Explanation Serotonine/SSRI

[Nicca]

Hi there!

I apologize in advance for my English (I am Swiss, speaking German...)

Could anyone explain me in simple words why SSRI helps people with anxiety or depression, even if it increases serotonine (or does it not?)?
I have read Ray Peats article about the serotonine and the SSRI. He says himself than SSRI can help but maybe not because it is increasing serotonine but because of inscreasing dopamine or other neurotransmitters. Sounds logical.

But what happens with the increased serotonine in the synaptic gap when taking an SSRI? Ok, when this increases something else like dopamine it would have a good effect on anxiety or depression. But still there is more serotonine in the synaptic gap that would, on the other hand, make the situation worse.

I also wonder why MDMA is able to make people happy. It is also related to increasing the serotonine in the synaptic gap (as SSRI do). But after taking it people feel often depressed. My thoughts on it: Maybe the good effect on MDMA is also dopamine related and not serotonine related. But because serotonine is high after the "trip" ones feels depressed. What's not logical there is that dopamine itself does not make ones feeling happy and loving. Dopamine makes fit, concentrated and (as cocaine does) in higher doses almost maniac. Taking MDMA then would not explain why people feel so happy just because of dopamine.

Well, I do not take drugs. But the effects of drugs like LSD or MDMA are interesting in terms of studying the neurotransmitters.

In my case the SSRI is working. I tried to get rid of it. In very small steps I reduced the dose. Reducing it to 2-3 miligrams worked just fine. But when reducing it to zero my heavy mood swings came back like the time before taking any SSRI. So I had to take again SSRI (as long as I did not find another helper). Only 3 miligrams helped me within 3 days to feel 50% better. But why if serotonine does not help?

I do not get it to be honest... can anyone explain?

 

[Dante]

Quoted from wikipedia - "Owing to the lack of a widely accepted comprehensive theory of the biology of mood disorders, there is no widely accepted theory of how these changes lead to the mood-elevating and anti-anxiety effects of SSRIs".
Some say it's due increased BDNF(a nerve growth factor) in the hippocampus (hippocampus shrinks in depression) , haidut wrote in a post that SSRIs are 5-HT2C antagonists and that is what explains most of their clinical effectiveness and they also increase allopregnanolone (a metabolite of pregnanolone) in the brain.
Apparently , someone has edited the mechanism of action section of SSRI's wikipedia page as it's quite different from what i saw 2-3 weeks ago. It was mentioned there that downregulation of 5-HT2c receptors after some weeks of treatment (an adaptive change because of too much extracellular serotonin) is one mechanism of action. That is not present there anymore.
I think a lot of SSRIs also make depression/suicidal thoughts worse initially. It's only after 4-5 weeks that they start kicking into effect.
Btw , which ssri are you taking ? Weaning of ssris will take atleast 2-3 weeks in my opinion (took me around that time) . You will have to endure the mood swings for some time as the brain reorganizes again.

 

[raypeatclips]

Someone asked Peat this question on a show.

 

[Nicca]

Thanks, that's exactly what I was looking for

 

[marteagal]

Maybe also helpful: A while ago, Danny Roddy referred to an interesting article called "Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response".

I have the PDF but I don't find it at the moment, so here's my summary from memory. Basically, the authors assume that serotonin causes damage to the brain in the first place which then activates compensatory mechanisms (i.e., an increase in neurotrophic factors). And that a temporary overshoot of this neurotrophic response may be responsible for the improvement of depressive symptoms.

If you follow this notion, then, I think, treatment "non-responders" would just represent people whose body is so seriously compromised that it doesn't have the resources to compensate the harm induced by serotonin.

 

[allblues]

Hi Nicca, may i ask how long you have taken the SSRI?
The workings of SSRI drugs are indeed complex, targeting and inhibiting the protein which binds serotonin, the SERT protein,
produces varying changes, which can be time-dependent.
For example, there seems to be a tendency for the drugs to "poop-out", lose effectiveness for some people after moderatly chronic use,
which signifies some changes happening.

 

[Iambecomedeath]

Two words : Downregulation and Desensitization. SSRI's work by downregulating and desensitizing serotonin receptors, so much of their effect ends up being 'anti-serotonin'.

 

[TurtleNeck]

Two words : Downregulation and Desensitization. SSRI's work by downregulating and desensitizing serotonin receptors, so much of their effect ends up being 'anti-serotonin'.

Research for that claim?