# My naloxone trial



## teal (Oct 9, 2019)

I've got six Nyxoid nasal sprays, each containing 1.8 mg naloxone. I used the first of them today, eight minutes ago. To get a smaller dose, I blew my nose right after taking the first dose. Got five more doses left for later.

Why try? In the British Journal of Psychiatry they write.

Nuller et al(2001) found a significant transient beneficial effect of naloxone infusion on symptoms of depersonalisation in 10 of 14 patients studied. This intriguing result suggests a possible role of the endogenous opioid system in the pathogenesis of depersonalisation, and the possibility that anti-opioid drugs may have therapeutic value. To date, this hypothesis has not been explored further in the literature, despite the impressive results from this pilot study.


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## Broken (Jan 1, 2017)

This is really interesting. What were the effects after taking it? I have thought of trying this myself but wouldnt know how to get hold of it. How did you get it in the uk? I will follow this thread am really intrigued to see how it goes


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## 35467 (Dec 31, 2010)

Several have tried it on the forum either as injection or nasal spray without effect. Doses of 4.mg have some injected . The "study" has never been replicated. This brings us to what is called the replication crisis in almost all fells. In social psychology under 45% of the "known things" can be replicated. Studies unto 80.years old have been rejected because they cannot be replicated -so the claims of false. In medicine there are also a replication crisis and i would say the many trials in relation to depersonalisation can be severely affected because many trials are so small, have often never been replicated. So, people who trys drugs and post it here becomes a kind of replication or supplement to data. Naloxone do not have it.

"In the past few years, there has been a growing controversy surrounding the validity of a number of cornerstone medical research papers. For example, Amgen, a US biotech company, attempted to replicate 53 high-impact cancer research studies and were reportedly able to replicate only six. Similarly, researchers from Bayer, a German pharmaceutical company, reported that they were only able to replicate 24 out of 67 studies. Moreover, John Ioannidis, MD, Professor of Medicine and Statistics at Stanford University-a strong voice in the replication debate-showedthat of 45 of the most influential clinical studies, only 44% were successfully replicated."

https://www.castoredc.com/blog/replication-crisis-medical-research/


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## teal (Oct 9, 2019)

Appreciated, Broken. What the effects are? Nothing so far. I will prolly take a whole dose tomorrow, then a double dose on Saturday, then a double dose on Sunday, and then I am out of Naloxone and all done. There is a study on Naltrexone (sic) and depersonlization as well. How I got it? I'll send you a PM. That said, I have much more faith in things like the magnet treatment used in more recent studies.

*UPDATE DAY 1*. It's three hours since I took the dose. I've got some lightheadedness and dizziness. It's not bothersome.

@Mayer-Gross, yeah, people posting here does indeed become some sort of anecdotal supplement to data. That's why I post.


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## 35467 (Dec 31, 2010)

I was convinced until 10.years ago that the opiopate system was the cause of depersonalisation -particularly the kappa receptor system. I think it plays a part in particularly the emotional numbing. People who could tolerate high doses of naltrexone (more than 100.mg) felt a slight reduction. Some who have tried buprenorphin that has a high affinity for kappa felt some reductions close to 20%. If the kappa opioid system play a signification role the reductions would be much higher on buprenorphin. It is not. Dynorphin are expressed in the medial prefronal cortex and can inhibit the amygdala and anxiety and likely make emotional numbing but other parts of the prefronal cortex is overactive in emotional suppression and will not be affected by it. In theory rTMS could affect these locations too.


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## Trith (Dec 31, 2019)

As I posted somewhere else, I am currently taking naltrexone and I experience a slight improvement in my derealization symptoms. It was more obvious the first time I tried it and now the effect seems to have faded away a bit, or perhaps it is hard to distinguish it because I have also started taking amisulpride.

I got it from my psychiatrist. I told him about the study and he simply offered to give me a prescription to try it. He told me he was comfortable giving me a prescription for that as it is something he is used to give to people, because he has a lot of patients dealing with alcoholism problems (which is the original purpose of naltrexone).

