[Guest]

Dr.,

I am trying to understand why adding Buspirone to an SSRI when an SSRI is partially effective is an effective approach (sometimes) for depression and/or anxiety.

If I understand correctly:

SSRIs block the 5HT uptake pumps, which results in increasde serotonin available to the 5HT receptors. Side effects are generally the result of the fact that all 5HT receptors are receiving more serotonin, as opposed to just the receptors which affect mood and anxiety

Buspirone is a 5HT1A receptor agonist, which basically stimulates that receptor to receive more serotonin, which apparently is a key receptor in alleviating anxiety It does not block other receptors or pumps, but, to a lesser degree, also stimulates dopamine receptors.

If a person has maximized the dose of the SSRI without full response, why would adding Buspirone be helpful. It is merely adding more serotonin, and if the dose is maximized, haevn't they already blocked up to 80% of the uptake?

Is it that the SSRI uptake is blockade too general, and not enough is getting to 5HT1A (doesn't seem so, otherwise Buspirone should be effective for depression on its own, or SSRIs would be developed with 5HT1A agonists as well)? Serzone is an SSRI plus it blocks other receptors to make more available to the key receptors, qwhich is similar to the above but the effectiveness of Serzone seems to be no greater than an SSRI alone. Or does the dopamine agonism create the additional effect?

Sorry so many questions, Thanks as always

[Guest]

I would take me too long to answer in full. In short, et it suffice to say, that the simplistic notion of depression being not enough serotonin and these agents replacing serotonin has been made so simplified in order to be easily understandable that it is not really true. The pump effects take place in 20 minutes, the clinical effects in four weeks (or so). We must be talking about "downstream effects". Furthermore, chemicals that do the direct opposite of SSRIs in the brain may also be anti depressants. So these simplified models that are so readily said by almost every doctor and TV commercial are seriously flawed. It is true that the SSRIs increase serotonin to begin with. It is not true that your system has more serotonin than it did eight weeks after being on the drug as down regulation of receptors occurs due to feedback loops. Does Buspar interfere with this down regulation--I don't know, but may that is the mechanism of action. Is Buspar an effective augmenter of anti anxiety. There are multiple reports with mixed results. There certainly is a literature which would support its use on empirical grounds.

I begin to ramble too much and will stop it here.
[quote] Dr. ,

I am trying to understand why adding Buspirone to an SSRI when an SSRI is partially effective is an effective approach (sometimes) for depression and/or anxiety... [/quote]