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Drugs route i decided to take for prevent Depression and Suicidality

depression ketamine suicidality sarcosine nsi-189

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#1 Zibibbo

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Posted 01 August 2017 - 11:12 AM


Hi.

I'm 26 yo.

 

Since 22 i suffered of depression

.

I've been cyclically in the tunnel (6month in, 6 month out) but i'm not diagnosed Bipolar.
Now i'm out the tunnel for the 3rd time and use my energy to prevent another episode

I suffered of strong suicidal thoughts and, also if i feel good now, i  know depression will be return and if i don't do something NOW, suicidal behavior will worsen later during years.

 

I've tryed 4 SSRI's.
It seems Fluoxetine and Venlafaxine did something but i cannot be sure at all and if they worked they started only after 3months.
Too much time and too many "suicidal crysis" in between.

I'm know pharmacology and the limits of the therapeutical effects of actual antidepressant terapies. 
At least, considering this and considering my personal history, i thought the better way is prevention and work over my brain with a full-spectrum therapy based over the last researches.

This is a bet. Side effects of drugs could bring me to a lowered quality of life then using standard treatment.
Personally i don't believe so no more.
Suicidal crysis were so strong in the past that i decide to run the risk.

So this is my actual\next therapy. It acts over different biological way, based over last recent research:

 

1)Serotoninergic way: Venlafaxine 70mg\day (standard dosage)
2)Glutamatergic way: Sarcosine 2gr\day
3)"Neurotrophic way": NSI-189

4)another gutamatergic way: R-ketamine

 

Don't wanna mix too many drugs (because of possible interactions and sides) so i'm testing combinations of two drugs per time.

 

The route:

 

Venlafaxine: ever. SSRIs are the major studied drug for depression so i consider it my main therapy.
Sarcosine&NSI-189: people use to cycle NSI 3-4 times\year. During non-NSI period i will substitute it with Sarconsine instead of taking nothing else.

Working over hyppocampus trophysm i hope NSI to revert depression hyppocampal damage and so lower the probability of fall again in depression.

R-ketamine: because of its rapid effect (hours) i will use it to fight depression if it will come again. It is also supposed to be effective against suicidal behavior\thoughts. It is possible to use R-ketamine weekly to prevent depression but as of now i feel more appropriate to do Sarcosine&NSI-189 cycle for prevention purposes.

 

Last notes:

1) as of now i'm under Venlafaxine+Sarcosine therapy. Never tryed NSI and R-ketamine but i'm working to get them.
2) everything i wrote it is based on a scientific base but in the end they become from my personal evalutions and my personal history. 
3) i'm a MD and i know pharmacology, anyway cure on itself is never safe. I know what i'm doing and i don't encourage none to do what i do. I just wrote a report end interested to discuss over it.


Thanks for your time.


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#2 jack black

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Posted 02 August 2017 - 03:36 AM

is there a question somewhere in the above post? IMHO, SSRI is not worth trying, as they are not a good depression treatment and have crippling side effects with chronic use. As MD you should know it well. 

Now, we belive antidepressive action of SSRI is really mediated by boosting BDNF, but SSRI do it indirectly and it takes forever.

Look for immediate ways of boosting BDNF. Simple google search here will give you plenty of ideas. 


Edited by jack black, 02 August 2017 - 03:36 AM.

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#3 jaiho

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Posted 02 August 2017 - 08:34 AM

 

 

they are not a good depression treatment and have crippling side effects with chronic use

 

This is incorrect, they are actually very useful for severe depression, and side effects are minimal. They are life changing for many people.

For the other substances such as NSI-189 & Sarcosine, the evidence is far less.

 

Ketamine is great but the effects are short lived. You need a 'maintenance' treatment for chronic depression such as SSRIs/SNRIs/TCAs/MAOIs.


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#4 hydrus

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Posted 02 August 2017 - 09:59 AM

SSRI can help some. At least they don't have that many side effects except when they have some. For many (including myself) they are cr*p an don't give you your life back.