In the paper, they use a low dose, around 6 mg/d. My prescription was for 50 mg pills, which is the smallest on the market. I cut them down to 6 mg, and the effect was good. Reality was a bit sharper, and I was more aware of the atmosphere of places, which was quite enjoyable. But I was still not in 3D, and I think I was still quite numb emotionally, no noticeable differences socially either. The effect lasted for about 12 hours. I tried increasing the dose to 25 mg. I did not notice further improvement in my symptoms, but I tended to feel a bit shitty emotionally, but I am not sure it is the medicine, perhaps also my random life circumstances. But that lasted for something like 12h too, so it could be related. I felt a bit like life had less purpose, and things were shitty.

Now I am taking 12 mg/d, but as I said I find the effect much more subtle than before.


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## 35467 (Dec 31, 2010)

it has a very short half-life. It is a acute treatment for a opiate overdose. It can never be a treatment for a disorder due to it short half-life.

"In one study the serum *half*-*life* in adults ranged from 30 to 81 minutes (mean 64 ± 12 minutes). In a neonatal study the mean plasma *half*-*life* was observed to be 3.1 ± 0.5 hours."

https://www.rxlist.com/narcan-drug.htm


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## 35467 (Dec 31, 2010)

teal said:


> @Mayer-Gross, yeah, people posting here does indeed become some sort of anecdotal supplement to data. That's why I post.


Well, the trail is likely false and a lie. The half-life of naloxone alone would put question into the claimed effect. Many have tried it here. A person that have had DP for most of his life from Switzerland called "huggybear" had his insurance company to pay for several high dose infusions at hospital without effect. He have deleted his profile and all posts. But, many others have posted their experiences too and none points towards it have any effects. There are many debates going 10.years back in the subject. There is none who have been able to make a replication that could not be viewed as placebo.

But, as i said. There is a replication crisis where at least 50% cannot be replicated in medicine and that is in studies with more empirical data sets. Because all trail in relation to DP is very small the replication crisis might be much higher in publication in relation to depersonalisation. There has been a "studies" with "trials" of lamotrigine with a high response rate and reductions that has been retracted because they where fraud. People do post here with reference to it despite it is openly retracted.

https://www.ncbi.nlm.nih.gov/pubmed/21192145


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## teal (Oct 9, 2019)

I've already got the naloxone, and I am giving it a shot.

I found one or two positive reports on Reddit, if I remember correctly. Once I am done, anyone curious about naloxone will have one more case to build on.

Trials suspected of being false or a lie need also to be rebutted. As of recently the BJP wrote about the Russian results as intriguing. The more nonresponders, the less intriguing, and vice versa.

I know full well that the results of many trials are un-replicatable.


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## 35467 (Dec 31, 2010)

You often have a placebo effect that might be close to 20-30% in some. So, many will report benefit of anything they do.Many posts on this forum about different things tried that worked is likely related to that. I never read it for the same reason, The awareness of a replication crisis is very recent and that trial goes 20.years back. But, the replication crisis is related to recent publications with a high citations. It can be publication with over 2000.citations. In social psychology it is 80.years old trials with high citations that now is being rejected . So, publication that might seem to have high standards have been published and more than 50% fails. Often are those doing the trials active with a partiality and selective in their perception of data. Many researchers are aware of it now. In the german DTI study of depersonalisation they say that they will avoid certain interpretations due to the risk of failure of replication of data. So, they have been aware of it. We also have our selective perceptions and hopes that do data will perceived in optimist ways there is no basis for.


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## Trith (Dec 31, 2019)

Mayer-Gross said:


> You often have a placebo effect that might be close to 20-30% in some. So, many will report benefit of anything they do


How do you know they only had a placebo effect? As far as I know, you need a proper study to rule out the placebo effect, but you also need a proper study if you want to prove it is the placebo effect.

And you say that some have an effect up to 20 - 30% due to placebo. How did you determine it was a placebo effect for specific individuals? Or perhaps you are talking about people who have tried something like homeopathy.


