibition of anxiety, stress and addiction is the medial prefrontal cortex and it has been found to be active with other structures in the prefrontal cortex in functional brain studies of depersonalisation. So, emotional inhibition is also done by other structures in the prefrontal cortex that will not be affected by a opioid antagonist. But, these debates are kept alive by ignorants . You can inhibit that response in the medial prefrontal cortex with rTMS and some trails have done it in with people with cocaine addition. But, the right ventrolateral prefrontal cortex that is active in emotional regulation might not be a supressor by itself but likely to mobilised other structures in the prefrontal cortex to regulate emotions. To use rTMS at the right VLPFC will inhibit the instruction to regulate emotions given to other areas in  the prefrontal cortex including the medial prefrontal cortex. A selective kappa antagonist if it existed would not cure depersonalisation disorder. It would likely give a reduction in symptoms of 20-30%

 

The role of the ventrolateral prefrontal cortex but also the angular gyrus in cognitive regulation of emotions can be read here.

https://www.ncbi.nlm...les/PMC4801480/



#16 teal

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Posted 23 October 2019 - 09:16 AM

Why is this thread even a debate?  There have been several with heroin addiction and depersonalisation disorder who has been on suboxone/buprenophine with a very low respons as 20 -30% reduction in symptoms.


If there were a study on DPDR showing a 20-30 % reduction in symptom severity following ALKS 5461 treatment, then that would be valuable, if not as a treatment then as a clue to which mechanisms are at play.

It would also be valuable to repeat the Russian study on Naloxone, seeing how many would benefit and to what extent. If it'd have no effect on all, that would also be a clue. At the time of writing the British Medical Journal writes the following about treatment of DPDR
"A study of lamotrigine as an adjunct therapy reported dose related benefits, as did studies using opiate antagonists"

https://www.bmj.com/...6/bmj.j745.full



#17 Mayer-Gross

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Posted 23 October 2019 - 10:54 AM

Totally irrelevent. The right VLPFC cortex that is active in depersonalisation works as a switch to other regions in the prefrontal cortex. We know that from basic research of different areas in the prefrontal cortex and functional studies of depersonalisation disorder. To inhibit the right VLPFC with rTMS will stop all inhibitions of emotions by the all areas of prefrontal cortex, including those areas that works though the opioid system. To inhibit the right VLPFC reduces depersonalisation with 45% on average -especially emotional numbing -but not dissociation.

 

The study with lamotrigine only mentions a reduction of 30% in 56% of those who tried. On this forum i would say that the response rate in lower among those who have tried. 



#18 teal

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Posted 23 October 2019 - 11:34 AM

The study with lamotrigine only mentions a reduction of 30% in 56% of those who tried.  

 

And this was as an adjunct to an antidepressive, I suppose. Which doesn't say much about lamotrigine monotherapy.

 

To inhibit the right VLPFC with rTMS will stop all inhibitions of emotions by the all areas of prefrontal cortex, including those areas that works though the opioid system. To inhibit the right VLPFC reduces depersonalisation with 45% on average -especially emotional numbing -but not dissociation. 

 

I take it it's this study you're referring to. "20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44%" It does look promising. Even though it's based on only seven patients.



#19 Mayer-Gross

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Posted 23 October 2019 - 12:11 PM

There was a trail with lamotrigine as mono-therapy prior to that without any response.https://www.ncbi.nlm...pubmed/12680746

 

Yes, the sample size is small. They didn't have any funding for a larger trial. Since 2016 there has been no funding for research at the depersonalisation research unit. Staff is highly reduced. 

 

But, we have functional studies of depersonalisation disorder and we have basic research into models on how the brain regulates emotions. So, we have an idea of the role of the right VLPFC is. We also know that numbing and dissociation might involve two related networks and that is the reason that people can get numbing reduced but not dissociation or dissociation reduced but not numbing. 

