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Re: Older drugs vs. newer drugs... » BrittPark

Posted by zeugma on January 19, 2003, at 20:37:30

In reply to Re: Older drugs vs. newer drugs... » jay, posted by BrittPark on January 19, 2003, at 16:57:45

>
> I think doctors prescribe SSRIs in preference to TCAs not so much because SSRIs are more effective (they're not), or because they have more tolerable side effects, but because they are safer in overdose. There might also be a bit of "Marketing" at work ;)
>
> Cheers,
>
> Britt

I suspect that this is the main reason too. It's understandable I guess, but also unfortunate and rather ironic, because what I have seen confirms my suspicions that TCA's are more effective in severe depression, especially long-term, than SSRI's.
Also, we have to consider the fact that TCA's were discovered by 'accident' whereas SSRI's were deliberately engineered. This may seem to favor the SSRI's, but inasmuch as we still don't know what depression IS, there's no guarantee that the deliberately designed drug is going to work better than the accidental product. I think really it's the reverse- given our ignorance of how depression works, it's inevitable that a drug designed to hit ONLY this 'target' is going to be dicey at best.

Also selectivity would seem to have another downside as well- more knowledgeable posters please correct me on this. If a drug is basically only inhibiting 5-HT reuptake, that results in a tremendously higher level of reuptake inhibition than any of the older drugs. If a TCA is equally selective for 5-HT and NE, then you would basically need to double the dosage of the TCA to get an equivalent level of 5-HT effect to an SSRI because half of its binding is going to NE. Actually, it's even less than that (again correct me if I'm wrong) because these are very 'dirty' drugs. So a lot of it is going to histamine, ACH inhibition, etc. Resulting in an even more dispersed level of action that might for all we know be more effective in alleviating depression.



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