Posted by linkadge on December 1, 2012, at 10:19:38
In reply to SSRI receptor downregulation. Linear relationship?, posted by Prefect on December 1, 2012, at 9:34:27
The receptor downregulation may or may not have anything to do with the efficacy of SSRIs.
This is a very early observation in the history of antidepressants - i.e. that chronic exposure toe the TCAs resulted in downregulation of serotonin and norepinephrine receptors. The problem is that there is no consistently documented 'upregulation' of these receptors in unmedicated depressed individuals, nor an explaination as to why such downregulation would result in a theraputic effect.
Really, its more of an observation that when you flood the brain with a particular neurotransmitter, the brain responds by making less receptors for that particular neurotransmitter. The same has been observed after chronic exposure to say cocaine or amphetamines. However, chronic exposure to stimulants works opposite to that of antidepressants, i.e. initial improvement in mood followed by progressive mood worsening.
I don't think that there would be a linear relationship between SSRI dose and receptor downregulation. The reason being is that SSRI dose is not related linearly to drug concentration, drug concentration is not linearly related to SERT receptor occupancy and SERT receptor occupancy is not linearly related to increase in serotonin levels.
The antipanic effect of SSRIs may be more related to the increase in gaba levels that occurs after adniminstration of the drugs. Such increase may occur because of drug interaction with neurosteroid synthesis.
If a higher dose is needed to get back to remission, i wouldn't worry about it. Sometimes after improvement, a lower dose can retain the effect.
Linkadge
poster:linkadge
thread:1032268
URL: http://www.dr-bob.org/babble/20121130/msgs/1032272.html