Antidepressants

[Transposony]

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Does anyone know why does most antidepressants including SSRIs take 4-6 weeks to be effective.
One exception being Mirtazapine which is an alpha 2 blocker.
What is the mechanism behind delayed action of SSRIs/SNRIs/TCA since they all increase serotonin/norepi ?

 

[Mr. Mojo Risin]

I don't remember the exact mechanism, but there's a lot of pre- and post-synaptic receptor modulation involved with SSRIs.

 

[Cokol]

There is a lot of debate about this in scientific community. Basic idea is that we don't know precise etiology of depression, so SSRIs affect a lot of other biomolecules - one of those substances is the primary causative agent of depression, we just don't know it yet.

Antidepressant efficacy due to its restorative properties. Stress (the most common precipitant of depressive episodes) reduces neurotrophins such as brain-derived neurotrophic factor (BDNF) and neuroprotective proteins such as B-cell lymphoma protein-2 (Bcl-2). The use of antidepressants in mice has been demonstrated to increase levels of BDNF and Bcl-2, suggesting that antidepressants may improve not only norepinephrine and serotonin levels, but also the overall health of neurons.

 

[Transposony]

I don't remember the exact mechanism, but there's a lot of pre- and post-synaptic receptor modulation involved with SSRIs.

If they were solely working at the receptor level then it should not take that long.
Even steriods don't take that long and they work at genetic level.
As Cokol suggested, 4-6 weeks points more towards a genetic level mechanism(s) involving synthesis of various (yet to be proven) factors.
I think we can safely assume that USMLE is not going ask about this since nobody knows.

 

[Mr. Mojo Risin]

If they were solely working at the receptor level then it should not take that long.
Even steriods don't take that long and they work at genetic level.
As Cokol suggested, 4-6 weeks points more towards a genetic level mechanism(s) involving synthesis of various (yet to be proven) factors.
I think we can safely assume that USMLE is not going ask about this since nobody knows.

Agreed. My response was not intended to mean that it was solely at the receptor level, but that its effects on receptor modulation and the downstream effects of this modulation has something to do with it. Without getting into specifics (which is clearly problematic given the fact that we don't know all of the specifics), my understanding from class is that there may be several "stages" of modulation, each playing a part of the big picture, and these take time to be established. Obviously there are many complex interactions taking place, and our current understanding (or lack thereof) prevents us from being able to concisely explain the multitude of mechanisms that are likely at play.