 

Some years back by accessing unpublished studies from industry  it was discovered that they are hardly better than a placebo. I think according to the data, substracting the placebo effect only one in 7 depressed people will benefit substanstially when given an SSRI. CBT was equally (non) effective.

 

 

 

 

 


Edited by jamme, 02 August 2017 - 10:09 AM.

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#5 sentics

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Posted 02 August 2017 - 10:38 AM

70 mg of venlafaxine is a very low dose; personally i didn't see depression relief until taking 225 mg. just food for thought, in case your stack doesn't work out.



#6 jack black

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Posted 02 August 2017 - 12:39 PM

they are not a good depression treatment and have crippling side effects with chronic use


This is incorrect, they are actually very useful for severe depression, and side effects are minimal. They are life changing for many people.

I wouldn't cansider loss of libido (sometimes permanent) as minimal, but yes, life changing for sure.
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#7 hydrus

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Posted 02 August 2017 - 01:02 PM

here is why I think SSRI alone are questionable treatments.
 
look at this typical result:
 

Remission rates, defined as an HAMD score of ≤7, in addition to response rates were reported. The rate of remission for patients taking venlafaxine (45%) was significantly greater than the rate for patients taking the SSRIs (35%) and placebo (25%).

 
http://www.medscape....rticle/462850_2
 
So basically SSRIs have a 35% remission rate. Doesn't sound to bad but don't forget that placebo has a 25% remission rate. Therefore SSRIs have only a 10% drug specific remission rate - the real effect of the drug. 10% is not much. You need to treat 10 people to cure 1 person.
 
 
Look at this:
 
https://en.wikipedia...needed_to_treat
 
 

Perfect drug 1.0 Everybody is cured with the pill; nobody without

Very good drug1.25 Ten take the pill; 8 cured by the pill, 1 cured by itself, 1 still sick.

Satisfactory drug   2.5 Ten take the pill; 4 cured by the pill, 3 cured by itself, 3 still sick.

High placebo effect 10 Ten take the pill; 6 cured but 5 of those would be cured anyway.

Low cure rate  10 Ten take the pill, one is cured by the pill, one cured by itself, 8 still have the disease.

Goes away by itself   10 Ten take the pill and 9 are cured; but 8 would have been cured anyway.

Sabotages cure  −10 Ten take the pill, two would have been cured without it, but with the pill, only one is cured, so NNH=10.

 

 

NTT of 10 is not a satisfactory drug. It is close to a low cure rate.

 

Most likely someone with a depressive illness who responds to a placebo will relapse sooner or later. I do not believe a placebo will be an effective long-term treatment for depression. 
 
Further SSRI trials with different agents would probably increase the chance of remission but if you didn't respond to the first SSRI the second is probably even less likely to work.


Edited by jamme, 02 August 2017 - 01:49 PM.


#8 Zibibbo

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Posted 03 August 2017 - 01:41 AM

SSRI is not worth trying, as they are not a good depression treatment 

Not if you suffer of non recurring, non paralyzing depression. It is known antidepressant are efficaceus with moderate-severe depression.
For mild depression antidepressant can worsen your life because of sexual sides. It is a question of good\evil balance of the meds but this is true for each molecule.

 

and have crippling side effects with chronic use

 

Antidepressant are intendend to be used not lifelong but maximum for 6-12 months or 24months if you had more then one major depressive episode.
Sometimes are prescribed lifelong if you suffer from recurring, cronic, depression because this condition it is so devastating that it is worth to take the meds lifetime with their sides, anyway i don't know about studyes about this, so i cannot say so much. I don't know if bad irreversible sides can arrive with long trateatments with SSRIs

Can you tell us more?



#9 Zibibbo

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Posted 03 August 2017 - 01:43 AM

 

For many (including myself) they are cr*p an don't give you your life back.

As already sayd it is more correct to say that they turn you life from IMPOSSIBLE to live to SURVIVABLE life.
Unfortunately everyone have to lower its own expectations about meds. We are far away from the discover of a good, efficaceous, treatments.
This is why as of day it is not correct to treat a person only with meds. A depressed-treated person need parental's and friend's care. 

