Are SSRI's generally considered more sedating than SNRI's?

[JohnBoy2000]

I ask because - looking at combination drugs for mirtazapine and atomoxetine to add an additional serotonergic component, I've tried Lexapro, and found it made me seriously lethargic.

Effexor on the other hands - doesn't really seem to have that effect.

Failing this - the other possibility is Sertraline - but, I'm curious as to whether the outcome of that would be more similar to Lexapro, both being SSRI's.

The difference with Effexor being - chemically, it's unrelated to any other SS/NRI - so perhaps it's outcome would not be consistent with what's typical?


Any experiences from those who have tried both Lexapro and Sertraline?

How would you compare them to one another?

 

[Pomzazed]

Generally yes, norephenephrine makes it more stimulaitng and jittery.

 

[bindingaffinity]

I have not tried Lexapro but I have been on racemic citalopram and found it to be sedating and dysphoric (sedating in a very different way than e.g. mirtazapine is sedating). Fluoxetine I didn't find to be either sedating or stimulating at all, and I've had psychiatrists refer to both fluoxetine and sertraline as relatively stimulating SSRIs.

Norepinephrine reuptake inhibition tends to be stimulating in all drugs, although the sedative effects of histamine H1 receptor antagonism cancels it out in tricyclic and tetracyclic antidepressants.

 

[AlphaMethylPhenyl]

Effexor has Pristiq as a metabolite, but really tends to more show a stimulant effect at higher doses, 150 and higher, even 300

 

[ox1234]

From experience SNRI's have been much more sedating. Tried Sertraline, ended up jittery and heart racing all night. Mirtazapine knocked me out.

 

[bindingaffinity]

Mirtazapine is not an SNRI. At low doses it's mostly an antihistamine sedative, and at higher doses it doesn't seem to affect serotonin levels at all, and the effects of histamine antagonism pretty much knock out any stimulation from the norepinephrine reuptake. See here for an informative (but highly opinionated and editorializing) overview of mirtazapine's actual clinical pharmacology: https://psychotropical.info/mirtazapine-dubious-evidence/

(I don't share the author's dim outlook on mirtazapine overall; although it may not be a great antidepressant for most people, it works for many. It's also a great sleep aid and in cats, an unparalleled appetite stimulant.)

 

[d1nach]

"MIRT has not been shown to be effective in obsessive compulsive disorder (OCD) or cataplexy, does not affect platelet serotonin, does not cause serotonergic side effects or toxicity in over-dose, and does not cause ST if mixed with MAOIs. This indicates clearly that MIRT is not altering serotonin levels in the brain to a clinically significant or meaningful extent."

Lol... Im not sure this guy knows what he is talking about.

 

[ox1234]

Ah my bad. Was convinced it was an snri!

 

[JohnBoy2000]

With Effexor previously - when I got to a dose of 225 mg - it became (at least temporarily), like rocket fuel.

I know its noradrenergic effect only becomes apparent at that dose for some reason, but - are there any additional components that causes Effexor to have a reputation as, in some cases, a euphoric agent?
Given that it's chemical structure is particularly unique among the SSRI/SNRI class, perhaps it has as yet undefined pharmacological components that may make it as such?
Like it is classed as a mild mu opioid agonist, if I have that correct? (and was it at one point used in treating opioid withdrawal syndrome?)

I know another dude that had a similar experience when they started him at 225 mg - he basically said it felt like a recreational drug high.


Now - of course I hadn't experienced that on Lexapro.

In terms of comparison as to the profiles of sertraline and Effexor - would sertraline be essentially similar to Lexapro - or does it have additional components that can give it that "rocket fuel" characterization?
I know it's a slight DRI but - how much that plays into its profile, I don't know.
Alternately - it's just a flat basic SSRI?

 

[JohnBoy2000]

Maybe a more concise way to phrase that would be:

Effexor is known to have a distinct "activating" effect.

Is Sertraline ever known to do as such also?