# Lowering SNRI caused DP, but not immediately, why ?



## dppara (Dec 17, 2014)

Just a thought, but might worth mentioning:

I noticed that lowering cymbalta from 60 to 30 mg per day caused super bad DP. But only after a weak or so.

I wonder if the receptor up/down regulation might be related (especially autoreceptors).

Can this give a hint into understanding DP ?


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## dppara (Dec 17, 2014)

ps. this link made me think about this : http://psyberspace.com.au/depression/theory.htm


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## dppara (Dec 17, 2014)

It seems that lowering Cymbalta from 60 mg to even 55 mg / day seem to cause DP.

Currently I am trying to switch from 60 mg cymbalta to 30 mg mirtazepine.

It seems that I need to decrease cymbalta very slowly.


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## dppara (Dec 17, 2014)

This happens almost immediately.


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## thy (Oct 7, 2015)

You took the words right out of my mouth.


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## dppara (Dec 17, 2014)

Ok, I agree, the picture is not clear. Last week eI was simultaniusly taking 30 mg Mirtazepine and lowered Cymbalta to 57 mgs from 60 mgs (5%) and went from 1 mg Mirtazepine to 30mg in a few days.

I progressively experienced DP without panic (in contrast - when I decreased Cymbalta to 30 mg from 60 mg - it resulted in a panic + DP combo - last year).

This DP was very strong.

What is not clear: was it the increase in mirtazepine or the decrease of cymbalta.

I will soon find out, as next I keep mirtazepine at a constant 1 mg (for sleep) and slowly decrease Cymbalta - and see if I get DP again.

The problem here is that I changed two meds at the same time.


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## dppara (Dec 17, 2014)

It seems it is the mirtazepine. I went today for a walk and took 15 mg mirtazepine 2.5 hours ago. I got full blow DP about 30 mins ago.

Anyway, I wonder why mirtazepine does this. Causes acute DP. Just like seroquel (25 mg).

Maybe because "Mirtazapine has recently been found to act as a weak (EC50 7.2 μM) κ-opioid receptor partial agonist.[79]" ?

https://en.m.wikipedia.org/wiki/Mirtazapine


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## dppara (Dec 17, 2014)

Here is what serouquel and mirtazepine have in common:

They are both antagonists for

5-HT2A, 5-HT2C, 5-HT7, α2A, α2C Histamine.

So which is the one to blame ?

LSD causes some DP (for me) which is a 5-HT agonist, so 5-HT can possibly be ruled out (because then 5-HT antagonist would help DP, not cause it).

*Antihistamine-theory:*
It would be interesting to see if a pure antihistamine (for sleep) causes DP.

Is it so that H1 antagonists cause DP in general, for someone else too (Elliott mentioned that for him H1 antagonist causes DP - in general )?

I have not yet tried pure antihistamines (that cross the brain barrier).

For example this one : https://en.m.wikipedia.org/wiki/Diphenhydramine

If histamine antagonist causes DP, then what do histamine agonist do? Help it?

But yeah, the H1 antagonist induced sleepy-ness might be related to DP,

since DP is - for-me - a sleepy-state, not 100% awake, it feels like the state that I

have when I am asleep and my body is disconnected during sleep.

*Aplha*:

Does a pure alpha antagonist cause DP ?

Why would it ?

I used to eat (https://en.wikipedia.org/wiki/Tizanidine - alpha agonist)

for muscle pain and I do not remember it affecting DP

in any way, it only made me sleepy. So this would be one reason to rule out this

explanation.


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## TDX (Jul 12, 2014)

> I always say that mirtazapine is basically a glorified anti-histamine sedative and I stick by that. Horrible drug imo, especially for DP. It's in my "basically worthless" category. Only thing it's good for is sleeping your life away (if it doesn't make your DP too bad to sleep).


For me Mirtazapine does not change anything, but it makes me sleep and eat more. For me it's one of the only useful drugs I found.



> Does a pure alpha antagonist cause DP ?


I think I remember a study where they gave people an alpha-adreno-antagonist together with Naltrexone which induced depersonalization. So maybe the alpha-antagonism could play a role.


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## TDX (Jul 12, 2014)

I looked in my data at the effects of Mirtazapine. 14 people tried it. For 13 it had no effect, for one person it made the depersonalization significantly worse.