 

  it was discovered that they are hardly better than a placebo

 

 Also published research report this. The correct point of view is that, fortunately or not, placebo effect result everytime to be strong when you study psychiatric deseases.
In other words.. it is the placebo that is strong, not the antidepressants that are wake/ unefficaceous.
Anyway you can ask a psychiatrist: they will tell you that in their pratice of 10-20 years they saw that in fact after SSRI introduction they can say a significant change in mood and symphotms in many impatients :-). Good psychiatrist don't use charts or manual to know if SSRI is having effect on you: they are able to recognize by themselves ;-) .

 



#10 CWF1986

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Posted 05 August 2017 - 06:14 PM

I'm not an MD, but I am curious about some things.

 

Why haven't you considered a tricyclic and/or stimulant/wellbutrin in addition to an SSRI or SNRI?  I know nortriptyline has some 5ht2 antagonism so it may help with ssri sides too.

 

And would about augmentation with abilify or buspar?  Or if you take a TCA low dose lithium?

 

I know of some extreme cases of treatment resistant depression where an MAOi, tca, and stimulant are taken together such as Parnate, Pamelor, and Dexedrine.  



#11 pamojja

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Posted 05 August 2017 - 07:51 PM

Antidepressant are intendend to be used not lifelong but maximum for 6-12 months or 24months if you had more then one major depressive episode.
Sometimes are prescribed lifelong if you suffer from recurring, cronic, depression because this condition it is so devastating that it is worth to take the meds lifetime with their sides, anyway i don't know about studyes about this, so i cannot say so much. I don't know if bad irreversible sides can arrive with long trateatments with SSRIs

Can you tell us more?

 

https://www.madiname...antsdepression/
 


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#12 hydrus

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Posted 06 August 2017 - 05:32 AM

I'm not an MD, but I am curious about some things.

 

Why haven't you considered a tricyclic and/or stimulant/wellbutrin in addition to an SSRI or SNRI?   

 

The problem is that SSRIs are marketed as the best way to treat depression while they are in reality often not curative. Doctors end up prescribing them because of the hype they received in the past 30 years not because they are the best class of AD.

 

Venlafaxine(Effexor) is more effective than SSRIs, it is an SSNRI.


Edited by jamme, 06 August 2017 - 05:41 AM.

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#13 Zibibbo

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Posted 08 August 2017 - 10:23 AM

 

 Why haven't you considered a tricyclic and/or stimulant/wellbutrin in addition to an SSRI or SNRI?  I know nortriptyline has some 5ht2 antagonism so it may help with ssri sides too.

 

And would about augmentation with abilify or buspar?  Or if you take a TCA low dose lithium?

 

Standard meds are decided by my experienced psy. As of now, i don't feel any sides. Anyway using meds for face sides of other meds could bring other sides too. 

Fluotexine and Venlafaxine seemed to work, so no reason to augment and maybe add other sides :-)
But i wanna be prepared and test other drugs for prevent future depressive drops with suicidal behavior\thoughts. I'll check if it is worth if by myself looking if i feel sides because of NSI, Sarcosine & friends and then make evaluation.

 

A stimulant like wellbrutin would be interesting. I feel (mentally) normal\ healthy but because i've no job (even if i'm working on my own projects) , have to face common difficulties typical of who live far from him original city and stay much time in my home... i feel a bit weak and sleepy and it affects my research for a job and for try to change my lifestyle (e.g: do sport!)


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#14 Zibibbo

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Posted 08 August 2017 - 10:52 AM

 

 

 

 

The problem is that SSRIs are marketed as the best way to treat depression while they are in reality often not curative. Doctors end up prescribing them because of the hype they received in the past 30 years not because they are the best class of AD.

 

Venlafaxine(Effexor) is more effective than SSRIs, it is an SSNRI.

 

 

Stupid and too simple question: wich is the best class of AD?
 


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#15 hydrus

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Posted 08 August 2017 - 11:32 AM

 

 

 

 

 

The problem is that SSRIs are marketed as the best way to treat depression while they are in reality often not curative. Doctors end up prescribing them because of the hype they received in the past 30 years not because they are the best class of AD.

