Posted by SLS on December 6, 2009, at 11:02:25
In reply to Re: The Three Day Blip Of Antidepressants, posted by bleauberry on December 6, 2009, at 9:50:28
> My theory of the 3-day blip is two-fold. First, the synapses feel good when they suddenly have more neurotransmitters than they are accustomed to. But then the feedback loops kick in, which takes about 3 days.
I disagree.
My theory: I think the loss of the blip improvement occurs as the consequence of a phenomenon known as accommodation. Basically, once the synaptic concentration of neurotransmitter surpasses a certain threshold, the postsynaptic neuron no longer has the time to fully repolarize and prepare itself for the next action potential. So, yes, there is an initial enhancement of neural activity, however, once the threshold of accomodation is reached, firings are reduced or cease, only to reappear two weeks later as postsynaptic receptors downregulate and allow for repolarization.
> At that time, I believe gene instruction for amino acid utilization is changed, receptor sensitivity is changed, and the production of neurotransmitters is slowed down or stopped. When production resumes after things have settled down in the new environment, that's when improvement comes...coincidentally it takes a few weeks...IF it is going to happen. That's a big IF, and a potential reason for nonresponse...the feedback loops rule and never adapt depending on one's genes.
I think the reduction in synthesis and release of neurotransmitter is immediate upon the initiation of treatment. This has nothing to do with gene expression. What is the result of gene expression is the downregulation of presynaptic autoreceptors. To allow the levels of neurotransmitter to recover. It is probably a matter of ratios between pre- and post- synaptic membrane sensitivities that determine the transduction and propogation of an action potential.
> SLS mentioned no numbers to support his views (in quotes below),Oops. No citations. Sorry. I had read this stuff a LONG time ago.
I guess we don't always have the time to search out citations to support all of our views, wouldn't you agree?
> As a sidenote, almost all the studies fail to show which stable depressed patients actually got much worse when starting a med. So much worse they had to drop out.
People drop out of clinical trials for a variety of reasons, including the emergence of side effects. Some people are unable to continue beyond two weeks because they cannot tolerate the persistance of their depression. Some people feel worse because the drug makes them feel worse. Others will begin to respond early and acquire the psychic energy to contemplate suicide more actively. This is usually a passing phase, although a critical one. My guess is that it is unusual for someone to experience a true exacerbation of their depression initially and go on to respond well to treatment afterwards.> The few studies that do include those numbers show the percentage to be in the range of 5% to 15%.
I would be interested to see one of these studies.
- Scott
poster:SLS
thread:928269
URL: http://www.dr-bob.org/babble/20091206/msgs/928316.html