How come Brintellix works for GAD as well, when it reduces GABA?

[SirSwede]

So, I am confused because I've learned that Brintellix:

"reduces the release of GABA through 3 different modes of action:
​

• 
  [*=1]Mode 1: blocks serotonin reuptake pump (serotonin transporter)
  [*=1]Mode 2: binds to G protein–linked receptors (full agonist at serotonin 1A receptors, partial agonist at serotonin 1B receptors, antagonist at serotonin 1D and serotonin 7 receptors)
  [*=1]Mode 3: binds to ion channel–linked receptors (antagonist at serotonin 3 receptors)"

We all now that decreased GABA leads to increased anxiety, increased aggressive behaviour, decreased social behaviour, decreased eye contact, and decreased bowel function. Yet, Brintellix is prescribe for GAD and there are some scattered reports of it even working for anxiety a bit! Why is that? Can someone please explain, what I am missing here?

(Source: https://stahlonline.cambridge.org/p...apeutics&name=Vortioxetine&Title=Therapeutics)

 

[Memantine]

Perhaps the GABAergic mechanism is specific to certain brain area's. Some GABAergic drugs cause depression as a side effect (for instance Vigabatrin or even some of the benzodiazepines) due to the inhibition of brain areas associated with happiness.

So this drug might disinhibit such brain areas selectively. Thats just hypothetical speaking, I do not know a lot about Brintellix.

 

[Kdem]

How does this drug decrease the release of GABA ? I´d like to know.

Probably a really bad drug to take while in benzo withdrawal ?

 

[serotonin2A]

The only mechanism that is probably relevant is 5-HT3 blockade. The other effects are typical of other antidepressants.

http://www.ncbi.nlm.nih.gov/pubmed/2066767
http://www.ncbi.nlm.nih.gov/pubmed/15541891

 

[PINKoPANaTHER]

Decreasing the ligand for a receptor, can, in theory, increase the sensitivity of the receptor complex/system. Similar to how naltrexone is used in certain addiction treatments. I, however, found naltrexone to be beyond useless, and dangerous (OD without central symptoms, liver enzyme elevation, severe depression etc.) but then again others swear by it (usually in low dose form, a new medical quackery fad)

 

[SirSwede]

Decreasing the ligand for a receptor, can, in theory, increase the sensitivity of the receptor complex/system. Similar to how naltrexone is used in certain addiction treatments. I, however, found naltrexone to be beyond useless, and dangerous (OD without central symptoms, liver enzyme elevation, severe depression etc.) but then again others swear by it (usually in low dose form, a new medical quackery fad)

That's very interesting. Thanks. Do you have enough knowledge about this theory, in order for you to feel that you are able to deepen your theoretization as far as vortioxetine and dosage go?

 

[Memantine]

Decreasing the ligand for a receptor, can, in theory, increase the sensitivity of the receptor complex/system. Similar to how naltrexone is used in certain addiction treatments. I, however, found naltrexone to be beyond useless, and dangerous (OD without central symptoms, liver enzyme elevation, severe depression etc.) but then again others swear by it (usually in low dose form, a new medical quackery fad)

I think that only counts for direct agonists/antagonists and not for the depletion of endogenous neurotransmitters.

 

[adder]

All these "new generation" antidepressants are SSRIs with 5-HT1 partial agonistic properties which are supposedly useful in GAD, so they're probably just as effective as an SSRI + buspirone which is shit in my experience. It's not like great selectivity at SERT is what you need for best antidepressant effect, but on paper all SSRIs are fairly selective but if they differ so much at therapeutic doses in their effects, then their selectivity is still weak in practice, numbers speak vilazodone and vortioxetine are no more selective than older SSRIs, so it's still a trial & error process of choosing the one with the least side effects for a specific patient. In my opinion going through some kind of katharsis during a psychedelic trip or MDMA session has a bigger chance of "healing" you from depression than any of these antidepressant drugs does. However, I've learned nothing's really going to work long-term if you go by yourself, loneliness and isolation make you depressed, and I bet they play a major role for all depressed people. You need to be both physically and psychologically close to other people to function healthily.