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## 35467 (Dec 31, 2010)

As i said the opioid system likely plays a role in depersonalisation but not more than 20-30% of the symptoms. Naloxone can never be a treatment due to its short half-life. If our opioid system is up-regulated it will return very quickly when the effect subsides. I think the trial overestimate reductions and setbacks. The same can be said about the rTMS trials. They do no do a follow up on people in months after to look for setbacks or more reductions. In theory some might in a rTMS have a 40% reduction in symptoms that could make more psychological approaches work and make more reductions.Some could return to the original state within a year. We don´t know. It could be both. The french study will look into that.


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## 35467 (Dec 31, 2010)

Trith said:


> How do you know they only had a placebo effect? As far as I know, you need a proper study to rule out the placebo effect, but you also need a proper study if you want to prove it is the placebo effect.
> 
> And you say that some have an effect up to 20 - 30% due to placebo. How did you determine it was a placebo effect for specific individuals? Or perhaps you are talking about people who have tried something like homeopathy.


Yes, and there is no control group in most studies to rule that out. But, if you look at the theories based on the opioid system in depersonalisation disorder the prime suspect in the part of the system related to kappa/dynorphin system. The affinity of naltrexone on that system is low. We know that from studies of the drug. It mostly affect the endorphins system in a dose of 50.mg and you need a dose 3-5.times higher to affect the the kappa/dynorphin system. The is simple pharmacology. So, to say that a low dose of naltrexone works is very unlikely as not have any affect at all on the opioid system. I have tried both naltrexone 50.mg and nalmefene 18.mg.

There is a placebo effect in almost everything to many people. People buy experience creams that don´t work and the think they look better ect.


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## curiousmind (Oct 31, 2019)

Mayer-Gross said:


> There has been a "studies" with "trials" of lamotrigine with a high response rate and reductions that has been retracted because they where fraud. People do post here with reference to it despite it is openly retracted.
> 
> https://www.ncbi.nlm.nih.gov/pubmed/21192145


This study claims a really high response rate. Do we know why it was retracted?


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## 35467 (Dec 31, 2010)

I remember when i first read it stroked me that they had the same surname and there was no other authors. So, family related. The other thing is the claim of being at out-pateint programme with such high numbers a patients in the former Sovjet. The awareness of depersonalisation is very low and so many people ending being referred to a outpatient programme sounds very unrealistic. Their response rate is also much higher than the english data. I think it is all made up.

it can be read here.https://www.researchgate.net/publication/49715384_Lamotrigine_in_the_Immediate_Treatment_of_Outpatients_With_Depersonalization_Disorder_Without_Psychiatric_Comorbidity_Randomized_Double-Blind_Placebo-Controlled_Study


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## teal (Oct 9, 2019)

Mayer-Gross said:


> The other thing is the claim of being at out-pateint programme with such high numbers a patients in the former Sovjet. The awareness of depersonalisation is very low and so many people ending being referred to a outpatient programme sounds very unrealistic. Their response rate is also much higher than the english data. I think it is all made up.


I think you're right.

A while back, maybe half a year, I found some reports on Reddit, in the comment section, about getting better on naloxone. I did this Google search now: site:reddit.com depersonalization naloxone OR narcan

And with those keywords, I took a quick look over the comment section, I didn't see any "I got better from naloxone", but I saw this.



> I'm on lamictal and it's doing great so far.





> I was sick for 5 years prior to this and then tried Lamacital and it cured me for 7 years . Unfortunately it just came back (...)


*So, DAY 2*.

I've taken a dose of Nyxoid 30 minutes ago. So far I feel nothing.

Update. One hour fifty minutes after taking the dose, I got diarrhea.


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## curiousmind (Oct 31, 2019)

Mayer-Gross said:


> I think it is all made up.


Definitely a suspicious trial, but why would anyone be interested in publishing fake information to the public, especially when it concerns such a delicate field of research?


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## teal (Oct 9, 2019)

*DAY 3*
Used two Nyxoid nasal sprays four minutes ago. So this is the first day with a double dose.
Update: During the day I got quite a lot of lightheadedness.


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## teal (Oct 9, 2019)

*DAY 4*
I got no sleep tonight. That happens sometimes. Rarely, but sometimes. It could be a side effect of yesterday's naloxone use, but hard to tell.

Four minutes ago I took two doses, i.e. two x 1.8 mg naloxone.

This is the last day.

