2 replies to this topic

[beez]

I just found something in another forum from Dr.Marianco. I heard about him before. He's considered some kind of guru.

He wrote about SSRI and side effects of SSRI. This here really concerns me cause if this is right then wouldn't this mean that

the often used combo SSRI + Wellbutrin (NDRI) would actually be totally risky cause Wellbutrin mainly works on NE and much less on DA?

I was actually considering adding Wellbutrin to Lexapro cause I know Wellbutrin and took it in the past as single drug where it didn't work.

I thought maybe taken together with a SSRI it could work better.

But now I'm concerned. I mean there are no antidepressants which are dopamine reuptake inhibitors. So there is no way of boosting DA.
 

 

Increasing serotonin is useful since it quickly reduces the perception of stress. Blocking stress is the most predictable effect of an SSRI. This results in a reduction in anxiety, a reduction of overall stress signals (e.g. norepinephrine, ACTH) to the adrenal glands - giving the adrenal glands some breathing room to rest and recover. Over time, as the adrenal glands recover from fatigue, their improved output can reduce norepinephrine levels, helping restore dopamine production, and reduce depressive and anxiety symptoms. Brain function changes to a more non-depressed state. The reduction in norepinephrine and increase in serotonin helps reduce premature ejaculation - which tends to be caused by high norepinephrine levels (since a burst of norepinephrine triggers orgasm, high norepinephrine levels can cause one to be trigger happy so to speak).

Excessively increasing serotonin levels, however, will reduce dopamine production from dopamine neurons. This will further increase norepinephrine production from norepinephrine neurons - since a tract from the dopamine neurons helps control norepinephrine production. The reduction of dopamine and increase in norepinephrine creates a side effect called akathisia. Symptoms include agitation, restlessness, insomnia, anxiety, tension, irritability, fidgetiness, etc. At its worse, it leads to a feeling of wanting to jump out of one's skin - leading sometimes to impulsive behaviors such as suicide. The increase in suicide risk from antidepressants lead to the FDA requiring warnings about this. Of course, they could not explain it as I have. I usually tell patients to reduce the dose themselves when they get akathisia - to prevent problems like suicide from even occurring.

 

 

Edited by beez, 22 May 2014 - 11:40 PM.

[Flex]

Could You explain more percisely how NE and Serotonine inhibits dopaminergic tone or ammount like e.g. via adrenergic a2 recetpors and so on.

I find these informations very interresting, but I know another reasons e.g. why people do suicide because of SNRI.

 

I heard it like this: Reputake inhibitors do as the name say inhibit the reputake, but therefore the storage went empty.

The NE storage refills after 3 days and the 5-ht(serotonin) refills after 2 weeks.

 

The Idea behind RI is that Your synapse get "trained" to increase the output of monoamines, this undergoes btw selfregulating mechanism like autoreceptor activation which inhibit the release when a overload occurs.

 

Basicaly Your Synapse trafficing of monoamines gets rather regulated than gained to the maximum.

This is the point where it helps against anxiety.

5-ht2a has been found as a main trigger of CRF production in the amygdala ( curoiusly 5-ht2c activation with e.g. trazodone makes me far more anxious) 

So decrasing/regulating  the 5-ht tone in the amygdala contributes to the anxiolytic effects.

 

If You take a SNRI Your motivation will curb up after 3 days, but not Your Depression.

You are therefore more prone to implement Your suicide plans without changing the gray,dark,hopeless perspective of the world, since the 5-ht still needs to refill for further 1 1/2 weeks

 

 

 

[Tom_]

You have got to stop researching things and taking them at face value!

The situation is infinately more complicated than with all of the monoamines acting as inhbitors and disinhibitors of the other monoamines depending on which receptor is being triggered.

 

The facts are NRI's are effective for depression. They can worsen anxiety, although they tend to improve that as well, so if the patient is particually anxious then it may be best to avoid NRI's. It however is not going to lead to a sudden increase in impusivity (since impusivity is controlled by a LACK of noradrenaline and dopamine in the PFC).

 

SRI's are just as likely to cause askinesia which is not associated with an increased risk of suicide.

 

I am not going to explain the biology or why the tit you qouted doesn't know there arse from there synaptic cleft, it would simply take to long and require me to spend an hour and a half pouring over at least three books to make sure I got it right. But let it be known it would involve more than just looking at two neurotransmitters to explain the whole suituation.