 

Venlafaxine(Effexor) is more effective than SSRIs, it is an SSNRI.

 

 

Stupid and too simple question: wich is the best class of AD?
 

 

 

Depends on how you define best. MAOIs are probably the most effective but they can have serious side effects.

 

I think many psychiatrists of the older generation feel that the older ADs(MAOIs, TCAs) are more effective. Maybe SNRIs are better than SSRIs.

 

Main advantage of SSRIs is that they are relatively safe compared to older ADs.

 

Also best depends on your brain chemistry. For some people SSRIs work well. I think a drug that affects more than 1 neurotransmitter system will tend to be more effective. I think the problem is that depression is more than low serotonin and raising serotonin alone will often not do the job or even do harm.


Edited by jamme, 08 August 2017 - 11:34 AM.


#16 jack black

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Posted 08 August 2017 - 12:53 PM

I think the problem is that depression is more than low serotonin and raising serotonin alone will often not do the job or even do harm.

Exactly, depression is basically status post cortex/hippocampus neuronal loss due to various causes (OP, I know they don't teach it in your med school).
To successfully treat depression is to regenerate those missing neurons. BDNF is the most effective way. The reason SSRI (sometimes) work is they increase BDNF but only slowly. They may also work by flooding with 5ht and causing downregulation of 5ht2a receptors that are responsible for a lot of mental disorders. Guess what, there are ways to target BDNF and 5ht2a directly.

Another thing about it, the healthcare business model that we currently have is not interested in cure or prevention, but rather life long treatment of symptoms. That's were the money is. Similar situation in targeted therapy in oncology, except treatments run $120,000/per year or much more. You either take that (up to $1000) pill a day for the rest of your life or you die. The choice is yours (and your insurance).

This is why healthcare funding will go belly up in USA, regardless of Obamacare or Trumpcare. Big pharma successfully highjacked the whole thing.

Edited by jack black, 08 August 2017 - 01:06 PM.

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#17 jaiho

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Posted 08 August 2017 - 02:20 PM

 

 

This is why healthcare funding will go belly up in USA, regardless of Obamacare or Trumpcare. Big pharma successfully highjacked the whole thing. 

 

There's no evidence that there is a cure being held away from the masses. The fact is, depression is an extremely complex disorder that we're only in the infancy of understanding.

We don't know if 5ht2a or BDNF are the reasons anti depressants work, we only know that they're involved.

The newer drug, NSI-189 which targets BDNF & Hippocampus neurogenesis should be far superior than SSRIs but the trials show that is not the case.

 


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#18 jack black

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Posted 08 August 2017 - 06:16 PM

[quote name="jaiho" post="823814" timestamp="1502202028"]


There's no evidence that there is a cure being held away from the masses. [u/quote]

No, I'm not crazy enough to claim that. What I'm saying the industry is not interested in finding cures or prevention. They look for chronic treatments instead. Fortunately, we have universities and other players that don't have those conflicts of interest. But as we heard from the man himself, funding for research will be cut.

Edited by jack black, 08 August 2017 - 06:17 PM.

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#19 CWF1986

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Posted 08 August 2017 - 08:51 PM

 

 

 Why haven't you considered a tricyclic and/or stimulant/wellbutrin in addition to an SSRI or SNRI?  I know nortriptyline has some 5ht2 antagonism so it may help with ssri sides too.

 

And would about augmentation with abilify or buspar?  Or if you take a TCA low dose lithium?

 

Standard meds are decided by my experienced psy. As of now, i don't feel any sides. Anyway using meds for face sides of other meds could bring other sides too. 

Fluotexine and Venlafaxine seemed to work, so no reason to augment and maybe add other sides :-)
But i wanna be prepared and test other drugs for prevent future depressive drops with suicidal behavior\thoughts. I'll check if it is worth if by myself looking if i feel sides because of NSI, Sarcosine & friends and then make evaluation.

