Posted by chemist on April 10, 2004, at 19:05:43
In reply to Re: ssri's effect on cognitive functioning??? » chemist, posted by SpaceFairy on April 10, 2004, at 2:11:50
spacefairy, you are right-on in re: the miasma of isoenzymes involved in metabolizing any drug. as you note - and i certainly agree - the goal is the pinpoint effective therapies and, sadly, this is currently done using the shotgun approach by most mental healthcare practitioners (``don't like prozac? try some remeron...how about paxil?'' etc.). the cognitive impairment by SSRIs or TCSa baffles me, and i am wont to attribute these effects to (very) particular genetic variations in subpopulations, as the receptors targeted by SSRIs/TCAs are not those implicated in neurodegenerative diseases (neuronal nicotine receptors, for one). in any event, all the white-papers by every manufacturer of an SSRI/TCA does in fact reflect what you correctly note in re: the hepatic pathway for metabolism. i stand corrected and wish you well...best, chemist
> Hi Chemist,
>
> Thanks for the reply. As I said yesterday this really isn't my field of expertise (well the nerurobiology isn't!), so I've been doing a bit of digging & managed to find out the following:
>
> "Some drugs are metabolized by the cytochrome P450 2D6 enzymes, individuals having a deficiency of this enzyme will have a higher toxicity of drugs metabolized by them. It is not possible to generalize which drugs are metabolized by the enzyme system, since different drugs undergo different pathways of metabolism. Yes, Pharmacogenetics can be used to select individual for particular therapy, though it still is a very expensive way of deciding.You are right in assuming that the test can bve carried out using a blood sample, this could be done by studying what is known as an ex-vivo system. That is you give the drug to the whole individual and then test for metabolites in the blood."
>
> and also:
>
> "This type of determination is still very much at the research stage but as you are probably aware has become a prime target to explain certain drug interactions. There are so many isoenzymes in the cytochrome P450 group that it is becoming increasingly difficult to keep up-to-date with them. Different types are involved with different drugs and just because one SSRI affects one subtype it does not follow that a similar SSRI will affect the same subtype, never mind the MAOIs et al. As far as I know the technology is available do the appropriate genotyping on a blood sample but it is not yet a routine test and is unlikely to be so for several years yet."
>
> As of for the risk of cognitive impairment, there have been short-term risks identified by many studies & case files (in individauls who are unable to metabolist these drugs), and also the PANES report (Lathe) outlines the possibility for longer term damage. As for the trycyclics, whilst I did not suffer any long-term cognitive problems with them I have been left with tardive tremor. Whilst there are a significant amount of people that find these drugs beneficial, we must also address the possibility that they can cause damage with others. After all, is that not why more & more research is looking at gli cells as being instrumental in mental health problems, with the aim of developing safer medications?
>
> Best wishes, SpaceFairy
>
poster:chemist
thread:331128
URL: http://www.dr-bob.org/babble/20040407/msgs/335009.html