This confirms that it might not be effective against depersonalization. But it suggests that a worsening of symptoms is not very common either.


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## TDX (Jul 12, 2014)

By the way: Can you be sure that it's the H1-antagonism that affects your symptoms? You tried antipsychotics and Mirtazapine which also have many other modes of actions. Maybe you should try a centrally acting H1-antagonist which is not an antidepressant or antipsychotic. Maybe Cyproheptadine is such a drug. According to "Feeling Unreal" Simeon even tried it on some patients, unfortunately without success.


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## dppara (Dec 17, 2014)

This is interesting.

Mirtazepine and Seroquel - for sure - sends me into DP land, but why ?

I don't know. But perhaps it is the alpha antagonist ?

A pure H1 antagonist would be good to try, I dunno where I can get that one. Would be a good control test.

Well, do they sell that in UK ? Without prescription? If yes, I can ask a friend to bring me some when they visit me in Helsinki.


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## dppara (Dec 17, 2014)

Why did Simeon try H1 antagonist? Is there any reason why it would help?


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## dppara (Dec 17, 2014)

This would then cause DP ? https://en.wikipedia.org/wiki/Yohimbine- alpha antagonist

Google search indicates : yes


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## TDX (Jul 12, 2014)

> Why did Simeon try H1 antagonist? Is there any reason why it would help?


According to her book she didn't try it because it's a H1-antagonist, but because it's an 5-HT_2A- and 5-HT_2C-antagonist. The idea was that LSD causes it's effect by binding to both of these receptors and that blocking both receptors might have an anti-depersonalisative effect. Unfortunately it's not that simple.



> This would then cause DP ? https://en.wikipedia.../wiki/Yohimbine- alpha antagonist


I remember that Yohimbine can indeed cause depersonalization. Not in normal people, but in people with PTSD.

Yohimbine is an alpha-antagonist, but not a H1-antagonist, while Cyproheptadine is a H1-antagonist, but not an alpha-antagonist. Maybe trying each of them and looking what they do might give some insight.

A problem might be that Quetiapine, Mirtazapine and Yohimbine bind to different alpha-receptor-subunits according to Wikipedia.



> Mirtazepine and Seroquel - for sure - sends me into DP land, but why ?


This would be interesting to know. I always thought that antipsychotics might worsen depersonalization in some people, because of it's D2-antagonism. The fact that some people respond to dopaminergic medications supports this view. But maybe this is wrong and it's because many antipsychotics are also affect other receptors. It would be interesting how widespread antagonism of histamine and alpha-receptors is among antipsychotics. Maybe dopaminergics don't improve depersonalization in some people, because of the dopaminergic effect, but because of the stimulating effect. It would be interesting to know how people with Depersonalization Disorder react to anti-Parkinson drugs.


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## dppara (Dec 17, 2014)

Also, what about this ? http://www.ncbi.nlm.nih.gov/pubmed/14572626, this alpha receptor is related to norephinephrine, somehow...


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## TDX (Jul 12, 2014)

The problem is that increasing noadrealine by SNRI does not appear to work against depersonalization.


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## dppara (Dec 17, 2014)

Hmm... what does alpha antagonism has to do with norephinephriene?

With me high, doses of cymbalta -SNRI (120 mg per day) were pretty bad but 60 was ok. Currently going down slowly to 30.

Interestingly bupropion made me (and others) also very sensitive to cannabis, and very low dose of cannabis induced DP in me (and others - as searched on internet - https://www.erowid.org/experiences/exp.php?ID=55751)while on bupropion, while without bupropion i could smoke more (3 years ago) until hitting DP.


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## TDX (Jul 12, 2014)

The problem is that we just don't know how Cannabis induces DP or DP-disorder. It's a complete mystery. Cannabis does not only bind to CB-receptors, but is also an NMDA-antagonist and kappa-opioid-agonist. Maybe it also has some serotonergic effects as there is evidence that it can also induce HPPD.


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## dppara (Dec 17, 2014)

Ok, interesting to hear.


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## dppara (Dec 17, 2014)

Btw, I am decreasing Cymbalta , slowly, trying to go from 60 mg to 30 mg and I just got a pretty bad (but thank God - short) DP episode.

I guess I need to decrease Cymbalta even slower than I am doing it now (-7 mg / week).


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