 

A stimulant like wellbrutin would be interesting. I feel (mentally) normal\ healthy but because i've no job (even if i'm working on my own projects) , have to face common difficulties typical of who live far from him original city and stay much time in my home... i feel a bit weak and sleepy and it affects my research for a job and for try to change my lifestyle (e.g: do sport!)

 

You mentioned suicidal ideation.  One possible prognosis of depression is death by suicide.  With so much at stake, I would be going with what's been tried and proven.  

 

But if you'e fairly stable right now, I can see how you'd like to try some other things before going down the more traditional route.

 

I'll continue to follow this thread to see how you do with these newer compounds.  Good luck!



#20 hydrus

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Posted 09 August 2017 - 04:29 AM

There's no evidence that there is a cure being held away from the masses.


There is also no evidence that industry is interested in finding a cure...

Edited by jamme, 09 August 2017 - 04:37 AM.

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#21 Zibibbo

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Posted 13 August 2017 - 07:17 PM

It is possible to avoid to talk about big pharma and not going off topic?

What about most recently evidences from NSI 189?


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#22 Mind_Paralysis

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Posted 14 August 2017 - 12:30 PM

The recent evidence suggest NSI-189 is not as effective as it was intended to be - however, it does appear to have some effect on some parts of depression. The actual efficacy-points was not disclosed, but it did not reach 0,5, which was the goal. However, if this means it only reached 0,4, like other AD's, then that doesn't mean the drug is necessarily BAD - just another route to treat depression.

 

HOWever... I would forget about all of that stuff above, because honestly, you DO strike me as someone potentially Bipolar, of one of the more atypical forms, which is being discussed as we speak (as to whether or not they exist or not - most likely they do, now we just have to describe them correctly).

 

I would try LAMOTRIGINE paired with something like BrexPiprazole or Aripiprazole - these are both two mood-stabilisers with robust antidepressant effects.

 

 

I suppose, if you truly start feeling suicidal, then intravenous Ketamine infusion IS the way to go - the effects are pretty damn strong. Remember though, that it's this route of administration which has the evidence of being effective against suicidal thoughts - NOT oral administration, or insufflation.

 

Here, have a look at this thread, which deals with similar issues, I went fairly deep on the litterature describing pharmacological treatment of suicidality there - it would appear as if Mirtazapine is a drug which might be useful, that, or AMITRIPTYLINE, which is the AD which causes the least Suicidal Ideation when treating depression.

 

http://www.longecity...ndpost&p=824104


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#23 Zibibbo

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Posted 14 August 2017 - 04:24 PM

The recent evidence suggest NSI-189 is not as effective as it was intended to be - however, it does appear to have some effect on some parts of depression. The actual efficacy-points was not disclosed, but it did not reach 0,5, which was the goal. However, if this means it only reached 0,4, like other AD's, then that doesn't mean the drug is necessarily BAD - just another route to treat depression.

 

HOWever... I would forget about all of that stuff above, because honestly, you DO strike me as someone potentially Bipolar, of one of the more atypical forms, which is being discussed as we speak (as to whether or not they exist or not - most likely they do, now we just have to describe them correctly).

 

I would try LAMOTRIGINE paired with something like BrexPiprazole or Aripiprazole - these are both two mood-stabilisers with robust antidepressant effects.

 

 

I suppose, if you truly start feeling suicidal, then intravenous Ketamine infusion IS the way to go - the effects are pretty damn strong. Remember though, that it's this route of administration which has the evidence of being effective against suicidal thoughts - NOT oral administration, or insufflation.

 

Here, have a look at this thread, which deals with similar issues, I went fairly deep on the litterature describing pharmacological treatment of suicidality there - it would appear as if Mirtazapine is a drug which might be useful, that, or AMITRIPTYLINE, which is the AD which causes the least Suicidal Ideation when treating depression.

 

http://www.longecity...ndpost&p=824104

Thanks for the reply.
I already asked for a mood stabilizer. The psy sayd i'm not BD so she disagreed. I sayd i know mood stabilyzer are used off laber for depression. She sayd isn't it. 
This made me confused.
Anyway i'm not a doctor and even if i studyed molecular biology and know psychopharmacology, i lack of clinical experience, so i'll do what doctor thinks is better for my case considering benefits\sides.