UPDATE. I got some sleep after taking the doses. Hard to fall asleep, as always, but I managed. Still I've had no positive effect of the Nyxoid. No positive effect whatsoever.


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## 35467 (Dec 31, 2010)

It is the part of the opioid system called kappa/dynorphin that is thought to make a aversive, numbing and dissociate state. There are no drugs selective for kappa. But, the part of the opioid system that morfin and heroine binds to is called MU or endorphin receptor. It give pleasure, one fells relaxed. "Runners high" is related to that. Naltrexone, naloxone and nalmefene blocks this effect. You cannot get "runners high" on them. Because the affinity for kappa is very low most people will not feel it takes DP symptoms but it may give them a more flat feeling as that endorphin system is taken out.


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## teal (Oct 9, 2019)

This is a bit of a digression, but when I was healthy I got a strong runner's high. All it took was some ten minutes of running, and there it was. But now, alas, every feeling I have is so watered out I scarcely feel a thing, runner's high included.


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## teal (Oct 9, 2019)

*CONCLUSION*
Four days, titrated the dose upwards and it had no effect whatsoever.

I feel somewhat better by things like taking a double dose of Ambien, but naloxone? Nope. I'll hopefully try Klonopin for the first time next week.


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## 35467 (Dec 31, 2010)

klonopin is the US tradename for clonazepam. In most of Europe it is traded as "Rivotril". When it is used with success in DP it is in a combination with a antidepressant.


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## teal (Oct 9, 2019)

I am trying clonazepam due to this paragraph, and the fact that Ambien has helped somewhat. Anyhow, I see that, like you write, it may work better with an antidepressant.

When lamotrigine cannot be tolerated or is ineffective, *clonazepam may be useful*, although the usual caveats regarding prescription of benzodiazepines apply. Although literature on the use of clonazepam in depersonalisation is scarce, one study found that it reduced levels of caffeine-induced derealisation in a single individual (Stein & Uhde, 1989). A role for anxiolytic drugs is also suggested by the data of Nuller (1982), and a recent case report describes an individual with primary depersonalisation successfully treated with a combination of clonazepam and citalopram (Sachdev, 2002). *As Sachdev notes, the same combination* has apparently been found effective by a number of contributors to an internet bulletin board for people with depersonalisation.

I am no fan of antidepressants. I was about to say they sap me for energy, but I haven't had much energy lately anyhow.


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## 35467 (Dec 31, 2010)

When I took 2,5 mg of Rivotril I was on Duloxetin 60.mg. It is the drug i tolerate the best. It can give some nausea if one starts with 60.mg at once so 30.mg is recommend the first week.


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## teal (Oct 9, 2019)

Mayer-Gross said:


> When I took 2,5 mg of Rivotril I was on Duloxetin 60.mg. It is the drug i tolerate the best. It can give some nausea if one starts with 60.mg at once so 30.mg is recommend the first week.


Oh, dang. I got a message today from my GP, about not getting clonazepam.

Valium. Would that somehow work, or? Your thoughts on this is appreciated, Mayer-Gross. I have taken Valium once before, but my memories of it is so vague.

As we know there is no blood test for F48.1. I've got a sky high score on the CDS, and lots of things mesh with DPD. The main reason I'd like to try clonazepam is to use it as a diagnostic tool. If I indeed get somewhat better, then it underpins that I have F48.1. I am not thinking about benzodiazepines as a permanent fix (they aren't), but like I wrote, primarily as a diagnostic tool


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## 35467 (Dec 31, 2010)

It can not be used as a diagnostic tool. I would guess that 20-30% might feel a response.So, if that is your idea,- drop it.

I know a danish women who felt nothing from it except being extremely tried. When it works it is the opposite. You fell much more energy and more present . I had tried other benzodiazepines prior to clonazepam without a similar effect. It could be that i was on other antidepressant. It likely shall be on a antidepressant that also works and you have been on for 4-6.weeks before such effect can be felt. There is no blodtest for any mental disorder and DNA test.


