9 replies to this topic

[AaronSD]

I stopped 60 mg daily cold, after being on for 2 years, back in 2008 and replaced it with 1,600 mg daily SAM-E (Nature Made).  My depression increased but not to an unbearable level, so it seemed to have an anti-depressant effect.  I did not experience any withdrawal symptoms other than the worsening depression.  I eventually started taking Pristiq, which was moderately effective, about 8 months later because SAM-E was expensive at the dose I was on and was not pulling me completely out of my depression.  Anyone out there with SAM-E experience?

[fishinghat]

Sam-e is probably a bad idea while withfrawing. Sam-e aides in the production of norepinephrine which is the basic compound used to make adrenaline that is why anxiety is one of hte most common side effects of Sam-e.

[AaronSD]

Sam-e is probably a bad idea while withfrawing. Sam-e aides in the production of norepinephrine which is the basic compound used to make adrenaline that is why anxiety is one of hte most common side effects of Sam-e.

I didn't have anxiety issues on SAM-E.  On the plus side, it is a natural substance and may help replace the effect of the norepinephrine reuptake activity of Cymbalta.

[thismoment]

The ingredients in placebos are natural substances too, and they work just as well as antidepressants. Why not take placebos?

[fishinghat]

While SAM-e increases the production of nor-epinephrine, cymbalta is diferent. SNRIs like cymbalta increase nor-epi during the first 2 months after that the prefrontal cortex picks up the increase level of circulating nor-epi and adrenaline and reduces sympathetic nervous signals to the adrenal gland which reduces adrenaline and nor-epi to pre-medication levels.

[AaronSD]

While SAM-e increases the production of nor-epinephrine, cymbalta is diferent. SNRIs like cymbalta increase nor-epi during the first 2 months after that the prefrontal cortex picks up the increase level of circulating nor-epi and adrenaline and reduces sympathetic nervous signals to the adrenal gland which reduces adrenaline and nor-epi to pre-medication levels.

How does cymbalta affect the production of norepinephrine by the noradrenergic neurons in the brain?  Is there a direct correlation between the concentration of norepinephrine in the bloodstream and synapses?

 

[fishinghat]

Because there are those on this site who do not have the biology background people like you and I have  I am going to try and give some detail for their sake so they can understand.

 

Dopamine, norepinephrine and epinephrine are all neurotransmitters used in various parts of our body. Dopamine can be converted to norepinephrine which can also be converted to adrenaline by the body. Whether they are used in there original form or converted to the next chemical in the line is sort of determined by supply and demand in the body as well as specific enzymes. One other note epinephrine is the same thing as adrenaline. A congress of scientists a few years back passed a recommendation that we only use the term epinephrine in the U.S. as it would be considered less 'scary' by patients as they are not familiar with the term.

 

Another thing to note; all organs in the body EXCEPT the adrenal gland and kidney (if I remember right) have both parasympathetic and sympathetic nerves going to them. The para/system carries signals to slow an organ or process down and the sympathetic carries signals to increase an organ or process. Now there are exceptions to this but in general it holds true. Without the parasympathetic nerve in the adrenal gland and kidney our body had to develop other means to control these two organs.

 

There is a small area in the prefrontal cortex (front of the brain) that is sensitive to adrenaline. As the level of adrenaline increases in your blood stream this area will decrease the signal coming through the sympathetic nerves to the adrenal gland and less noradrenaline (norepinephrine) and adrenaline is produced. This decreases the amount in the blood stream and available to the synapses in the body..

 

What Aaron was referring to was an area in the brain stem called the locus coeruleus which produces ,most of the norepinephrine for use in the brain neurons. This process is not fully understood at this time. The general thinking is that this norepinephrine is NOT transported through the brain by the blood but by special transport mechanisms (who the heck knows how!! lol). To answer Aaron's question I could not find any research on the issue of if Cymbalta exercises any control of the norepinephrine in the brain. I am going to look a little more though and will let you know what I find.

 

An as far as 'is there a direct correlation of norepinephrine and the blood stream and synapses?". Yes there is . Because of the flight or fight response of norepinephrine and epinephrine there is a feedback mechanism to the release and activity of the enzymes responsible for transport and use of these two in the synapses. So the greater the amount of adrenaline in the blood, the greater amount transported into neurons for use. Now I am going to contradict that statement (lol) by listing some exceptions. Less is taken up by nonessential organs during these emergencies. Like the stomach, spleen, and even the brains cognitive areas. That is why during emergency events many people panic and don't think clearly. Areas that DO take up more adrenaline when it is available include striated and cardiac muscles. These areas will be necessary whether we fight or flight.  I hope everyone can follow this and Aaron I will let you know if I find out something specific on the control mechanism of Cymbalta on the norepinephrine in the brain.

[fishinghat]

Hey, what you know Aaron I did find one.

 

http://www.ncbi.nlm....pubmed/16650830

 

IT says that cymbalta acts as a typical ssri in the brain but showed NO snri effect (no change in nor-epi levels). Interesting.

[AaronSD]

Hey, what you know Aaron I did find one.

 

http://www.ncbi.nlm....pubmed/16650830

 

IT says that cymbalta acts as a typical ssri in the brain but showed NO snri effect (no change in nor-epi levels). Interesting.

Interesting...wonder how those results coorelate to the human brain.  I was hoping ritalin, which increases norepinephrine levels, would help me wean off cymbalta.  These results may explain why I didn't find cymbalta as activating as effexor, which is (apparently) a SNRI.  Thanks for bringing the science in, by the way.  I worked in pharmaceutical basic R&D (Novartis and others) for years and it's nice to feel inspired to read research papers again.

[fishinghat]

Anytime Aaron.  It may be that the effexor may be more 'brain' active than cymbalta.  Here is wishing you the best on your fight with cymbalta.