 

Here is one who had rTMS done a the right VLPFC after mapping with a MRI-neuronavigation was used; 

 

"So today, my VLPFC was targeted at 1HZ per second I believe? Point is, it fucking worked. Probably a 20-30% reduction in numbness. I particularly noticed when I was driving I looked at the clouds-and they looked like they used to. Really. I have tried tons of meds, and none of them has ever produced an effect remotely close to what I'm experiencing now. There really is something to this, and I'll definetly be continuing with more sessions. More to follow!"

 

https://www.dpselfhe...vlpfc/?hl=vlpfc



#20 Mayer-Gross

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Posted 23 October 2019 - 12:17 PM

The role of the right VLPFC in emotional regulation,- basic research.https://www.ncbi.nlm...les/PMC2742320/



#21 teal

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Posted 23 October 2019 - 01:41 PM

Since 2016 there has been no funding for research at the depersonalisation research unit. Staff is highly reduced. 

 

For heaven's sake!

 
Here we have a forum of 20.000 members. On Reddit there are 17.000 people following the subreddit for DPDR. According to population-based surveys the prevalence of DPDR is about 1-2 %. There ought to be clamor for research spending. But rather they've reduced the staff and cut the funding at the only research unit for DPDR. Hurray.
 
I've always thought the ME/CFS community have been utterly unsuccessful at getting enough attention and thereby funding for studies, but I guess with regards to DPDR it's another story entirely.
 
spending-me-cfs-slett.jpg
 
 
 
Basic research is good. I like basic research. But at the same time, I've seen time and time again that what's true in a model hasn't been successfully translated into effective treatment. It's very (!) good though that case studies and small studies support their findings.
 
Anyways. So here we have professional medical doctors, with a will to help a huge patient group, but who's had their spending cut. And we have private rTMS clinics, opting to give ineffective treatment, making money in the process.
 
If the people behind the private rTMS clinics aren't totally unscrupulous, then it would benefit all of us if they were matched with the researchers, getting them on the right path to offer better treatment for us all.


#22 Mayer-Gross

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Posted 23 October 2019 - 01:52 PM

There is the first patient interest group for depersonalisation disorder in UK. They are just started but they have been in contact with politicians to get funding for research and more understanding of the disorder, so people can get the right diagnosis sooner.

https://www.unrealuk.org/aboutus 



#23 teal

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Posted 23 October 2019 - 02:02 PM

So, I've done some research and see that the costs of neuronavigation systems, including software, equipment and operative instruments ranges anywhere from $250,000 to just under $1 million.

 

For the sake of the example, let's say they charged regular prices, plus a premium of $2,500 for every treatment with neuronavigated rTMS. Then they'd need 100 patients to recover the costs if they went for the cheapest equipment, and 400 patients if they went for the most expensive.

 

We, as a people, have sent men to the Moon; we should be able to convince a clinic that this is the path to go. If everything fails, and fails miserably, they'd still have the machine to sell second hand. Or conversely, they could buy second hand equipment in the first place, cutting the costs and risks further.

 

Source for the claim for the costs for neuronavigation equipment.



#24 Mayer-Gross

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Posted 23 October 2019 - 03:06 PM

Well your research is totally wrong. Neuronavigation is used in brain surgery and in rTMS. The cost your are giving is for brain surgery with operation equipment that can be calibrated for operation. Will you open our brains too with a russian doctor and someone who has replied to your mail in Lagos?

 

The cost of neuronavigation for rTMS is; . "We note that the cost of our set-up is much lower than many commercial systems in the market (<$5000 vs $50,000). Our results also showed that the tracking performance of the system was on a par with other high-end commercial systems"

 

https://www.ncbi.nlm...les/PMC5738908/

 

Your assumption are also wrong. The reason there is not neuronavigation is because you do not need it for most disorders like depression or OCD. Localisation with the use of neuronavigation will also increase the cost for the patient with 500-700 euros- that is a cost 95% of patients can avoid because they don't need for location. rTMS is also relatively new on the private european market. From around 2017

 

 You need neuronavigation for disorders that are very atypical for the normal rTMS clinic right now and are regarded as "off-label" because of the small trails done. You also need someone who are highly skilled into the publications into the disorder and understanding the basic research into cognitive regulation of emotions.

Such a person is not likely to find in a rTMS clinic but in a university as a researcher.  






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