Posted by Brainbeard on June 21, 2009, at 6:10:58
In reply to Re: What are TCa's like?, posted by newo38 on June 15, 2009, at 22:30:57
I like your story, Bleauberry. I'm a fan of Gillman myself too. I do think though that Gillman is a bit one-sided in his critique of the newer antidepressants. The commercial theatre of the pharmaceutical industry and the striving for drugs that hit a single target are only part of the story. There are valid and rational reasons behind the development of the SSRIs, as Dr. Preskorn so eloquently explains in his online book about these drugs (http://www.preskorn.com/books/ssri_toc.html). Selectivity doesn't just mean hitting only one target, but also avoiding hitting the wrong targets, which, in the end, is what TCA's do. Gillman thinks that the side-effects of the TCA's have been greatly exaggerated for commercial purposes. On the one hand, he's right; on the other hand, the side-effects of the TCA's CAN be disproportionally inconvenient, and their possible lethality IS a major drawback for a certain group of people.
Still, the SSRIs aren't by far as ideal as the pharmaceutical industry would have them to be; their side-effects, especially in the long-term, can actually be quite DEPRESSING.
Plus, the multiple action of the TCA's still makes for a unique combination of therapeutic qualities that can only be approached by augmenting SSRIs with at least one other drug.
It must be said, though, that clomipramine is such a strong SRI that it offers all the side-effects of a tertiary amine TCA *PLUS* the side-effects of a strong SSRI (loss of libido, possibly teeth grinding etc.) Nevertheless, emotional numbing might be prevented with clomipramine by the NRI action of its metabolite.That's another point I would like to mention just for completeness: taking a tertiary amine TCA in practice means taking TWO drugs, namely the teriary amine TCA and its active metabolite.
The most important ones:imipramine (relatively strong, mildly sedative SNRI) -> desipramine (strong NRI). Since desipramine potentially has a half-life of more than hundred hours, and imipramine a half-life of less than 24 hours, the desipramine tends to dominate on higher dosages.
amitriptyline (dirty, sedative, anxiolytic NSRI -> nortriptyline (sedative, anxiolytic NRI)
clomipramine (strong, sedative, anxiolytic SRI and SNRI) -> desmethylclomipramine (NRI). Also with clomipramine, the metabolite has a longer half-life, so on higher dosages the NRI-action is boosted significantly more than the SRI-action. In fact, clomipramine is such a strong SRI that even 10mg is enough to reach the amount of serotonin reuptake inhibition that a typical therapeutic dose of an SSRI delivers (http://archpsyc.ama-assn.org/cgi/content/full/60/4/386).
Combining an SSRI with a TCA is indeed a great idea. I'm thinking of combining the low dose imipramine I'm taking now with sertraline (Zoloft). Combining TCA's by themselves is also a great possibility, although apparently not much explored. I'm thinking of combining my imipramine with low dose amitriptyline.
HyperFocus made a necessary point: fluoxetine (Prozac) elevates TCA-levels enormously; paroxetine (Paxil/Seroxat) elevates them considerably; and sertraline (Zoloft) elevates them considerably as well on higher dosages. Fluvoxamine (Luvox), although not a 2D6-inhibitor, inhibits 1A2 and 3A4 and thereby elevates clomipramine levels enormously. Interestingly, since fluvoxamine inhibits clomipramine's conversion to desmethylclomipramine, it boosts clomipramine's SRI-action while blocking its NRI-action, which can be helpful for some people. I've been on a combination of 150mg fluvoxamine and only 10mg of clomipramine and it worked wonders.Finally, as an introduction to the marvellous Ken Gillman I recommend his online-article 'Tricyclic antidepressant pharmacology and therapeutic drug interactions updated' (http://www3.interscience.wiley.com/cgi-bin/fulltext/121665024/HTMLSTART?CRETRY=1&SRETRY=0). His website (http://www.psychotropical.com/) is a bit... dirty, I suppose would be the right word; although hitting multiple targets, I mean, treating a variety of subjects.
Cheers to all of you.
poster:Brainbeard
thread:901060
URL: http://www.dr-bob.org/babble/20090620/msgs/902389.html