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## teal (Oct 9, 2019)

Mayer-Gross said:


> It can not be used as a diagnostic tool. I would guess that 20-30% might feel a response.So, if that is your idea,- drop it.
> 
> I know a danish women who felt nothing from it except being extremely tried. When it works it is the opposite. You fell much more energy and more present . I had tried other benzodiazepines prior to clonazepam without a similar effect. It could be that i was on other antidepressant. It likely shall be on a antidepressant that also works and you have been on for 4-6.weeks before such effect can be felt. There is no blodtest for any mental disorder and DNA test.


The blood test comment was meant as a sigh. I haven't got a diagnosis in the F-realm of ICD, so if I indeed get better, that would indicate we're talking about an F-diagonsis. That's what I meant by "diagnostic tool". As a tool it would not be precise as a scalpel, but blunt as a stone.

Much appreciated, your comments about other benzos. I looked over my digital journal now, and see I have used diazepam on some occations for sleep long, long ago. Sometimes I got somewhat better the next day, but most days not.


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## 35467 (Dec 31, 2010)

A very odd way to get a diagnosis. You most have a medical history with symptoms you have reported that are in journals. There are scales for the disorder that can be used. If you had a reduction of 30% on clonazepam it would still be very subjective and not something that can be evaluated from the outside. If there are no psychiatrists in your country aware of depersonalisation then it will change nothing. It the UK it is also very underdiagnose despite there have been a research unit for 20.years. The whole foundation of the charity "Unreal" is not about treatment but to bring awareness of the existence to those who suffer from it and health care professional. You may just be in a situation where it is not there.

Here is the situation in Germany;"However, a German study found a 12-month prevalence of 0.007 based on diagnoses given by clinicians, which suggests DPD is severely underdiagnosed, making research challenging in this population.3 Individuals with DPD experience recurrent episodes of feeling detached from oneself (depersonalization) and/or the external world (derealization). Other clinical phenomena of DPD include emotional numbing and somatosensory distortions.4"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158023/


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## teal (Oct 9, 2019)

Mayer-Gross said:


> If you had a reduction of 30% on clonazepam it would still be very subjective and not something that can be evaluated from the outside.


Yeah, so it wouldn't be to evaluate it from the outside, but for myself. I've never seriously explored psychiatric diagnosis before. Only had them thoroughly excluded by a professional early in my case history (excluded mood disorders, excluded schizophrenia, excluded personality disorders, etc).

But I now have become aware of DPD, and I score really high on the Cambridge Depersonalization Scale, so I think it's a great fit. Pretty much everything fits. So, for my own sake, if a psychotropic drug would make me (temporarily) better, then that would be good to know. It would underpin the rest.


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## 35467 (Dec 31, 2010)

So, you are hoping for a conformation that you suffer from this refractory/difficult to treat condition by having a response to a treatment of it that do not formally exist. Sounds very reasonable to me.


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## teal (Oct 9, 2019)

Something that underpins something is not a confirmation. It's just something that underpins something. So, there are no good treatments of DPD. No good treatments. But Anthony S. David et al. writes this about clonazepam.

Regarding treatment for depersonalisation disorder

4 e clonazepam is useful in some patients.

You won't find such treatment advice for say A49.3. I don't want to discuss my medical history here out in the open, but yes, I do really think it would be valuable to know if I could get better by a psychotropic drug. I don't see what's off about that. Just like if someone got better by corticosteroids it would indicate they have some sort of inflammation, though what type and the cause would not be known. It would only be an indication.


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## 35467 (Dec 31, 2010)

I got better on clonazepam 2.5 mg in 2004. I didn't know i had DP but the effect will go away after some 5-6. months due to tolerance and you likely have to use the same amount of time to get of it and you have been on it. Everybody develops tolerance to a benzodiazepine. We tried to find an alternative among the antiepileptic drugs that also affect the GABA system like gabapentine and topiramat. Because of tolerance and the effect in short in the few it works does that you can not be compered with the treatment of a inflammation.

But, you would also take it without have been on a antidepressant for some time. That would really increase your chances.


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## 35467 (Dec 31, 2010)

I think the chances on a combination of lamictal and antidepressant is just as high as clonazepam. There should be no problem with tolerance if it works. It is much easier to get a prescription on lamictal than clonazepam. I was by the way offered some years ago to start on clonazepam again by the last psychiatrist i saw . I refused that because if it worked i would develop tolerance to it within 5-6.months.


