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gaba and treatment resistance?

Posted by linkadge on September 11, 2010, at 20:38:55

Hi, I have been reading a few articles on how many psychiatric disorders are associated with low levels of GABA. For instance, the following breif article refers to studies suggesting that the more treatment resistant the patient is, the lower their gaba levels.

http://mentalhealthupdate.blogspot.com/2010/03/gaba-and-depression.html

I know a lot of of SSRI users lose response to their medications over time. Some stop taking them and complain that the drugs don't work again. SSRIs appear to increase the release of GABA in certain areas of the brain (parietal cortex, frontal cortex etc.) Others complain of insensitivity to light and sound, and further sensitivity towards other psychiatric medications in general.

Could it be possible that long term use of antidepressants drugs actually lowers inhibitory neurotransmission, pulling things towards excitory - hence the efficacy of augmentation with mood stabilizers, anticonvulsants, lithium, benzodiazapines etc?

There is some preliminary evidence too that gabaergics are effective for preventing relapse into drug abuse (i.e. meth, cocaine etc.). The gaba-b agonist baclofin appears to have anti-tollerance, anti-craving effects. Yet, long term SSRI use (and cocaine) upregulates GABA-b receptors. Could it be that the upregulation of GABA-b receptors is some mechanism behind drug sensitization. I.e. slowly shifting the balance to excitory?

Could it be that antidepressants (monoamine uptake inhibitors) are almost working like street drugs to somehow sensitize the brain. Drugs like cocaine and venlafaxine upregulate d3 receptors. In the case of cocaine, this process is linked to sensitization. For venlafaxine, this process is supposedly linked to a theraputic effect (heh).

Anyway, I think perhaps treatment resitance could be seen as a form of sensitization, and that drugs which help drug addicts kick craving and relapse, could help major depressives regain homeostatis.


Linkadge



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poster:linkadge thread:962114
URL: http://www.dr-bob.org/babble/20100908/msgs/962114.html