Tolerance to SSRIs

[plumbus-nine]

Yeah, does this happen by SERT upregulation or only at receptor level? Read repeatedly that certain fixed doses of a SSRI agent are supposed to inhibit a certain amount of transmitters but also that SERT upregulates at least with releasers (fun fact, setotonin itself downregulates SERT). So makes it sense to push SSRI dose upwards when one stops to respond to one or will this just promote secondary effects?

 

[AlphaMethylPhenyl]

There are a variety of mechanisms by which the brain functions to regain homeostasis in the presence of abnormal activity. Decreased endogenous release, receding receptors, increased uptake..and so on.

Past our elementary understanding of how drugs work in the brain, usually, fast responses to SSRIs are in fact hypo/manic episodes.

SSRIs are more sophisticated mood-elevating agents than something like a stimulant. And very safe. So unless via mania, they tend to keep working if one continues therapy.

Though we have a handful of SSRIs, each has special utility of some sort or other in treating it's own psychopathology with exception.

Higher doses are usually reserved for anxiety. But the two are oftentimes intertwined.

Probably the closest we can come to explaining how they work is by increasing brain-derived neurotrophic factor in the dendate gyrus.