Posted by King Vultan on March 5, 2004, at 11:11:36
In reply to Re: Anyone suffer paradoxical depression with TCAs? » King Vultan, posted by sb417 on March 5, 2004, at 2:02:16
> > > > IMO, SSRIs would be more likely to cause a paradoxical depression than tricyclics in general. Why? The initial target of SSRIs is the presynaptic serotonin 1A receptor, which is inhibitory. Blocking serotonin reuptake causes these receptors to be pummelled with serotonin. If a person is so depressed that their serotonin neurons aren't really firing anyway, a person won't notice any immediate change in mood, but if a person's serotonin neurons are still firing at a moderate level, the stimulation of these inhibitory 1A receptors may cause the serotonin neuron to slow down its firing rate, triggering a worse depression.
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> Todd, that is very interesting. How would you explain a somewhat favorable response to an ssri initially, but a severe worsening of the depression 10 days to two weeks after starting the ssri?
I suppose one could imagine a case where a person has a small amount of serotonin available, and with the SSRI blocking reuptake, less serotonin is reabsorbed into the neuron and more makes it to its postsynaptic target (this is a postsynaptic receptor confusingly labeled as 1A also, but it is not inhibitory as is the presynaptic 1A autoreceptor). The stimulation of this receptor causes an immediate improvement in mood.However, some of the extra serotonin that is available from blocking reuptake also begins stimulating the presynaptic 1A autoreceptor. This has the effect of slowing down the firing rate of the serotonin neuron, causing an increase in depression, perhaps even to a point where a person is more depressed then before he began therapy.
Todd
poster:King Vultan
thread:319923
URL: http://www.dr-bob.org/babble/20040304/msgs/320634.html