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## teal (Oct 9, 2019)

Some people get symptom relief from corticosteroids without having an inflammation; some people don't improve by corticosteriods yet still have an inflammation. So to use diagnostic terms, neither the specificity or sensitivity is 100 %. I guess back in 2004 when you got better from clonazepam it made you less prone to think something like mononucleosis could be driving your symptoms, if you ever thought so.

Anyways, did you feel some sort of improvement instantaneously on clonazepam? I get instantaneous improvement from Ambien. I used to get instantaneous improvement from alcohol, a single unit of alcohol was enough. That was long ago, and now alcohol doesn't have such an effect. Or, well, I tried two units of alcohol just recently, and it did nothing. But I don't want to try a higher dose. Why it no longer works, I dunno. It could be that I need to break some sort of threshold, needing a higher dose, and it could be the disease has progressed and changed since it broke out.

I know full well about withdrawl. I have had Ambien withdrawl, which ain't good, but have never tried anything stronger. You could say using benzos is playing with fire, and I would agree, but I can limit the number of pills I get to less than a full box, and decide that I shall only take 0.5 mg one day, wait some days, try a higher dose, etc.

I don't want a dead-end diagnosis by a public health care system that doesn't do a damn thing. I have no faith in a psychiatrist who has nothing to offer but to perform an interview he/she has just looked up how to do and has never done before.


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## 35467 (Dec 31, 2010)

But, the majority with depersonalisation who tries clonazepam do not benefit from it,- so it is not a diagnostic tool. When i had such a paradoxical reaction there was thought in neurological causes like epilepsy because nobody knew about depersonalisation. I have never by myself thought i suffered from anything somatic. Some psychtrists had over the time thought it could be a neurolocal condition that didn't had enough clair symptoms yet. So, i was though a examination for that.

But, some will say that since clonazepam works depersonalisation disorder dosn´t exist because it is a anxiety disorder with symptoms of depersonalisation/derealisation. You have go to therapy for anxiety. That is the position among some psychiatrists have here in Denmark.


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## 35467 (Dec 31, 2010)

I do not think that 0.5.mg of clonazepam will make any significant reductions in depersonalisation if it should work. i tried to reduce it from the 2.5 mg i remember and i felt it. My psychiatrist was happy something worked and was ok with giving me it. He said we could go as high as 2.mg -3.times a day. 6.mg in total and see if more symptoms would go away. He had to stop shortly after due to illness


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## teal (Oct 9, 2019)

> I have never by myself thought i suffered from anything somatic.


I have never thought I suffered from anything psychiatric. Mononucleosis, CFS and lots of other diagnosis have been suggested.


> But, the majority with depersonalisation who tries clonazepam do not benefit from it,- so it is not a diagnostic tool.


The majority who tries picking a lock with a binder clip fails, but that doesn't mean a binder clip is not a tool, it just means it's not a good tool, not a professional tool. If I'd take clonazepam and nothing happens, then whatever, but if I'd take clonazepam and I'd get some sort of instantaneous relief, then that would indicate my symptoms are psychiatric. Such an indication would be valuable to me. I guess it wouldn't be valuable to you, but to me, yes. Sure, sure, people with neurological conditions can also improve from benzos (absolutely!), but nonetheless it would be an indication I am on the right track.


> But, some will say that since clonazepam works depersonalisation disorder dosn´t exist because it is a anxiety disorder with symptoms of depersonalisation/derealisation. You have go to therapy for anxiety. That is the position among some psychiatrists have here in Denmark.


Bully for me that such people aren't in charge of me. If I'd get better, then I'd think "gee this means an F-diagnosis is more probable", and the only F-diagnosis that hasn't been ruled out, which gives anhedonia, is F48.1, where I score off the charts on the symptom scale. Getting such affirmation would be encouraging going forth, when making attempts at getting further treatment.

If I'd get access to clonazepam, which I won't do in the near future, then I'd try 0.5 mg and then wait, then a bigger dose, say 1.0 mg, then wait, then a bigger dose, so on and so forth. Much appreciated what you write about doses! That you needed a higher dose!


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