I'm really interested in Ketamine, i need to do extensive trial on me. Maybe adding this treatment could improve my SI\ depression coping.
As of now i've tried 2 ketamine analogous, fluorodeschloroketamine and descholoroketamine, intranasal, but had only bad results. I hope R-ketamine wich i've recently obtained would answer some questions.


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#24 jack black

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Posted 14 August 2017 - 05:32 PM

Anyway i'm not a doctor and even if i studyed molecular biology and know psychopharmacology, i lack of clinical experience, so i'll do what doctor thinks is better for my case considering benefits\sides.
 

 

 

Interesting, in your very first post you clearly indicated you were a physician and and you were well sure of your own treatment plan:

 

 

3) i'm a MD and i know pharmacology, anyway cure on itself is never safe. I know what i'm doing and i don't encourage none to do what i do. I just wrote a report end interested to discuss over it.



#25 Jiminy Glick

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Posted 14 August 2017 - 10:53 PM

Do you get an adequate amount of tryptophan, phenylalanine, and magnesium in your diet? Also what are your reasons for being suicidal and can you change those perceived negative things? Both chemistry and psychology play a part in behavior. 


Edited by Jiminy Glick, 14 August 2017 - 11:19 PM.


#26 Zibibbo

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Posted 15 August 2017 - 07:57 PM

@jack black:
MD (master's degree) in Molecular Biology. So i know pharmacology, biology, anatomy, pathology.
But i'm not a physician neither a psychiatrist (MD in medicine + 4 years specialization in my country).

I cannot see where i was wrong. Let us know.

#27 Zibibbo

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Posted 15 August 2017 - 08:23 PM

@Gymini Glik

Don't know why but i experienced acute and long-term fear ("angst" in deutsch) and this is recurring. A claustrophobic feeling.

When it arrive it is tremendously painful and the only way to stop this suffer my head is able to think is suicide.

In general there is not a direct, definite cause wich i can link to.
Talking with a psy we found it is linked with my inner need of recognition by the external world (job, friend, love).

#28 Jiminy Glick

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Posted 15 August 2017 - 09:36 PM

@Gymini Glik

Don't know why but i experienced acute and long-term fear ("angst" in deutsch) and this is recurring. A claustrophobic feeling.

When it arrive it is tremendously painful and the only way to stop this suffer my head is able to think is suicide.

In general there is not a direct, definite cause wich i can link to.
Talking with a psy we found it is linked with my inner need of recognition by the external world (job, friend, love).

 

It seems to me that there is a lot of anxiety involved in that as well. I would look into amino acids (tryptophan, phenylalanine, taurine, glycine, creatine, and others), magnesium, and a multivitamin. 



#29 jack black

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Posted 16 August 2017 - 01:40 AM

@jack black:
MD (master's degree) in Molecular Biology. So i know pharmacology, biology, anatomy, pathology.
But i'm not a physician neither a psychiatrist (MD in medicine + 4 years specialization in my country).

I cannot see where i was wrong. Let us know.

Lost in translation. MD means medical doctor in USA.

From your description it sounds like bad anxiety and not depression. SSRI is wrong treatment for that.
Look into tianeptine and lithium. You can either get a script or buy it OTC.

Edited by jack black, 16 August 2017 - 01:45 AM.


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#30 Finn

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Posted 16 August 2017 - 04:04 AM

@jack black:
MD (master's degree) in Molecular Biology. So i know pharmacology, biology, anatomy, pathology.
But i'm not a physician neither a psychiatrist (MD in medicine + 4 years specialization in my country).

I cannot see where i was wrong. Let us know.

 

In English language abbreviation MD usually refers to Doctor of Medicine, from the Latin Medicinae Doctor (MD). 

 

Master's degree is abbreviated usually MA (Master of Arts) or MS or MSc or MSci (Master of Science) depending on the degree. 


Edited by Finn, 16 August 2017 - 04:06 AM.

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